專(zhuān)利名稱(chēng):吸水鏈霉菌17997生物合成格爾德霉素的基因簇的制作方法
技術(shù)領(lǐng)域:
本發(fā)明涉及從抗生素產(chǎn)生菌中克隆并獲得抗生素生物合成基因簇序列,用于提高抗生素產(chǎn)量或改造其結(jié)構(gòu),以獲得性能更好的新抗生素。
背景技術(shù):
吸水鏈霉菌17997是從我國(guó)土壤中分離得到的一株放線菌,經(jīng)鑒定其產(chǎn)生格爾德霉素(geldanamycin-Gdn)。格爾德霉素具有抗菌、抗原蟲(chóng)及抗腫瘤活性,它在體內(nèi)、外能抑制癌基因表達(dá)產(chǎn)物,并可特異性地與熱休克蛋白Hsp90結(jié)合。近年來(lái),由于其具有結(jié)構(gòu)獨(dú)特、作用機(jī)制新穎等特點(diǎn),格爾德霉素在醫(yī)藥及生物學(xué)領(lǐng)域備受關(guān)注。格爾德霉素衍生物作為抗腫瘤藥物已在NCI等單位進(jìn)行I期臨床試驗(yàn)。此外,本所還發(fā)現(xiàn)格爾德霉素具有良好的廣譜抗病毒作用(陶佩珍等,1997,1998,2001)。
格爾德霉素屬于苯醌型安莎霉素類(lèi)抗生素。已知安莎霉素類(lèi)抗生素是由一個(gè)脂肪族安莎鏈通過(guò)酰胺鍵橋接作用,連接在苯或萘發(fā)色基團(tuán)的非鄰近位置而形成的。苯或萘發(fā)色基團(tuán)的合成是由不尋常的3-氨基-5-羥基苯甲酸(AHBA)作為起始單位;脂肪族安莎鏈?zhǔn)怯傻图?jí)脂肪酸經(jīng)聚酮合酶(TypeI PKS)催化縮合而形成。安莎霉素類(lèi)抗生素中利福霉素、napthomycin、ansatrinin、ansamitocin及絲裂霉素C的生物合成途徑已有較多研究,它們的生物合成基因簇已得到克隆。目前,格爾德霉素生物合成的分子生物學(xué)背景還不十分清楚,相關(guān)生物合成基因未見(jiàn)報(bào)道。
由于安莎霉素類(lèi)抗生素結(jié)構(gòu)類(lèi)似,推測(cè)它們生物合成途徑相似。因此有可能利用部分已知基因序列克隆并獲得格爾德霉素生物合成基因。發(fā)明目的本發(fā)明的目的在于利用現(xiàn)今發(fā)展的分子生物學(xué)手段,以安莎類(lèi)化合物生物合成基因保守序列(AHBA基因)克隆相關(guān)基因,以此為探針,克隆并獲得格爾德霉素生物合成基因簇,從而為提高格爾德霉素發(fā)酵產(chǎn)量和優(yōu)化改造其結(jié)構(gòu)奠定基礎(chǔ)。
發(fā)明內(nèi)容
1.克隆部分AHBA合酶基因利用生物學(xué)軟件Vector NTIsuit6.0程序?qū)CBI數(shù)據(jù)庫(kù)中所有登錄的含AHBA結(jié)構(gòu)抗生素rifamycinB,ansatrieninA,napthomycin,mitomycinC,ansamitocin等的AHBA合酶編碼序列分析,根據(jù)其氨基酸序列的保守區(qū)設(shè)計(jì)一對(duì)簡(jiǎn)并引物上游引物 5′-AGA TTCGAGCRSGAGTTCGC-3′BamHI
下游引物 5′-GCA GGAMCATSGCCATGTAG-3′其中R=A/G,S=G/C,M=A/C以S.hygroscopicus17997菌種(本所菌種保藏中心保存)基因組DNA為模板,在LATaq酶作用下進(jìn)行PCR反應(yīng),結(jié)果擴(kuò)增出755bp特異性條帶(圖1)。將755bpPCR產(chǎn)物測(cè)序分析,結(jié)果顯示,該P(yáng)CR產(chǎn)物編碼的氨基酸與已知的利福霉素產(chǎn)生菌Amycolatopsis mediterranei中的AHBA合酶;ansatrienin,napthomycin的產(chǎn)生菌S.collinus和ansamitocin的產(chǎn)生菌Actinosynnema pretiosum中的AHBA合酶保守區(qū)高度同源,其同源性比較如下 2.格爾德霉素生物合成基因的克隆與序列分析755bpPCR產(chǎn)物序列分析結(jié)果說(shuō)明已克隆到了AHBA合酶的部分編碼基因。隨后以此PCR產(chǎn)物為探針,選擇高嚴(yán)謹(jǐn)度的雜交條件與S.hygroscopicus17997基因文庫(kù)進(jìn)行菌落雜交和Southern分子雜交。最終從文庫(kù)中篩選獲得陽(yáng)性克隆,并經(jīng)Southern分子雜交證明在BamHI 4.0kb片段處有雜交信號(hào)的有7個(gè),其BamHI酶切圖譜及相互關(guān)系如圖2。以鳥(niǎo)槍克隆方法對(duì)BamHI 4.0kb所在柯斯質(zhì)粒pCGBA10進(jìn)行了大規(guī)模的測(cè)序。然后將測(cè)序結(jié)果拼接,測(cè)序結(jié)果以FramPlot程序分析讀碼框,通過(guò)Blast程序與NCBI數(shù)據(jù)庫(kù)中序列進(jìn)行同源性比較及保守序列分析,證明該基因簇負(fù)責(zé)格爾德霉素的生物合成。目前本發(fā)明獲得的序列已送交Genbank的有以下1-21個(gè)基因,其情況如下1.gdnM(Genbank收錄號(hào)為AF521894)參與生物合成調(diào)節(jié)的新基因,其基因大小為819bp,編碼由273個(gè)氨基酸組成的蛋白。atggggtcat gtggcggcgg tccacgagcc gcgcttgtca tcggcgtgat gaagattgag 60Met Gly Ser Cys Gly Gly Gly Pro Arg Ala Ala Leu Val Ile Gly Val Met Lys Ile Gluccatcgttac gcataccggc aacggctggc accatggctg ccatgtccgc cgggccgccc 120Pro Ser Leu Arg Ile Pro Ala Thr Ala Gly Thr Met Ala Ala Met Ser Ala Gly Pro Prottccgtctcg cacgagccgc cgtgttcgcg gcgatgtgcg tcgtggtgac ggcgctcgga 180Phe Arg Leu Ala Arg Ala Ala Val Phe Ala Ala Met Cys Val Val Val Thr Ala Leu Glycacgtgctga tgtccggtgac aggctgccgg tgtgggccgt ggccgccgc cttcgccgga 240His Val Leu Met Ser Gly Asp Arg Leu Pro Val Trp Ala Val Ala Ala Ala Phe Ala Glyacggcggccg gtgcgtggtgg gttgcggggc gggagcacgg tgcgctggc cgtgaccggg 300Thr Ala Ala Gly Ala Trp Trp Val Ala Gly Arg Glu His Gly Ala Leu Ala Val Thr Glygcgaccgtgg tcgcgcaattc ggcctccata tggccttccg gttcgcgga gacggcagtc 360Ala Thr Val Val Ala Gln Phe Gly Leu His Met Ala Phe Arg Phe Ala Glu Thr Ala Valgccccagcgg cgggaagcgcc atgggtgacg ggatgtccgg tatgcgggg cggcatgggc 420Ala Pro Ala Ala Gly Ser Ala Met Gly Asp Gly Met Ser Gly Met Arg Gly Gly Met Glygccgccccga tgagcggcgcc gccatgggtc atatgcacga tggcatggg ccatatgcgc 480Ala Ala Pro Met Ser Gly Ala Ala Met Gly His Met His Asp Gly Met Gly His Met Argcatggcgcgg acgcgatctcc tccgccgcgc cgtccatgag tcatctgcc gtggccctgg 540His Gly Ala Asp Ala Ile Ser Ser Ala Ala Pro Ser Met Ser His Leu Pro Trp Pro Trpgcgggtccgg gcggggcgggc atggccacgg cccacctgct cgccgccct gatctgcggg 600Ala Gly Pro Gly Gly Ala Gly Met Ala Thr Ala His Leu Leu Ala Ala Leu Ile Cys Glyctgtggctgt ggcgcggcgaa cgggccgcct tccggctcgg ccgcgcgct cgcggccctg 660Leu Trp Leu Trp Arg Gly Glu Arg Ala Ala Phe Arg Leu Gly Arg Ala Leu Ala Ala Leuctgttcgtcc cgctcgtcct cgccctgcgca tcctgggcgc gggtgtcac tccgccgccc 720Leu Phe Val Pro Leu Val Leu Ala Leu Arg Ile Leu Gly Ala Gly Val Thr Pro Pro Progcatggacct ccgcaccggc cgtcgcccgcc ggccgcgcgg agtcctgct gcggcacgtc 780Ala Trp Thr Ser Ala Pro Ala Val Ala Arg Arg Pro Arg Gly Val Leu Leu Arg His Valatcctgcgca gagggccacc gaggcggttc gccatccgc 819Ile Leu Arg Arg Gly Pro Pro Arg Arg Phe Ala Ile Arg該基因產(chǎn)物顯示與Streptomyces coelicolor A3(2)假定的膜蛋白同源,但同源性較低。2.gdnQ(Genbank收錄號(hào)為AF521894) 氧化還原酶基因,為一個(gè)不完整的ORF,其基因大小為1233bp,編碼411個(gè)氨基酸的蛋白。gtgagccagt tcatagaaga tgtccggaac tcatcgatgc ccgcatccga cgactcaacc 60Val Ser Gln Phe Ile Glu Asp Val Arg Asn Ser Ser Met Pro Ala Ser Asp Asp Ser Thrggcgcgtgtc cgcctgccgc cgttgccccg agccaggagt cgtccatgtc cgctggcccc 120Gly Ala Cys Pro Pro Ala Ala Val Ala Pro Ser Gln Glu Ser Ser Met Ser Ala Gly Proctcgccccgg ccaccccatg gcgcagggcg acgggtgccg ctgtacgtcc tcgtcccgct 180Leu Ala Pro Ala Thr Pro Trp Arg Arg Ala Thr Gly Ala Ala Val Arg Pro Arg Pro Alaggccgcggcc atcgccgtga tcggctacta cctgcccctg ctcggcatcc gcctcgccgc 240Gly Arg Gly His Arg Arg Asp Arg Leu Leu Pro Ala Pro Ala Arg His Pro Pro Arg Argcttcctggcc gtcgacatcg ccgcgggcga gatcgcccgc ggccgcgcca ccatcccggc 300Leu Pro Gly Arg Arg His Arg Arg Gly Arg Asp Arg Pro Arg Pro Arg His His Pro Glycgcctgaccc cggtttgcca tctcggcaat atgttttgcc tcgatggagg gtgggctcgc 360Arg Leu Thr Pro Val Cys His Leu Gly Asn Met Phe Cys Leu Asp Gly Gly Trp Ala Argatggttgccg tggaggtggt caaggtggcc gatgagctga agaacgcctt tgacgtggtg 420Met Val Ala Val Glu Val Val Lys Val Ala Asp Glu Leu Lys Asn Ala Phe Asp Val Valgtgatcggcg gtggcgccgc tgggctgagc ggggcgctgat gctggcccg gtcgcggcgt 480Val Ile Gly Gly Gly Ala Ala Gly Leu Ser Gly Ala Leu Met Leu Ala Arg Ser Arg Argtcggtggtgg tgatcgacgc gggcgccccg cgcaacgcccc ggcctcggc ggtgcacgga 540Ser Val Val Val Ile Asp Ala Gly Ala Pro Arg Asn Ala Pro Ala Ser Ala Val His Glyctgctggccc gggacgggat ccctccggcc gagttggtggc ccggggccg ggccgaggtc 600Leu Leu Ala Arg Asp Gly Ile Pro Pro Ala Glu Leu Val Ala Arg Gly Arg Ala Glu Valcgcggctacg gcggtcaggt ggtgtccggc gaggtgggcgc cgtgacccg ggaggagtcc 660Arg Gly Tyr Gly Gly Gln Val Val Ser Gly Glu Val Gly Ala Val Thr Arg Glu Glu Sergggggcttcc aggtggccct gaccgatggc cggaccgtacg tgcgcgccg gttgctgctg 720Gly Gly Phe Gln Val Ala Leu Thr Asp Gly Arg Thr Val Arg Ala Arg Arg Leu Leu Leugccaccgggc tggtcgacga gttgccggac atcccggggct gcggtcccg gtggggccgg 780Ala Thr Gly Leu Val Asp Glu Leu Pro Asp Ile Pro Gly Leu Arg Ser Arg Trp Gly Arggatgtgctgc actgtccgta ctgccacggc tgggaggtccg cgaccaggc catcggcgta 840Asp Val Leu His Cys Pro Tyr Cys His Gly Trp Glu Val Arg Asp Gln Ala Ile Gly Valctggggagcg ggccgctgtc ggtgcaccag gcgctgctgtt ccgtcagtg gagcgacgat 900Leu Gly Ser Gly Pro Leu Ser Val His Gln Ala Leu Leu Phe Arg Gln Trp Ser Asp Aspgtcaccttct tcccccacac cctgccgtcg ccgtccggcga ggaggcgga gcagctggcc 960Val Thr Phe Phe Pro His Thr Leu Pro Ser Pro Ser Gly Glu Glu Ala Glu Gln Leu Alagcccgtggca tccgtgtggt ggacggcgag gtggcgtcct tggagatcgt cgaggaccgc 1020Ala Arg Gly Ile Arg Val Val Asp Gly Glu Val Ala Ser Leu Glu Ile Val Glu Asp Argctcgtcggcg tgcggctggg cgacggcggc gtggtcgagcg cgaggcgct ggccgtcgcg 1080Leu Val Gly Val Arg Leu Gly Asp Gly Gly Val Val Glu Arg Glu Ala Leu Ala Val Alaccgcggatgg tggcacacgc cggtctcctg gcggggctcgg gctgcggcc ggtggagcat 1140Pro Arg Met Val Ala His Ala Gly Leu Leu Ala Gly Leu Gly Leu Arg Pro Val Glu Hisccgagcggcg gcggtgagca catcccgtcc gacgcgaccg ggcgcaccga ggtgtccggg 1200Pro Ser Gly Gly Gly Glu His Ile Pro Ser Asp Ala Thr Gly Arg Thr Glu Val Ser Glygtgtgggtcg cgggcaatgt caccgatctg gcg1233Val Trp Val Ala Gly Asn Val Thr Asp Leu Ala該基因產(chǎn)物顯示與Streptomyces coelicolor氧化還原酶有較高的同源性,一致性為42%,相似性為52%。S.coelicolor ------------------------------------------------------------ 1gdnQ.pro VSQFIEDVRNSSMPASDDSTGACPPAAVAPSQESSMSAGPLAPATPWRRATGAAVRPRPA 60S.coelicolor ------------------------------------------------------------ 1gdnQ.pro GRGHRRDRLLPAPARHPPRRLPGRRHRRGRDRPRPRHHPGRLTPVCHLGNMFCLDGGWAR 120 S.coelicolor PVAQVGTSAAAGALAGIEMNKMLAIADTDAALQKLSGGSPKGATG338gdnQ.pro L--------------------------------------------4103.gdnS(Genbank收錄號(hào)為AF521894)編碼δ因子基因,其大小為630bp,編碼由210個(gè)氨基酸組成的蛋白。atgccttctg ccacgctgcc cgccgcaccg ataagagccg tgcacggcct tgccaccgcg 60Met Pro Ser Ala Thr Leu Pro Ala Ala Pro Ile Arg Ala Val His Gly Leu Ala Thr Alagcgaacgacc accaggtcac cgaatgggcg ctggccgccc gggacggcga ccgcgaggcg 120Ala Asn Asp His Gln Val Thr Glu Trp Ala Leu Ala Ala Arg Asp Gly Asp Arg Glu Alagtcgaccact tcatccgcgc cacctaccgc gatgtgcgcc gtttcgtgct ccacctcagc 180Val Asp His Phe Ile Arg Ala Thr Tyr Arg Asp Val Arg Arg Phe Val Leu His Leu Sergccgatccgc atggttgtga ggacctcgcc caggagacgt atctgcgggc gctgaccggg 240Ala Asp Pro His Gly Cys Glu Asp Leu Ala Gln Glu Thr Tyr Leu Arg Ala Leu Thr Glyctgccgcgct tcgccggtcg ctcatcggcc cggacgtggc tgctgtcgat cgcccgccgt 300Leu Pro Arg Phe Ala Gly Arg Ser Ser Ala Arg Thr Trp Leu Leu Ser Ile Ala Arg Arggtggtcgtcg accgctaccg cacggccgcc gcccgtcccc gtacgttgga cgcggacgac 360Val Val Val Asp Arg Tyr Arg Thr Ala Ala Ala Arg Pro Arg Thr Leu Asp Ala Asp Asptggcaggagg cggccgaacg ggcgcagccc gccgggctcc ccgggttcga cgagggggtg 420Trp Gln Glu Ala Ala Glu Arg Ala Gln Pro Ala Gly Leu Pro Gly Phe Asp Glu Gly Valgcgctgatgg acctgctggc ggcgctcgcc ccggcacgcc gtgagatgtt cctcctcacc 480Ala Leu Met Asp Leu Leu Ala Ala Leu Ala Pro Ala Arg Arg Glu Met Phe Leu Leu Thraaggtgctcg gcctgccgta cgcggacgcc gcgaccgcga ccggctgccc catcggcacc 540Lys Val Leu Gly Leu Pro Tyr Ala Asp Ala Ala Thr Ala Thr Gly Cys Pro Ile Gly Thrgtacgctcgc gcgtggcccg cgcccgtgag gacatctccg cgctgctggc cgcggccgag 600Val Arg Ser Arg Val Ala Arg Ala Arg Glu Asp Ile Ser Ala Leu Leu Ala Ala Ala Gluaaggccgcgg gaccggtgcc gttggtgggc630Lys Ala Ala Gly Pro Val Pro Leu Val Gly該基因產(chǎn)物顯示與Streptomyces coelicolorA3(2)SigmaE編碼的δ因子同源,一致性為63%,相似性為73%。 δ因子與RNA聚合酶的核心酶(α2ββ’)結(jié)合,而產(chǎn)生有活性的RNA聚合酶(α2ββ’δ)以識(shí)別基因的啟動(dòng)子序列。δ因子在鏈霉菌基因的表達(dá)調(diào)控中起重要作用。天藍(lán)色鏈霉菌中的SigmaE-δ因子與氧化壓力有關(guān),它可調(diào)控硫氧還蛋白和硫氧還蛋白還原酶操縱子的轉(zhuǎn)錄及表達(dá)。而硫氧還蛋白和硫氧還蛋白還原酶存在于內(nèi)酰胺類(lèi)抗生素產(chǎn)生菌中,它可保證內(nèi)酰胺類(lèi)抗生素生物合成中關(guān)鍵前體物丙氨酰-半胱氨酰-纈胺酰三肽處于還原狀態(tài),從而使內(nèi)酰胺類(lèi)抗生素正常合成。格爾德霉素具有內(nèi)酰胺結(jié)構(gòu),硫氧還蛋白和硫氧還蛋白還原酶的還原系統(tǒng),可使格爾德霉素前體芳香環(huán)上的氨基處于還原狀態(tài),避免異常氧化,從而使酰胺鍵正常形成。4.gdnP(Genbank收錄號(hào)為AF521894)磷酸化酶基因,其大小為993bp,編碼由331個(gè)氨基酸組成的蛋白。atgaggtccg ccggaccatc ggcgccatcg aacgggtcta cgcctcggcc cggatccacc 60Met Arg Ser Ala Gly Pro Ser Ala Pro Ser Asn Gly Ser Thr Pro Arg Pro Gly Ser Thrgggaggtccg ggagtcggcg tcggtgtgac cgcaccggcc gaccgccccg ccgcaccggc 120Gly Arg Ser Gly Ser Arg Arg Arg Cys Asp Arg Thr Gly Arg Pro Pro Arg Arg Thr Glytccgctccca tccgccccct cccttccctc gccatccctt tcgtcgtctt ccccttctcc 180Ser Ala Pro Ile Arg Pro Leu Pro Ser Leu Ala Ile Pro Phe Val Val Phe Pro Phe Serggaccacgtt ctttcagacc gcgttctttc ggaccgcatt cttcggaccg cgttcttcgg 240Gly Pro Arg Ser Phe Arg Pro Arg Ser Phe Gly Pro His Ser Ser Asp Arg Val Leu Argaccgcacccg agacccggac cggcggtccg ccgtaccggc ccgcaccacg ggagtgctca 300Thr Ala Pro Glu Thr Arg Thr Gly Gly Pro Pro Tyr Arg Pro Ala Pro Arg Glu Cys Seratgaacaccc atccgatcag tcatggcggc ccgctctccg gcgcgggtgt cgcccccatc 360Met Asn Thr His Pro Ile Ser His Gly Gly Pro Leu Ser Gly Ala Gly Val Ala Pro Ileacctcggtgg tcttcgacct cgacggtgtc ctcgtcaaca gcttcgcggt gatgcgcgag 420Thr Ser Val Val Phe Asp Leu Asp Gly Val Leu Val Asn Ser Phe Ala Val Met Arg Glugcgttcaccc tcgcctacgc cgaggtcgtc ggcgacggtg agccaccctt cgaggagtac 480Ala Phe Thr Leu Ala Tyr Ala Glu Val Val Gly Asp Gly Glu Pro Pro Phe Glu Glu Tyraaccggcatc tgggccgcta cttccccgac atcatgcgga tcatgggtct tccgctggag 540Asn Arg His Leu Gly Arg Tyr Phe Pro Asp Ile Met Arg Ile Met Gly Leu Pro Leu Gluatggagggcc cgttcgtccg cgagagctac cggctcgccc acctggtgga gatgttcgac 600Met Glu Gly Pro Phe Val Arg Glu Ser Tyr Arg Leu Ala His Leu Val Glu Met Phe Aspggtgtgccag agctgctgtc ggagctgcgc caccgcgggt tacgactcgc cgtggccacc 660Gly Val Pro Glu Leu Leu Ser Glu Leu Arg His Arg Gly Leu Arg Leu Ala Val Ala Thrgggaagagcg gaccccgggc gcgttcgctg ctcgacaccc tcggcatccg tgggcagttc 720Gly Lys Ser Gly Pro Arg Ala Arg Ser Leu Leu Asp Thr Leu Gly Ile Arg Gly Gln Phecacgtggtcc tcggctcgga cgaggtggcc cggcccaagc ccgcgccgga catcgtgctg 780His Val Val Leu Gly Set Asp Glu Val Ala Arg Pro Lys Pro Ala Pro Asp Ile Val Leuaaggcgatgg acatgatgga cgcggacccc gaccggaccg tgatggtcgg ggacgcggtg 840Lys Ala Met Asp Met Met Asp Ala Asp Pro Asp Arg Thr Val Met Val Gly Asp Ala Valaccgacctgg ccagcgcgcg gggggccggg atcaccgccg tggccgcgat gtggggtgag 900Thr Asp Leu Ala Ser Ala Arg Gly Ala Gly Ile Thr Ala Val Ala Ala Met Trp Gly Gluaccgacgaga agaccctgct cgcggcggag cccgatgtga tcctgcacaa gccggcggaa 960Thr Asp Glu Lys Thr Leu Leu Ala Ala Glu Pro Asp Val Ile Leu His Lys Pro Ala Gluctgctgtcgc tgtgccccga ggtgacggtt cca 993Leu Leu Ser Leu Cys Pro Glu Val Thr Val Pro該基因產(chǎn)物顯示與ansatrienin AHBA生物合成所需的磷酸酶AnsH有高同源性,一致性為78%,相似性為88%。此外它還顯示與napthomycin、rifamycin及mitomycinC的磷酸酶有很好的同源性,NapH一致性為69%,相似性為80%;RifM 一致性為69%,相似性為80%;MitJ一致性為57%,相似性為68%。gdnP.pro MRSAGPSAPSNGSTPRPGSTGRSGSRRRCDRTGRPPRRTGSAPIRPLPSLAIPFVVFPFS 60AnsH.pro ------------------MTGTAG--RRVG-PGCRPCRTAAAPAP--------------- 24MitJ.pro ------------------------------------------------------------ 1RifM.pro ------------------------------------------------------------ 1napH.pro ------------------------------------------------------------ 1ansam.pr ------------------------------------------------------------ 1 ansam.pr ------------------------------------------------------------ 1 5.gdnO(Genbank收錄號(hào)為AF521894)AHBA生物合成中氧化還原酶基因,其大小為1131bp,終止密碼與下游基因起始密碼有重疊,可能與下游基因gdnP處于一個(gè)轉(zhuǎn)錄單位,編碼由377個(gè)氨基酸組成的蛋白。atgagcgccc cgtccatcgg cgagccgccg atcaggaccg ccgtggtggg gctgggatgg 60Met Ser Ala Pro Ser Ile Gly Glu Pro Pro Ile Arg Thr Ala Val Val Gly Leu Gly Trpgcggcccgct cgatctggct gccccggctc cgccacaacc ccgccttcac cgtgaccgcc 120Ala Ala Arg Ser Ile Trp Leu Pro Arg Leu Arg His Asn Pro Ala Phe Thr Val Thr Alagcggtggatc ccgacgagcg cggccgcgcg gccgtcgccg aggcggaggg catggaccgg 180Ala Val Asp Pro Asp Glu Arg Gly Arg Ala Ala Val Ala Glu Ala Glu Gly Met Asp Argctgccggtgc tggcggccgt ccacgacctc gaccccgccg aggtggacct ggcggtggtc 240Leu Pro Val Leu Ala Ala Val His Asp Leu Asp Pro Ala Glu Val Asp Leu Ala Val Valgcggtgccca accatctgca ctgtgcggtc gccgccgagc tgctggccaa gggcattccg 300Ala Val Pro Asn His Leu His Cys Ala Val Ala Ala Glu Leu Leu Ala Lys Gly Ile Progtgttcctgg agaagccggt gtgcctgacc tccgaggagg ccgagcggct ggccgaagcg 360Val Phe Leu Glu Lys Pro Val Cys Leu Thr Ser Glu Glu Ala Glu Arg Leu Ala Glu Alagagcgctcgg gcggcgcgat gctgctggcc ggcagcgcgg cgcggtaccg cgccgatgtg 420Glu Arg Ser Gly Gly Ala Met Leu Leu Ala Gly Ser Ala Ala Arg Tyr Arg Ala Asp Valcgcgggctgt accggatcgc cgcccggctg ggccatatcc gtcatgtcga gctcgcctgg 480Arg Gly Leu Tyr Arg Ile Ala Ala Arg Leu Gly His Ile Arg His Val Glu Leu Ala Trpgtgcggtcac gcggcgtgcc cgaccggggc ggctggttca cccagcggtc gctcgcgggc 540Val Arg Ser Arg Gly Val Pro Asp Arg Gly Gly Trp Phe Thr Gln Arg Ser Leu Ala Glyggcggggcgc tggtcgacct gggctggcat ctgttcgaca tcgcggttcc gctgctgggc 600Gly Gly Ala Leu Val Asp Leu Gly Trp His Leu Phe Asp Ile Ala Val Pro Leu Leu Glyaccgccgcgt tccggcacgc catcgggacc gtgtcctccg acttcatcgt ccagcggtcc 660Thr Ala Ala Phe Arg His Ala Ile Gly Thr Val Ser Ser Asp Phe Ile Val Gln Arg Sertcccgggccg cgtggcgcgg cgacgacggc gacggcccgg cgctcctggg cgccaacggg 720Ser Arg Ala Ala Trp Arg Gly Asp Asp Gly Asp Gly Pro Ala Leu Leu Gly Ala Asn Glyggtgccaccg atgtcgagga caccgcacgc ggattcctca tcaccgacga cggccgttcg 780Gly Ala Thr Asp Val Glu Asp Thr Ala Arg Gly Phe Leu Ile Thr Asp Asp Gly Arg Sergtcgtgctgc acgcgagctg ggcctcgcac gaggaactgg acaccacccg ggtgacgatc 840Val Val Leu His Ala Ser Trp Ala Ser His Glu Glu Leu Asp Thr Thr Arg Val Thr Ilegacggcagcg cgggcagcgc caccctgcgc tgcaccttcg gattcagccc gaaccgcctc 900Asp Gly Ser Ala Gly Ser Ala Thr Leu Arg Cys Thr Phe Gly Phe Ser Pro Asn Arg Leugagaagtcca ccctgacccg taccgtcgac ggtacgaccc ggccggtggc cgtacccacc 960Glu Lys Ser Thr Leu Thr Arg Thr Val Asp Gly Thr Thr Arg Pro Val Ala Val Pro Thrgaaccggtcg gcaccgagta cgaccggcag ctcgacctgc ttcccgcgca actgcgcgac 1020Glu Pro Val Gly Thr Glu Tyr Asp Arg Gln Leu Asp Leu Leu Pro Ala Gln Leu Arg Aspccggccgggc ggggccgggt gatcgatgag gtccgccgga ccatcggcgc catcgaacgg 1080Pro Ata Gly Arg Gly Arg Val Ile Asp Glu Val Arg Arg Thr Ile Gly Ala Ile Glu Arggtctacgcct cggcccggat ccaccgggag gtccgggagt cggcgtcggtg 1131Val Tyr Ala Ser Ala Arg Ile His Arg Glu Val Arg Glu Ser Ala Ser Val該基因產(chǎn)物顯示與ansatrienin AHBA生物合成所需的氧化還原酶有高同源性,AnsG一致性為57%,相似性為64%。此外,與其它含AHBA結(jié)構(gòu)抗生素AHBA合成相關(guān)的氧化還原酶也有同源性,ansamitocins一致性為50%,相似性為59%。
6.gdnA(Genbank收錄號(hào)為AF521894)AHBA合酶基因,其大小為1152bp,該基因終止密碼與其下游基因gdnO有重疊,可能這兩個(gè)基因處于同一轉(zhuǎn)錄單位,編碼由384個(gè)氨基酸組成的蛋白。gtgcgactgc gatccgagct gcccgcatgg ccgcagtacg gcgacgagga gcgcgaggcc 60Val Arg Leu Arg Ser Glu Leu Pro Ala Trp Pro Gln Tyr Gly Asp Glu Glu Arg Glu Alactcatccggg ctctggatca ggggcaatgg tggcgtatcg ggggcggtga ggtcgacgcc 120Leu Ile Arg Ala Leu Asp Gln Gly Gln Trp Trp Arg Ile Gly Gly Gly Glu Val Asp Alattcgaggcgg agttcgccgc ggcccatgga agcgagcacg ccctggcggt caccaacggg 180Phe Glu Ala Glu Phe Ala Ala Ala His Gly Ser Glu His Ala Leu Ala Val Thr Asn Glyacgcatgcgc tggagctcgc cctcgaagtg ctcggggtcg gcgccgactc cgaggtgatc 240Thr His Ala Leu Glu Leu Ala Leu Glu Val Leu Gly Val Gly Ala Asp Ser Glu Val Ilegttcccgcgt tcaccttcat ctcgtcctcg caggcggctc agcggctggg cgcggtggcc 300Val Pro Ala Phe Thr Phe Ile Ser Ser Ser Gln Ala Ala Gln Arg Leu Gly Ala Val Alagtgcccgtgg acgtggaccc ggacacgtac tgcatcgatc cctcagcggt cgaggcggcc 360Val Pro Val Asp Val Asp Pro Asp Thr Tyr Cys Ile Asp Pro Ser Ala Val Glu Ala Alaatcggcccga aaacccgcgc gatcatgccg gtgcacatgg cgggccagatg tgcgacatg 420Ile Gly Pro Lys Thr Arg Ala Ile Met Pro Val His Met Ala Gly Gln Met Cys Asp Metgacgcgctgg gcaagctgtc cgccgactcg ggggtgccgc tgatccagga cgcggcccat 480Asp Ala Leu Gly Lys Leu Ser Ala Asp Ser Gly Val Pro Leu Ile Gln Asp Ala Ala Hisgcgcacggtg cgcggtggcg cggtcagaag gtcggtgagc tgggctcggt cgccgcgttc 540Ala His Gly Ala Arg Trp Arg Gly Gln Lys Val Gly Glu Leu Gly Ser Val Ala Ala Pheagcttccaga acggaaagct gatgacggcc ggcgagggcg gcgccgtgct cttccccgat 600Ser Phe Gln Asn Gly Lys Leu Met Thr Ala Gly Glu Gly Gly Ala Val Leu Phe Pro Aspgccgagatgt acgagagggg cttcgtccgg cacagctgtg gacgtccgcg caccgaccgc 660Ala Glu Met Tyr Glu Arg Gly Phe Val Arg His Ser Cys Gly Arg Pro Arg Thr Asp Argggctacttcc accgcacctc gggctccaac ttccggctga acgagttctc cgcatcggta 720Gly Tyr Phe His Arg Thr Ser Gly Ser Asn Phe Arg Leu Asn Glu Phe Ser Ala Ser Valctgcgcgccc aactcacccg cctggacggc cagatcacca cgcgtgagca gcgctggccg 780Leu Arg Ala Gln Leu Thr Arg Leu Asp Gly Gln Ile Thr Thr Arg Glu Gln Arg Trp Progtgctgagca ggctgctcgc cgagatcccc ggtgtggtac cgcagtcgcg cgacgaccgc 840Val Leu Ser Arg Leu Leu Ala Glu Ile Pro Gly Val Val Pro Gln Ser Arg Asp Asp Argggtgaccgca atccgcacta catggcgatg ttccgggtgc cgggcatcac cgaggagcgc 900Gly Asp Arg Asn Pro His Tyr Met Ala Met Phe Arg Val Pro Gly Ile Thr Glu Glu Argcgtgcgaagg tcgtcgacac cctcatcgag cgcggggtgc ccgcgttcgt cgcgttccgc 960Arg Ala Lys Val Val Asp Thr Leu Ile Glu Arg Gly Val Pro Ala Phe Val Ala Phe Arggcggtctacc gtacggacgc cttctgggag gtcgcggcgc cggatctgac ggtggacgaa 1020Ala Val Tyr Arg Thr Asp Ala Phe Trp Glu Val Ala Ala Pro Asp Leu Thr Val Asp Gluctcgcccgcc gctgcccgca ctccgaggcg ctcacccgcg actgcctttg gctgcaccac 1080Leu Ala Arg Arg Cys Pro His Ser Glu Ala Leu Thr Arg Asp Cys Leu Trp Leu His Hiscgggtgttgc tgggcagcga ggagcagatg cacgaagtgg ccgccgtcgt cgccgatgtg 1140Arg Val Leu Leu Gly Ser Glu Glu Gln Met His Glu Val Ala Ala Val Val Ala Asp Valctcgcgggcg ca 1152Leu Ala Gly Ala該基因產(chǎn)物顯示與ansatrieninAHBA生物合成所需的AHBA合酶AnsF有高同源性,一致性為73%,相似性為78%。它還顯示了與其它含AHBA結(jié)構(gòu)的抗生素的AHBA合酶有同源性ansamitocins產(chǎn)生菌Actinosynnema pretiosum subsp.auranticum一致性為68%,相似性為77%;rifamycin(RifK)一致性為65%,相似性為76%;napthomycin(NapF)一致性為60%,相似性為70%。該基因推測(cè)的氨基酸大小也與已知的AHBA合酶氨基酸大小相似。
該基因產(chǎn)物催化AHBA合成的最后一步,它的功能是將5-脫氧5-氨基-3脫氫莽草酸(aminoDHS)芳香化為AHBA。此外,該基因產(chǎn)物還顯示與多種來(lái)源的氨基轉(zhuǎn)移酶有一定的同源性,例如,它與streptomycin產(chǎn)生菌Streptomycetesgriseus中編碼L-谷氨酰胺青蟹-肌糖-氨基轉(zhuǎn)移酶同源,一致性為34%,相似性為48%。從同源性分析,AHBA合酶除了在AHBA形成的最后步驟起催化作用,它很可能具有類(lèi)似氨基轉(zhuǎn)移酶的第二功能,在氮的引入方面發(fā)揮作用。7.gdnE(Genbank收錄號(hào)為AF521894)AHBA生物合成所需的氨基脫氫奎尼酸(amino-DHQ)脫水酶基因,其大小為444bp,該基因轉(zhuǎn)錄方向與gdnA相反,編碼由148個(gè)氨基酸組成的蛋白。gtgaggtgcc cattgagcag gctgttgttg gtgaacggac cgaatctcgg catactcggc 60Val Arg Cys Pro Leu Ser Arg Leu Leu Leu Val Asn Gly Pro Asn Leu Gly Ile Leu Glyaagcgccagc ccgagatcta cggcacggat acgcttcagg acatcgagcg ctgggtcggg 120Lys Arg Gln Pro Glu Ile Tyr Gly Thr Asp Thr Leu Gln Asp Ile Glu Arg Trp Val Glygaagaggtcg cggagcgcgg ctggaaagtg gattcctacc agttcgatgg cgaagcggag 180Glu Glu Val Ala Glu Arg Gly Trp Lys Val Asp Ser Tyr Gln Phe Asp Gly Glu Ala Gluatcatccaga ccattcaggg gaactacgac acggtcggtg ccatcatcaa tccggccgcg 240Ile Ile Gln Thr Ile Gln Gly Asn Tyr Asp Thr Val Gly Ala Ile Ile Asn Pro Ala Alactcatgatgg ccggatgggg ccttcgggac gcactggcga actatccgcg gccctggata 300Leu Met Met Ala Gly Trp Gly Leu Arg Asp Ala Leu Ala Asn Tyr Pro Arg Pro Trp Ilegaagtgcatc tgtcgaatgt ctgggcccgt gagcagttcc gccatgagtc ggtgaccgga 360Glu Val His Leu Ser Asn Val Trp Ala Arg Glu Gln Phe Arg His Glu Ser Val Thr Glyccgctggccg cgggtgtcat cttcgggctc ggcgccctgg gctaccggct cgccgcccgc 420Pro Leu Ala Ala Gly Val Ile Phe Gly Leu Gly Ala Leu Gly Tyr Arg Leu Ala Ala Arggccctgctcg acaaggtgcc ggac 444Ala Leu Leu Asp Lys Val Pro Asp該基因產(chǎn)物顯示與ansatrienin的AHBA生物合成所需的氨基脫氫奎尼酸(amino-DHQ)脫水酶AnsE有高同源性,一致性為68%,相似性為81%。它還顯示了與其它含AHBA結(jié)構(gòu)的抗生素的氨基脫氫奎尼酸脫水酶有同源性rifamycin(rifJ)一致性為67%,相似性為78%;mitomycin C(MmcF)一致性為65%,相似性為79%。
AnsE.pro S----- 138MmcF.pro D----- 145rifJ.pro SPNGLR 174gdnE.pro ------ 148GdnE功能是使5-脫氧-5-氨基-3-脫氫奎尼酸(amino-DHQ)去掉水分子,轉(zhuǎn)變?yōu)?-脫氧-5-氨基-3-脫氫莽草酸(amino-DHS)。8.gdnK(Genbank收錄號(hào)為AF521894)AHBA生物合成所需的激酶基因,其大小為882bp,該基因轉(zhuǎn)錄方向與gdnE相同,且從讀碼框分析來(lái)看它們可能處于同一轉(zhuǎn)錄單位,編碼由294個(gè)氨基酸組成的蛋白。gtggcgctgc gcctcgaaca cgacgacctc ggcatcagcg aatcctcctt ccgctggccc 60Val Ala Leu Arg Leu Glu His Asp Asp Leu Gly Ile Ser Glu Ser Ser Phe Arg Trp Progagccggacg gtacggacgc catgacgtcc gcgtccggtg gcgccacccg cgatctggac 120Glu Pro Asp Gly Thr Asp Ala Met Thr Ser Ala Ser Gly Gly Ala Thr Arg Asp Leu Aspctgctggcgc gccacatcag ggagctgtgt gcgggccgac ccgagcggct cacaggtgtc 180Leu Leu Ala Arg His Ile Arg Glu Leu Cys Ala Gly Arg Pro Glu Arg Leu Thr Gly Valggggtcgcga tgcccgccac cctcgacgcc accggcacgg tcaccgcctg gcccggccgt 240Gly Val Ala Met Pro Ala Thr Leu Asp Ala Thr Gly Thr Val Thr Ala Trp Pro Gly Argcccagctggg ccggagtgga tctgcgcggc gcgctgtccg ccctcttcgg ccacgccgag 300Pro Ser Trp Ala Gly Val Asp Leu Arg Gly Ala Leu Ser Ala Leu Phe Gly His Ala Glugtgcgctgcg ccgacgacgg cgatctggcc gccctcgccg aagcacacga agcccgctgc 360Val Arg Cys Ala Asp Asp Gly Asp Leu Ala Ala Leu Ala Glu Ala His Glu Ala Arg Cyscccgacctgc tctatctcgg cgtcggcacc gggataggcg gtggcatcgt gctgaacggg 420Pro Asp Leu Leu Tyr Leu Gly Val Gly Thr Gly Ile Gly Gly Gly Ile Val Leu Asn Glyaaacccgtgc ccggtgtggg ccgcggctcc tgcgaagtcg gccacctggt cgtggaccgc 480Lys Pro Val Pro Gly Val Gly Arg Gly Ser Cys Glu Val Gly His Leu Val Val Asp Arggacggaccgc tgtgcgactg cggtcggcgc ggctgcgtcc aggcggcggc ctcgggcccg 540Asp Gly Pro Leu Cys Asp Cys Gly Arg Arg Gly Cys Val Gln Ala Ala Ala Ser Gly Progcgaccctgc gcagggcggc gcggagacgg gacgaggagg tgaccttcac cgcgctgcgc 600Ala Thr Leu Arg Arg Ala Ala Arg Arg Arg Asp Glu Glu Val Thr Phe Thr Ala Leu Argcaagcggtgc gcggcggaaa gccgtgggcg gtggcgtcgc tgcgggagag cggcagggcc 660Gln Ala Val Arg Gly Gly Lys Pro Trp Ala Val Ala Ser Leu Arg Glu Ser Gly Arg Alactggccgcgg ccgtgaccgg cgtatgcgaa ctgctccatc cctcgctcgt gctgatcggc 720Leu Ala Ala Ala Val Thr Gly Val Cys Glu Leu Leu His Pro Ser Leu Val Leu Ile Glyggagggtttg ccgcggcgat gccggagctg gtggcgatgg tggccgagcg gacggcggag 780Gly Gly Phe Ala Ala Ala Met Pro Glu Leu Val Ala Met Val Ala Glu Arg Thr Ala Gluctggggcgcc ccggccatcc accgccaccg gtccggcccg cgcgactggg cgggctgtcc 840Leu Gly Arg Pro Gly His Pro Pro Pro Pro Val Arg Pro Ala Arg Leu Gly Gly Leu Sertcactgcacg gcgccgtgct gctggccagg ggactgccgg ac 882Ser Leu His Gly Ala Val Leu Leu Ala Arg Gly Leu Pro Asp該基因產(chǎn)物顯示與mitomycinC AHBA生物合成所需的激酶MitS有高同源性,一致性為46%,相似性為51%。它還顯示了與其它含AHBA結(jié)構(gòu)的抗生素的激酶有同源性rifamycin(RifN)一致性為44%,相似性為53%;napthomycin(NapI)一致性為41%,相似性為47%。
9.gdnT(Genbank收錄號(hào)為AF521894)功能未知的新基因,其大小為774bp,編碼由258個(gè)氨基酸組成的蛋白。atgctgcgcc actacgacgc catcggactg ctgcgcccgg cccatgtcga ccccgccacc 60Met Leu Arg His Tyr Asp Ala Ile Gly Leu Leu Arg Pro Ala His Val Asp Pro Ala Thrggctaccgcc actactcggc cgcccagctc agccgcctga accgggtcat cgcgctcaaa 120Gly Tyr Arg His Tyr Ser Ala Ala Gln Leu Ser Arg Leu Asn Arg Val Ile Ala Leu Lysgagctcggct tcaccctcca gcaggtgcgg gacatcgtgg acgagaaggt cggcaccgag 180Glu Leu Gly Phe Thr Leu Gln Gln Val Arg Asp Ile Val Asp Glu Lys Val Gly Thr Glugagctgcgcg gcatgctgcg gttgcgccgg gccgagctgg aagccacggt ggaagccgtg 240Glu Leu Arg Gly Met Leu Arg Leu Arg Arg Ala Glu Leu Glu Ala Thr Val Glu Ala Valgcggcacggc tggtgcaggt cgaggcgagg ctccggtcga tcgaaagcga ggggcacatg 300Ala Ala Arg Leu Val Gln Val Glu Ala Arg Leu Arg Ser Ile Glu Ser Glu Gly His Metcccaccgacg acgtcgtcat caagagggtc cccgcggtgc gggtggcgga gctcaccgcg 360Pro Thr Asp Asp Val Val Ile Lys Arg Val Pro Ala Val Arg Val Ala Glu Leu Thr Alaaccgccgcca gcttcgaccc gcaggacatc agcccggtca tcacacccct ctacgaagag 420Thr Ala Ala Ser Phe Asp Pro Gln Asp Ile Ser Pro Val Ile Thr Pro Leu Tyr Glu Gluctgttccggc ggctcgacgc tgcgggcatc accccgacgg gccctggtgt cgcatactac 480Leu Phe Arg Arg Leu Asp Ala Ala Gly Ile Thr Pro Thr Gly Pro Gly Val Ala Tyr Tyrgaggacgccc cggaaggcgg cggcgccatc agtgtgcacg ccgccgtcca ggtgtccgcc 540Glu Asp Ala Pro Glu Gly Gly Gly Ala Ile Ser Val His Ala Ala Val Gln Val Ser Alaccgtcacggg acggcgatga cctccggatc ctcgatctgc cgcccatcga ccacgccgcc 600Pro Ser Arg Asp Gly Asp Asp Leu Arg Ile Leu Asp Leu Pro Pro Ile Asp His Ala Alaaccatcgtcc accgcggccc gatggacgcc gtggtgccca cggcccaggc cctggcccat 660Thr Ile Val His Arg Gly Pro Met Asp Ala Val Val Pro Thr Ala Gln Ala Leu Ala Histggattgacg gcaacggcta ccggtcgacc ggctaccccc gggagatcac cctggagtgc 720Trp Ile Asp Gly Asn Gly Tyr Arg Ser Thr Gly Tyr Pro Arg Glu Ile Thr Leu Glu Cysccggagaacc gtgcggaatg ggtcacggaa ctccagacac cggtggtcca ggtc 774Pro Glu Asn Arg Ala Glu Trp Val Thr Glu Leu Gln Thr Pro Val Val Gln Val該基因產(chǎn)物顯示與Streptomyces reticuli的orf1有高同源性,一致性為128/172(74%),相似性為140/172(80%)。orf1.pro ------------------------------------------------------------ 1gdnT.pro MLRHYDAIGLLRPAHVDPATGYRHYSAAQLSRLNRVIALKELGFTLQQVRDIVDEKVGTE 60 另外它還顯示了與一種固氮菌的轉(zhuǎn)錄調(diào)節(jié)子同源(31%)。氨基酸序列分析顯示,在其N(xiāo)端含有兩個(gè)結(jié)構(gòu)域一個(gè)具有helix-turn-helix結(jié)構(gòu),與具有水銀抗性操縱子調(diào)節(jié)蛋白merR的編碼序列高度同源(98.6%);另一個(gè)與細(xì)菌調(diào)節(jié)蛋白Brp保守區(qū)高度同源(100.0%),氨基酸序列分析顯示,在其N(xiāo)端含有兩個(gè)結(jié)構(gòu)域一個(gè)具有helix-turn-helix結(jié)構(gòu),與具有水銀抗性操縱子調(diào)節(jié)蛋白的編碼序列高度同源GdnT 11 FTIGDFARHGRVSVRMLRHYDAIGLLRPAHVDPATGYRHYSAAQLSRLNRVIALKELGFT 70merR 1YTIGEVAKLAGVSVRTLRYYERIGLLPPPIRTEG-GYRLYSDEDLERLRFIKRLKELGFS 59GdnT 71 LQQVRDIVD 79merR 60 LEEIKELLE68GdnT 14 GDFARHGRVSVRMLRHYDAIGLLRPAHVDPATGYRHY 50Brp 1GEVAKLAGVSVETLRYYEKIGLLPPP-VRTEGGYRRY 36這兩個(gè)結(jié)構(gòu)域都屬于merR轉(zhuǎn)錄調(diào)節(jié)因子家族,它們還顯示與多藥運(yùn)輸調(diào)節(jié)因子及Streptomyces coelicolor A3(2)的merR家族的轉(zhuǎn)錄調(diào)節(jié)因子保守區(qū)同源。MerR家族與調(diào)節(jié)細(xì)菌對(duì)外界壓力如毒性物質(zhì)、氧自由基等的反應(yīng)密切相關(guān)。MerR蛋白通過(guò)其N(xiāo)端保守的DNA結(jié)合結(jié)構(gòu)域與共激活因子結(jié)合,調(diào)節(jié)細(xì)胞膜上多藥運(yùn)輸系統(tǒng)中蛋白的表達(dá),從而抵抗外界壓力。由此表明該基因產(chǎn)物與抗性機(jī)制有關(guān)。抗性相關(guān)基因位于抗生素的起始單位AHBA基因簇中,提示已接近生物合成基因簇的邊界。10.gdnB(Genbank收錄號(hào)AF521895)格爾德霉素脂肪族安莎鏈聚酮合酶基因,大小為2115bp,編碼705個(gè)氨基酸組成的蛋白。gtggctctgc cggaggaaca tcgggtccag gcggcggggt tcgggcttca tccggcactc 60Val Ala Leu Pro Glu Glu His Arg Val Gln Ala Ala Gly Phe Gly Leu His Pro Ala Leuctcgacgcgg ccatgcacac catcgccttc cacgaccgag acgaagccga tgcggagctc 120Leu Asp Ala Ala Met His Thr Ile Ala Phe His Asp Arg Asp Glu Ala Asp Ala Glu Leugtgctgccgt tcgcctatcg agaggtggcg ttgcatgctt cgggggcttc ggcgctgcgg 180Val Leu Pro Phe Ala Tyr Arg Glu Val Ala Leu His Ala Ser Gly Ala Ser Ala Leu Arggtacgcgtaa caccgtccgg cccgaacgcc atgaccctcg acctggccga tggctccggg 240Val Arg Val Thr Pro Ser Gly Pro Asn Ala Met Thr Leu Asp Leu Ala Asp Gly Ser Glygccccggttg cctcggtggg ctcggtggtg tcgcgtccgg tcggcgccga gcacttcggc 300Ala Pro Val Ala Ser Val Gly Ser Val Val Ser Arg Pro Val Gly Ala Glu His Phe Glyacggtggcga cggcggaccg gatgttccgc gtcgcatggg aggaactgcc gattcagccg 360Thr Val Ala Thr Ala Asp Arg Met Phe Arg Val Ala Trp Glu Glu Leu Pro Ile Gln Progacggcacga ccgcggaacc cgtaccggtg gccgatgccg aggacgtgca ccgtctggtc 420Asp Gly Thr Thr Ala Glu Pro Val Pro Val Ala Asp Ala Glu Asp Val His Arg Leu Valacggcgccag agacctcacc gcccgatgtg ctgttgctgg acctgggcgg tggcgtcggc 480Thr Ala Pro Glu Thr Ser Pro Pro Asp Val Leu Leu Leu Asp Leu Gly Gly Gly Val Glyggtggttcgg ccgacgtacg cgagctgacc ggacgggcgt tgcgcgttgt acagacgtgg 540Gly Gly Ser Ala Asp Val Arg Glu Leu Thr Gly Arg Ala Leu Arg Val Val Gln Thr Trpctggaggagc cctcgttggc gttgagtcgg ctggtcgtgg tgacgcgggg cgccgtggcc 600Leu Glu Glu Pro Ser Leu Ala Leu Ser Arg Leu Val Val Val Thr Arg Gly Ala Val Alagtccgggaga gcgatccggt cgatccggcg atggcagcgg tatgggggct gatgggatcc 660Val Arg Glu Ser Asp Pro Val Asp Pro Ala Met Ala Ala Val Trp Gly Leu Met Gly Sergcacaagcgg agaaccccgg gcgcatcctc ctcctcgaca tcgatcaagg gacgataccg 720Ala Gln Ala Glu Asn Pro Gly Arg Ile Leu Leu Leu Asp Ile Asp Gln Gly Thr Ile Proaccccgctac tgcccgcact gctcgtcggt gaccagcacc aactggccct acgcgacacc 780Thr Pro Leu Leu Pro Ala Leu Leu Val Gly Asp Gln His Gln Leu Ala Leu Arg Asp Thracctgcttca cccgccacct catccgtgtg ctggatgcgc cgcagtccgg tccgggtggt 840Thr Cys Phe Thr Arg His Leu Ile Arg Val Leu Asp Ala Pro Gln Ser Gly Pro Gly Glyttggaggacg tgggtgggac ggtactggtg acgggtggga cgggggcgtt gggtgcggtg 900Leu Glu Asp Val Gly Gly Thr Val Leu Val Thr Gly Gly Thr Gly Ala Leu Gly Ala Valgtggcacggc atctggtggc ggtgcacggg atgcggagtg tggtgttggc gagccggaat 960Val Ala Arg His Leu Val Ala Val His Gly Met Arg Ser Val Val Leu Ala Ser Arg Asngggcttgagg cacccggcgc cgccgagttg gaggcggagc tggtgaaggc gggtgcgcgc 1020Gly Leu Glu Ala Pro Gly Ala Ala Glu Leu Glu Ala Glu Leu Val Lys Ala Gly Ala Arggtacgcatcg tcgcgtgtga tgtggcggac cgggacgcgg tggccgggct gctggacgcc 1080Val Arg Ile Val Ala Cys Asp Val Ala Asp Arg Asp Ala Val Ala Gly Leu Leu Asp Alagtcccggcag acgctccgtt gtcggcggtg gtgcatacgg ccggtgttct ggatgacggt 1140Val Pro Ala Asp Ala Pro Leu Ser Ala Val Val His Thr Ala Gly Val Leu Asp Asp Glygtgctgacgg cgttgacccc ggaacgtatg gacgcggtgc tccggccgaa ggtggacggc 1200Val Leu Thr Ala Leu Thr Pro Glu Arg Met Asp Ala Val Leu Arg Pro Lys Val Asp Glygcactccatc tccacgagct gacccggcac ctgggcctgt ccgccttcgt cctgttctcc 1260Ala Leu His Leu His Glu Leu Thr Arg His Leu Gly Leu Ser Ala Phe Val Leu Phe Sertccgccgccg gcaccctcgg caacgcgggt cagggcaact acgccgccgc caacgcctac 1320Ser Ala Ala Gly Thr Leu Gly Asn Ala Gly Gln Gly Asn Tyr Ala Ala Ala Asn Ala Tyrctcgacgcgc tggcccatcg acgccgggcc caggggctgc cggcagtatc cctcgcctgg 1380Leu Asp Ala Leu Ala His Arg Arg Arg Ala Gln Gly Leu Pro Ala Val Ser Leu Ala Trpggcatgtggc agcaggccgc gggaacgggg atgaccggcc gtctcggcga tgccgagcag 1440Gly Met Trp Gln Gln Ala Ala Gly Thr Gly Met Thr Gly Arg Leu Gly Asp Ala Glu Glncgccggatga cacgcggcgg ggtggccccc ttgtccccgg ccgagggcat ggagctcttc 1500Arg Arg Met Thr Arg Gly Gly Val Ala Pro Leu Ser Pro Ala Glu Gly Met Glu Leu Phegacactgcgc tgcgtatggc cgaacccacg gtcctcccca tcaaactgga cctcggtgcg 1560Asp Thr Ala Leu Arg Met Ala Glu Pro Thr Val Leu Pro Ile Lys Leu Asp Leu Gly Alactccgcgccc aggccgccac cggggcggtg cagccgttgc tgcaccggct ggtgccaccg 1620Leu Arg Ala Gln Ala Ala Thr Gly Ala Val Gln Pro Leu Leu His Arg Leu Val Pro Progtccgccgag ccactcgcgc cacggccgag cagggcctgg tgaccggccg gctggcgggc 1680Val Arg Arg Ala Thr Arg Ala Thr Ala Glu Gln Gly Leu Val Thr Gly Arg Leu Ala Glygcgacccccg aggagcggga gcggatcctg ctggagatgg tccagcagga ggccgcccgg 1740Ala Thr Pro Glu Glu Arg Glu Arg Ile Leu Leu Glu Met Val Gln Gln Glu Ala Ala Arggtcctgggac actcggcggc tgccacgctc gaccccgatg tgctgttcac cgagatcggc 1800Val Leu Gly His Ser Ala Ala Ala Thr Leu Asp Pro Asp Val Leu Phe Thr Glu Ile Glyctggactccc tgatggcggt ggaactacgc gatcgcctgg ccaagcgcac cgcgctgcgg 1860Leu Asp Ser Leu Met Ala Val Glu Leu Arg Asp Arg Leu Ala Lys Arg Thr Ala Leu Argttgcctccca gctttgtctt cgaccacccc accctccgga tgctggcccg gcagctgtgg 1920Leu Pro Pro Ser Phe Val Phe Asp His Pro Thr Leu Arg Met Leu Ala Arg Gln Leu Trpgacgagctgg agaaagccga tacggacgct cccgccgcat ccgccccgac tcccgcatcc 1980Asp Glu Leu Glu Lys Ala Asp Thr Asp Ala Pro Ala Ala Ser Ala Pro Thr Pro Ala Sergccgaaactc ccgcatccgc cccaaccgcc ggagccaccc cgtcacccgg agccaccccg 2040Ala Glu Thr Pro Ala Ser Ala Pro Thr Ala Gly Ala Thr Pro Ser Pro Gly Ala Thr Protcacccggag ccaccccgtc acccggagcc actctgccac ccgcgcccac cccgccttcc 2100Ser Pro Gly Ala Thr Pro Ser Pro Gly Ala Thr Leu Pro Pro Ala Pro Thr Pro Pro Sergagccgccc aggag 2115Gly Ala Ala Gln Glu該基因產(chǎn)物顯示與rifamycin I型PKS rif的模塊9和10有較高的同源性(40%),相似性50%;此外還與rifB的模塊4-6同源(39%),相似性49%。
rifPKS9-10.pro ------------------------------------------------------------ 1564gdnB-pks.pro ------------------------------------------------------------ 522rifpks4-6.pro AVRGGKFFVPRITRAEPSGAAVFRPDGTVLISGAGALGGLVARRLVERHGVRKLVLASRR 2996rifPKS9-10.pro ------------------------------------------------------------ 1564gdnB-pks.pro ------------------------------------------------------------ 522rifpks4-6.pro GRDADGVADLVADLAADVSVVACDVSDRAQVAALLDEHRPTAVVHTAGVIDAGVIETLDR 3056rifPKS9-10.pro ------------------------------------------------------------ 1564gdnB-pks.pro ------------------------------------------------------------ 522rifpks4-6.pro DRLATVFAPKVDAVRHLDELTRDRDLDAFVVYSSVSAVFMGAGSGSYAAANAFLDGLMAN 3116rifPKS9-10.pro ------------------------------------------------------------ 1564gdnB-pks.pro ------------------------------------------------------------ 522rifpks4-6.pro RRAAGLPGLSLAWGLWDQSTGMAAGTDEATRARMSRRGGLQIMTQAEGMDLFDAALSSAE 3176rifPKS9-10.pro ------------------------------------------------------------ 1564gdnB-pks.pro ------------------------------------------------------------ 522 保守結(jié)構(gòu)域分析,在氨基酸N端572-636位氨基酸存在一個(gè)磷酸泛酰巰基乙胺的附著位點(diǎn)(見(jiàn)圖4),磷酸泛酰巰基乙胺是ACP的輔基,它作為一個(gè)搖臂攜帶脂肪酸合成的中間物,由一個(gè)酶轉(zhuǎn)到另一個(gè)酶的活性位置上,合成聚酮體。11.gdnF(Genbank收錄號(hào)為AF521895)酰胺合酶基因,大小為1026bpDNA,該基因起始密碼與其上游基因的終止密碼有重疊,可能處于同一轉(zhuǎn)錄單位。編碼由342個(gè)氨基酸組成的蛋白。gtgggacgag ctggagaaag ccgatacgga cgctcccgcc gcatccgccc cgactcccgc 60Val Gly Arg Ala Gly Glu Ser Arg Tyr Gly Arg Ser Arg Arg Ile Arg Pro Asp Ser Argatccgccgaa actcccgcat ccgccccaac cgccggagcc accccgtcac ccggagccac 120Ile Arg Arg Asn Ser Arg Ile Arg Pro Asn Arg Arg Ser His Pro Val Thr Arg Ser Hiscccgtcaccc ggagccaccc cgtcacccgg agccactctg ccacccgcgc ccaccccgcc 180Pro Val Thr Arg Ser His Pro Val Thr Arg Ser His Ser Ala Thr Arg Ala His Pro Alattccggagcc gcccaggagt gagccctgcc cagcccagca caactccact cggcagaccg 240Phe Arg Ser Arg Pro Gly Val Ser Pro Ala Gln Pro Ser Thr Thr Pro Leu Gly Arg Progcaccgaccg aagcggcaa gaaagggatc gcacatgttc agcacggacac gtacctggcg 300Ala Pro Thr Glu Ala Ala Arg Lys Gly Ser His Met Phe Ser Thr Asp Thr Tyr Leu Alacatctggggt ttccccagc cgcccgcccc caccctgccg aacctccggca gttgcaccgc 360His Leu Gly Phe Pro Gln Pro Pro Ala Pro Thr Leu Pro Asn Leu Arg Gln Leu His Argggccatctga tggcggtcc cttacgacac caaccacacc caccgcctcag cgcggagaac 420Gly His Leu Met Ala Val Pro Tyr Asp Thr Asn His Thr His Arg Leu Ser Ala Glu Asnatggccgaca tcgatatcg acaaggcatt cgaggccatc gtgccgaccgg cgccggtggc 480Met Ala Asp Ile Asp Ile Asp Lys Ala Phe Glu Ala Ile Val Pro Thr Gly Ala Gly Glyatgtgcctgg agctgaaca ccctgttcgc ccagttgctc cgcgagctggg ctatgacctg 540Met Cys Leu Glu Leu Asn Thr Leu Phe Ala Gln Leu Leu Arg Glu Leu Gly Tyr Asp Leugacgtcatca gcggaggca cgtatctgcc cggtgacatc ttcgcccccga ccccgagcac 600Asp Val Ile Ser Gly Gly Thr Tyr Leu Pro Gly Asp Ile Phe Ala Pro Asp Pro Glu Hisatgctgatgc tcgtccgtat cgacgggcag gagtggctgg ccgatgtggg gcacgccggt 660Met Leu Met Leu Val Arg Ile Asp Gly Gln Glu Trp Leu Ala Asp Val Gly His Ala Glyctctgtttca ccgagccgct gcgcctgtcc gaggaggtgc agtggcagta cggctgcgct 720Leu Cys Phe Thr Glu Pro Leu Arg Leu Ser Glu Glu Val Gln Trp Gln Tyr Gly Cys Alattccggctga tccggcggga tggctatctc gtgctccagg ccaagaccct ggaccacgac 780Phe Arg Leu Ile Arg Arg Asp Gly Tyr Leu Val Leu Gln Ala Lys Thr Leu Asp His Asptggcgcacca cctaccgctt caccaccgag cccaggacct atgacgcctg ggccggggtc 840Trp Arg Thr Thr Tyr Arg Phe Thr Thr Glu Pro Arg Thr Tyr Asp Ala Trp Ala Gly Valggtgagggca atggcccggc catcctggcg gcgatgcgcc gacgcaggcg cgccatcgac 900Gly Glu Gly Asn Gly Pro Ala Ile Leu Ala Ala Met Arg Arg Arg Arg Arg Ala Ile Aspaaggggcagg tcttcctcac caacaacatg ttcacgatcg tggagaacgg ccatgagaag 960Lys Gly Gln Val Phe Leu Thr Asn Asn Met Phe Thr Ile Val Glu Asn Gly His Glu Lysgtcaccctcc tcgtcgatcc ggaacggcgc gcccaggtgc tcgacacgta ctgggacggt 1020Val Thr Leu Leu Val Asp Pro Glu Arg Arg Ala Gln Val Leu Asp Thr Tyr Trp Asp Glycgcgac 1026Arg Asp該基因產(chǎn)物顯示與rifamycin酰胺合酶有較高同源性(37%)相似性50%;gdnF.pro VGRAGESRYGRSRRIRPDSRIRRNSRIRPNRRSHPVTRSHPVTRSHPVTRSHSATRAHPA 60RIFF.pro ------------------------------------------------------------ 1 另外它還與多種來(lái)源的芳香胺?;D(zhuǎn)移酶同源;氨基酸序列分析顯示,在111-275氨基酸位含N-?;D(zhuǎn)移酶結(jié)構(gòu)域(見(jiàn)圖4),這一結(jié)構(gòu)域可能是安莎類(lèi)抗生素特異針對(duì)芳香起始單位的裝配結(jié)構(gòu)域,該基因產(chǎn)物的功能是通過(guò)將PKS的?;D(zhuǎn)移至AHBA的氨基上以此形成獨(dú)特的內(nèi)酰胺環(huán)結(jié)構(gòu)。12.gdnG(Genbank收錄號(hào)為AF521895)單加氧酶基因,大小為1224bp DNA,編碼由408個(gè)氨基酸組成的蛋白。atgaaattcg gtttgctgta cggggcgcag ctgccccgac cctggaccca ggactccgaa 60Met Lys Phe Gly Leu Leu Tyr Gly Ala Gln Leu Pro Arg Pro Trp Thr Gln Asp Ser Glucaccgcctgt tcaacgagat gttggacgag atcgagctgg ccgaccggct gggcttcgac 120His Arg Leu Phe Asn Glu Met Leu Asp Glu Ile Glu Leu Ala Asp Arg Leu Gly Phe Aspcatgtgtggt gtcctgagca ccacttcctg gaggagtact cgcacatgtc cgcgccggag 180His Val Trp Cys Pro Glu His His Phe Leu Glu Glu Tyr Ser His Met Ser Ala Pro Glugcgttcctcg gcgcggtcag ccagcgcacc agccgcatcc gcatcggcca cgcggtggcc 240Ala Phe Leu Gly Ala Val Ser Gln Arg Thr Ser Arg Ile Arg Ile Gly His Ala Val Alactgatgcctc cggcgttcaa tccgacggca cgggtcgccg agcggatcgc cacgctggac 300Leu Met Pro Pro Ala Phe Asn Pro Thr Ala Arg Val Ala Glu Arg Ile Ala Thr Leu Aspctgctctccg acggccgggt ggacttcggc acgggcgagt ccaccacccc caccgagctg 360Leu Leu Ser Asp Gly Arg Val Asp Phe Gly Thr Gly Glu Ser Thr Thr Pro Thr Glu Leuggcggattcg gcgtggagcg ctccgtgaaa cgggaccagt gggcggaggc ggtggacgcc 420Gly Gly Phe Gly Val Glu Arg Ser Val Lys Arg Asp Gln Trp Ala Glu Ala Val Asp Alagtcgcccgga tgttcgtcga ggagcccttc gccggatacg agggcaagta cgtgtccgcc 480Val Ala Arg Met Phe Val Glu Glu Pro Phe Ala Gly Tyr Glu Gly Lys Tyr Val Ser Alaccgatccgca atgtgctgcc caagacccgg cagaagccac atccgccgat gtggatggcc 540Pro Ile Arg Asn Val Leu Pro Lys Thr Arg Gln Lys Pro His Pro Pro Met Trp Met Alatgcgggaacc gggacgcgat ccgcaccgcg gccgccaagg ggctcggcgc gctgaacttc 600cys Gly Asn Arg Asp Ala Ile Arg Thr Ala Ala Ala Lys Gly Leu Gly Ala Leu Asn Phetccttcttcg ggccggcgga gaccaagaag tgggtcgacg cctactactc gggcatcgaa 660Ser Phe Phe Gly Pro Ala Glu Thr Lys Lys Trp Val Asp Ala Tyr Tyr Ser Gly Ile Glutcggcggact gtgtgcccgc cgcgttcgcc gtcaacgcac agatcgccgc gaccatcccg 720ser Ala Asp Cys Val Pro Ala Ala Phe Ala Val Asn Ala Gln Ile Ala Ala Thr Ile Proatgttctgcc accgggacga gaccacggcc gtggaacgcg ccgtcgacgg cgtccagttc 780Met Phe Cys His Arg Asp Glu Thr Thr Ala Val Glu Arg Ala Val Asp Gly Val Gln Phettcaacttcg gcctcggctt ctacgcgggc ttcggcaccg ccgcaccggc ccgcacccgg 840Phe Asn Phe Gly Leu Gly Phe Tyr Ala Gly Phe Gly Thr Ala Ala Pro Ala Arg Thr Argctgtgggagg agttccagcg cgaccgcgac aagcagggca tgggccgctc ctccttcggc 900Leu Trp Glu Glu Phe Gln Arg Asp Arg Asp Lys Gln Gly Met Gly Arg Ser Ser Phe Glyaagcccggaa tgccgctggg caatccggcc cggggcgcgg tgggcactcc gcaccagata 960Lys Pro Gly Met Pro Leu Gly Asn Pro Ala Arg Gly Ala Val Gly Thr Pro His Gln Ilecgcgacttcc tgcggctgca cgaggaggcc ggactggacc aggcgatctt cctcgtccag 1020Arg Asp Phe Leu Arg Leu His Glu Glu Ala Gly Leu Asp Gln Ala Ile Phe Leu Val Glnggcggtggca cccggcacga gcacatccgc gaatcgctgg agctcttcgc caatgaggtg 1080Gly Gly Gly Thr Arg His Glu His Ile Arg Glu Ser Leu Glu Leu Phe Ala Asn Glu Valatgcccgagt tcaaggagcg cgatgaggcc gccgtacggc tgaagacggc ccggctccag 1140Met Pro Glu Phe Lys Glu Arg Asp Glu Ala Ala Val Arg Leu Lys Thr Ala Arg Leu Glncccgccatcg acgccgccat ggcccggcgc gagccgccac ggacggccga ccccgactac 1200Pro Ala Ile Asp Ala Ala Met Ala Arg Arg Glu Pro Pro Arg Thr Ala Asp Pro Asp Tyrtcatccccgc ccggagccag agc 1224Ile Ile Pro Ala Arg Ser Gln Ser該基因產(chǎn)物顯示與rifamycin的單加氧酶Rif17同源(26%),相似性(43%),。 此基因產(chǎn)物可能涉及末端的酰胺結(jié)構(gòu)形成(Silakowski,B.et al.J.Biol.Chem.1999.274(52),37391-37399)。13.gdnH(Genbank收錄號(hào)為AF521895)細(xì)胞色素P450、羥基化酶基因,大小為1239bp,編碼由413個(gè)氨基酸組成的蛋白。gtgtccgggc gccacttcga acaaggagaa cgtggtaccg ccatggctga cacccccgaa 60Val Ser Gly Arg His Phe Glu Gln Gly Glu Arg Gly Thr Ala Met Ala Asp Thr Pro Glugaagaactcc gcatcctcga cccgcagtcc gtcgcgcagg agctgcgcaa gcacggcccg 120Glu Glu Leu Arg Ile Leu Asp Pro Gln Ser Val Ala Gln Glu Leu Arg Lys His Gly Procctcggcaga tcacgatgca cggcaccacg gcgtggctcg tctcccggta cgaggaggtc 180Pro Arg Gln Ile Thr Met His Gly Thr Thr Ala Trp Leu Val Ser Arg Tyr Glu Glu Valcgggactgtc tcggacaccc cggaatgagc ccggccgccg cctacgccgc ctcccagggc 240Arg Asp Cys Leu Gly His Pro Gly Met Ser Pro Ala Ala Ala Tyr Ala Ala Ser Gln Glycagaccaatc cggtgagcg ggttgttcgag gacacggtgg ccggtaccaa tccgccccag 300Gln Thr Asn Pro Val Ser Gly Leu Phe Glu Asp Thr Val Ala Gly Thr Asn Pro Pro Glncacacccggc tgcgcaggc tgctggccaa ggcgttcacgg tacgcagagt ggagagtctg 360His Thr Arg Leu Arg Arg Leu Leu Ala Lys Ala Phe Thr Val Arg Arg Val Glu Ser Leucggccacggg tgcaggaga tcaccgacac actgctggacc ggatcgccgt cgacggccgg 420Arg Pro Arg Val Gln Glu Ile Thr Asp Thr Leu Leu Asp Arg Ile Ala Val Asp Gly Arggccgacctcg tcagcgcgc tggccattcc gctgcccatgc aggtgatctg cgaactcctc 480Ala Asp Leu Val Ser Ala Leu Ala Ile Pro Leu Pro Met Gln Val Ile Cys Glu Leu Leuggtgtgccca tcgccgacc gcaccgaatt ccaccagtgg gccgatctgat gctcacgccc 540Gly Val Pro Ile Ala Asp Arg Thr Glu Phe His Gln Trp Ala Asp Leu Met Leu Thr Proccgctggacc cggacaccg ccgcgcgttc ccaggacgcc tccgccaagct gtggacgtat 600Pro Leu Asp Pro Asp Thr Ala Ala Arg Ser Gln Asp Ala Ser Ala Lys Leu Trp Thr Tyratggaggacc tcgccgagg ccaggcggaa ggccccggag gacgacctgat cagcgatctg 660Met Glu Asp Leu Ala Glu Ala Arg Arg Lys Ala Pro Glu Asp Asp Leu Ile Ser Asp Leuatgtccgcac acgaggacgac cggctcagcc accgcgaggt ggtcgccacc gcccggatg 720Met Ser Ala His Glu Asp Asp Arg Leu Ser His Arg Glu Val Val Ala Thr Ala Arg Metatgctgatcg cggggtacga gctgaccggc agcttcatca gcaacgcggt tttctcgctg 780Met Leu Ile Ala Gly Tyr Glu Leu Thr Gly Ser Phe Ile Ser Asn Ala Val Phe Ser Leuctgtcccagc ccgaccagat ggaactgctg cgcaaggacc ccgagctggc cgggcgcggt 840Leu Ser Gln Pro Asp Gln Met Glu Leu Leu Arg Lys Asp Pro Glu Leu Ala Gly Arg Glyctggaggagc tgctccggca cgccgggccg ggcattctca tcgtgcgttt cgccaacgag 900Leu Glu Glu Leu Leu Arg His Ala Gly Pro Gly Ile Leu Ile Val Arg Phe Ala Asn Glugacgtggaga tcggctccgt atccatccgc gccggcgacc aggtgctcct ggacatggac 960Asp Val Glu Ile Gly Ser Val Ser Ile Arg Ala Gly Asp Gln Val Leu Leu Asp Met Aspgccgcacact ccgacccggc gcacttcacc gacggcgagc ggctggacct cacgagggac 1020Ala Ala His Ser Asp Pro Ala His Phe Thr Asp Gly Glu Arg Leu Asp Leu Thr Arg Asptcggccgtac acctccagtt cggccatggc atccactact gcatcggcgc gccgctggcc 1080Ser Ala Val His Leu Gln Phe Gly His Gly Ile His Tyr Cys Ile Gly Ala Pro Leu Alaagggtggagg ggcagatcgc cctggagagc ctggtgcggc ggttccccgg gcttcggctg 1140Arg Val Glu Gly Gln Ile Ala Leu Glu Ser Leu Val Arg Arg Phe Pro Gly Leu Arg Leuagcgttcccg ccgccgagat cagccatagc aagaacccgt tcatccgctc gctgaccgcg 1200Ser Val Pro Ala Ala Glu Ile Ser His Ser Lys Asn Pro Phe Ile Arg Ser Leu Thr Alactgcccgtcg agttcgaggc tcagcagcc cgtagcgggg 1239Leu Pro Val Glu Phe Glu Ala Gln Gln Pro Val Ala Gly該基因產(chǎn)物顯示與細(xì)胞色素P450、6-脫氧紅霉內(nèi)酯B(6-DEB)羥化酶EryF有較高的同源性(38%),相似性56%。 ERYF.pro ---- 404gdnH.pro PVAG 413氨基酸序列分析顯示,含有細(xì)胞色素P450結(jié)構(gòu)域(見(jiàn)圖5)。gdnH與gdnG為結(jié)構(gòu)修飾基因,可能參與格爾德霉素苯醌形成時(shí)氧化修飾步驟。14.orf1(Genbank收錄號(hào)AF521895)DNA修復(fù)蛋白,大小為678bp,,編碼由226個(gè)氨基酸組成的蛋白。atgaacgccc tgatcccccg tccacgcctc gaggtggccc ccggcgccgt ccatgtgccg 60Met Asn Ala Leu Ile Pro Arg Pro Arg Leu Glu Val Ala Pro Gly Ala Val His Val Proagctggctca ccctcgaaca gcagcgggag ctggtcctcg cctgccgggg ctgggccacc 120Ser Trp Leu Thr Leu Glu Gln Gln Arg Glu Leu Val Leu Ala Cys Arg Gly Trp Ala Thrggcccggtcc cgatccggca caccaagctg ccgcgcgggg gcgtcatgtc ggtgcgcacg 180Gly Pro Val Pro Ile Arg His Thr Lys Leu Pro Arg Gly Gly Val Met Ser Val Arg Thrgtgtgcatcg gctggcactg gcagccctac gcctacaccc gcaccgccga cgatgtgaac 240Val cys Ile Gly Trp His Trp Gln Pro Tyr Ala Tyr Thr Arg Thr Ala Asp Asp Val Asnggcgcccggg tcgccgaatt ccccgactgg atggtcgagt tgggccgtcg cgccctggtc 300Gly Ala Arg Val Ala Glu Phe Pro Asp Trp Met Val Glu Leu Gly Arg Arg Ala Leu Valgacgcgtacg acgacgagac ggccggtgag gggtacaccc ccgacaccgc gctcatcaac 360Asp Ala Tyr Asp Asp Glu Thr Ala Gly Glu Gly Tyr Thr Pro Asp Thr Ala Leu Ile Asnttctacgacg cccaggcgaa gctgggcatg caccaggaca aggacgagag gtcatccgcc 420Phe Tyr Asp Ala Gln Ala Lys Leu Gly Met His Gln Asp Lys Asp Glu Arg Ser Ser Alaccggtggtct cgctcaccat cggcgacagc tgtgtcttcc gcttcggcaa caccgagacc 480Pro Val Val Ser Leu Thr Ile Gly Asp Ser Cys Val Phe Arg Phe Gly Asn Thr Glu Thrcgtaccaagc cgtacaccga cctcgaactc gcttccgggga tctgttcgt cttcggaggc 540Arg Thr Lys Pro Tyr Thr Asp Leu Glu Leu Ala Ser Gly Asp Leu Phe Val Phe Gly Glyccctcccgct acgcctatca cgccgtcccc aggatcctgc ccggaaccgg tgacccggcc 600Pro Ser Arg Tyr Ala Tyr His Ala Val Pro Arg Ile Leu Pro Gly Thr Gly Asp Pro Alaaccggactga agtccgggcg gctgaacatc accatgcggg tcaccggtct ggccgatccc 660Thr Gly Leu Lys Ser Gly Arg Leu Asn Ile Thr Met Arg Val Thr Gly Leu Ala Asp Procagtcgtcag tcgtcccg 678Gln Ser Ser Val Val Pro該基因產(chǎn)物顯示與Streptomyces coelicolor A3(2)中推測(cè)的DNA修復(fù)蛋白(Drep)有高同源性(60%),相似性70%,它還與Corynebacterium glutamicum中烷基化的DNA修復(fù)蛋白(Cg10)同源(42%),相似性56%。
15.orf2(Genbank收錄號(hào)AF521895)功能未知蛋白,大小為726bp DNA,編碼由242個(gè)氨基酸組成的蛋白。atgagcacca cgaacgacac cgcacgcatc catcagcgcg tggccgcggc cgactggcca 60Met Ser Thr Thr Asn Asp Thr Ala Arg Ile His Gln Arg Val Ala Ala Ala Asp Trp Procagctggccg aggagctgga cacctacggg tgcgcgctca ctccacggct gctgaccccc 120Gln Leu Ala Glu Glu Leu Asp Thr Tyr Gly Cys Ala Leu Thr Pro Arg Leu Leu Thr Progcccagtgcg cccgcatcgc cgggctgtac gggcaggacg agcagttcag gaacacgatc 180Ala Gln Cys Ala Arg Ile Ala Gly Leu Tyr Gly Gln Asp Glu Gln Phe Arg Asn Thr Ilegacatggccc gccaccgctt cggctccgga cagtaccgct acttcaccca tgacctgccc 240Asp Met Ala Arg His Arg Phe Gly Ser Gly Gln Tyr Arg Tyr Phe Thr His Asp Leu Progaaccggtgg ccgagctgcg cgccgcgctc tatccgcggc tgctgaccat cgcgcgtgac 300Glu Pro Val Ala Glu Leu Arg Ala Ala Leu Tyr Pro Arg Leu Leu Thr Ile Ala Arg Asptgggcggagc ggctcggccg cccggcgccc tggccggaca gcctcgagaa gtggctggcc 360Trp Ala Glu Arg Leu Gly Arg Pro Ala Pro Trp Pro Asp Ser Leu Glu Lys Trp Leu Alaatgtgtcatg aggccggaca ggaccgctcc gcgcagatcc tgctgcgcta cggccccggc 420Met Cys His Glu Ala Gly Gln Asp Arg Ser Ala Gln Ile Leu Leu Arg Tyr Gly Pro Glygactggaacg ccctgcaccg ggacgtattc ggcgacatgc tcttcccgct ccaggtggtg 480Asp Trp Asn Ala Leu His Arg Asp Val Phe Gly Asp Met Leu Phe Pro Leu Gln Val Valatcgggctcg acgcgtacggc acggactac acgggcgggg agttcctgct ggtcgagcag 540Ile Gly Leu Asp Ala Tyr Gly Thr Asp Tyr Thr Gly Gly Glu Phe Leu Leu Val Glu Glncggccccgcg cccagtcccgg ggcaccacg accgtcctcc agcagggcca cggcctgatc 600Arg Pro Arg Ala Gln Ser Arg Gly Thr Thr Thr Val Leu Gln Gln Gly His Gly Leu Ilettcaccaccc gtgaccgtccc gtggccacc aagcgcggct ggtcggccgg tgtgatgcgg 660Phe Thr Thr Arg Asp Arg Pro Val Ala Thr Lys Arg Gly Trp Ser Ala Gly Val Met Argcacggggtca gcacggtgcgt tccgggcgc cgccacgcat tggggctggt cttccacgac 720His Gly Val Ser Thr Val Arg Ser Gly Arg Arg His Ala Leu Gly Leu Val Phe His Aspgccgcc 726Ala Ala16.orf3(Genbank收錄號(hào)AF521895)抗DNA損傷的甲基轉(zhuǎn)移酶,大小為504bpDNA,編碼由168個(gè)氨基酸組成的蛋白。tgacggtcc acacgacgat cgacagcccg ctcggcgagc tgctgctggt gggcgaggag60Met Thr Val His Thr Thr Ile Asp Ser Pro Leu Gly Glu Leu Leu Leu Val Gly Glu Glutccgccaccg cgccgggggg caccgcactc atctccctgt ccgtgcccgg ccagaagggc 120Ser Ala Thr Ala Pro Gly Gly Thr Ala Leu Ile Ser Leu Ser Val Pro Gly Gln Lys Glyggggccgtcg tccaggacgg ttggagcgag gatgccgagg cgttcaccga gatcgtctcc 180Gly Ala Val Val Gln Asp Gly Trp Ser Glu Asp Ala Glu Ala Phe Thr Glu Ile Val Sercagttgcgct cctacttcga cggcgagcgc acccgcttcg acatcgagtg cgtcgagggc 240Gln Leu Arg Ser Tyr Phe Asp Gly Glu Arg Thr Arg Phe Asp Ile Glu Cys Val Glu Glyggtacggact tccagcgcag ggtctggcag gcgctggagg ccattccgta cggcaccact 300Gly Thr Asp Phe Gln Arg Arg Val Trp Gln Ala Leu Glu Ala Ile Pro Tyr Gly Thr Thrgtcagctacg gcgacatcgc ccggcagatc ggcgccccgc gcacggccgt ccgctccgtc 360Val Ser Tyr Gly Asp Ile Ala Arg Gln Ile Gly Ala Pro Arg Thr Ala Val Arg Ser Valggcaccgcga tcggccgcaa tccactgctg gtcgtgcggc cctgccaccg ggtcatcggc 420Gly Thr Ala Ile Gly Arg Asn Pro Leu Leu Val Val Arg Pro Cys His Arg Val Ile Glygccaccggcg cactgaccgg ctatgcgggc ggactggagc gcaagcagcg actcctcgtt 480Ala Thr Gly Ala Leu Thr Gly Tyr Ala Gly Gly Leu Glu Arg Lys Gln Arg Leu Leu ValCacgagggcg ccctccagac cgcc 504His Glu Gly Ala Leu Gln Thr Ala該基因產(chǎn)物顯示與Streptomyces coelicolor A3(2)的甲基化DNA-[蛋白]-半胱氨酸-硫-甲基轉(zhuǎn)移酶(S_MDP)有高同源性(53%),相似性61%;它還顯示與分枝桿菌的6-氧-甲基鳥(niǎo)嘌呤-甲基轉(zhuǎn)移酶(M_OGT)同源(45%),相似性56%。 S_MDP.pro LPATPR 186M_OGT.pro LFD--- 165orf3-.pro ------ 168該酶通過(guò)將氧-6位的烷基轉(zhuǎn)移到該酶的半胱氨酸殘基上,從而修復(fù)DNA上烷基化的鳥(niǎo)嘌呤。格爾德霉素結(jié)構(gòu)分析顯示,它含有烷基而且在苯醌上的烷基較活潑,有可能將DNA烷基化造成DNA的損傷,可能該基因與orf1共同參與機(jī)體抗損傷的自我保護(hù)作用。17.orf4(Genbank收錄號(hào)AF521895)為一個(gè)新基因,大小為618bpDNA,編碼由206個(gè)氨基酸組成的蛋白。atgcacgagg gacacggcca ccaggagtac atcgtcacgt ccgaccccga ggcggtggcc 60Met His Glu Gly His Gly His Gln Glu Tyr Ile Val Thr Ser Asp Pro Glu Ala Val Alacgtgtccggg cctccttgct gcgcaccctg ccagtggccg catgggccgg ggtggccagt 120Arg Val Arg Ala Ser Leu Leu Arg Thr Leu Pro Val Ala Ala Trp Ala Gly Val Ala Sergccgtggtca tcgtctcggc cgtggccctc gtcctcttcg ccctcggcca cagcgcctcc 180Ala Val Val Ile Val Ser Ala Val Ala Leu Val Leu Phe Ala Leu Gly His Ser Ala Sercggctgtggg tcctggtgtt cgcctggccc gcggcgttcc tcggctatga cgccaggcgc 240Arg Leu Trp Val Leu Val Phe Ala Trp Pro Ala Ala Phe Leu Gly Tyr Asp Ala Arg Argcgattcgccg atatacggcg gctgaagcgg acctgggcgg cgaaagaggt gtccccggtg 300Arg Phe Ala Asp Ile Arg Arg Leu Lys Arg Thr Trp Ala Ala Lys Glu Val Ser Pro Valgcgatgcgcc tctccgccga gggcctgcgc tgcgccatcg actccgcccc ggagcccgtt 360Ala Met Arg Leu Ser Ala Glu Gly Leu Arg Cys Ala Ile Asp Ser Ala Pro Glu Pro Valttcctcccct ggtccgcgat cgcccaggtg cgggtgacgg gccagggcct cagcacggtg 420Phe Leu Pro Trp Ser Ala Ile Ala Gln Val Arg Val Thr Gly Gln Gly Leu Ser Thr Valcgggtcgatc tcgcccccgg cgtgtccgcc accacccccg gggtcagcgg gctggagcag 480Arg Val Asp Leu Ala Pro Gly Val Ser Ala Thr Thr Pro Gly Val Ser Gly Leu Glu Glncccgaggccc ggatgcgcat gcggcgcgcc tggaacggcg ggatgcggct gcgcttcacc 540Pro Glu Ala Arg Met Arg Met Arg Arg Ala Trp Asn Gly Gly Met Arg Leu Arg Phe Thrgtctacgccc tccgccagcc gatcagcgag atcgaccagg ctctcggcca cttctcgaac 600Val Tyr Ala Leu Arg Gln Pro Ile Ser Glu Ile Asp Gin Ala Leu Gly His Phe Ser Asngggcggatcg gtatccgc 618Gly Arg Ile Gly Ile Arg18.orf5(Genbank收錄號(hào)AF521895)與轉(zhuǎn)錄調(diào)節(jié)有關(guān)基因,大小為2721bpDNA,編碼由907個(gè)氨基酸組成的蛋白。atgggaggac gtgctcgtcc ggctcggcga cggctggggc ccctgtcgta tacgcgaagc 60Met Gly Gly Arg Ala Arg Pro Ala Arg Arg Arg Leu Gly Pro Leu Ser Tyr Thr Arg Sergtcgccggg caggcgttca tcttgcagct tctgctgatc ctggttctgg tggccgcggcg 120Val Ala Gly Gln Ala Phe Ile Leu Gln Leu Leu Leu Ile Leu Val Leu Val Ala Ala Alagtggtggcc gtcgcagcgg atgcccggag ccacagcacg accgacgctc gccggcgatcc 180Val Val Ala Val Ala Ala Asp Ala Arg Ser His Ser Thr Thr Asp Ala Arg Arg Arg Serctcgcggtc gccgagacct tggcacactc ccccggaatg gcccgggccc tgaccagcgac 240Leu Ala Val Ala Glu Thr Leu Ala His Ser Pro Gly Met Ala Arg Ala Leu Thr Ser Aspcggccgacg tcgctgctgg agtcgcatgc ggaggcggcg cggaagagatc aggcgtcgac 300Arg Pro Thr Ser Leu Leu Glu Ser His Ala Glu Ala Ala Arg Lys Arg Ser Gly Val Aspagcgtcgtgg tgttcaaca ctcatggcat ccgcctcacc caccccgagaa ggcattgatc 360Ser Val Val Val Phe Asn Thr His Gly Ile Arg Leu Thr His Pro Glu Lys Ala Leu Ileggcaagcgga tcgtcggac cggccgggct ggtgcgggac gagctgaaagg caagacgatc 420Gly Lys Arg Ile Val Gly Pro Ala Gly Leu Val Arg Asp Glu Leu Lys Gly Lys Thr Ileacggagtcct tccaggcca gccagggccc gtccgtggtc tcggcggtccc cgtcaccagg 480Thr Glu Ser Phe Gln Ala Ser Gln Gly Pro Ser Val Val Ser Ala Val Pro Val Thr Arggccgacggca ccttcctcg gcggtgtgtc cgtcggggtc aagatcgcgag cgtgaacagc 540Ala Asp Gly Thr Phe Leu Gly Gly Val Ser Val Gly Val Lys Ile Ala Ser Val Asn Sergaggtggacc gtcggctac cgctgctgct cggcagtggc accggggcact ggccctggcc 600Glu Val Asp Arg Arg Leu Pro Leu Leu Leu Gly Ser Gly Thr Gly Ala Leu Ala Leu Alatcgggcgggg cggcgctga tgagcaggcg ggtgcggcgg cagacccacgg cctgggcgcc 660Ser Gly Gly Ala Ala Leu Met Ser Arg Arg Val Arg Arg Gln Thr His Gly Leu Gly Alagcggagatga cgcggatgt acgagcacca tgacgcggtg ttgcgctcggt ccgcgaaggg 720Ala Glu Met Thr Arg Met Tyr Glu His His Asp Ala Val Leu Arg Ser Val Arg Glu Glygtgctggtcc tgaccgcggg cgggcggctg ctggtggtca acgacgaggc ccgggaactg 780Val Leu Val Leu Thr Ala Gly Gly Arg Leu Leu Val Val Asn Asp Glu Ala Arg Glu Leuctcgggctgg ctccggacgc ggaggggcgg cgcatcgacg agctcggcct cgaaccgcac 840Leu Gly Leu Ala Pro Asp Ala Glu Gly Arg Arg Ile Asp Glu Leu Gly Leu Glu Pro Hisctgacgcaac tgctggcgtc gggacggcgc gtcaccgacg aggtgcaccc ccgcggggat 900Leu Thr Gln Leu Leu Ala Ser Gly Arg Arg Val Thr Asp Glu Val His Pro Arg Gly Aspcgactactgg cggtcaatat gcggtccacg gaccgtgcgg gcgatcccgc cggaaacgtg 960Arg Leu Leu Ala Val Asn Met Arg Ser Thr Asp Arg Ala Gly Asp Pro Ala Gly Asn Valgtgacgctga gggacaccac cgcgctgcgg gtgctgtccg accgggccga gcaagccggt 1020Val Thr Leu Arg Asp Thr Thr Ala Leu Arg Val Leu Ser Asp Arg Ala Glu Gln Ala Glygagcggctga agctgctgtc cgacgccggg gtgcggatca gctccagcct ggagctgacg 1080Glu Arg Leu Lys Leu Leu Ser Asp Ala Gly Val Arg Ile Ser Ser Ser Leu Glu Leu Thrggcaccgcgg agaagctggt ggacgtggcc gtcccccggt tcgccgacat cgtctcggtc 1140Gly Thr Ala Glu Lys Leu Val Asp Val Ala Val Pro Arg Phe Ala Asp Ile Val Ser Valgaactgctgg agcccgtgct gcgcggcgag gagcccgagc cgccgtacga gccactggcg 1200Glu Leu Leu Glu Pro Val Leu Arg Gly Glu Glu Pro Glu Pro Pro Tyr Glu Pro Leu Alaccgcaccgga ccgccgtcgg cggagatccc cccgacggcc tcgtcttccg cgtgggcgag 1260Pro His Arg Thr Ala Val Gly Gly Asp Pro Pro Asp Gly Leu Val Phe Arg Val Gly Glucgagtcgtct acgcaccctc cacaccgcag agccgggccg tgaaggccgg agccgccgtc 1320Arg Val Val Tyr Ala Pro Ser Thr Pro Gln Ser Arg Ala Val Lys Ala Gly Ala Ala Valctcctgaccg atctgacggg ccccggcgag tcgccgagcg accactccgc cccgtaccag 1380Leu Leu Thr Asp Leu Thr Gly Pro Gly Glu Ser Pro Ser Asp His Ser Ala Pro Tyr Glntcccccgggc aatcggccac gtacagtgcc gagacccggc gcctcctcga ccgcggggtc 1440Ser Pro Gly Gln Ser Ala Thr Tyr Ser Ala Glu Thr Arg Arg Leu Leu Asp Arg Gly Valcactcgctga tcaccgtccc gctgcggttc cgcggggtca ccctcggcct ggccaccttc 1500His Ser Leu Ile Thr Val Pro Leu Arg Phe Arg Gly Val Thr Leu Gly Leu Ala Thr Phetggcggaccc ggcccggtga gccgttcgac gaggcggatc tggcgatcgc cggggagctg 1560Trp Arg Thr Arg Pro Gly Glu Pro Phe Asp Glu Ala Asp Leu Ala Ile Ala Gly Glu Leugccgtgcgca ccgccgtatg tgtcgacaac gcccgccgct acgcccgcga acacaccatg 1620Ala Val Arg Thr Ala Val Cys Val Asp Asn Ala Arg Arg Tyr Ala Arg Glu His Thr Metgtcaccacct tgcagcgcac cctcctcccc agcggtctgc ccgatcagga cgccgtgcgg 1680Val Thr Thr Leu Gln Arg Thr Leu Leu Pro Ser Gly Leu Pro Asp Gln Asp Ala Val Arggtggcgtccc gctatctgcc cgcacagggc gagacgggcg gatcctggtt cgatgtgatc 1740Val Ala Ser Arg Tyr Leu Pro Ala Gln Gly Glu Thr Gly Gly Ser Trp Phe Asp Val Ilecctctccccg gggcccgggt cgcgctggtc gtcgggaagg tggccgggca gggcctgcac 1800Pro Leu Pro Gly Ala Arg Val Ala Leu Val Val Gly Lys Val Ala Gly Gln Gly Leu Hisgccgcggcca cgatggggcg gctgcgcacc gcggtgcaga acttctcggc cctggacgtg 1860Ala Ala Ala Thr Met Gly Arg Leu Arg Thr Ala Val Gln Asn Phe Ser Ala Leu Asp Valcccccggatg agctcctctc ccatctggac gagctggtca cccgtctcga cctggagcgc 1920Pro Pro Asp Glu Leu Leu Ser His Leu Asp Glu Leu Val Thr Arg Leu Asp Leu Glu Arggaggccgatt cggacgacgt ccggatcacg ggcgccacct gcctgtacgc gatccacgac 1980Glu Ala Asp Ser Asp Asp Val Arg Ile Thr Gly Ala Thr Cys Leu Tyr Ala Ile His Asptcggtgtccg gccactgcgc catggcccgg gccggcgatc cgggcatcgc cgtgacccac 2040Ser Val Ser Gly His Cys Ala Met Ala Arg Ala Gly Asp Pro Gly Ile Ala Val Thr Hisccggacggca ccgtggacct ccctgcggta cccatcggcc cggccctggg catgggcggg 2100Pro Asp Gly Thr Val Asp Leu Pro Ala Val Pro Ile Gly Pro Ala Leu Gly Met Gly Glygagccgttcg aggcggtcgg cctctcgctg cccgccgcaa gccggctggt gctgtacacc 2160Glu Pro Phe Glu Ala Val Gly Leu Ser Leu Pro Ala Ala Ser Arg Leu Val Leu Tyr Thraacggccttc ttgaagggga aggccaagcc gccgacaccg gcctcgacct gctgcgccgc 2220Asn Gly Leu Leu Glu Gly Glu Gly Gln Ala Ala Asp Thr Gly Leu Asp Leu Leu Arg Argaccctcgcgg ccgagccgga cctcggcccg gacgagacct gccggagcct tttcgacacc 2280Thr Leu Ala Ala Glu Pro Asp Leu Gly Pro Asp Glu Thr Cys Arg Ser Leu Phe Asp Thrgtgcttccgg cccacccgag cgacgatgtg gcgctgctgg tggcccggac ccgcctgctc 2340Val Leu Pro Ala His Pro Ser Asp Asp Val Ala Leu Leu Val Ala Arg Thr Arg Leu Leugccccggaga acgtggccga gtgggatgt gccgttcgacc tggcggcggt cgccccgctg 2400Ala Pro Glu Asn Val Ala Glu Trp Asp Val Pro Phe Asp Leu Ala Ala Val Ala Pro Leucgcgccacct gcacccggaa actgcgggcg tggggcctgg aggacgccgc gtacaccgcc 2460Arg Ala Thr Cys Thr Arg Lys Leu Arg Ala Trp Gly Leu Glu Asp Ala Ala Tyr Thr Alagagctgatca tcagtgaact gatcaccaa cgccctgcgg tacggctcccc tcccgtacgc 2520Glu Leu Ile Ile Ser Glu Leu Ile Thr Asn Ala Leu Arg Tyr Gly Ser Pro Pro Val Argatacggctgc tgcgcggccg cggcctgatc ttcgaggtct ccgacggcag cagcaccgca 2580Ile Arg Leu Leu Arg Gly Arg Gly Leu Ile Phe Glu Val Ser Asp Gly Ser Ser Thr Alaccccatctgc ggcgggccgc gatcaccgac gagggcggcc gcgggctgtt cctcgtcgcc 2640Pro His Leu Arg Arg Ala Ala Ile Thr Asp Glu Gly Gly Arg Gly Leu Phe Leu Val Alacagttcgccc agcgctgggg cacccgctac accccgcacg gcaaggtcat ctgggccgag 2700Gln Phe Ala Gln Arg Trp Gly Thr Arg Tyr Thr Pro His Gly Lys Val Ile Trp Ala Glugcggccctgg acggcggcct c 2721Ala Ala Leu Asp Gly Gly Leu該基因產(chǎn)物與Streptomyces coelicolorA3(2)中假定的膜傳感蛋白(IMSP)有很好的同源性(51%),相似性(63%)。
分析氨基酸序列,存在3個(gè)保守結(jié)構(gòu)域(δ因子-PP2C磷酸酶、K+通道、cGMP磷酸二酯酶)保守結(jié)構(gòu)域的同源性分析顯示,該基因產(chǎn)物與δ因子調(diào)節(jié)蛋白磷酸酶類(lèi)似,說(shuō)明可能與轉(zhuǎn)錄調(diào)節(jié)有關(guān)。orf5561VASRYLPAQGETGGSWFDVIPLPGARVALVVGKVAGQGLHAAATMGRLRTAVQNFSALDV 620PP2C_sig6 IAQYYEDAT-QVGGDYYDVVALPEGRLLIAIADVMGKGLAAALAMGMARSALRTLLSEGI 64orf5621PPDELLSHLDELVTRLDLEREADSDDVRITGATCLYAIHDSVSGHCAMARAGDPGIAVTH 680PP2C_sig65 SLSQILERLNRAIYENEEDG--------MFATLFLALYDFATGTLSYANAGHSPPYLLR 115orf5681PDGTVDLPAVPIGPALGMGGE-PFEAVGLSLPAASRLVLYTNGLLEGEGQAADTGLDLLR 739PP2C_sig116ADGGLVEILTDLGAPLGLEPDVEVDVRELTLEPGDLLLLYTDGLT--EARSPFFGEERLE 173orf5740RTLAAEPDLGPDETCRSLFDTVL---PAHPSDD 769PP2C_sig174ELLEALLGSAPQEIAQEILAELLEFAGGRGEDD 206orf5228 EHHDAVLRSVREGVLVLTAGGRLLVVNDEARELLGLAP-DAEGRRIDELGLEPHLTQLLA 286K+1 ERLRAILESLPDGVFVLDLDGRILYANPAAEELLGYSPEELIGKSLLELIHPEDREELQE 60orf5287 SGRR 290K+61 RLQR 64orf5478 RGVHSLITVPLRFRGVTLGLATFWRTRPGEPFDEADLAIAGELAVRTAVCVDNARRYARE 537cGMP89QLIRSFLAVPLVAGGELLGVLALHRKDSPRPFTEEEEELLQALANQLAIALALAQLYEEL 148orf5538 H 538cGMP149 R 14919.orf6(Genbank收錄號(hào)AF521895)蛋白水解酶基因,大小為969bpDNA,編碼由323個(gè)氨基酸組成的蛋白。gtgagaacag ctcgccgtac caggagacgt ggccggttga ccgccgcggt gtccggtctg 60Val Arg Thr Ala Arg Arg Thr Arg Arg Arg Gly Arg Leu Thr Ala Ala Val Ser Gly Leuttcatcacgg cagccctcgc gacagtcggt acgagtgcgg ccgcttcctc cgcgagacc120Phe Ile Thr Ala Ala Leu Ala Thr Val Gly Thr Ser Ala Ala Ala Ser Ser Ala Met Thrgccacgtccg cgcccagtgc caccgccacg cccccgtccg tatccacgcc cgtgtccggc 180Ala Thr Ser Ala Pro Ser Ala Thr Ala Thr Pro Pro Ser Val Ser Thr Pro Val Ser Glygccgccacgc ccgtgtccgg cgccgcctcg tccgtgtccg gcgccgcctc ggctgtggca 240Ala Ala Thr Pro Val Ser Gly Ala Ala Ser Ser Val Ser Gly Ala Ala Ser Ala Val Alatccctggatg tcccgggcac cgcctggacc gtggacgagc gcaccggaac gctgcgagtc 300Ser Leu Asp Val Pro Gly Thr Ala Trp Thr Val Asp Glu Arg Thr Gly Thr Leu Arg Valctcgtcggtt ccacggcccg ggaagccgat ctggccaggc tcgaccgcac cgccgagcgc 360Leu Val Gly Ser Thr Ala Arg Glu Ala Asp Leu Ala Arg Leu Asp Arg Thr Ala Glu Argttcggcggca cgatcaccgt ggagcggctc gacggtccgc tgcggaccct gctctccggt 420Phe Gly Gly Thr Ile Thr Val Glu Arg Leu Asp Gly Pro Leu Arg Thr Leu Leu Ser Glyggcgacggga tccactccac cacggggctg cgctgctccg cgggggtcaa tgtgcaaagc 480Gly Asp Gly Ile His Ser Thr Thr Gly Leu Arg Cys Ser Ala Gly Val Asn Val Gln Serggcaccacgt attacttcgt cacggccggc cactgcaccg acgccgcccc cacctggtac 540Gly Thr Thr Tyr Tyr Phe Val Thr Ala Gly His Cys Thr Asp Ala Ala Pro Thr Trp Tyraccggctccg atgcgaccac cccggtcggt tcgacgaccg ccaccagctt cccgggcaat 600Thr Gly Ser Asp Ala Thr Thr Pro Val Gly Ser Thr Thr Ala Thr Ser Phe Pro Gly Asngactacggcg tcgtccggta caccaacacg gccgttccgc accccgggac cgtgggaacc 660Asp Tyr Gly Val Val Arg Tyr Thr Asn Thr Ala Val Pro His Pro Gly Thr Val Gly Thrgtggacatca ccgggaccgc caccgcctac gtcggccagc aggtctgccg ccggggtgcc 720Val Asp Ile Thr Gly Thr Ala Thr Ala Tyr Val Gly Gln Gln Val Cys Arg Arg Gly Alaacgaccggcg tccggtgcgg tcaggtcatc gcgctcaacg ccaccgtcaa ctacggcggc 780Thr Thr Gly Val Arg Cys Gly Gln Val Ile Ala Leu Asn Ala Thr Val Asn Tyr Gly Glyggtgatgtcg tctccggcct gatccagacc aatatctgcg ccgagccggg cgacagcggc 840Gly Asp Val Val Ser Gly Leu Ile Gln Thr Asn Ile Cys Ala Glu Pro Gly Asp Ser Glyggtccgctct acgcgggcga caagatcatc ggcattctct cgggcggctc cggggactgc 900Gly Pro Leu Tyr Ala Gly Asp Lys Ile Ile Gly Ile Leu Ser Gly Gly Ser Gly Asp Cysgcgaccggag gcaccacctt ctaccagccg atccaggagg tgctgagcgc ctacggcctc 960Ala Thr Gly Gly Thr Thr Phe Tyr Gln Pro Ile Gln Glu Val Leu Ser Ala Tyr Gly Leuaccgtctac 969Thr Val Tyr該基因產(chǎn)物顯示與灰色鏈霉菌的蛋白酶B前體SGPB有很好的同源性(58%),相似性(74%)。
SGPB屬于肽酶家族,也是裂解蛋白酶的家族,均有蛋白質(zhì)水解酶活性,而且該酶對(duì)大的脂肪族氨基酸或芳香族氨基酸有首選的特異性。以上19個(gè)格爾德霉素生物合成基因編碼框的排列組織情況見(jiàn)圖620.gdnC(Genbank AF521896)PKS基因,大小為1659bpDNA,編碼由553個(gè)氨基酸組成的蛋白。gtggcaccaa cgccccgtca tctggaacag gcggccccga cggcgaccga gtcggccgat 60Val Ala Pro Thr Pro Arg His Leu Glu Gln Ala Ala Pro Thr Ala Thr Glu Ser Ala Aspccggcgctgt cctggccgaa gggcgtccct gtgccgctgg tggtgtccgg ccgaggcgcc 120Pro Ala Leu Ser Trp Pro Lys Gly Val Pro Val Pro Leu Val Val Ser Gly Arg Gly Alagcggcgctcg ccgcccaggc gcaacggcta cggaccttcg tagccgacga gccgcaactc 180Ala Ala Leu Ala Ala Gln Ala Gln Arg Leu Arg Thr Phe Val Ala Asp Glu Pro Gln Leugacttgagcg aactcggcta cgcgttgggt tgtggtcggg cggggttgtc ggatcgtggg 240Asp Leu Ser Glu Leu Gly Tyr Ala Leu Gly Cys Gly Arg Ala Gly Leu Ser Asp Arg Glygtggtggtgg cgggtggtcg tgaggagttg ttggtggggt tgggtgggtt ggtgcggggt 300Val Val Val Ala Gly Gly Arg Glu Glu Leu Leu Val Gly Leu Gly Gly Leu Val Arg Glygaggggggtg tgggtgtggt gtcgggttcg gtggtgcgtg gtcggttggg ggtgttgttt 360Glu Gly Gly Val Gly Val Val Ser Gly Ser Val Val Arg Gly Arg Leu Gly Val Leu Phegctggtcagg ggtgtcagcg ggtggggatg gggcgtggg ttgtatgaggt gttcccggtg 420Ala Gly Gln Gly Cys Gln Arg Val Gly Met Gly Arg Gly Leu Tyr Glu Val Phe Pro Valttccgggatg ccttcgacgc ggtgtgtgag gtgttggatc gggagttggg tgcgggtggt 480Phe Arg Asp Ala Phe Asp Ala Val Cys Glu Val Leu Asp Arg Glu Leu Gly Ala Gly Glygtggtgggtt cggtgcggga ggtggtgttc gggggtgggg ggttgttgga gcggacggtg 540Val Val Gly Ser Val Arg Glu Val Val Phe Gly Gly Gly Gly Leu Leu Glu Arg Thr Valtttgctcagg cggggttgtt cgccgtggag gtggggttgt tccggttggt ggagtcgtgg 600Phe Ala Gln Ala Gly Leu Phe Ala Val Glu Val Gly Leu Phe Arg Leu Val Glu Ser Trpggtgtggtgg tggatgtggt gggtgggcat tcggtgggtg aggtgacggc ggcgtatgtg 660Gly Val Val Val Asp Val Val Gly Gly His Ser Val Gly Glu Val Thr Ala Ala Tyr Valgcgggtgtgt tgtcgttgga ggatgcggcg gtgttggtgg cggcgcgggg tcggttgatg 720Ala Gly Val Leu Ser Leu Glu Asp Ala Ala Val Leu Val Ala Ala Arg Gly Arg Leu Metgaggcgttgc cggagggtgg ggcgatggtg gcggtggctg cgggtgagga ggtggtgcgg 780Glu Ala Leu Pro Glu Gly Gly Ala Met Val Ala Val Ala Ala Gly Glu Glu Val Val Argcctttgctgg tgtcggcggt ggatattgcg gcggtgaacg ggcccgaagc ggtggtgctc 840Pro Leu Leu Val Ser Ala Val Asp Ile Ala Ala Val Asn Gly Pro Glu Ala Val Val Leutccggtgatg aggagccggt actacgggtt gcgcgcgatt tgtcggatca ggggtgtcgg 900Ser Gly Asp Glu Glu Pro Val Leu Arg Val Ala Arg Asp Leu Ser Asp Gln Gly Cys Argacgaggcgtt tggcggtttc gcatgcgttc cattccgccc gtatggagcc gatgctggag 960Thr Arg Arg Leu Ala Val Ser His Ala Phe His Ser Ala Arg Met Glu Pro Met Leu Glugagttccggg aggcgatcgc cgatctgtcg ttctcggcgc cggtgattcc tctggtgtcg 1020Glu Phe Arg Glu Ala Ile Ala Asp Leu Ser Phe Ser Ala Pro Val Ile Pro Leu Val Seraatgtgaccg ggcggttggc ggatgcggag accgtgtgtt cgccggagta ctgggtggag 1080Ash Val Thr Gly Arg Leu Ala Asp Ala Glu Thr Val Cys Ser Pro Glu Tyr Trp Val Glucatgtgcgtt cggccgtgcg gttcgcggac ggtgtgcggg cgctcgctga ctacggtgtg 1140His Val Arg Ser Ala Val Arg Phe Ala Asp Gly Val Arg Ala Leu Ala Asp Tyr Gly Valggcacctatc tggagttggc gccggatgcg gtgttgtccg cgatggttgg tgattgtcta 1200Gly Thr Tyr Leu Glu Leu Ala Pro Asp Ala Val Leu Ser Ala Met Val Gly Asp Cys Leuccggaagggt cggctgctga gagtgtggtg gtgccgtcgc tgcggcggga gggcgacgag 1260Pro Glu Gly Ser Ala Ala Glu Ser Val Val Val Pro Ser Leu Arg Arg Glu Gly Asp Gluccccgtgcgc tgatgaccgc catcgctcag ctgcatgtgg caggcgtacc catcgacttc 1320Pro Arg Ala Leu Met Thr Ala Ile Ala Gln Leu His Val Ala Gly Val Pro Ile Asp Pheggtgccctgt tcggtgccac ggttctgccc acccatattt cggctctgcc gacgtatgcg 1380Gly Ala Leu Phe Gly Ala Thr Val Leu Pro Thr His Ile Ser Ala Leu Pro Thr Tyr Alattccagcggg agcattactg gttggtgggg gacgggcgtg gagccggcga tgtggcgtcc 1440Phe Gln Arg Glu His Tyr Trp Leu Val Gly Asp Gly Arg Gly Ala Gly Asp Val Ala Sergccgggctgg cgggggtgga gcatccattc ctgggcgcga tgacggaggt gcccgggtcg 1500Ala Gly Leu Ala Gly Val Glu His Pro Phe Leu Gly Ala Met Thr Glu Val Pro Gly Serggtgaggtgt tgttctcctc gcggttgtcg ttggggtctca tccgtggct ggccgatcat 1560Gly Glu Val Leu Phe Ser Ser Arg Leu Ser Leu Gly Ser His Pro Trp Leu Ala Asp Hisgtggctgcgg gtgcggtgtt gttgccgggt gcggcgtttg tggagttggt ggtgcggagc 1620Val Ala Ala Gly Ala Val Leu Leu Pro Gly Ala Ala Phe Val Glu Leu Val Val Arg Sertggacgatga ggtgggctgc ggtggggtgg aggagctgg 1659Trp Thr Met Arg Trp Ala Ala Val Gly Trp Arg Ser Trp該基因與rifamycin rif9的I型PKS同源(41%),相似性(51%)。gdnC.pro ------------------------------------------------------------ 1rif9.pro MATDEKLLKYLKRVTAELHSLRKQGARHADEPLAVVGMACRFPGGVSSPEDLWQLVAGGV 60gdnC.pro ------------------------------------------------------------ 1rif9.pro DALSDFPDDRGWELDGLFDPDPDHPGTSYTSQGGFLRGAGLFDAGLFGISPREALVMDPQ 120gdnC.pro ------------------------------------------------------------ 1rif9.pro QRVLLETSWEALEDAGVDPLSLKGSDVGVFSGVFTQGYGAGAITPDLEAFAGIGAASSVA 180gdnC.pro ------------------------------------------------------------ 1rifg.pro SGRVSYVFGLEGPAVTIDTACSSSLVAIHLAAQALRAGECSMALAGGATVMPTPGTFVAF 240gdnC.pro ------------------------------------------------------------ 1rif9.pro SRQRVLAADGRSKAFSSTADGTGWAEGAGVLVLERLSVAQERGHRILAVLRGSAVNQDGA 300gdnC.pro ------------------------------------------------------------ 1rif9.pro SNGLTAPNGPSQQRVIRKALAGAGLVASDVDVVEAHGTGTALGDPIEAQALLATYGQGRE 360 氨基酸序列分析發(fā)現(xiàn)在氨基酸120-421位置含有一個(gè)保守結(jié)構(gòu)域(見(jiàn)圖7),該結(jié)構(gòu)域?yàn)轷;D(zhuǎn)移酶結(jié)構(gòu)域(AT),編碼丙二?;D(zhuǎn)移酶。21.gdnD(Genbank AF521896)PKS基因,為一不完整的ORF,大小為3339bpDNA,編碼1113個(gè)氨基酸。gtgggcgccg taccgctcca ggaaccgctc ggcgtaggcg gggccgaacc aggggtcctc 60Val Gly Ala Val Pro Leu Gln Glu Pro Leu Gly Val Gly Gly Ala Glu Pro Gly Val Leugtcgatctcc agctcgcggg cggccagggc gatgtcggcg tggcggtcgg cgaccccgag 120Val Asp Leu Gln Leu Ala Gly Gly Gln Gly Asp Val Gly Val Ala Val Gly Asp Pro Glugcggccgacg tcgatcacgc cggtgacccg gcaggtcccg gggtcgagca ggacgttgtt 180Ala Ala Asp Val Asp His Ala Gly Asp Pro Ala Gly Pro Gly Val Glu Gln Asp Val Valggggcacagg tcgccatggc agacgaccag gtcctccttc tcgggacggg tgcggtcgag 240Gly Ala Gln Val Ala Met Ala Asp Asp Gln Val Leu Leu Leu Gly Thr Gly Ala Val Gluctccgccagg agctggtcgc cggtccaccc ggcccgctcc tcctgcaggt cgtcgaggtc 300Leu Arg Gln Glu Leu Val Ala Gly Pro Pro Gly Pro Leu Leu Leu Gln Val Val Glu Valcaccaggccc tcggcgacgt tccgccgggc ctcggcgacc gccgcgtcga ggcgccggtc 360His Gln Ala Leu Gly Asp Val Pro Pro Gly Leu Gly Asp Arg Arg Val Glu Ala Pro Valgaaggggcag tcctccacgg gcagctcgtg gagggcgcgg gccagctccg ccatcgcctc 420Glu Gly Ala Val Leu His Gly Gln Leu Val Glu Gly Ala Gly Gln Leu Arg His Arg Leugaccacggcg aaccgctggt gctcgggcca ctcctcggcc gccgcgacgc cggggacggc 480Asp His Gly Glu Pro Leu Val Leu Gly Pro Leu Leu Gly Arg Arg Asp Ala Gly Asp Glyctccgtgacg agccacgcgg cggtgtcgtc ggcaccgcgc tcgacgacgc gggggacggg 540Leu Arg Asp Glu Pro Arg Gly Gly Val Val Gly Thr Ala Leu Asp Asp Ala Gly Asp Glygatcgggtgg atgtggtgca gccggtgtcg tttgcggtga tggtggggtt ggcgcgggtg 600Asp Arg Val Asp Val Val Gln Pro Val Ser Phe Ala Val Met Val Gly Leu Ala Arg Valtggttggcgg ctggtgtggt gccgtcggtg gtggtgggtc attcgcaggg ggagattgcg 660Trp Leu Ala Ala Gly Val Val Pro Ser Val Val Val Gly His Ser Gln Gly Glu Ile Alagctgcgtgtg tggcgggtgg gttgtcgttg gaggacgcgg tgcgggtggt ggtgttgcgg 720Ala Ala Cys Val Ala Gly Gly Leu Ser Leu Glu Asp Ala Val Arg Val Val Val Leu Argagtcgtgcgg tggcggctgg gctctcgggc cgtggcggga tggtgtcgtt ggcggtgggt 780Ser Arg Ala Val Ala Ala Gly Leu Ser Gly Arg Gly Gly Met Val Ser Leu Ala Val Glygtggcggagg cggaggggtt ggttgagcgg tggtcggggc gtatcgaggt ggcggcggtg 840Val Ala Glu Ala Glu Gly Leu Val Glu Arg Trp Ser Gly Arg Ile Glu Val Ala Ala Valaatgggccgt tgtcggtggt ggtggctggt gagccggatg ccttgcgggg gttggtggcg 900Asn Gly Pro Leu Ser Val Val Val Ala Gly Glu Pro Asp Ala Leu Arg Gly Leu Val Alagagtgtgagg gcgcgggggt gcgggcgcgg tgggttgatg tggattacgc ctcgcatacg 960Glu Cys Glu Gly Ala Gly Val Arg Ala Arg Trp Val Asp Val Asp Tyr Ala Ser His Thrgcgcaggtgg aggcggtcga gggggagttg gctcggtcgt tggcgcaaat tcgtccggtg 1020Ala Gln Val Glu Ala Val Glu Gly Glu Leu Ala Arg Ser Leu Ala Gln Ile Arg Pro Valtcctcacgta ttccgttctt ttcgacggtg gaggctgggt ggctggacac ggccgagctg 1080Ser Ser Arg Ile Pro Phe Phe Ser Thr Val Glu Ala Gly Trp Leu Asp Thr Ala Glu Leugacgccgggt actggtaccg gaatctgcgg agcaccgtgc gcttcgcgcc gtcgatcgac 1140Asp Ala Gly Tyr Trp Tyr Arg Asn Leu Arg Ser Thr Val Arg Phe Ala Pro Ser Ile Aspcggttgatcg aggaaggctt tgcggcgttt gtcgaagtga gcgcgcatcc ggtgctgacg 1200Arg Leu Ile Glu Glu Gly Phe Ala Ala Phe Val Glu Val Ser Ala His Pro Val Leu Thratgggcatcg aggcggcggc ggagcgggcg gacgttgggc cggtcgtggt gaccgggacg 1260Met Gly Ile Glu Ala Ala Ala Glu Arg Ala Asp Val Gly Pro Val Val Val Thr Gly Thrctccgccggg atcagggtga tatgcgtcgt gtgctcactt ccctggccga ggtgtacgta 1320Leu Arg Arg Asp Gln Gly Asp Met Arg Arg Val Leu Thr Ser Leu Ala Glu Val Tyr Valcgcggtgtcc ccgtgaactg gaccaccctg ctgggcgaca tcccggcgcg cgccgcgttg 1380Arg Gly Val Pro Val Asn Trp Thr Thr Leu Leu Gly Asp Ile Pro Ala Arg Ala Ala Leugatctgccga cgtacgcctt ccagcatcag cactactggc tgaagaacgc cattcccacc 1440Asp Leu Pro Thr Tyr Ala Phe Gln His Gln His Tyr Trp Leu Lys Asn Ala Ile Pro Thrgatgcgggag ccatcgacga tcagcttccg ggcctggtcg aactgcccgc cgagaccggc 1500Asp Ala Gly Ala Ile Asp Asp Gln Leu Pro Gly Leu Val Glu Leu Pro Ala Glu Thr Glygccttgaccg ctcgccttct tggggagtcc acgcaggaac aggaacgcat cctgctcaag 1560Ala Leu Thr Ala Arg Leu Leu Gly Glu Ser Thr Gln Glu Gln Glu Arg Ile Leu Leu Lysaccgttcgcc aggagaccgc gagcgtcttg ggccactcct cgctggacgc cattgaaccg 1620Thr Val Arg Gln Glu Thr Ala Ser Val Leu Gly His Ser Ser Leu Asp Ala Ile Glu Progacatggtgt tcaaccagat cggcttcgac tcggccaccg cagtacagct gcgaaaccgt 1680Asp Met Val Phe Asn Gln Ile Gly Phe Asp Ser Ala Thr Ala Val Gln Leu Arg Asn Argctgaacgcgc tcaccgaccg gactctgccg accaccctgc tcttcgacta ccccacgccc 1740Leu Asn Ala Leu Thr Asp Arg Thr Leu Pro Thr Thr Leu Leu Phe Asp Tyr Pro Thr Proctgatcctcg ccgacttcct gcgtgacgaa ctcatcgggg acacggcggc cccggagggg 1800Leu Ile Leu Ala Asp Phe Leu Arg Asp Glu Leu Ile Gly Asp Thr Ala Ala Pro Glu Glygtgccggaag cgacagcggc gccgggggat gtgtcgaccg agccggtggc gatcgtgggt 1860Val Pro Glu Ala Thr Ala Ala Pro Gly Asp Val Ser Thr Glu Pro Val Ala Ile Val Glyatggcgtgcc ggctgccggg tggcgtctcc accccggaag agctatggga cctggtgctt 1920Met Ala Cys Arg Leu Pro Gly Gly Val Ser Thr Pro Glu Glu Leu Trp Asp Leu Val Leucaggggcggg acggggtcag cgacttcccc gtgaaccgtg gctgggatct ggagaatctg 1980Gln Gly Arg Asp Gly Val Ser Asp Phe Pro Val Asn Arg Gly Trp Asp Leu Glu Asn Leuttccacccgg acccggacca ccccgctacc agctatgcgc accaaggcgg atttctgcac 2040Phe His Pro Asp Pro Asp His Pro Ala Thr Ser Tyr Ala His Gln Gly Gly Phe Leu Hisgacgccgggg agtttgacgc gggtttcttc gggatctcac cacgcgaggc actggccgtg 2100Asp Ala Gly Glu Phe Asp Ala Gly Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Valgacccgcaac agcgtctgat gctggaaacc tcgtgggaag cgctggaacg cgccgggatc 2160Asp Pro Gln Gln Arg Leu Met Leu Glu Thr Ser Trp Glu Ala Leu Glu Arg Ala Gly Ilegacccgacca cgctgcgggg caaggacgtc ggtgtcttct ccggtgtgac gtaccacaac 2220Asp Pro Thr Thr Leu Arg Gly Lys Asp Val Gly Val Phe Ser Gly Val Thr Tyr His Asntacggctcgg gcgtggagcc ggttcccgcc gagctcgaag gcatgctggg gctcggcgcc 2280Tyr Gly Ser Gly Val Glu Pro Val Pro Ala Glu Leu Glu Gly Met Leu Gly Leu Gly Alatcggcgagcg tgctgtcagg gcgggtgtcg tatgcgctgg gcttcgaggg gccgtcggtc 2340Ser Ala Ser Val Leu Ser Gly Arg Val Ser Tyr Ala Leu Gly Phe Glu Gly Pro Ser Valgcggtggaca cggcgtgctc ctcgtccctg gtggcgttgc acttggcggc gcaggcgttg 2400Ala Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Ala Gln Ala Leucgagcaggcg agtgctcgat cgcccttgcc ggtggggtc acggtgatgcc gactcccggt 2460Arg Ala Gly Glu Cys Ser Ile Ala Leu Ala Gly Gly Val Thr Val Met Pro Thr Pro Glyatcttcatcg ccttctcacg gcagcgcggc atgtcggtcg atggccggtg caagtcgttc 2520Ile Phe Ile Ala Phe Ser Arg Gln Arg Gly Met Ser Val Asp Gly Arg Cys Lys Ser Phetcggcgtcgg cggacggtac ggggtgggcc gagggtgtgg gtgtgctggc gctggagcgg 2580Ser Ala Ser Ala Asp Gly Thr Gly Trp Ala Glu Gly Val Gly Val Leu Ala Leu Glu Argctgtcggacg cggagcgaaa cggccatcgg gtgttggcgg tggtgcgggg cagtgcggtg 2640Leu Ser Asp Ala Glu Arg Asn Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Valaatcaggacg gtgcgtcgaa tgggttgacg gcgccgaatg gtccgtcgca gcagcgtgtc 2700Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Valattcggcagg cgctggccag tgcgggtgtg tcggctgccg aggtggatgt ggtcgaggca 2760Ile Arg Gln Ala Leu Ala Ser Ala Gly Val Ser Ala Ala Glu Val Asp Val Val Glu Alacatggcacgg gtacggcgct gggcgatccc attgaggcgc aggcggtgt tggccacgtat 2820His Gly Thr Gly Thr Ala Leu Gly Asp Pro Ile Glu Ala Gln Ala Val Leu Ala Thr Tyrggccaggatc gtgatcggcc tttgttgatg gggtcgttga agtcgaatat cggtcatgcg 2880Gly Gln Asp Arg Asp Arg Pro Leu Leu Met Gly Ser Leu Lys Ser Asn Ile Gly His Alacaggcggccg cgggtgtggc tggtgtgatc aagatggtgt tggcgctgcg gcatggcatc 2940Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Leu Ala Leu Arg His Gly Ilegctcctcgga cgttgcatgt ggacgagccg acctcgcagg tggattggtc gacgggtgcg 3000Ala Pro Arg Thr Leu His Val Asp Glu Pro Thr Ser Gln Val Asp Trp Ser Thr Gly Alagtggagctgt tgaccgagga gcgggtgtgg cctgaggtgg gtcgtcctcg ccgggctgga 3060Val Glu Leu Leu Thr Glu Glu Arg Val Trp Pro Glu Val Gly Arg Pro Arg Arg Ala Glygtgtccgcgt tcggggtcag tggcaccaac gccccgtcat ctggaacagg cggccccgac 3120Val Ser Ala Phe Gly Val Ser Gly Thr Asn Ala Pro Ser Ser Gly Thr Gly Gly Pro Aspggcgaccgag tcggccgatc cggcgctgtc ctggccgaag ggcgtccctg tgccgctggt 3180Gly Asp Arg Val Gly Arg Ser Gly Ala Val Leu Ala Glu Gly Arg Pro Cys Ala Ala Glyggtgtccggc cgaggcgccg cggcgctcgc cgcccaggcg caacggctac ggaccttcgt 3240Gly Val Arg Pro Arg Arg Arg Gly Ala Arg Arg Pro Gly Ala Thr Ala Thr Asp Leu Argagccgacgag ccgcaactcg acttgagcga actcggctac gcgttgggtt gtggtcgggc 3300Ser Arg Arg Ala Ala Thr Arg Leu Glu Arg Thr Arg Leu Arg Val Gly Leu Trp Ser GlyGgggttgtcg gatcgtgggg tggtggtggc gggtggtcg 3339Gly Val Val Gly Ser Trp Gly Gly Gly Gly Gly Trp Ser該基因與Riff-3rifamycin I型PKS module 1-3同源性(52%);spnASaccharopolyspora spinosa(刺糖多孢菌)PKS裝配和延伸元件1同源性(53%),涉及spinosyn糖苷的生物合成;VeneStreptomyces venezuelae,I型PKS同源性(56%);AVESStreptomyces avermitilis產(chǎn)生的大環(huán)內(nèi)酯類(lèi)抗生素avermectin I型PKS-AVES同源性(54%)4;TylGStreptomyces fradiae產(chǎn)生的tylactone合酶起始模塊和模塊1,2同源性(56%). rif1-3 VDEEVAS----------------------------------------------------- 3608SpnASAGPGSGSVVDVP----------------------------------------------- 1435AVESVDATGPADLTEPQEEAAEPECVADAVTEMSAEPECVADAMSEMSAECVAEAVSDKSAEPE 3151tylGPEAPDVTDVTEALEAPDATEAEGAKAPGSPEE---------------------------- 3051veneVAMAGTAGTSEVAEGSEASEAP--AAPGSREA---------------------------- 3079gdnD--SSGTG----------------------------------------------------- 1037 氨基酸序列分析發(fā)現(xiàn)含典型的I型PKS保守的結(jié)構(gòu)域(見(jiàn)圖8)包括酰基轉(zhuǎn)移酶(AT)、?;d體蛋白(ACP)、β-酮?;厦?KS)的N端結(jié)構(gòu)域、β-酮?;厦?KS)的C端結(jié)構(gòu)域、、硫酯酶的N端結(jié)構(gòu)域。
本發(fā)明從柯斯質(zhì)粒pCGBA10中還克隆并分析了另外5個(gè)參與格爾德霉素從胞內(nèi)輸出機(jī)制的新基因。22.gdn1基因大小為1479bp,編碼493個(gè)氨基酸。gtggccgctg ctgccgcgct gagcgcgtgc ggcacaccgg aagcacacgg aagacccacg 60Val Ala Ala Ala Ala Ala Leu Ser Ala Cys Gly Thr Pro Glu Ala His Gly Arg Pro Thrggggtggcga tggagccggc ggcaccggcg cagtacgtac tgatcactca gtgcttgcag 120Gly Val Ala Met Glu Pro Ala Ala Pro Ala Gln Tyr Val Leu Ile Thr Gln Cys Leu Glnaacgacttct tcctcaacct ggactgccag ttgtccctgc cggacagcgc cgtctccaag 180Asn Asp Phe Phe Leu Asn Leu Asp Cys Gln Leu Ser Leu Pro Asp Ser Ala Val Ser Lysctgctgctgg acagcgagag cggtgcgtcc ctccacacgg agggccaccg cagggtcctg 240Leu Leu Leu Asp Ser Glu Ser Gly Ala Ser Leu His Thr Glu Gly His Arg Arg Val Leutccgagtcgg agctgcgccg ttcgcccctg gcccgtttcc tcgacgccac cgtgggctcc 300Ser Glu Ser Glu Leu Arg Arg Ser Pro Leu Ala Arg Phe Leu Asp Ala Thr Val Gly Sercgtacgcgcg gacacgggga cggggttctg catctgatca acatccgtga ctggcatgtc 360Arg Thr Arg Gly His Gly Asp Gly Val Leu His Leu Ile Asn Ile Arg Asp Trp His Valccgggagaga catacgacct ggagcgcagg cagtacgggg cccattgcga ggccgacacc 420Pro Gly Glu Thr Tyr Asp Leu Glu Arg Arg Gln Tyr Gly Ala His Cys Glu Ala Asp Thrtggggggcgg cgtacgtcga cgggctcacg gacctgctgg ccccggatga gcgcgcgccc 480Trp Gly Ala Ala Tyr Val Asp Gly Leu Thr Asp Leu Leu Ala Pro Asp Glu Arg Ala Progcggacggcg agggcggctg gggcgggaaa ctccatgtcc accatgtgcg gtccaacacc 540Ala Asp Gly Glu Gly Gly Trp Gly Gly Lys Leu His Val His His Val Arg Ser Asn Thrctcttcgact tccagcacag cgccggcgga cgtcccgacc tcagcgaacc ggcgccgctg 600Leu Phe Asp Phe Gln His Ser Ala Gly Gly Arg Pro Asp Leu Ser Glu Pro Ala Pro Leuaccacactgc tggacggtct gctgggcgat ggacgtcagg agacgacgca tgtcgcggtg 660Thr Thr Leu Leu Asp Gly Leu Leu Gly Asp Gly Arg Gln Glu Thr Thr His Val Ala Valgtcggcgtcc tcaccgatat caaggtccag ctgctgctga ccggtatccg ctcccgctac 720Val Gly Val Leu Thr Asp Ile Lys Val Gln Leu Leu Leu Thr Gly Ile Arg Ser Arg Tyrgacgtacggc agctcgtcgt ctccgacgcg ctcaccgcca gcaggaccct ggagcgccat 780Asp Val Arg Gln Leu Val Val Ser Asp Ala Leu Thr Ala Ser Arg Thr Leu Glu Arg Hisctgacggcgc tggacttctg ccagcgtgtg ctgcgcaccg aggtgatgat cggcctggcg 840Leu Thr Ala Leu Asp Phe Cys Gln Arg Val Leu Arg Thr Glu Val Met Ile Gly Leu Alagagctggccc gtttcctggg ctcccggccg gacgacgacc ggctgtcccg tggcggggac 900Glu Leu Ala Arg Phe Leu Gly Ser Arg Pro Asp Asp Asp Arg Leu Ser Arg Gly Gly Aspgaggagttcg tgggctactc ctcatacatc caggacaagc agggcatcct gtcgtacgag 960Glu Glu Phe Val Gly Tyr Ser Ser Tyr Ile Gln Asp Lys Gln Gly Ile Leu Ser Tyr Glugacgccagga tgcgggacta tcgcatccag acctcggaac gcctccggcg gacgcagcac 1020Asp Ala Arg Met Arg Asp Tyr Arg Ile Gln Thr Ser Glu Arg Leu Arg Arg Thr Gln Hisacggtcggct tcgccagcaa gttcctgctg gggctgggca cctgtctgct ggtcagcgcc 1080Thr Val Gly Phe Ala Ser Lys Phe Leu Leu Gly Leu Gly Thr Cys Leu Leu Val Ser Alacttgtgctgt cgctcgtcgg cgtcttcctc ccgggccgta tcgggtggca gagccccgcc 1140Leu Val Leu Ser Leu Val Gly Val Phe Leu Pro Gly Arg Ile Gly Trp Gln Ser Pro Alagtgctcgggg cgctcgggg ggggcagatcg tcacgttgtt cttcacccg gccggtcaga1200Val Leu Gly Ala Leu Gly Val Gly Gln Ile Val Thr Leu Phe Phe Thr Arg Pro Val Argtcggtgcagg acgcgctgg cggaggagac catctaccgga tgatcctgga gagccgcagc 1260Ser Val Gln Asp Ala Leu Ala Glu Glu Thr Ile Tyr Arg Met Ile Leu Glu Ser Arg Serctgaaggtgg ccctggcgc ggttccacat caccacggcc accgcgctccg acggcatgac 1320Leu Lys Val Ala Leu Ala Arg Phe His Ile Thr Thr Ala Thr Ala Leu Arg Arg His Aspgatgtgaacg gccaatccg acgccctggc acgccagttg gagatcctgga gaagatcgac 1380Asp Val Asn Gly Gln Ser Asp Ala Leu Ala Arg Gln Leu Glu Ile Leu Glu Lys Ile Aspacggccgact tcgaacggct gaaacagctg ggggtgaccc cgcgggccga atcgtccggg 1440Thr Ala Asp Phe Glu Arg Leu Lys Gln Leu Gly Val Thr Pro Arg Ala Glu Ser Ser Glyacggggcggc cccgcagaag aatccgctca caggtttcc 1479Thr Gly Arg Pro Arg Arg Arg Ile Arg Ser Gln Val Ser23.gdn2基因大小為1521bp,編碼507個(gè)氨基酸。atgtcaacac cacctatcgc cggtgacgac cagacgccgc gccggctrag gctgcgccgc 60Met Ser Thr Pro Pro Ile Ala Gly Asp Asp Gln Thr Pro Arg Arg XXX Arg Leu Arg Argcgcagggccg acgccgaccg cgggcgccgg ggcgggcggg catccgcacg gcggttcccc 120Arg Arg Ala Asp Ala Asp Arg Gly Arg Arg Gly Gly Arg Ala Ser Ala Arg Arg Phe Progatggcgccc tgccgcagcc cgagcccgtc gcgtcggatg tcatccgggc cggtgacagc 180Asp Gly Ala Leu Pro Gln Pro Glu Pro Val Ala Ser Asp Val Ile Arg Ala Gly Asp Seracctggctcc gggaccgggc gcgcaagcac ggcgcgtcgg cggccacccg gaaggtcttc 240Thr Trp Leu Arg Asp Arg Ala Arg Lys His Gly Ala Ser Ala Ala Thr Arg Lys Val Phegacccctggg tcctggccgg cccggaccgg gtgccctact tcgccgaact ggccagtctg 300Asp Pro Trp Val Leu Ala Gly Pro Asp Arg Val Pro Tyr Phe Ala Glu Leu Ala Ser Leucgcaaccggg tcaagcaccg gctcgccgag gagcatgcgc gagccgagga ggacggcgcg 360Arg Asn Arg Val Lys His Arg Leu Ala Glu Glu His Ala Arg Ala Glu Glu Asp Gly Alactggaggcga gccgggtcag ggcggccgcc accgcggccg gagagcggct ggagcgggcc 420Leu Glu Ala Ser Arg Val Arg Ala Ala Ala Thr Ala Ala Gly Glu Arg Leu Glu Arg Alagggcagcggc rggtcgtcct ggagcggcagc agacggtcac caccgcccag ctggaccgg 480Gly Gln Arg XXX Val Val Leu Glu Arg Gln Gln Thr Val Thr Thr Ala Gln Leu Asp Argctggcgcggc gggccgaccg gtggcagacc ttccgcgaca ccgtgcgggg cggtttcgag 540Leu Ala Arg Arg Ala Asp Arg Trp Gln Thr Phe Arg Asp Thr Val Arg Gly Gly Phe Glucgccggtggc tgcgcgcccg tatgcctgcc gacggcagcg acgggaccga ccccggacgg 600Arg Arg Trp Leu Arg Ala Arg Met Pro Ala Asp Gly Ser Asp Gly Thr Asp Pro Gly Argcagggcgcca cccggcgcga ggacgagccg gagaccaccg gccacgccag ctggcaggcg 660Gln Gly Ala Thr Arg Arg Glu Asp Glu Pro Glu Thr Thr Gly His Ala Ser Trp Gln Alagtgtccgaac ccgatccggt ggcggaggcg gacgcggccg accgcgccct gtccaccagg 720Val Ser Glu Pro Asp Pro Val Ala Glu Ala Asp Ala Ala Asp Arg Ala Leu Ser Thr Arggcggcgtggg agggcgcggc ggcgcgcccc gggatgccgc gctggatgaa gctcggtgtg 780Ala Ala Trp Glu Gly Ala Ala Ala Arg Pro Gly Met Pro Arg Trp Met Lys Leu Gly Valctggccgcgt tggtcgtggt ggaactgccc gtctactact cggtgttcga gaatctgcac 840Leu Ala Ala Leu Val Val Val Glu Leu Pro Val Tyr Tyr Ser Val Phe Glu Asn Leu Hisggtgtcgggc gcttcgccga tctgctctcc tacagcctca tggtggccgt ggcggtggcg 900Gly Val Gly Arg Phe Ala Asp Leu Leu Ser Tyr Ser Leu Met Val Ala Val Ala Val Alaatgatcctcg ccccgcatat cgcgggctgg atactgcggc ggcgctccgc caccggtgcg 960Met Ile Leu Ala Pro His Ile Ala Gly Trp Ile Leu Arg Arg Arg Ser Ala Thr Gly Alagtccggctgt cggccgtgcc cgccctcgcc ctgctgggcg tgtgggcgta cggcgcctgg 1020Val Arg Leu Ser Ala Val Pro Ala Leu Ala Leu Leu Gly Val Trp Ala Tyr Gly Ala Trpgcgctggggg atctgcgggc caaggtggcg ttccgggagg agcctccgct ggatctgccg 1080Ala Leu Gly Asp Leu Arg Ala Lys Val Ala Phe Arg Glu Glu Pro Pro Leu Asp Leu Procccgatgtgg ccgcggacgt gggcgacagc gtgcgcaacc cgccgagcct cctggagtcc 1140Pro Asp Val Ala Ala Asp Val Gly Asp Ser Val Arg Asn Pro Pro Ser Leu Leu Glu Serctgcatctgg acgcgcagag cgtgacctgg atgttcgtcg cgctgctgct gctctccggc 1200Leu His Leu Asp Ala Gln Ser Val Thr Trp Met Phe Val Ala Leu Leu Leu Leu Ser Glygggatcgcct tcctgatcgg gctgggcgag gagcatccgt atctcgcggc gtaccggacc 1260Gly Ile Ala Phe Leu Ile Gly Leu Gly Glu Glu His Pro Tyr Leu Ala Ala Tyr Arg Thracggccgagc ggctgcggga gctggagcgg gacatggaga cggatctcgc gggttccgag 1320Thr Ala Glu Arg Leu Arg Glu Leu Glu Arg Asp Met Glu Thr Asp Leu Ala Gly Ser Glucgtgccaagg aggccgaggc caccctgggt gcccgcgcgg aggcccgccg cgcggcccat 1380Arg Ala Lys Glu Ala Glu Ala Thr Leu Gly Ala Arg Ala Glu Ala Arg Arg Ala Ala Hisgaggcgcggc tctacgcggt cgacgatctc tacgaagccg cggcccacgc ctatctggac 1440Glu Ala Arg Leu Tyr Ala Val Asp Asp Leu Tyr Glu Ala Ala Ala His Ala Tyr Leu Aspggggtggcca tggagtccag cgatccggcg gtcacggagg ccgccatgcg gctgtccaag 1500Gly Val Ala Met Glu Ser Ser Asp Pro Ala Val Thr Glu Ala Ala Met Arg Leu Ser Lyscagtggccgc tgctgccgcg c 1521Gln Trp Pro Leu Leu Pro Arg24.gdn3基因大小為1791bp,編碼597個(gè)氨基酸.atgatcaaag acgccaggcc cccggaaccg ttccagtatg acccggcgtc aggcatctac 60Met Ile Lys Asp Ala Arg Pro Pro Glu Pro Phe Gln Tyr Asp Pro Ala Ser Gly Ile Tyrgagggcgttc tccggttgac ttccgggcgt tttcaggagc gggccctatg gggagcattc 120Glu Gly Val Leu Arg Leu Thr Ser Gly Arg Phe Gln Glu Arg Ala Leu Trp Gly Ala Pheccgggtacca cctcaccgat acggtctgac agagaatcca atcgacatcc acatcggcat 180Pro Gly Thr Thr Ser Pro Ile Arg Ser Asp Arg Glu Ser Asn Arg His Pro His Arg Hiscgacaacggc atccacatcg gcgtcggcta catcggccgc gaaccctttg cgggagaaag 240Arg Gln Arg His Pro His Arg Arg Arg Leu His Arg Pro Arg Thr Leu Cys Gly Arg Lyscggaatacca ctgtccgcaa tgcggctgtc cggtgcggga atttccgtac cggggaaatc 300Arg Asn Thr Thr Val Arg Asn Ala Ala Val Arg Cys Gly Asn Phe Arg Thr Gly Glu Ilegggggatcca tttccatgat cacatctgac agtgtcaacg gggtggtgcg ccgcggcagg 360Gly Gly Ser Ile Ser Met Ile Thr Ser Asp Ser Val Asn Gly Val Val Arg Arg Gly Argctcggccgta ccgcccgctt cgcggcccgc tggcggggca agcgcgacgg cgcgcgcggc 420Leu Gly Arg Thr Ala Arg Phe Ala Ala Arg Trp Arg Gly Lys Arg Asp Gly Ala Arg Glygtcccccgca tcgtgctccc ggagccgtcc ggggagcagc ggagcaagac gccgccgccc 480Val Pro Arg Ile Val Leu Pro Glu Pro Ser Gly Glu Gln Arg Ser Lys Thr Pro Pro Proatcgagccac ccgctcccga actgctgatc accccttacg tgatggaggt gcggaccggc 540Ile Glu Pro Pro Ala Pro Glu Leu Leu Ile Thr Pro Tyr Val Met Glu Val Arg Thr Glygtccgccgaa ccaccgagca gatgcgctcc gccctcatcg ggcgggagca cgccctgctc 600Val Arg Arg Thr Thr Glu Gln Met Arg Ser Ala Leu Ile Gly Arg Glu His Ala Leu Leuagcaggttgc gcgccgagtc ggtgcgcgtg gtcacccagt acgacgtccg cgaggacccc 660Ser Arg Leu Arg Ala Glu Ser Val Arg Val Val Thr Gln Tyr Asp Val Arg Glu Asp Procggcccgcgg sgctcgcgcg ctacggccac tgggtgggtc agtggcgcac cagcgtggac 720Arg Pro Ala XXX Leu Ala Arg Tyr Gly His Trp Val Gly Gln Trp Arg Thr Ser Val Aspcggtgccgat cgcatgccca tgccgtggtg gaccaggcca atcagcgact nssnmtgmta 780Arg Cys Arg Ser His Ala His Ala Val Val Asp Gln Ala Asn Gln Arg XXX XXX XXX XXXmtgggacgcg gtgmgcgaga cccaccccca gctctcccgc ctcccccggc gcccgcccgg 840XXX Gly Arg Gly XXX Arg Asp Pro Pro Pro Ala Leu Pro Pro Pro Pro Ala Pro Ala Argggactggctg cccggccggg tggagctgga ccggtcctgg taccagcccg acgtctggct 900Gly Leu Ala Ala Arg Pro Gly Gly Ala Gly Pro Val Leu Val Pro Ala Arg Arg Leu Alagctggccgac gacgacagca cgcggacggc cacctcccgg gcgctgcaca tactcgaacg 960Ala Gly Arg Arg Arg Gln His Ala Asp Gly His Leu Pro Gly Ala Ala His Thr Arg Thrgcagaacacc gaccgcktcg acrggaggac cgcgtgatga ccgtccacac tcccgytccg 1020Ala Glu His Arg Pro XXX Arg XXX Glu Asp Arg Val Met Thr Val His Thr Pro XXX Progagcgccckg ccgyccggsg gcacggaaac cggcggcacg gaaaccggcg gcgcgcgctg 1080Glu Arg XXX Ala XXX Arg XXX His Gly Asn Arg Arg His Gly Asn Arg Arg Arg Ala LeucccgccgSgc tggtgctcgc tctckcggcg gccgccacgg cctgcggctc cgacgagccg 1140Pro Ala XXX Leu Val Leu Ala Leu XXX Ala Ala Ala Thr Ala Cys Gly Ser Asp Glu Protcacgctact cgcagacatg tggtgtcgtg gtcgacggct ccggctcggc cgacgcctcc 1200Ser Arg Tyr Ser Gln Thr Cys Gly Val Val Val Asp Gly Ser Gly Ser Ala Asp Ala Sercggaccggct tcgacgcgga ggccaagctc aaggccaccc tccagacgtt cctgtcggac 1260Arg Thr Gly Phe Asp Ala Glu Ala Lys Leu Lys Ala Thr Leu Gln Thr Phe Leu Ser Aspaagaagtgcc gcaagacgtc cttcgccccc ataaccaagg tttccgaggc gtcgaagtgc 1320Lys Lys Cys Arg Lys Thr Ser Phe Ala Pro Ile Thr Lys Val Ser Glu Ala Ser Lys Cyscaggtcagcc cgctcgacct ggacccggac acctcgaaga ccgccgaccg cgagcggacc 1380Gln Val Ser Pro Leu Asp Leu Asp Pro Asp Thr Ser Lys Thr Ala Asp Arg Glu Arg Thrcgcaccgcca tgcgtgccgt cgccctctcc aacgccctga agctgctgcg ctgcgcccag 1440Arg Thr Ala Met Arg Ala Val Ala Leu Ser Asn Ala Leu Lys Leu Leu Arg Cys Ala Glnaaggaggagc ccggctccga tgtgctcggc gggctgtcgc gcatcgcgct gtccaagccg 1500Lys Glu Glu Pro Gly Ser Asp Val Leu Gly Gly Leu Ser Arg Ile Ala Leu Ser Lys Proagcggtgacg acgcgtcgtt cgacgtcctg gtggtcagcg acttcgacca gggcgacacc 1560Ser Gly Asp Asp Ala Ser Phe Asp Val Leu Val Val Ser Asp Phe Asp Gln Gly Asp Thrgacttccggc tcgggcggca ggacctgtcc accgccacca gccgccggac cgtcatcgac 1620Asp Phe Arg Leu Gly Arg Gln Asp Leu Ser Thr Ala Thr Ser Arg Arg Thr Val Ile Aspgacttcctca agtcgcacgg caaaccgaag ctgtccggcg ccgatgtcta cccggtgggc 1680Asp Phe Leu Lys Ser His Gly Lys Pro Lys Leu Ser Gly Ala Asp Val Tyr Pro Val Glytacggcatga agtaccacac cgacacctyc cggtacgagc agttcaacgc cttctggacg 1740Tyr Gly Met Lys Tyr His Thr Asp Thr XXX Arg Tyr Glu Gln Phe Asn Ala Phe Trp Thrgagcttctgg aggggagggt caaggcacat gtcaacacca cctatcgccg g1791Glu Leu Leu Glu Gly Arg Val Lys Ala His Val Asn Thr Thr Tyr Arg Arg25.gdn4基因大小為705bp,編碼235個(gè)氨基酸。gtggagaacg tcccagagcg cgcagagccc acgctccgga tcagtcagac acacttcccg 60Val Glu Asn Val Pro Glu Arg Ala Glu Pro Thr Leu Arg Ile Ser Gln Thr His Phe Progtggagaccc tgggtcccgg gcggcgcctg gccgtctggt cgcaggggtg cggactggcc 120Val Glu Thr Leu Gly Pro Gly Arg Arg Leu Ala Val Trp Ser Gln Gly Cys Gly Leu Alatgcgccggct gtatgtcccg gcacacctgg gatccgcgag gcggcgcctc tcgtacggtg 180Cys Ala Gly Cys Met Ser Arg His Thr Trp Asp Pro Arg Gly Gly Ala Ser Arg Thr Valtcgtccctgc tcgggctgtg gcgcgaggcg ttggcgcgcg gcgcggacgg gctgacgatc 240Ser Ser Leu Leu Gly Leu Trp Arg Glu Ala Leu Ala Arg Gly Ala Asp Gly Leu Thr Ileagcggcgggg agccgctcga ccagcccgcc gctctggagg ccctgctggc cggggcggtg 300Ser Gly Gly Glu Pro Leu Asp Gln Pro Ala Ala Leu Glu Ala Leu Leu Ala Gly Ala Valcgggcccgtg cggaggcggt ggcatcgggc ggcccggcgg cgggccgtga gatcgacatc 360Arg Ala Arg Ala Glu Ala Val Ala Ser Gly Gly Pro Ala Ala Gly Arg Glu Ile Asp Ilectcctctaca cggggtacga ggaggacgaa gtggagcgtg acgcggcgcg ctccgccgcc 420Leu Leu Tyr Thr Gly Tyr Glu Glu Asp Glu Val Glu Arg Asp Ala Ala Arg Ser Ala Alagtccgccacg ccgatgcgct ggtgaccgga cgcttccggg tggccgagcc caccgcgctg 480Val Arg His Ala Asp Ala Leu Val Thr Gly Arg Phe Arg Val Ala Glu Pro Thr Ala Leugtgtggcgcg gctcggcgaa ccagcgcata cggccgcgta cggcgcgcgg gtgggcgcgc 540Val Trp Arg Gly Ser Ala Asn Gln Arg Ile Arg Pro Arg Thr Ala Arg Gly Trp Ala Argtaccaggagc atctgrmmcg racggagagc gggccgcgtc tacaggtggw cgagggggag 600Tyr Gln Glu His Leu XXX XXX Thr Glu Ser Gly Pro Arg Leu Gln Val XXX Glu Gly Gluggcgatgtgc ggctctacgg agtgccgcgg cgcggcgaac tggtcgagct ggagcgtcgg 660Gly Asp Val Arg Leu Tyr Gly Val Pro Arg Arg Gly Glu Leu Val Glu Leu Glu Arg Argttgcggcggg cggggatcgc cctcaccggt gcgagctggc gcccc 705Leu Arg Arg Ala Gly Ile Ala Leu Thr Gly Ala Ser Trp Arg Pro26.gdn5基因大小為1218bp,編碼406個(gè)氨基酸。atgtgcggct ctacggagtg ccgcggcgcg gcgaactggt cgagctggag cgtcggttgc 60Met Cys Gly Ser Thr Glu Cys Arg Gly Ala Ala Asn Trp Ser Ser Trp Ser Val Gly Cysggcgggcggg gatcgccctc accggtgcga gctggcgccc ctgagcgggg gcgcccgnct 120Gly Gly Arg Gly Ser Pro Ser Pro Val Arg Ala Gly Ala Pro Glu Arg Gly Arg Pro XXXcgggtggcag ggcgcgccgc gaccccggaa gccgtggcct cggcggctgt ggtgcttgcg 180Arg Val Ala Gly Arg Ala Ala Thr Pro Glu Ala Val Ala Ser Ala Ala Val Val Leu Alagcagcggacc ttgtggcggt ggccttggcg gctgtggtcc ctatggctgg gtgctcggcg 240Ala Ala Asp Leu Val Ala Val Ala Leu Ala Ala Val Val Pro Met Ala Gly Cys Ser Alagcgatggcct cggcggytgt ggtccttgcg gcasgggccg ttgtggcaga gcgccctgtg 300Ala Met Ala Ser Ala XXX Val Val Leu Ala Ala XXX Ala Val Val Ala Glu Arg Pro Valgcggtggtct cggcggctgc gatcctctac gccggacgca tcgtggccgg catcaccggc 360Ala Val Val Ser Ala Ala Ala Ile Leu Tyr Ala Gly Arg Ile Val Ala Gly Ile Thr Glygccacaggtg cggttgctgg cgcctatatc gccgacatca ccgatgggga agatcgggct 420Ala Thr Gly Ala Val Ala Gly Ala Tyr Ile Ala Asp Ile Thr Asp Gly Glu Asp Arg Alacgccacttcg ggctcatgag cgcttgtttc ggcgtgggta tggtggcagg ccccgtggcc 480Arg His Phe Gly Leu Met Ser Ala Cys Phe Gly Val Gly Met Val Ala Gly Pro Val Alagggggactgt tgggcgccat ctccttgcat gcaccattcc ttgcggcggc ggtgctcaac 540Gly Gly Leu Leu Gly Ala Ile Ser Leu His Ala Pro Phe Leu Ala Ala Ala Val Leu Asnggcctcaacc tactactggg ctgcttccta atgcaggagt cgcataaggg agagcgtcga 600Gly Leu Asn Leu Leu Leu Gly Cys Phe Leu Met Gln Glu Ser His Lys Gly Glu Arg Argccgatgccct tgagagcctt caacccagtc agctccttcc ggtgggcgcg gggcatgact 660Pro Met Pro Leu Arg Ala Phe Asn Pro Val Ser Ser Phe Arg Trp Ala Arg Gly Met Thratcgtcgccg cacttatgac tgtcttcttt atcatgcaac tcgtaggaca ggtgccggca 720Ile Val Ala Ala Leu Met Thr Val Phe Phe Ile Met Gln Leu Val Gly Gln Val Pro Alagcgctctggg tcattttcgg cgaggaccgc tttcgctgga gcgcgacgat gatcggcctg 780Ala Leu Trp Val Ile Phe Gly Glu Asp Arg Phe Arg Trp Ser Ala Thr Met Ile Gly Leutcgcttgcgg tattcggaat cttgcacgcc ctcgctcaag ccttcgtcac tggtcccgcc 840Ser Leu Ala Val Phe Gly Ile Leu His Ala Leu Ala Gln Ala Phe Val Thr Gly Pro Alaaccaaacgtt tcggcgagaa gcaggccatt atcgccggca tggcggccga cgcgctgggc 900Thr Lys Arg Phe Gly Glu Lys Gln Ala Ile Ile Ala Gly Met Ala Ala Asp Ala Leu GlyTacgtcttgc tggcgttcgc gacgcgaggc tggatggcct tccccattat gattcttctc 960Tyr Val Leu Leu Ala Phe Ala Thr Arg Gly Trp Met Ala Phe Pro Ile Met Ile Leu Leugcttccggcg gcatcgggat gcccgcgttg caggccatgc tgtccaggca ggtagatgac 1020Ala Ser Gly Gly Ile Gly Met Pro Ala Leu Gln Ala Met Leu Ser Arg Gln Val Asp Aspgaccatcagg gacagcttca aggatcgctc gcggctctta ccagcctaac ttcgatcatt 1080Asp His Gln Gly Gln Leu Gln Gly Ser Leu Ala Ala Leu Thr Ser Leu Thr Ser Ile Ileggaccgctga tcgtcacggc gatttatgcc gcctcggcga gcacatggaa cgggttggca 1140Gly Pro Leu Ile Val Thr Ala Ile Tyr Ala Ala Ser Ala Ser Thr Trp Asn Gly Leu Alatggattgtag gcgccgccct ataccttgtc tgcctccccg cgttgcgtcg cggtgcatgg 1200Trp Ile Val Gly Ala Ala Leu Tyr Leu Val Cys Leu Pro Ala Leu Arg Arg Gly Ala Trpagccgggcca cctcgacc 1218Ser Arg Ala Thr Ser Thr該基因與四環(huán)素抗性基因(tetrac)高度同源(93%),相似性(93%),已知四環(huán)素抗性基因編碼外排蛋白,負(fù)責(zé)將抗生素排出胞外。Gdn1-5基因連鎖,故可以認(rèn)為這組基因與格爾德霉素的輸出胞外相關(guān)。 發(fā)明效果本發(fā)明克隆獲得了格爾德霉素的生物合成基因,可用于旨在提高該抗生素產(chǎn)量或結(jié)構(gòu)改造的基因操作。
圖1 以AHBA保守序列設(shè)計(jì)引物PCR產(chǎn)物電泳其中1 分子量標(biāo)記200bp ladder2 PCR產(chǎn)物755bp3 分子量標(biāo)記λDNA/HindIII圖2含BamHI 4.0kb片段基因簇酶譜分析其中pCGBA1、pCGBA10、pCGBA12、pCGBA9、pCGBA13、pCGBA15、pCGBA17為陽(yáng)性克隆柯斯質(zhì)粒編號(hào)圖3 gdnB氨基酸保守結(jié)構(gòu)域其中pp-binding為磷酸泛酰巰基乙胺的附著位點(diǎn)圖4 gdnF氨基酸保守結(jié)構(gòu)域其中Acyltransf2為N-?;D(zhuǎn)移酶結(jié)構(gòu)域圖5 gdnH氨基酸保守結(jié)構(gòu)域其中含有P450結(jié)構(gòu)域圖6格爾德霉素生物合成基因編碼框排列組織7gdnC氨基酸保守結(jié)構(gòu)域圖8gdnD氨基酸保守結(jié)構(gòu)域其中Acyl_transf酰基轉(zhuǎn)移酶(AT); ?;d體蛋白(ACP);Ketoacyl-syntβ-酮?;厦?KS)的N端結(jié)構(gòu)域;Ketoacyl-synt_cβ-酮?;厦?KS)的C端結(jié)構(gòu)域; 硫酯酶的N端結(jié)構(gòu)域.
序列表<110>中國(guó)醫(yī)學(xué)科學(xué)院醫(yī)藥生物技術(shù)研究所<120>吸水鏈霉菌17997生物合成格爾德霉素的基因簇<160>52<170>PatentIn version 3.1<210>1<211>1233<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(1233)<223><400>1gtg agc cag ttc ata gaa gat gtc cgg aac tca tcg atg ccc gca tcc 48Val Ser Gln Phe Ile Glu Asp Val Arg Asn Ser Ser Met Pro Ala Ser1 5 10 15gac gac tca acc ggc gcg tgt ccg cct gcc gcc gtt gcc ccg agc cag 96Asp Asp Ser Thr Gly Ala Cys Pro Pro Ala Ala Val Ala Pro Ser Gln20 25 30gag tcg tcc atg tcc gct ggc ccc ctc gcc ccg gcc acc cca tgg cgc 144Glu Ser Ser Met Ser Ala Gly Pro Leu Ala Pro Ala Thr Pro Trp Arg35 40 45agg gcg acg ggt gcc gct gta cgt cct cgt ccc gct ggc cgc ggc cat 192Arg Ala Thr Gly Ala Ala Val Arg Pro Arg Pro Ala Gly Arg Gly His50 55 60cgc cgt gat cgg cta cta cct gcc cct gct cgg cat ccg cct cgc cgc 240Arg Arg Asp Arg Leu Leu Pro Ala Pro Ala Arg His Pro Pro Arg Arg65 70 75 80ctt cct ggc cgt cga cat cgc cgc ggg cga gat cgc ccg cgg ccg cgc 288Leu Pro Gly Arg Arg His Arg Arg Gly Arg Asp Arg Pro Arg Pro Arg85 90 95cac cat ccc ggc cgc ctg acc ccg gtt tgc cat ctc ggc aat atg ttt 336His His Pro Gly Arg Leu Thr Pro Val Cys His Leu Gly Asn Met Phe100 105 110tgc ctc gat gga ggg tgg gct cgc atg gtt gcc gtg gag gtg gtc aag 384Cys Leu Asp Gly Gly Trp Ala Arg Met Val Ala Val Glu Val Val Lys115 120 125gtg gcc gat gag ctg aag aac gcc ttt gac gtg gtg gtg atc ggc ggt 432Val Ala Asp Glu Leu Lys Asn Ala Phe Asp Val Val Val Ile Gly Gly130 135 140ggc gcc gct ggg ctg agc ggg gcg ctg atg ctg gcc cgg tcg cgg cgt 480Gly Ala Ala Gly Leu Ser Gly Ala Leu Met Leu Ala Arg Ser Arg Arg145 150 155 160tcg gtg gtg gtg atc gac gcg ggc gcc ccg cgc aac gcc ccg gcc tcg 528Ser Val Val Val Ile Asp Ala Gly Ala Pro Arg Asn Ala Pro Ala Ser165 170 175gcg gtg cac gga ctg ctg gcc cgg gac ggg atc cct ccg gcc gag ttg 576Ala Val His Gly Leu Leu Ala Arg Asp Gly Ile Pro Pro Ala Glu Leu180 185 190gtg gcc cgg ggc cgg gcc gag gtc cgc ggc tac ggc ggt cag gtg gtg 624Val Ala Arg Gly Arg Ala Glu Val Arg Gly Tyr Gly Gly Gln Val Val195 200 205tcc ggc gag gtg ggc gcc gtg acc cgg gag gag tcc ggg ggc ttc cag 672Ser Gly Glu Val Gly Ala Val Thr Arg Glu Glu Ser Gly Gly Phe Gln210 215 220gtg gcc ctg acc gat ggc cgg acc gta cgt gcg cgc cgg ttg ctg ctg 720Val Ala Leu Thr Asp Gly Arg Thr Val Arg Ala Arg Arg Leu Leu Leu225 230 235 240gcc acc ggg ctg gtc gac gag ttg ccg gac atc ccg ggg ctg cgg tcc 768Ala Thr Gly Leu Val Asp Glu Leu Pro Asp Ile Pro Gly Leu Arg Ser245 250 255cgg tgg ggc cgg gat gtg ctg cac tgt ccg tac tgc cac ggc tgg gag 816Arg Trp Gly Arg Asp Val Leu His Cys Pro Tyr Cys His Gly Trp Glu260 265 270gtc cgc gac cag gcc atc ggc gta ctg ggg agc ggg ccg ctg tcg gtg 864Val Arg Asp Gln Ala Ile Gly Val Leu Gly Ser Gly Pro Leu Ser Val275 280 285cac cag gcg ctg ctg ttc cgt cag tgg agc gac gat gtc acc ttc ttc 912His Gln Ala Leu Leu Phe Arg Gln Trp Ser Asp Asp Val Thr Phe Phe290 295 300ccc cac acc ctg ccg tcg ccg tcc ggc gag gag gcg gag cag ctg gcc 960Pro His Thr Leu Pro Ser Pro Ser Gly Glu Glu Ala Glu Gln Leu Ala305 310 315 320gcc cgt ggc atc cgt gtg gtg gac ggc gag gtg gcg tcc ttg gag atc 1008Ala Arg Gly Ile Arg Val Val Asp Gly Glu Val Ala Ser Leu Glu Ile325 330 335gtc gag gac cgc ctc gtc ggc gtg cgg ctg ggc gac ggc ggc gtg gtc 1056Val Glu Asp Arg Leu Val Gly Val Arg Leu Gly Asp Gly Gly Val Val340 345 350gag cgc gag gcg ctg gcc gtc gcg ccg cgg atg gtg gca cac gcc ggt 1104Glu Arg Glu Ala Leu Ala Val Ala Pro Arg Met Val Ala His Ala Gly355 360 365ctc ctg gcg ggg ctc ggg ctg cgg ccg gtg gag cat ccg agc ggc ggc 1152Leu Leu Ala Gly Leu Gly Leu Arg Pro Val Glu His Pro Ser Gly Gly
370 375 380ggt gag cac atc ccg tcc gac gcg acc ggg cgc acc gag gtg tcc ggg 1200Gly Glu His Ile Pro Ser Asp Ala Thr Gly Arg Thr Glu Val Ser Gly385 390 395 400gtg tgg gtc gcg ggc aat gtc acc gat ctg gcg 1233Val Trp Val Ala Gly Asn Val Thr Asp Leu Ala405 410<210>2<211>411<212>PRT<213>Streptomyces hygroscopicus<400>2Val Ser Gln Phe Ile Glu Asp Val Arg Asn Ser Ser Met Pro Ala Ser1 5 10 15Asp Asp Ser Thr Gly Ala Cys Pro Pro Ala Ala Val Ala Pro Ser Gln20 25 30Glu Ser Ser Met Ser Ala Gly Pro Leu Ala Pro Ala Thr Pro Trp Arg35 40 45Arg Ala Thr Gly Ala Ala Val Arg Pro Arg Pro Ala Gly Arg Gly His50 55 60Arg Arg Asp Arg Leu Leu Pro Ala Pro Ala Arg His Pro Pro Arg Arg65 70 75 80Leu Pro Gly Arg Arg His Arg Arg Gly Arg Asp Arg Pro Arg Pro Arg85 90 95His His Pro Gly Arg Leu Thr Pro Val Cys His Leu Gly Asn Met Phe100 105 110Cys Leu Asp Gly Gly Trp Ala Arg Met Val Ala Val Glu Val Val Lys115 120 125Val Ala Asp Glu Leu Lys Asn Ala Phe Asp Val Val Val Ile Gly Gly130 135 140Gly Ala Ala Gly Leu Ser Gly Ala Leu Met Leu Ala Arg Ser Arg Arg145 150 155 160Ser Val Val Val Ile Asp Ala Gly Ala Pro Arg Asn Ala Pro Ala Ser165 170 175Ala Val His Gly Leu Leu Ala Arg Asp Gly Ile Pro Pro Ala Glu Leu180 185 190Val Ala Arg Gly Arg Ala Glu Val Arg Gly Tyr Gly Gly Gln Val Val195 200 205Ser Gly Glu Val Gly Ala Val Thr Arg Glu Glu Ser Gly Gly Phe Gln210 215 220Val Ala Leu Thr Asp Gly Arg Thr Val Arg Ala Arg Arg Leu Leu Leu225 230 235 240Ala Thr Gly Leu Val Asp Glu Leu Pro Asp Ile Pro Gly Leu Arg Ser245 250 255Arg Trp Gly Arg Asp Val Leu His Cys Pro Tyr Cys His Gly Trp Glu260 265 270Val Arg Asp Gln Ala Ile Gly Val Leu Gly Ser Gly Pro Leu Ser Val275 280 285His Gln Ala Leu Leu Phe Arg Gln Trp Ser Asp Asp Val Thr Phe Phe290 295 300Pro His Thr Leu Pro Ser Pro Ser Gly Glu Glu Ala Glu Gln Leu Ala305 310 315 320Ala Arg Gly Ile Arg Val Val Asp Gly Glu Val Ala Ser Leu Glu Ile325 330 335Val Glu Asp Arg Leu Val Gly Val Arg Leu Gly Asp Gly Gly Val Val340 345 350Glu Arg Glu Ala Leu Ala Val Ala Pro Arg Met Val Ala His Ala Gly355 360 365Leu Leu Ala Gly Leu Gly Leu Arg Pro Val Glu His Pro Ser Gly Gly370 375 380Gly Glu His Ile Pro Ser Asp Ala Thr Gly Arg Thr Glu Val Ser Gly385 390 395 400Val Trp Val Ala Gly Asn Val Thr Asp Leu Ala405 410<210>3<211>819<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(819)<223><400>3atg ggg tca tgt ggc ggc ggt cca cga gcc gcg ctt gtc atc ggc gtg 48Met Gly Ser Cys Gly Gly Gly Pro Arg Ala Ala Leu Val Ile Gly Val1 5 10 15atg aag att gag cea tcg tta cgc ata ccg gca acg get ggc ace atg 96Met Lys Ile Glu Pro Ser Leu Arg Ile Pro Ala Thr Ala Gly Thr Met20 25 30gct gcc atg tcc gcc ggg ccg ccc ttc cgt ctc gca cga gcc gcc gtg 144Ala Ala Met Ser Ala Gly Pro Pro Phe Arg Leu Ala Arg Ala Ala Val35 40 45ttc gcg gcg atg tgc gtc gtg gtg acg gcg ctc gga cac gtg ctg atg 192Phe Ala Ala Met Cys Val Val Val Thr Ala Leu Gly His Val Leu Met50 55 60tcc ggt gac agg ctg ccg gtg tgg gcc gtg gcc gcc gcc ttc gcc gga 240Ser Gly Asp Arg Leu Pro Val Trp Ala Val Ala Ala Ala Phe Ala Gly65 70 75 80acg gcg gcc ggt gcg tgg tgg gtt gcg ggg cgg gag cac ggt gcg ctg 288Thr Ala Ala Gly Ala Trp Trp Val Ala Gly Arg Glu His Gly Ala Leu85 90 95gcc gtg acc ggg gcg acc gtg gtc gcg caa ttc ggc ctc cat atg gcc 336Ala Val Thr Gly Ala Thr Val Val Ala Gln Phe Gly Leu His Met Ala100 105 110ttc cgg ttc gcg gag acg gca gtc gcc cca gcg gcg gga agc gcc atg 384Phe Arg Phe Ala Glu Thr Ala Val Ala Pro Ala Ala Gly Ser Ala Met115 120 125ggt gac ggg atg tcc ggt atg cgg ggc ggc atg ggc gcc gcc ccg atg 432Gly Asp Gly Met Ser Gly Met Arg Gly Gly Met Gly Ala Ala Pro Met130 135 140agc ggc gcc gcc atg ggt cat atg cac gat ggc atg ggc cat atg cgc 480Ser Gly Ala Ala Met Gly His Met His Asp Gly Met Gly His Met Arg145 150 155 160cat ggc gcg gac gcg atc tcc tcc gcc gcg ccg tcc atg agt cat ctg 528His Gly Ala Asp Ala Ile Ser Ser Ala Ala Pro Ser Met Ser His Leu165 170 175ccg tgg ccc tgg gcg ggt ccg ggc ggg gcg ggc atg gcc acg gcc cac 576Pro Trp Pro Trp Ala Gly Pro Gly Gly Ala Gly Met Ala Thr Ala His180 185 190ctg ctc gcc gcc ctg atc tgc ggg ctg tgg ctg tgg cgc ggc gaa cgg 624Leu Leu Ala Ala Leu Ile Cys Gly Leu Trp Leu Trp Arg Gly Glu Arg195 200205gcc gcc ttc cgg ctc ggc cgc gcg ctc gcg gcc ctg ctg ttc gtc ccg 672Ala Ala Phe Arg Leu Gly Arg Ala Leu Ala Ala Leu Leu Phe Val Pro210 215 220ctc gtc ctc gcc ctg cgc atc ctg ggc gcg ggt gtc act ccg ccg ccc 720Leu Val Leu Ala Leu Arg Ile Leu Gly Ala Gly Val Thr Pro Pro Pro225 230 235 240gca tgg acc tcc gca ccg gcc gtc gcc cgc cgg ccg cgc gga gtc ctg 768Ala Trp Thr Ser Ala Pro Ala Val Ala Arg Arg Pro Arg Gly Val Leu245 250 255ctg cgg cac gtc atc ctg cgc aga ggg cca ccg agg cgg ttc gcc atc 816Leu Arg His Val Ile Leu Arg Arg Gly Pro Pro Arg Arg Phe Ala Ile260 265 270cgc 819Arg<210>4<211>273<212>PRT<213>Streptomyces hygroscopicus<400>4Met Gly Ser Cys Gly Gly Gly Pro Arg Ala Ala Leu Val Ile Gly Val1 5 10 15Met Lys Ile Glu Pro Ser Leu Arg Ile Pro Ala Thr Ala Gly Thr Met20 25 30Ala Ala Met Ser Ala Gly Pro Pro Phe Arg Leu Ala Arg Ala Ala Val35 40 45Phe Ala Ala Met Cys Val Val Val Thr Ala Leu Gly His Val Leu Met50 55 60Ser Gly Asp Arg Leu Pro Val Trp Ala Val Ala Ala Ala Phe Ala Gly65 70 75 80Thr Ala Ala Gly Ala Trp Trp Val Ala Gly Arg Glu His Gly Ala Leu85 90 95Ala Val Thr Gly Ala Thr Val Val Ala Gln Phe Gly Leu His Met Ala100 105 110Phe Arg Phe Ala Glu Thr Ala Val Ala Pro Ala Ala Gly Ser Ala Met115 120 125Gly Asp Gly Met Ser Gly Met Arg Gly Gly Met Gly Ala Ala Pro Met130 135 140Ser Gly Ala Ala Met Gly His Met His Asp Gly Met Gly His Met Arg145 150 155 160His Gly Ala Asp Ala Ile Ser Ser Ala Ala Pro Ser Met Ser His Leu165 170 175Pro Trp Pro Trp Ala Gly Pro Gly Gly Ala Gly Met Ala Thr Ala His180 185 190Leu Leu Ala Ala Leu Ile Cys Gly Leu Trp Leu Trp Arg Gly Glu Arg195 200 205Ala Ala Phe Arg Leu Gly Arg Ala Leu Ala Ala Leu Leu Phe Val Pro210 215 220Leu Val Leu Ala Leu Arg Ile Leu Gly Ala Gly Val Thr Pro Pro Pro225 230 235 240Ala Trp Thr Ser Ala Pro Ala Val Ala Arg Arg Pro Arg Gly Val Leu245 250 255Leu Arg His Val Ile Leu Arg Arg Gly Pro Pro Arg Arg Phe Ala Ile260 265 270Arg<210>5<211>630<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(630)<223><400>5atg cct tct gcc acg ctg ccc gcc gca ccg ata aga gcc gtg cac ggc 48Met Pro Ser Ala Thr Leu Pro Ala Ala Pro Ile Arg Ala Val His Gly1 5 10 15ctt gcc acc gcg gcg aac gac cac cag gtc acc gaa tgg gcg ctg gcc 96Leu Ala Thr Ala Ala Asn Asp His Gln Val Thr Glu Trp Ala Leu Ala20 25 30gcc cgg gac ggc gac cgc gag gcg gtc gac cac ttc atc cgc gcc acc 144Ala Arg Asp Gly Asp Arg Glu Ala Val Asp His Phe Ile Arg Ala Thr35 40 45tac cgc gat gtg cgc cgt ttc gtg ctc cac ctc agc gcc gat ccg cat 192Tyr Arg Asp Val Arg Arg Phe Val Leu His Leu Ser Ala Asp Pro His50 55 60ggt tgt gag gac crc gcc cag gag acg tat ctg cgg gcg ctg acc ggg 240Gly Cys Glu Asp Leu Ala Gln Glu Thr Tyr Leu Arg Ala Leu Thr Gly65 70 75 80ctg ccg cgc ttc gcc ggt cgc tca tcg gcc cgg acg tgg ctg ctg tcg 288Leu Pro Arg Phe Ala Gly Arg Ser Ser Ala Arg Thr Trp Leu Leu Ser85 90 95atc gcc cgc cgt gtg gtc gtc gac cgc tac cgc acg gcc gcc gcc cgt 336Ile Ala Arg Arg Val Val Val Asp Arg Tyr Arg Thr Ala Ala Ala Arg100 105 110ccc cgt acg ttg gac gcg gac gac tgg cag gag gcg gcc gaa cgg gcg 384Pro Arg Thr Leu Asp Ala Asp Asp Trp Gln Glu Ala Ala Glu Arg Ala115 120 125cag ccc gcc ggg ctc ccc ggg ttc gac gag ggg gtg gcg ctg atg gac 432Gln Pro Ala Gly Leu Pro Gly Phe Asp Glu Gly Val Ala Leu Met Asp130 135 140ctg ctg gcg gcg ctc gcc ccg gca cgc cgt gag atg ttc ctc ctc acc 480Leu Leu Ala Ala Leu Ala Pro Ala Arg Arg Glu Met Phe Leu Leu Thr145 150 155 160aag gtg ctc ggc ctg ccg tac gcg gac gcc gcg acc gcg acc ggc tgc 528Lys Val Leu Gly Leu Pro Tyr Ala Asp Ala Ala Thr Ala Thr Gly Cys165 170 175ccc atc ggc acc gta cgc tcg cgc gtg gcc cgc gcc cgt gag gac atc 576Pro Ile Gly Thr Val Arg Ser Arg Val Ala Arg Ala Arg Glu Asp Ile180 185 190tcc gcg ctg ctg gcc gcg gcc gag aag gcc gcg gga ccg gtg ccg ttg 624Ser Ala Leu Leu Ala Ala Ala Glu Lys Ala Ala Gly Pro Val Pro Leu195 200 205gtg ggc 630Val Gly210<210>6<211>210<212>PRT<213>Streptomyces hygroscopicus<400>6Met Pro Ser Ala Thr Leu Pro Ala Ala Pro Ile Arg Ala Val His Gly1 5 10 15Leu Ala Thr Ala Ala Asn Asp His Gln Val Thr Glu Trp Ala Leu Ala20 25 30Ala Arg Asp Gly Asp Arg Glu Ala Val Asp His Phe Ile Arg Ala Thr35 40 45Tyr Arg Asp Val Arg Arg Phe Val Leu His Leu Ser Ala Asp Pro His50 55 60Gly Cys Glu Asp Leu Ala Gln Glu Thr Tyr Leu Arg Ala Leu Thr Gly65 70 75 80Leu Pro Arg Phe Ala Gly Arg Ser Ser Ala Arg Thr Trp Leu Leu Ser85 90 95Ile Ala Arg Arg Val Val Val Asp Arg Tyr Arg Thr Ala Ala Ala Arg100 105 110Pro Arg Thr Leu Asp Ala Asp Asp Trp Gln Glu Ala Ala Glu Arg Ala115 120 125Gln Pro Ala Gly Leu Pro Gly Phe Asp Glu Gly Val Ala Leu Met Asp130 135 140Leu Leu Ala Ala Leu Ala Pro Ala Arg Arg Glu Met Phe Leu Leu Thr145 150 155 160Lys Val Leu Gly Leu Pro Tyr Ala Asp Ala Ala Thr Ala Thr Gly Cys165 170 175Pro Ile Gly Thr Val Arg Ser Arg Val Ala Arg Ala Arg Glu Asp Ile180 185 190Ser Ala Leu Leu Ala Ala Ala Glu Lys Ala Ala Gly Pro Val Pro Leu195 200 205Val Gly210<210>7<211>993<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(993)<223><400>7atg agg tcc gcc gga cca tcg gcg cca tcg aac ggg tct acg cct cgg 48Met Arg Ser Ala Gly Pro Ser Ala Pro Ser Asn Gly Ser Thr Pro Arg1 5 10 15ccc gga tcc acc ggg agg tcc ggg agt cgg cgt cgg tgt gac cgc acc 96Pro Gly Ser Thr Gly Arg Ser Gly Ser Arg Arg Arg Cys Asp Arg Thr20 25 30ggc cga ccg ccc cgc cgc acc ggc tcc gct ccc atc cgc ccc ctc cct 144Gly Arg Pro Pro Arg Arg Thr Gly Ser Ala Pro Ile Arg Pro Leu Pro35 40 45tcc ctc gcc atc cct ttc gtc gtc ttc ccc ttc tcc gga cca cgt tct 192Ser Leu Ala Ile Pro Phe Val Val Phe Pro Phe Ser Gly Pro Arg Ser50 55 60ttc aga ccg cgt tct ttc gga ccg cat tct tcg gac cgc gtt ctt cgg 240Phe Arg Pro Arg Ser Phe Gly Pro His Ser Ser Asp Arg Val Leu Arg65 70 75 80acc gca ccc gag acc cgg acc ggc ggt ccg ccg tac cgg ccc gca cca 288Thr Ala Pro Glu Thr Arg Thr Gly Gly Pro Pro Tyr Arg Pro Ala Pro85 90 95cgg gag tgc tca atg aac acc cat ccg atc agt cat ggc ggc ccg ctc 336Arg Glu Cys Ser Met Asn Thr His Pro Ile Ser His Gly Gly Pro Leu100 105 110tcc ggc gcg ggt gtc gcc ccc atc acc tcg gtg gtc ttc gac ctc gac 384Ser Gly Ala Gly Val Ala Pro Ile Thr Ser Val Val Phe Asp Leu Asp115 120 125ggt gtc ctc gtc aac agc ttc gcg gtg atg cgc gag gcg ttc acc ctc 432Gly Val Leu Val Asn Ser Phe Ala Val Met Arg Glu Ala Phe Thr Leu130 135 140gcc tac gcc gag gtc gtc ggc gac ggt gag cca ccc ttc gag gag tac 480Ala Tyr Ala Glu Val Val Gly Asp Gly Glu Pro Pro Phe Glu Glu Tyr145 150 155 160aac cgg cat ctg ggc cgc tac ttc ccc gac atc atg cgg atc atg ggt 528Asn Arg His Leu Gly Arg Tyr Phe Pro Asp Ile Met Arg Ile Met Gly165 170 175ctt ccg ctg gag atg gag ggc ccg ttc gtc cgc gag agc tac cgg ctc 576Leu Pro Leu Glu Met Glu Gly Pro Phe Val Arg Glu Ser Tyr Arg Leu180 185 190gcc cac ctg gtg gag atg ttc gac ggt gtg cca gag ctg ctg tcg gag 624Ala His Leu Val Glu Met Phe Asp Gly Val Pro Glu Leu Leu Ser Glu195 200 205ctg cgc cac cgc ggg tta cga ctc gcc gtg gcc acc ggg aag agc gga 672Leu Arg His Arg Gly Leu Arg Leu Ala Val Ala Thr Gly Lys Ser Gly210 215 220ccc cgg gcg cgt tcg ctg ctc gac acc ctc ggc atc cgt ggg cag ttc 720Pro Arg Ala Arg Ser Leu Leu Asp Thr Leu Gly Ile Arg Gly Gln Phe225 230 235 240cac gtg gtc ctc ggc tcg gac gag gtg gcc cgg ccc aag ccc gcg ccg 768His Val Val Leu Gly Ser Asp Glu Val Ala Arg Pro Lys Pro Ala Pro245 250 255gac atc gtg ctg aag gcg atg gac atg atg gac gcg gac ccc gac cgg 816Asp Ile Val Leu Lys Ala Met Asp Met Met Asp Ala Asp Pro Asp Arg260 265 270acc gtg atg gtc ggg gac gcg gtg acc gac ctg gcc agc gcg cgg ggg 864Thr Val Met Val Gly Asp Ala Val Thr Asp Leu Ala Ser Ala Arg Gly275 280 285gcc ggg atc acc gcc gtg gcc gcg atg tgg ggt gag acc gac gag aag 912Ala Gly Ile Thr Ala Val Ala Ala Met Trp Gly Glu Thr Asp Glu Lys290 295 300acc ctg ctc gcg gcg gag ccc gat gtg atc ctg cac aag ccg gcg gaa 960Thr Leu Leu Ala Ala Glu Pro Asp Val Ile Leu His Lys Pro Ala Glu305 310 315 320ctg ctg tcg ctg tgc ccc gag gtg acg gtt cca 993Leu Leu Ser Leu Cys Pro Glu Val Thr Val Pro325 330<210>8<211>331<212>PRT<213>Streptomyces hygroscopicus<400>8Met Arg Ser Ala Gly Pro Ser Ala Pro Ser Asn Gly Ser Thr Pro Arg1 5 10 15Pro Gly Ser Thr Gly Arg Ser Gly Ser Arg Arg Arg Cys Asp Arg Thr20 25 30Gly Arg Pro Pro Arg Arg Thr Gly Ser Ala Pro Ile Arg Pro Leu Pro35 40 45Ser Leu Ala Ile Pro Phe Val Val Phe Pro Phe Ser Gly Pro Arg Ser50 55 60Phe Arg Pro Arg Ser Phe Gly Pro His Ser Ser Asp Arg Val Leu Arg65 70 75 80Thr Ala Pro Glu Thr Arg Thr Gly Gly Pro Pro Tyr Arg Pro Ala Pro85 90 95Arg Glu Cys Ser Met Asn Thr His Pro Ile Ser His Gly Gly Pro Leu100 105 110Ser Gly Ala Gly Val Ala Pro Ile Thr Ser Val Val Phe Asp Leu Asp115 120 125Gly Val Leu Val Asn Ser Phe Ala Val Met Arg Glu Ala Phe Thr Leu130 135 140Ala Tyr Ala Glu Val Val Gly Asp Gly Glu Pro Pro Phe Glu Glu Tyr145 150 155 160Asn Arg His Leu Gly Arg Tyr Phe Pro Asp Ile Met Arg Ile Met Gly165 170 175Leu Pro Leu Glu Met Glu Gly Pro Phe Val Arg Glu Ser Tyr Arg Leu180 185 190Ala His Leu Val Glu Met Phe Asp Gly Val Pro Glu Leu Leu Ser Glu195 200 205Leu Arg His Arg Gly Leu Arg Leu Ala Val Ala Thr Gly Lys Ser Gly210 215 220Pro Arg Ala Arg Ser Leu Leu Asp Thr Leu Gly Ile Arg Gly Gln Phe225 230 235 240His Val Val Leu Gly Ser Asp Glu Val Ala Arg Pro Lys Pro Ala Pro245 250 255Asp Ile Val Leu Lys Ala Met Asp Met Met Asp Ala Asp Pro Asp Arg260 265 270Thr Val Met Val Gly Asp Ala Val Thr Asp Leu Ala Ser Ala Arg Gly275 280 285Ala Gly Ile Thr Ala Val Ala Ala Met Trp Gly Glu Thr Asp Glu Lys290 295 300Thr Leu Leu Ala Ala Glu Pro Asp Val Ile Leu His Lys Pro Ala Glu305 310 315 320Leu Leu Ser Leu Cys Pro Glu Val Thr Val Pro325 330<210>9<211>1131<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(1131)<223><400>9atg agc gcc ccg tcc atc ggc gag ccg ccg atc agg acc gcc gtg gtg 48Met Ser Ala Pro Ser Ile Gly Glu Pro Pro Ile Arg Thr Ala Val Val1 5 10 15ggg ctg gga tgg gcg gcc cgc tcg atc tgg ctg ccc cgg ctc cgc cac 96Gly Leu Gly Trp Ala Ala Arg Ser Ile Trp Leu Pro Arg Leu Arg His20 25 30aac ccc gcc ttc acc gtg acc gcc gcg gtg gat ccc gac gag cgc ggc 144Asn Pro Ala Phe Thr Val Thr Ala Ala Val Asp Pro Asp Glu Arg Gly35 40 45cgc gcg gcc gtc gcc gag gcg gag ggc atg gac cgg ctg ccg gtg ctg 192Arg Ala Ala Val Ala Glu Ala Glu Gly Met Asp Arg Leu Pro Val Leu50 55 60gcg gcc gtc cac gac ctc gac ccc gcc gag gtg gac ctg gcg gtg gtc 240Ala Ala Val His Asp Leu Asp Pro Ala Glu Val Asp Leu Ala Val Val65 70 75 80gcg gtg ccc aac cat ctg cac tgt gcg gtc gcc gcc gag ctg ctg gcc 288Ala Val Pro Asn His Leu His Cys Ala Val Ala Ala Glu Leu Leu Ala85 90 95aag ggc att ccg gtg ttc ctg gag aag ccg gtg tgc ctg acc tcc gag 336Lys Gly Ile Pro Val Phe Leu Glu Lys Pro Val Cys Leu Thr Ser Glu100 105 110gag gcc gag cgg ctg gcc gaa gcg gag cgc tcg ggc ggc gcg atg ctg 384Glu Ala Glu Arg Leu Ala Glu Ala Glu Arg Ser Gly Gly Ala Met Leu115 120 125ctg gcc ggc agc gcg gcg cgg tac cgc gcc gat gtg cgc ggg ctg tac 432Leu Ala Gly Ser Ala Ala Arg Tyr Arg Ala Asp Val Arg Gly Leu Tyr130 135 140cgg atc gcc gcc cgg ctg ggc cat atc cgt cat gtc gag ctc gcc tgg 480Arg Ile Ala Ala Arg Leu Gly His Ile Arg His Val Glu Leu Ala Trp145 150 155 160gtg cgg tca cgc ggc gtg ccc gac cgg ggc ggc tgg ttc acc cag cgg 528Val Arg Ser Arg Gly Val Pro Asp Arg Gly Gly Trp Phe Thr Gln Arg165 170 175tcg ctc gcg ggc ggc ggg gcg ctg gtc gac ctg ggc tgg cat ctg ttc 576Ser Leu Ala Gly Gly Gly Ala Leu Val Asp Leu Gly Trp His Leu Phe180 185 190gac atc gcg gtt ccg ctg ctg ggc acc gcc gcg ttc cgg cac gcc atc 624Asp Ile Ala Val Pro Leu Leu Gly Thr Ala Ala Phe Arg His Ala Ile195 200 205ggg acc gtg tcc tcc gac ttc atc gtc cag cgg tcc tcc cgg gcc gcg 672Gly Thr Val Ser Ser Asp Phe Ile Val Gln Arg Ser Ser Arg Ala Ala210 215 220tgg cgc ggc gac gac ggc gac ggc ccg gcg ctc ctg ggc gcc aac ggg 720Trp Arg Gly Asp Asp Gly Asp Gly Pro Ala Leu Leu Gly Ala Asn Gly225 230 235 240ggt gcc acc gat gtc gag gac acc gca cgc gga ttc ctc atc acc gac 768Gly Ala Thr Asp Val Glu Asp Thr Ala Arg Gly Phe Leu Ile Thr Asp245 250 255gac ggc cgt tcg gtc gtg ctg cac gcg agc tgg gcc tcg cac gag gaa 816Asp Gly Arg Ser Val Val Leu His Ala Ser Trp Ala Ser His Glu Glu260 265 270ctg gac acc acc cgg gtg acg atc gac ggc agc gcg ggc agc gcc acc 864Leu Asp Thr Thr Arg Val Thr Ile Asp Gly Ser Ala Gly Ser Ala Thr
275 280 285ctg cgc tgc acc ttc gga ttc agc ccg aac cgc ctc gag aag tcc acc 912Leu Arg Cys Thr Phe Gly Phe Ser Pro Asn Arg Leu Glu Lys Ser Thr290 295 300ctg acc cgt acc gtc gac ggt acg acc cgg ccg gtg gcc gta ccc acc 960Leu Thr Arg Thr Val Asp Gly Thr Thr Arg Pro Val Ala Val Pro Thr305 310 315 320gaa ccg gtc ggc acc gag tac gac cgg cag ctc gac ctg ctt ccc gcg 1008Glu Pro Val Gly Thr Glu Tyr Asp Arg Gln Leu Asp Leu Leu Pro Ala325 330 335caa ctg cgc gac ccg gcc ggg cgg ggc cgg gtg atc gat gag gtc cgc 1056Gln Leu Arg Asp Pro Ala Gly Arg Gly Arg Val Ile Asp Glu Val Arg340 345 350cgg acc atc ggc gcc atc gaa cgg gtc tac gcc tcg gcc cgg atc cac 1104Arg Thr Ile Gly Ala Ile Glu Arg Val Tyr Ala Ser Ala Arg Ile His355 360 365cgg gag gtc cgg gag tcg gcg tcg gtg 1131Arg Glu Val Arg Glu Ser Ala Ser Val370 375<210>10<211>377<212>PRT<213>Streptomyces hygroscopicus<400>10Met Ser Ala Pro Ser Ile Gly Glu Pro Pro Ile Arg Thr Ala Val Val1 5 10 15Gly Leu Gly Trp Ala Ala Arg Ser Ile Trp Leu Pro Arg Leu Arg His20 25 30Asn Pro Ala Phe Thr Val Thr Ala Ala Val Asp Pro Asp Glu Arg Gly35 40 45Arg Ala Ala Val Ala Glu Ala Glu Gly Met Asp Arg Leu Pro Val Leu50 55 60Ala Ala Val His Asp Leu Asp Pro Ala Glu Val Asp Leu Ala Val Val65 70 75 80Ala Val Pro Asn His Leu His Cys Ala Val Ala Ala Glu Leu Leu Ala85 90 95Lys Gly Ile Pro Val Phe Leu Glu Lys Pro Val Cys Leu Thr Ser Glu100 105 110Glu Ala Glu Arg Leu Ala Glu Ala Glu Arg Ser Gly Gly Ala Met Leu115 120 125Leu Ala Gly Ser Ala Ala Arg Tyr Arg Ala Asp Val Arg Gly Leu Tyr130 135 140Arg Ile Ala Ala Arg Leu Gly His Ile Arg His Val Glu Leu Ala Trp145 150 155 160Val Arg Ser Arg Gly Val Pro Asp Arg Gly Gly Trp Phe Thr Gln Arg165 170 175Ser Leu Ala Gly Gly Gly Ala Leu Val Asp Leu Gly Trp His Leu Phe180 185 190Asp Ile Ala Val Pro Leu Leu Gly Thr Ala Ala Phe Arg His Ala Ile195 200 205Gly Thr Val Ser Ser Asp Phe Ile Val Gln Arg Ser Ser Arg Ala Ala210 215 220Trp Arg Gly Asp Asp Gly Asp Gly Pro Ala Leu Leu Gly Ala Asn Gly225 230 235 240Gly Ala Thr Asp Val Glu Asp Thr Ala Arg Gly Phe Leu Ile Thr Asp245 250 255Asp Gly Arg Ser Val Val Leu His Ala Ser Trp Ala Ser His Glu Glu260 265 270Leu Asp Thr Thr Arg Val Thr Ile Asp Gly Ser Ala Gly Ser Ala Thr275 280 285Leu Arg Cys Thr Phe Gly Phe Ser Pro Asn Arg Leu Glu Lys Ser Thr290 295 300Leu Thr Arg Thr Val Asp Gly Thr Thr Arg Pro Val Ala Val Pro Thr305 310 315 320Glu Pro Val Gly Thr Glu Tyr Asp Arg Gln Leu Asp Leu Leu Pro Ala325 330 335Gln Leu Arg Asp Pro Ala Gly Arg Gly Arg Val Ile Asp Glu Val Arg340 345 350Arg Thr Ile Gly Ala Ile Glu Arg Val Tyr Ala Ser Ala Arg Ile His355 360 365Arg Glu Val Arg Glu Ser Ala Ser Val370 375<210>11<211>1152<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(1152)<223><400>11gtg cga ctg cga tcc gag ctg ccc gca tgg ccg cag tac ggc gac gag 48Val Arg Leu Arg Ser Glu Leu Pro Ala Trp Pro Gln Tyr Gly Asp Glu1 5 10 15gag cgc gag gcc ctc atc cgg gct ctg gat cag ggg caa tgg tgg cgt 96Glu Arg Glu Ala Leu Ile Arg Ala Leu Asp Gln Gly Gln Trp Trp Arg20 25 30atc ggg ggc ggt gag gtc gac gcc ttc gag gcg gag ttc gccgcg gcc 144Ile Gly Gly Gly Glu Val Asp Ala Phe Glu Ala Glu Phe Ala Ala Ala35 40 45cat gga agc gag cac gcc ctg gcg gtc acc aac ggg acg cat gcg ctg 192His Gly Ser Glu His Ala Leu Ala Val Thr Asn Gly Thr His Ala Leu50 55 60gag ctc gcc ctc gaa gtg ctc ggg gtc ggc gcc gac tcc gag gtg atc 240Glu Leu Ala Leu Glu Val Leu Gly Val Gly Ala Asp Ser Glu Val Ile65 70 75 80gtt ccc gcg ttc acc ttc atc tcg tcc tcg cag gcg gct cag cgg ctg 288Val Pro Ala Phe Thr Phe Ile Ser Ser Ser Gln Ala Ala Gln Arg Leu85 90 95ggc gcg gtg gcc gtg ccc gtg gac gtg gac ccg gac acg tac tgc atc 336Gly Ala Val Ala Val Pro Val Asp Val Asp Pro Asp Thr Tyr Cys Ile100 105 110gat ccc tca gcg gtc gag gcg gcc atc ggc ccg aaa acc cgc gcg atc 384Asp Pro Ser Ala Val Glu Ala Ala Ile Gly Pro Lys Thr Arg Ala Ile115 120 125atg ccg gtg cac atg gcg ggc cag atg tgc gac atg gac gcg ctg ggc 432Met Pro Val His Met Ala Gly Gln Met Cys Asp Met Asp Ala Leu Gly130 135 140aag ctg tcc gcc gac tcg ggg gtg ccg ctg atc cag gac gcg gcc cat 480Lys Leu Ser Ala Asp Ser Gly Val Pro Leu Ile Gln Asp Ala Ala His145 150 155 160gcg cac ggt gcg cgg tgg cgc ggt cag aag gtc ggt gag ctg ggc tcg 528Ala His Gly Ala Arg Trp Arg Gly Gln Lys Val Gly Glu Leu Gly Ser165 170 175gtc gcc gcg ttc agc ttc cag aac gga aag ctg atg acg gcc ggc gag 576Val Ala Ala Phe Ser Phe Gln Asn Gly Lys Leu Met Thr Ala Gly Glu180 185 190ggc ggc gcc gtg ctc ttc ccc gat gcc gag atg tac gag agg ggc ttc 624Gly Gly Ala Val Leu Phe Pro Asp Ala Glu Met Tyr Glu Arg Gly Phe195 200 205gtc cgg cac agc tgt gga cgt ccg cgc acc gac cgc ggc tac ttc cac 672Val Arg His Ser Cys Gly Arg Pro Arg Thr Asp Arg Gly Tyr Phe His210 215 220cgc acc tcg ggc tcc aac ttc cgg ctg aac gag ttc tcc gca tcg gta 720Arg Thr Ser Gly Ser Asn Phe Arg Leu Asn Glu Phe Ser Ala Ser Val225 230 235 240ctg cgc gcc caa ctc acc cgc ctg gac ggc cag atc acc acg cgt gag 768Leu Arg Ala Gln Leu Thr Arg Leu Asp Gly Gln Ile Thr Thr Arg Glu245 250 255cag cgc tgg ccg gtg ctg agc agg ctg ctc gcc gag atc ccc ggt gtg 816Gln Arg Trp Pro Val Leu Ser Arg Leu Leu Ala Glu Ile Pro Gly Val
260 265 270gta ccg cag tcg cgc gac gac cgc ggt gac cgc aat ccg cac tac atg 864Val Pro Gln Ser Arg Asp Asp Arg Gly Asp Arg Asn Pro His Tyr Met275 280 285gcg atg ttc cgg gtg ccg ggc atc acc gag gag cgc cgt gcg aag gtc 912Ala Met Phe Arg Val Pro Gly Ile Thr Glu Glu Arg Arg Ala Lys Val290 295 300gtc gac acc ctc atc gag cgc ggg gtg ccc gcg ttc gtc gcg ttc cgc 960Val Asp Thr Leu Ile Glu Arg Gly Val Pro Ala Phe Val Ala Phe Arg305 310 315 320gcg gtc tac cgt acg gac gcc ttc tgg gag gtc gcg gcg ccg gat ctg 1008Ala Val Tyr Arg Thr Asp Ala Phe Trp Glu Val Ala Ala Pro Asp Leu325 330 335acg gtg gac gaa ctc gcc cgc cgc tgc ccg cac tcc gag gcg ctc acc 1056Thr Val Asp Glu Leu Ala Arg Arg Cys Pro His Ser Glu Ala Leu Thr340 345 350cgc gac tgc ctt tgg ctg cac cac cgg gtg ttg ctg ggc agc gag gag 1104Arg Asp Cys Leu Trp Leu His His Arg Val Leu Leu Gly Ser Glu Glu355 360 365cag atg cac gaa gtg gcc gcc gtc gtc gcc gat gtg ctc gcg ggc gca 1152Gln Met His Glu Val Ala Ala Val Val Ala Asp Val Leu Ala Gly Ala370 375 380<210>12<211>384<212>PRT<213>Streptomyces hygroscopicus<400>12Val Arg Leu Arg Ser Glu Leu Pro Ala Trp Pro Gln Tyr Gly Asp Glu1 5 10 15Glu Arg Glu Ala Leu Ile Arg Ala Leu Asp Gln Gly Gln Trp Trp Arg20 25 30Ile Gly Gly Gly Glu Val Asp Ala Phe Glu Ala Glu Phe Ala Ala Ala35 40 45His Gly Ser Glu His Ala Leu Ala Val Thr Asn Gly Thr His Ala Leu50 55 60Glu Leu Ala Leu Glu Val Leu Gly Val Gly Ala Asp Ser Glu Val Ile65 70 75 80Val Pro Ala Phe Thr Phe Ile Ser Ser Ser Gln Ala Ala Gln Arg Leu85 90 95Gly Ala Val Ala Val Pro Val Asp Val Asp Pro Asp Thr Tyr Cys Ile100 105 110Asp Pro Ser Ala Val Glu Ala Ala Ile Gly Pro Lys Thr Arg Ala Ile115 120 125Met Pro Val His Met Ala Gly Gln Met Cys Asp Met Asp Ala Leu Gly
130 135 140Lys Leu Ser Ala Asp Ser Gly Val Pro Leu Ile Gln Asp Ala Ala His145 150155 160Ala His Gly Ala Arg Trp Arg Gly Gln Lys Val Gly Glu Leu Gly Ser165 170 175Val Ala Ala Phe Ser Phe Gln Asn Gly Lys Leu Met Thr Ala Gly Glu180 185 190Gly Gly Ala Val Leu Phe Pro Asp Ala Glu Met Tyr Glu Arg Gly Phe195 200 205Val Arg His Ser Cys Gly Arg Pro Arg Thr Asp Arg Gly Tyr Phe His210 215 220Arg Thr Ser Gly Ser Asn Phe Arg Leu Asn Glu Phe Ser Ala Ser Val225 230 235 240Leu Arg Ala Gln Leu Thr Arg Leu Asp Gly Gln Ile Thr Thr Arg Glu245 250 255Gln Arg Trp Pro Val Leu Ser Arg Leu Leu Ala Glu Ile Pro Gly Val260 265 270Val Pro Gln Ser Arg Asp Asp Arg Gly Asp Arg Asn Pro His Tyr Met275 280 285Ala Met Phe Arg Val Pro Gly Ile Thr Glu Glu Arg Arg Ala Lys Val290 295 300Val Asp Thr Leu Ile Glu Arg Gly Val Pro Ala Phe Val Ala Phe Arg305 310 315 320Ala Val Tyr Arg Thr Asp Ala Phe Trp Glu Val Ala Ala Pro Asp Leu325 330 335Thr Val Asp Glu Leu Ala Arg Arg Cys Pro His Ser Glu Ala Leu Thr340 345 350Arg Asp Cys Leu Trp Leu His His Arg Val Leu Leu Gly Ser Glu Glu355 360 365Gln Met His Glu Val Ala Ala Val Val Ala Asp Val Leu Ala Gly Ala370 375 380<210>13<211>444<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(444)<223><400>13gtg agg tgc cca ttg agc agg ctg ttg ttg gtg aac gga ccg aat ctc 48Val Arg Cys Pro Leu Ser Arg Leu Leu Leu Val Asn Gly Pro Asn Leu1 5 10 15ggc ata ctc ggc aag cgc cag ccc gag atc tac ggc acg gat acg ctt 96Gly Ile Leu Gly Lys Arg Gln Pro Glu Ile Tyr Gly Thr Asp Thr Leu20 25 30cag gac atc gag cgc tgg gtc ggg gaa gag gtc gcg gag cgc ggc tgg 144Gln Asp Ile Glu Arg Trp Val Gly Glu Glu Val Ala Glu Arg Gly Trp35 40 45aaa gtg gat tcc tac cag ttc gat ggc gaa gcg gag atc atc cag acc 192Lys Val Asp Ser Tyr Gln Phe Asp Gly Glu Ala Glu Ile Ile Gln Thr50 55 60att cag ggg aac tac gac acg gtc ggt gcc atc atc aat ccg gcc gcg 240Ile Gln Gly Asn Tyr Asp Thr Val Gly Ala Ile Ile Asn Pro Ala Ala65 70 75 80ctc atg atg gcc gga tgg ggc ctt cgg gac gca ctg gcg aac tat ccg 288Leu Met Met Ala Gly Trp Gly Leu Arg Asp Ala Leu Ala Asn Tyr Pro85 90 95cgg ccc tgg ata gaa gtg cat ctg tcg aat gtc tgg gcc cgt gag cag 336Arg Pro Trp Ile Glu Val His Leu Ser Asn Val Trp Ala Arg Glu Gln100 105 110ttc cgc cat gag tcg gtg acc gga ccg ctg gcc gcg ggt gtc atc ttc 384Phe Arg His Glu Ser Val Thr Gly Pro Leu Ala Ala Gly Val Ile Phe115 120 125ggg ctc ggc gcc ctg ggc tac cgg ctc gcc gcc cgc gcc ctg ctc gac 432Gly Leu Gly Ala Leu Gly Tyr Arg Leu Ala Ala Arg Ala Leu Leu Asp130 135140aag gtg ccg gac 444Lys Val Pro Asp145<210>14<211>148<212>PRT<213>Streptomyces hygroscopicus<400>14Val Arg Cys Pro Leu Ser Arg Leu Leu Leu Val Asn Gly Pro Asn Leu1 5 10 15Gly Ile Leu Gly Lys Arg Gln Pro Glu Ile Tyr Gly Thr Asp Thr Leu20 25 30Gln Asp Ile Glu Arg Trp Val Gly Glu Glu Val Ala Glu Arg Gly Trp35 40 45Lys Val Asp Ser Tyr Gln Phe Asp Gly Glu Ala Glu Ile Ile Gln Thr50 55 60Ile Gln Gly Asn Tyr Asp Thr Val Gly Ala Ile Ile Asn Pro Ala Ala65 70 75 80Leu Met Met Ala Gly Trp Gly Leu Arg Asp Ala Leu Ala Asn Tyr Pro85 90 95Arg Pro Trp Ile Glu Val His Leu Ser Asn Val Trp Ala Arg Glu Gln
100 105 110Phe Arg His Glu Ser Val Thr Gly Pro Leu Ala Ala Gly Val Ile Phe115 120 125Gly Leu Gly Ala Leu Gly Tyr Arg Leu Ala Ala Arg Ala Leu Leu Asp130 135 140Lys Val Pro Asp145<210>15<211>882<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(882)<223><400>15gtg gcg ctg cgc ctc gaa cac gac gac ctc ggc atc agc gaa tcc tcc 48Val Ala Leu Arg Leu Glu His Asp Asp Leu Gly Ile Ser Glu Ser Ser1 5 10 15ttc cgc tgg ccc gag ccg gac ggt acg gac gcc atg acg tcc gcg tcc 96Phe Arg Trp Pro Glu Pro Asp Gly Thr Asp Ala Met Thr Ser Ala Ser20 25 30ggt ggc gcc acc cgc gat ctg gac ctg ctg gcg cgc cac atc agg gag 144Gly Gly Ala Thr Arg Asp Leu Asp Leu Leu Ala Arg His Ile Arg Glu35 40 45ctg tgt gcg ggc cga ccc gag cgg ctc aca ggt gtc ggg gtc gcg atg 192Leu Cys Ala Gly Arg Pro Glu Arg Leu Thr Gly Val Gly Val Ala Met50 55 60ccc gcc acc ctc gac gcc acc ggc acg gtc acc gcc tgg ccc ggc cgt 240Pro Ala Thr Leu Asp Ala Thr Gly Thr Val Thr Ala Trp Pro Gly Arg65 70 75 80ccc agc tgg gcc gga gtg gat ctg cgc ggc gcg ctg tcc gcc ctc ttc 288Pro Ser Trp Ala Gly Val Asp Leu Arg Gly Ala Leu Ser Ala Leu Phe85 90 95ggc cac gcc gag gtg cgc tgc gcc gac gac ggc gat ctg gcc gcc ctc 336Gly His Ala Glu Val Arg Cys Ala Asp Asp Gly Asp Leu Ala Ala Leu100 105 110gcc gaa gca cac gaa gcc cgc tgc ccc gac ctg ctc tat ctc ggc gtc 384Ala Glu Ala His Glu Ala Arg Cys Pro Asp Leu Leu Tyr Leu Gly Val115 120 125ggc acc ggg ata ggc ggt ggc atc gtg ctg aac ggg aaa ccc gtg ccc 432Gly Thr Gly Ile Gly Gly Gly Ile Val Leu Asn Gly Lys Pro Val Pro130 135 140ggt gtg ggc cgc ggc tcc tgc gaa gtc ggc cac ctg gtc gtg gac cgc 480Gly Val Gly Arg Gly Ser Cys Glu Val Gly His Leu Val Val Asp Arg145 150 155 160gac gga ccg ctg tgc gac tgc ggt cgg cgc ggc tgc gtc cag gcg gcg 528Asp Gly Pro Leu Cys Asp Cys Gly Arg Arg Gly Cys Val Gln Ala Ala165 170 175gcc tcg ggc ccg gcg acc ctg cgc agg gcg gcg cgg aga cgg gac gag 576Ala Ser Gly Pro Ala Thr Leu Arg Arg Ala Ala Arg Arg Arg Asp Glu180 185 190gag gtg acc ttc acc gcg ctg cgc caa gcg gtg cgc ggc gga aag ccg 624Glu Val Thr Phe Thr Ala Leu Arg Gln Ala Val Arg Gly Gly Lys Pro195 200 205tgg gcg gtg gcg tcg ctg cgg gag agc ggc agg gcc ctg gcc gcg gcc 672Trp Ala Val Ala Ser Leu Arg Glu Ser Gly Arg Ala Leu Ala Ala Ala210 215 220gtg acc ggc gta tgc gaa ctg ctc cat ccc tcg ctc gtg ctg atc ggc 720Val Thr Gly Val Cys Glu Leu Leu His Pro Ser Leu Val Leu Ile Gly225 230 235 240gga ggg ttt gcc gcg gcg atg ccg gag ctg gtg gcg atg gtg gcc gag 768Gly Gly Phe Ala Ala Ala Met Pro Glu Leu Val Ala Met Val Ala Glu245 250 255cgg acg gcg gag ctg ggg cgc ccc ggc cat cca ccg cca ccg gtc cgg 816Arg Thr Ala Glu Leu Gly Arg Pro Gly His Pro Pro Pro Pro Val Arg260 265 270ccc gcg cga ctg ggc ggg ctg tcc tca ctg cac ggc gcc gtg ctg ctg 864Pro Ala Arg Leu Gly Gly Leu Ser Ser Leu His Gly Ala Val Leu Leu275 280 285gcc agg gga ctg ccg gac 882Ala Arg Gly Leu Pro Asp290<210>16<211>294<212>PRT<213>Streptomyces hygroscopicus<400>16Val Ala Leu Arg Leu Glu His Asp Asp Leu Gly Ile Ser Glu Ser Ser1 5 10 15Phe Arg Trp Pro Glu Pro Asp Gly Thr Asp Ala Met Thr Ser Ala Ser20 25 30Gly Gly Ala Thr Arg Asp Leu Asp Leu Leu Ala Arg His Ile Arg Glu35 40 45Leu Cys Ala Gly Arg Pro Glu Arg Leu Thr Gly Val Gly Val Ala Met50 55 60Pro Ala Thr Leu Asp Ala Thr Gly Thr Val Thr Ala Trp Pro Gly Arg65 70 75 80Pro Ser Trp Ala Gly Val Asp Leu Arg Gly Ala Leu Ser Ala Leu Phe85 90 95Gly His Ala Glu Val Arg Cys Ala Asp Asp Gly Asp Leu Ala Ala Leu100 105 110Ala Glu Ala His Glu Ala Arg Cys Pro Asp Leu Leu Tyr Leu Gly Val115 120 125Gly Thr Gly Ile Gly Gly Gly Ile Val Leu Asn Gly Lys Pro Val Pro130 135 140Gly Val Gly Arg Gly Ser Cys Glu Val Gly His Leu Val Val Asp Arg145 150 155 160Asp Gly Pro Leu Cys Asp Cys Gly Arg Arg Gly Cys Val Gln Ala Ala165 170 175Ala Ser Gly Pro Ala Thr Leu Arg Arg Ala Ala Arg Arg Arg Asp Glu180 185 190Glu Val Thr Phe Thr Ala Leu Arg Gln Ala Val Arg Gly Gly Lys Pro195 200 205Trp Ala Val Ala Ser Leu Arg Glu Ser Gly Arg Ala Leu Ala Ala Ala210 215 220Val Thr Gly Val Cys Glu Leu Leu His Pro Ser Leu Val Leu Ile Gly225 230 235 240Gly Gly Phe Ala Ala Ala Met Pro Glu Leu Val Ala Met Val Ala Glu245 250 255Arg Thr Ala Glu Leu Gly Arg Pro Gly His Pro Pro Pro Pro Val Arg260 265 270Pro Ala Arg Leu Gly Gly Leu Ser Ser Leu His Gly Ala Val Leu Leu275 280 285Ala Arg Gly Leu Pro Asp290<210>17<211>849<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(849)<223><400>17gtg tca ggc gct gca ctc gga gac atc atg ttc acc atc gga gac ttc 48Val Ser Gly Ala Ala Leu Gly Asp Ile Met Phe Thr Ile Gly Asp Phe1 5 10 15gcc cgg cac ggc cgt gtc tcg gtc cgg atg ctg cgc cac tac gac gcc 96Ala Arg His Gly Arg Val Ser Val Arg Met Leu Arg His Tyr Asp Ala20 25 30atc gga ctg ctg cgc ccg gcc cat gtc gac ccc gcc acc ggc tac cgc 144Ile Gly Leu Leu Arg Pro Ala His Val Asp Pro Ala Thr Gly Tyr Arg35 40 45cac tac tcg gcc gcc cag ctc agc cgc ctg aac cgg gtc atc gcg ctc 192His Tyr Ser Ala Ala Gln Leu Ser Arg Leu Asn Arg Val Ile Ala Leu50 55 60aaa gag ctc ggc ttc acc ctc cag cag gtg cgg gac atc gtg gac gag 240Lys Glu Leu Gly Phe Thr Leu Gln Gln Val Arg Asp Ile Val Asp Glu65 70 75 80aag gtc ggc acc gag gag ctg cgc ggc atg ctg cgg ttg cgc cgg gcc 288Lys Val Gly Thr Glu Glu Leu Arg Gly Met Leu Arg Leu Arg Arg Ala85 90 95gag ctg gaa gcc acg gtg gaa gcc gtg gcg gca cgg ctg gtg cag gtc 336Glu Leu Glu Ala Thr Val Glu Ala Val Ala Ala Arg Leu Val Gln Val100 105 110gag gcg agg ctc cgg tcg atc gaa agc gag ggg cac atg ccc acc gac 384Glu Ala Arg Leu Arg Ser Ile Glu Ser Glu Gly His Met Pro Thr Asp115 120 125gac gtc gtc atc aag agg gtc ccc gcg gtg cgg gtg gcg gag ctc acc 432Asp Val Val Ile Lys Arg Val Pro Ala Val Arg Val Ala Glu Leu Thr130 135 140gcg acc gcc gcc agc ttc gac ccg cag gac atc agc ccg gtc atc aca 480Ala Thr Ala Ala Ser Phe Asp Pro Gln Asp Ile Ser Pro Val Ile Thr145 150 155 160ccc ctc tac gaa gag ctg ttc cgg cgg ctc gac gct gcg ggc atc acc 528Pro Leu Tyr Glu Glu Leu Phe Arg Arg Leu Asp Ala Ala Gly Ile Thr165 170 175ccg acg ggc cct ggt gtc gca tac tac gag gac gcc ccg gaa ggc ggc 576Pro Thr Gly Pro Gly Val Ala Tyr Tyr Glu Asp Ala Pro Glu Gly Gly180 185 190ggc gcc atc agt gtg cac gcc gcc gtc cag gtg tcc gcc ccg tca cgg 624Gly Ala Ile Ser Val His Ala Ala Val Gln Val Ser Ala Pro Ser Arg195 200 205gac ggc gat gac ctc cgg atc crc gat ctg ccg ccc atc gac cac gcc 672Asp Gly Asp Asp Leu Arg Ile Leu Asp Leu Pro Pro Ile Asp His Ala210 215 220gcc acc atc gtc cac cgc ggc ccg atg gac gcc gtg gtg ccc acg gcc 720Ala Thr Ile Val His Arg Gly Pro Met Asp Ala Val Val Pro Thr Ala225 230 235 240cag gcc ctg gcc cat tgg att gac ggc aac ggc tac cgg tcg acc ggc 768Gln Ala Leu Ala His Trp Ile Asp Gly Asn Gly Tyr Arg Ser Thr Gly245 250 255tac ccc cgg gag atc acc ctg gag tgc ccg gag aac cgt gcg gaa tgg 816Tyr Pro Arg Glu Ile Thr Leu Glu Cys Pro Glu Asn Arg Ala Glu Trp260 265 270gtc acg gaa ctc cag aca ccg gtg gtc cag gtc849Val Thr Glu Leu Gln Thr Pro Val Val Gln Val275 280<210>18<211>283<212>PRT<213>Streptomyces hygroscopicus<400>18Val Ser Gly Ala Ala Leu Gly Asp Ile Met Phe Thr Ile Gly Asp Phe1 5 10 15Ala Arg His Gly Arg Val Ser Val Arg Met Leu Arg His Tyr Asp Ala20 25 30Ile Gly Leu Leu Arg Pro Ala His Val Asp Pro Ala Thr Gly Tyr Arg35 40 45His Tyr Ser Ala Ala Gln Leu Ser Arg Leu Asn Arg Val Ile Ala Leu50 55 60Lys Glu Leu Gly Phe Thr Leu Gln Gln Val Arg Asp Ile Val Asp Glu65 70 75 80Lys Val Gly Thr Glu Glu Leu Arg Gly Met Leu Arg Leu Arg Arg Ala85 90 95Glu Leu Glu Ala Thr Val Glu Ala Val Ala Ala Arg Leu Val Gln Val100 105 110Glu Ala Arg Leu Arg Ser Ile Glu Ser Glu Gly His Met Pro Thr Asp115 120 125Asp Val Val Ile Lys Arg Val Pro Ala Val Arg Val Ala Glu Leu Thr130 135 140Ala Thr Ala Ala Ser Phe Asp Pro Gln Asp Ile Ser Pro Val Ile Thr145 150 155 160Pro Leu Tyr Glu Glu Leu Phe Arg Arg Leu Asp Ala Ala Gly Ile Thr165 170 175Pro Thr Gly Pro Gly Val Ala Tyr Tyr Glu Asp Ala Pro Glu Gly Gly180 185 190Gly Ala Ile Ser Val His Ala Ala Val Gln Val Ser Ala Pro Ser Arg195 200 205Asp Gly Asp Asp Leu Arg Ile Leu Asp Leu Pro Pro Ile Asp His Ala210 215 220Ala Thr Ile Val His Arg Gly Pro Met Asp Ala Val Val Pro Thr Ala225 230 235 240Gln Ala Leu Ala His Trp Ile Asp Gly Asn Gly Tyr Arg Ser Thr Gly245 250 255Tyr Pro Arg Glu Ile Thr Leu Glu Cys Pro Glu Asn Arg Ala Glu Trp260 265 270Val Thr Glu Leu Gln Thr Pro Val Val Gln Val275 280<210>19<211>2115<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(2115)<223><400>19gtg gct ctg ccg gag gaa cat cgg gtc cag gcg gcg ggg ttc ggg ctt 48Val Ala Leu Pro Glu Glu His Arg Val Gln Ala Ala Gly Phe Gly Leu1 5 10 15cat ccg gca ctc ctc gac gcg gcc atg cac acc atc gcc ttc cac gac 96His Pro Ala Leu Leu Asp Ala Ala Met His Thr Ile Ala Phe His Asp20 25 30cga gac gaa gcc gat gcg gag ctc gtg ctg ccg ttc gcc tat cga gag 144Arg Asp Glu Ala Asp Ala Glu Leu Val Leu Pro Phe Ala Tyr Arg Glu35 40 45gtg gcg ttg cat gct tcg ggg gct tcg gcg ctg cgg gta cgc gta aca 192Val Ala Leu His Ala Ser Gly Ala Ser Ala Leu Arg Val Arg Val Thr50 55 60ccg tcc ggc ccg aac gcc atg acc ctc gac ctg gcc gat ggc tcc ggg 240Pro Ser Gly Pro Asn Ala Met Thr Leu Asp Leu Ala Asp Gly Ser Gly65 70 75 80gcc ccg gtt gcc tcg gtg ggc tcg gtg gtg tcg cgt ccg gtc ggc gcc 288Ala Pro Val Ala Ser Val Gly Ser Val Val Ser Arg Pro Val Gly Ala85 90 95gag cac ttc ggc acg gtg gcg acg gcg gac cgg atg ttc cgc gtc gca 336Glu His Phe Gly Thr Val Ala Thr Ala Asp Arg Met Phe Arg Val Ala100 105 110tgg gag gaa ctg ccg att cag ccg gac ggc acg acc gcg gaa ccc gta 384Trp Glu Glu Leu Pro Ile Gln Pro Asp Gly Thr Thr Ala Glu Pro Val115 120 125ccg gtg gcc gat gcc gag gac gtg cac cgt ctg gtc acg gcg cca gag 432Pro Val Ala Asp Ala Glu Asp Val His Arg Leu Val Thr Ala Pro Glu130 135 140acc tca ccg ccc gat gtg ctg ttg ctg gac ctg ggc ggt ggc gtc ggc 480Thr Ser Pro Pro Asp Val Leu Leu Leu Asp Leu Gly Gly Gly Val Gly145 150 155 160ggt ggt tcg gcc gac gta cgc gag ctg acc gga cgg gcg ttg cgc gtt 528Gly Gly Ser Ala Asp Val Arg Glu Leu Thr Gly Arg Ala Leu Arg Val165 170 175gta cag acg tgg ctg gag gag ccc tcg ttg gcg ttg agt cgg ctg gtc 576Val Gln Thr Trp Leu Glu Glu Pro Ser Leu Ala Leu Ser Arg Leu Val
180 185 190gtg gtg acg cgg ggc gcc gtg gcc gtc cgg gag agc gat ccg gtc gat 624Val Val Thr Arg Gly Ala Val Ala Val Arg Glu Ser Asp Pro Val Asp195 200 205ccg gcg atg gca gcg gta tgg ggg ctg atg gga tcc gca caa gcg gag 672Pro Ala Met Ala Ala Val Trp Gly Leu Met Gly Ser Ala Gln Ala Glu210 215 220aac ccc ggg cgc atc ctc ctc ctc gac atc gat caa ggg acg ata ccg 720Asn Pro Gly Arg Ile Leu Leu Leu Asp Ile Asp Gln Gly Thr Ile Pro225 230 235 240acc ccg cta ctg ccc gca ctg ctc gtc ggt gac cag cac caa ctg gcc 768Thr Pro Leu Leu Pro Ala Leu Leu Val Gly Asp Gln His Gln Leu Ala245 250 255cta cgc gac acc acc tgc ttc acc cgc cac ctc atc cgt gtg ctg gat 816Leu Arg Asp Thr Thr Cys Phe Thr Arg His Leu Ile Arg Val Leu Asp260 265 270gcg ccg cag tcc ggt ccg ggt ggt ttg gag gac gtg ggt ggg acg gta 864Ala Pro Gln Ser Gly Pro Gly Gly Leu Glu Asp Val Gly Gly Thr Val275 280 285ctg gtg acg ggt ggg acg ggg gcg ttg ggt gcg gtg gtg gca cgg cat 912Leu Val Thr Gly Gly Thr Gly Ala Leu Gly Ala Val Val Ala Arg His290 295 300ctg gtg gcg gtg cac ggg atg cgg agt gtg gtg ttg gcg agc cgg aat 960Leu Val Ala Val His Gly Met Arg Ser Val Val Leu Ala Ser Arg Asn305 310 315 320ggg ctt gag gca ccc ggc gcc gcc gag ttg gag gcg gag ctg gtg aag 1008Gly Leu Glu Ala Pro Gly Ala Ala Glu Leu Glu Ala Glu Leu Val Lys325 330 335gcg ggt gcg cgc gta cgc atc gtc gcg tgt gat gtg gcg gac cgg gac 1056Ala Gly Ala Arg Val Arg Ile Val Ala Cys Asp Val Ala Asp Arg Asp340 345 350gcg gtg gcc ggg ctg ctg gac gcc gtc ccg gca gac gct ccg ttg tcg 1104Ala Val Ala Gly Leu Leu Asp Ala Val Pro Ala Asp Ala Pro Leu Ser355 360 365gcg gtg gtg cat acg gcc ggt gtt ctg gat gac ggt gtg ctg acg gcg 1152Ala Val Val His Thr Ala Gly Val Leu Asp Asp Gly Val Leu Thr Ala370 375 380ttg acc ccg gaa cgt atg gac gcg gtg ctc cgg ccg aag gtg gac ggc 1200Leu Thr Pro Glu Arg Met Asp Ala Val Leu Arg Pro Lys Val Asp Gly385 390 395 400gca ctc cat ctc cac gag ctg acc cgg cac ctg ggc ctg tcc gcc ttc 1248Ala Leu His Leu His Glu Leu Thr Arg His Leu Gly Leu Ser Ala Phe405 410 415gtc ctg ttc tcc tcc gcc gcc ggc acc ctc ggc aac gcg ggt cag ggc 1296Val Leu Phe Ser Ser Ala Ala Gly Thr Leu Gly Asn Ala Gly Gln Gly420 425 430aac tac gcc gcc gcc aac gcc tac ctc gac gcg ctg gcc cat cga cgc 1344Asn Tyr Ala Ala Ala Asn Ala Tyr Leu Asp Ala Leu Ala His Arg Arg435 440 445cgg gcc cag ggg ctg ccg gca gta tcc ctc gcc tgg ggc atg tgg cag 1392Arg Ala Gln Gly Leu Pro Ala Val Ser Leu Ala Trp Gly Met Trp Gln450 455 460cag gcc gcg gga acg ggg atg acc ggc cgt ctc ggc gat gcc gag cag 1440Gln Ala Ala Gly Thr Gly Met Thr Gly Arg Leu Gly Asp Ala Glu Gln465 470 475 480cgc cgg atg aca cgc ggc ggg gtg gcc ccc ttg tcc ccg gcc gag ggc 1488Arg Arg Met Thr Arg Gly Gly Val Ala Pro Leu Ser Pro Ala Glu Gly485 490 495atg gag ctc ttc gac act gcg ctg cgt atg gcc gaa ccc acg gtc ctc 1536Met Glu Leu Phe Asp Thr Ala Leu Arg Met Ala Glu Pro Thr Val Leu500 505 510ccc atc aaa ctg gac ctc ggt gcg ctc cgc gcc cag gcc gcc acc ggg 1584Pro Ile Lys Leu Asp Leu Gly Ala Leu Arg Ala Gln Ala Ala Thr Gly515 520 525gcg gtg cag ccg ttg ctg cac cgg ctg gtg cca ccg gtc cgc cga gcc 1632Ala Val Gln Pro Leu Leu His Arg Leu Val Pro Pro Val Arg Arg Ala530 535 540act cgc gcc acg gcc gag cag ggc ctg gtg acc ggc cgg ctg gcg ggc 1680Thr Arg Ala Thr Ala Glu Gln Gly Leu Val Thr Gly Arg Leu Ala Gly545 550 555 560gcg acc ccc gag gag cgg gag cgg atc ctg ctg gag atg gtc cag cag 1728Ala Thr Pro Glu Glu Arg Glu Arg Ile Leu Leu Glu Met Val Gln Gln565 570 575gag gcc gcc cgg gtc ctg gga cac tcg gcg gct gcc acg ctc gac ccc 1776Glu Ala Ala Arg Val Leu Gly His Ser Ala Ala Ala Thr Leu Asp Pro580 585 590gat gtg ctg ttc acc gag atc ggc ctg gac tcc ctg atg gcg gtg gaa 1824Asp Val Leu Phe Thr Glu Ile Gly Leu Asp Ser Leu Met Ala Val Glu595 600 605cta cgc gat cgc ctg gcc aag cgc acc gcg ctg cgg ttg cct ccc agc 1872Leu Arg Asp Arg Leu Ala Lys Arg Thr Ala Leu Arg Leu Pro Pro Ser610 615 620ttt gtc ttc gac cac ccc acc ctc cgg atg ctg gcc cgg cag ctg tgg 1920Phe Val Phe Asp His Pro Thr Leu Arg Met Leu Ala Arg Gln Leu Trp625 630 635 640gac gag ctg gag aaa gcc gat acg gac gct ccc gcc gca tcc gcc ccg 1968Asp Glu Leu Glu Lys Ala Asp Thr Asp Ala Pro Ala Ala Ser Ala Pro645 650 655act ccc gca tcc gcc gaa act ccc gca tcc gcc cca acc gcc gga gcc 2016Thr Pro Ala Ser Ala Glu Thr Pro Ala Ser Ala Pro Thr Ala Gly Ala660 665 670acc ccg tca ccc gga gcc acc ccg tca ccc gga gcc acc ccg tca ccc 2064Thr Pro Ser Pro Gly Ala Thr Pro Ser Pro Gly Ala Thr Pro Ser Pro675 680 685gga gcc act ctg cca ccc gcg ccc acc ccg cct tcc gga gcc gcc cag 2112Gly Ala Thr Leu Pro Pro Ala Pro Thr Pro Pro Ser Gly Ala Ala Gln690 695 700gag 2115Glu705<210>20<211>705<212>PRT<213>Streptomyces hygroscopicus<400>20Val Ala Leu Pro Glu Glu His Arg Val Gln Ala Ala Gly Phe Gly Leu1 5 10 15His Pro Ala Leu Leu Asp Ala Ala Met His Thr Ile Ala Phe His Asp20 25 30Arg Asp Glu Ala Asp Ala Glu Leu Val Leu Pro Phe Ala Tyr Arg Glu35 40 45Val Ala Leu His Ala Ser Gly Ala Ser Ala Leu Arg Val Arg Val Thr50 55 60Pro Ser Gly Pro Asn Ala Met Thr Leu Asp Leu Ala Asp Gly Ser Gly65 70 75 80Ala Pro Val Ala Ser Val Gly Ser Val Val Ser Arg Pro Val Gly Ala85 90 95Glu His Phe Gly Thr Val Ala Thr Ala Asp Arg Met Phe Arg Val Ala100 105 110Trp Glu Glu Leu Pro Ile Gln Pro Asp Gly Thr Thr Ala Glu Pro Val115 120 125Pro Val Ala Asp Ala Glu Asp Val His Arg Leu Val Thr Ala Pro Glu130 135 140Thr Ser Pro Pro Asp Val Leu Leu Leu Asp Leu Gly Gly Gly Val Gly145 150 155 160Gly Gly Ser Ala Asp Val Arg Glu Leu Thr Gly Arg Ala Leu Arg Val165 170 175Val Gln Thr Trp Leu Glu Glu Pro Ser Leu Ala Leu Ser Arg Leu Val180 185 190Val Val Thr Arg Gly Ala Val Ala Val Arg Glu Ser Asp Pro Val Asp195 200 205Pro Ala Met Ala Ala Val Trp Gly Leu Met Gly Ser Ala Gln Ala Glu
210 215 220Asn Pro Gly Arg Ile Leu Leu Leu Asp Ile Asp Gln Gly Thr Ile Pro225 230 235 240Thr Pro Leu Leu Pro Ala Leu Leu Val Gly Asp Gln His Gln Leu Ala245 250 255Leu Arg Asp Thr Thr Cys Phe Thr Arg His Leu Ile Arg Val Leu Asp260 265 270Ala Pro Gln Ser Gly Pro Gly Gly Leu Glu Asp Val Gly Gly Thr Val275 280 285Leu Val Thr Gly Gly Thr Gly Ala Leu Gly Ala Val Val Ala Arg His290 295 300Leu Val Ala Val His Gly Met Arg Ser Val Val Leu Ala Ser Arg Asn305 310 315 320Gly Leu Glu Ala Pro Gly Ala Ala Glu Leu Glu Ala Glu Leu Val Lys325 330 335Ala Gly Ala Arg Val Arg Ile Val Ala Cys Asp Val Ala Asp Arg Asp340 345 350Ala Val Ala Gly Leu Leu Asp Ala Val Pro Ala Asp Ala Pro Leu Ser355 360 365Ala Val Val His Thr Ala Gly Val Leu Asp Asp Gly Val Leu Thr Ala370 375 380Leu Thr Pro Glu Arg Met Asp Ala Val Leu Arg Pro Lys Val Asp Gly385 390 395 400Ala Leu His Leu His Glu Leu Thr Arg His Leu Gly Leu Ser Ala Phe405 410 415Val Leu Phe Ser Ser Ala Ala Gly Thr Leu Gly Asn Ala Gly Gln Gly420 425 430Asn Tyr Ala Ala Ala Asn Ala Tyr Leu Asp Ala Leu Ala His Arg Arg435 440 445Arg Ala Gln Gly Leu Pro Ala Val Ser Leu Ala Trp Gly Met Trp Gln450 455 460Gln Ala Ala Gly Thr Gly Met Thr Gly Arg Leu Gly Asp Ala Glu Gln465 470 475 480Arg Arg Met Thr Arg Gly Gly Val Ala Pro Leu Ser Pro Ala Glu Gly485 490 495Met Glu Leu Phe Asp Thr Ala Leu Arg Met Ala Glu Pro Thr Val Leu500 505 510Pro Ile Lys Leu Asp Leu Gly Ala Leu Arg Ala Gln Ala Ala Thr Gly515 520 525Ala Val Gln Pro Leu Leu His Arg Leu Val Pro Pro Val Arg Arg Ala530 535 540Thr Arg Ala Thr Ala Glu Gln Gly Leu Val Thr Gly Arg Leu Ala Gly545 550 555 560Ala Thr Pro Glu Glu Arg Glu Arg Ile Leu Leu Glu Met Val Gln Gln
565 570 575Glu Ala Ala Arg Val Leu Gly His Ser Ala Ala Ala Thr Leu Asp Pro580 585 590Asp Val Leu Phe Thr Glu Ile Gly Leu Asp Ser Leu Met Ala Val Glu595 600 605Leu Arg Asp Arg Leu Ala Lys Arg Thr Ala Leu Arg Leu Pro Pro Ser610 615 620Phe Val Phe Asp His Pro Thr Leu Arg Met Leu Ala Arg Gln Leu Trp625 630 635 640Asp Glu Leu Glu Lys Ala Asp Thr Asp Ala Pro Ala Ala Ser Ala Pro645 650 655Thr Pro Ala Ser Ala Glu Thr Pro Ala Ser Ala Pro Thr Ala Gly Ala660 665 670Thr Pro Ser Pro Gly Ala Thr Pro Ser Pro Gly Ala Thr Pro Ser Pro675 680 685Gly Ala Thr Leu Pro Pro Ala Pro Thr Pro Pro Ser Gly Ala Ala Gln690 695 700Glu705<210>21<211>1026<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(1026)<223><400>21gtg gga cga gct gga gaa agc cga tac gga cgc tcc cgc cgc atc cgc 48Val Gly Arg Ala Gly Glu Ser Arg Tyr Gly Arg Ser Arg Arg Ile Arg1 5 10 15ccc gac tcc cgc atc cgc cga aac tcc cgc atc cgc ccc aac cgc cgg 96Pro Asp Ser Arg Ile Arg Arg Asn Ser Arg Ile Arg Pro Asn Arg Arg20 25 30agc cac ccc gtc acc cgg agc cac ccc gtc acc cgg agc cac ccc gtc 144Ser His Pro Val Thr Arg Ser His Pro Val Thr Arg Ser His Pro Val35 40 45acc cgg agc cac tct gcc acc cgc gcc cac ccc gcc ttc cgg agc cgc 192Thr Arg Ser His Ser Ala Thr Arg Ala His Pro Ala Phe Arg Ser Arg50 55 60cca gga gtg agc cct gcc cag ccc agc aca act cca ctc ggc aga ccg 240Pro Gly Val Ser Pro Ala Gln Pro Ser Thr Thr Pro Leu Gly Arg Pro65 70 75 80gca ccg acc gaa gcg gca aga aag gga tcg cac atg ttc agc acg gac 288Ala Pro Thr Glu Ala Ala Arg Lys Gly Ser His Met Phe Ser Thr Asp85 90 95acg tac ctg gcg cat ctg ggg ttt ccc cag ccg ccc gcc ccc acc ctg 336Thr Tyr Leu Ala His Leu Gly Phe Pro Gln Pro Pro Ala Pro Thr Leu100 105 110ccg aac ctc cgg cag ttg cac cgc ggc cat ctg atg gcg gtc cct tac 384Pro Asn Leu Arg Gln Leu His Arg Gly His Leu Met Ala Val Pro Tyr115 120 125gac acc aac cac acc cac cgc ctc agc gcg gag aac atg gcc gac atc 432Asp Thr Asn His Thr His Arg Leu Ser Ala Glu Asn Met Ala Asp Ile130 135 140gat atc gac aag gca ttc gag gcc atc gtg ccg acc ggc gcc ggt ggc 480Asp Ile Asp Lys Ala Phe Glu Ala Ile Val Pro Thr Gly Ala Gly Gly145 150 155 160atg tgc ctg gag ctg aac acc ctg ttc gcc cag ttg ctc cgc gag ctg 528Met Cys Leu Glu Leu Asn Thr Leu Phe Ala Gln Leu Leu Arg Glu Leu165 170 175ggc tat gac ctg gac gtc atc agc gga ggc acg tat ctg ccc ggt gac 576Gly Tyr Asp Leu Asp Val Ile Ser Gly Gly Thr Tyr Leu Pro Gly Asp180 185 190atc ttc gcc ccc gac ccc gag cac atg ctg atg ctc gtc cgt atc gac 624Ile Phe Ala Pro Asp Pro Glu His Met Leu Met Leu Val Arg Ile Asp195 200 205ggg cag gag tgg ctg gcc gat gtg ggg cac gcc ggt ctc tgt ttc acc 672Gly Gln Glu Trp Leu Ala Asp Val Gly His Ala Gly Leu Cys Phe Thr210 215 220gag ccg ctg cgc ctg tcc gag gag gtg cag tgg cag tac ggc tgc gct 720Glu Pro Leu Arg Leu Ser Glu Glu Val Gln Trp Gln Tyr Gly Cys Ala225 230 235 240ttc cgg ctg atc cgg cgg gat ggc tat ctc gtg ctc cag gcc aag acc 768Phe Arg Leu Ile Arg Arg Asp Gly Tyr Leu Val Leu Gln Ala Lys Thr245 250 255ctg gac cac gac tgg cgc acc acc tac cgc ttc acc acc gag ccc agg 816Leu Asp His Asp Trp Arg Thr Thr Tyr Arg Phe Thr Thr Glu Pro Arg260 265 270acc tat gac gcc tgg gcc ggg gtc ggt gag ggc aat ggc ccg gcc atc 864Thr Tyr Asp Ala Trp Ala Gly Val Gly Glu Gly Asn Gly Pro Ala Ile275 280 285ctg gcg gcg atg cgc cga cgc agg cgc gcc atc gac aag ggg cag gtc 912Leu Ala Ala Met Arg Arg Arg Arg Arg Ala Ile Asp Lys Gly Gln Val290 295 300ttc ctc acc aac aac atg ttc acg atc gtg gag aac ggc cat gag aag 960Phe Leu Thr Asn Asn Met Phe Thr Ile Val Glu Asn Gly His Glu Lys305 310 315 320gtc acc ctc ctc gtc gat ccg gaa cgg cgc gcc cag gtg ctc gac acg 1008Val Thr Leu Leu Val Asp Pro Glu Arg Arg Ala Gln Val Leu Asp Thr325 330 335tac tgg gac ggt cgc gac 1026Tyr Trp Asp Gly Arg Asp340<210>22<211>342<212>PRT<213>Streptomyces hygroscopicus<400>22Val Gly Arg Ala Gly Glu Ser Arg Tyr Gly Arg Ser Arg Arg Ile Arg1 5 10 15Pro Asp Ser Arg Ile Arg Arg Asn Ser Arg Ile Arg Pro Asn Arg Arg20 25 30Ser His Pro Val Thr Arg Ser His Pro Val Thr Arg Ser His Pro Val35 40 45Thr Arg Ser His Ser Ala Thr Arg Ala His Pro Ala Phe Arg Ser Arg50 55 60Pro Gly Val Ser Pro Ala Gln Pro Ser Thr Thr Pro Leu Gly Arg Pro65 70 75 80Ala Pro Thr Glu Ala Ala Arg Lys Gly Ser His Met Phe Ser Thr Asp85 90 95Thr Tyr Leu Ala His Leu Gly Phe Pro Gln Pro Pro Ala Pro Thr Leu100 105 110Pro Asn Leu Arg Gln Leu His Arg Gly His Leu Met Ala Val Pro Tyr115 120 125Asp Thr Asn His Thr His Arg Leu Ser Ala Glu Asn Met Ala Asp Ile130 135 140Asp Ile Asp Lys Ala Phe Glu Ala Ile Val Pro Thr Gly Ala Gly Gly145 150 155 160Met Cys Leu Glu Leu Asn Thr Leu Phe Ala Gln Leu Leu Arg Glu Leu165 170 175Gly Tyr Asp Leu Asp Val Ile Ser Gly Gly Thr Tyr Leu Pro Gly Asp180 185 190Ile Phe Ala Pro Asp Pro Glu His Met Leu Met Leu Val Arg Ile Asp195 200 205Gly Gln Glu Trp Leu Ala Asp Val Gly His Ala Gly Leu Cys Phe Thr210215 220Glu Pro Leu Arg Leu Ser Glu Glu Val Gln Trp Gln Tyr Gly Cys Ala225 230 235 240Phe Arg Leu Ile Arg Arg Asp Gly Tyr Leu Val Leu Gln Ala Lys Thr245 250 255Leu Asp His Asp Trp Arg Thr Thr Tyr Arg Phe Thr Thr Glu Pro Arg
260 265 270Thr Tyr Asp Ala Trp Ala Gly Val Gly Glu Gly Asn Gly Pro Ala Ile275 280 285Leu Ala Ala Met Arg Arg Arg Arg Arg Ala Ile Asp Lys Gly Gln Val290 295 300Phe Leu Thr Asn Asn Met Phe Thr Ile Val Glu Asn Gly His Glu Lys305 310 315 320Val Thr Leu Leu Val Asp Pro Glu Arg Arg Ala Gln Val Leu Asp Thr325 330 335Tyr Trp Asp Gly Arg Asp340<210>23<211>1224<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(1224)<223><400>23atg aaa ttc ggt ttg ctg tac ggg gcg cag ctg ccc cga ccc tgg acc 48Met Lys Phe Gly Leu Leu Tyr Gly Ala Gln Leu Pro Arg Pro Trp Thr1 5 10 15cag gac tcc gaa cac cgc ctg ttc aac gag atg ttg gac gag atc gag 96Gln Asp Ser Glu His Arg Leu Phe Asn Glu Met Leu Asp Glu Ile Glu20 25 30ctg gcc gac cgg ctg ggc ttc gac cat gtg tgg tgt cct gag cac cac 144Leu Ala Asp Arg Leu Gly Phe Asp His Val Trp Cys Pro Glu His His35 40 45ttc ctg gag gag tac tcg cac atg tcc gcg ccg gag gcg ttc ctc ggc 192Phe Leu Glu Glu Tyr Ser His Met Ser Ala Pro Glu Ala Phe Leu Gly50 55 60gcg gtc agc cag cgc acc agc cgc atc cgc atc ggc cac gcg gtg gcc 240Ala Val Ser Gln Arg Thr Ser Arg Ile Arg Ile Gly His Ala Val Ala65 70 75 80ctg atg cct ccg gcg ttc aat ccg acg gca cgg gtc gcc gag cgg atc 288Leu Met Pro Pro Ala Phe Asn Pro Thr Ala Arg Val Ala Glu Arg Ile85 90 95gcc acg ctg gac ctg ctc tcc gac ggc cgg gtg gac ttc ggc acg ggc 336Ala Thr Leu Asp Leu Leu Ser Asp Gly Arg Val Asp Phe Gly Thr Gly100 105 110gag tcc acc acc ccc acc gag ctg ggc gga ttc ggc gtg gag cgc tcc 384Glu Ser Thr Thr Pro Thr Glu Leu Gly Gly Phe Gly Val Glu Arg Ser115 120 125gtg aaa cgg gac cag tgg gcg gag gcg gtg gac gcc gtc gcc cgg atg 432Val Lys Arg Asp Gln Trp Ala Glu Ala Val Asp Ala Val Ala Arg Met130 135 140ttc gtc gag gag ccc ttc gcc gga tac gag ggc aag tac gtg tcc gcc 480Phe Val Glu Glu Pro Phe Ala Gly Tyr Glu Gly Lys Tyr Val Ser Ala145 150 155 160ccg atc cgc aat gtg ctg ccc aag acc cgg cag aag cca cat ccg ccg 528Pro Ile Arg ASn Val Leu Pro Lys Thr Arg Gln Lys Pro His Pro Pro165 170 175atg tgg atg gcc tgc ggg aac cgg gac gcg atc cgc acc gcg gcc gcc 576Met Trp Met Ala Cys Gly Asn Arg Asp Ala Ile Arg Thr Ala Ala Ala180 185 190aag ggg ctc ggc gcg ctg aac ttc tcc ttc ttc ggg ccg gcg gag acc 624Lys Gly Leu Gly Ala Leu Asn Phe Ser Phe Phe Gly Pro Ala Glu Thr195 200 205aag aag tgg gtc gac gcc tac tac tcg ggc atc gaa tcg gcg gac tgt 672Lys Lys Trp Val Asp Ala Tyr Tyr Ser Gly Ile Glu Ser Ala Asp Cys210 215 220gtg ccc gcc gcg ttc gcc gtc aac gca cag atc gcc gcg acc atc ccg 720Val Pro Ala Ala Phe Ala Val Asn Ala Gln Ile Ala Ala Thr Ile Pro225 230 235 240atg ttc tgc cac cgg gac gag acc acg gcc gtg gaa cgc gcc gtc gac 768Met Phe Cys His Arg Asp Glu Thr Thr Ala Val Glu Arg Ala Val Asp245 250 255ggc gtc cag ttc ttc aac ttc ggc ctc ggc ttc tac gcg ggc ttc ggc 816Gly Val Gln Phe Phe Asn Phe Gly Leu Gly Phe Tyr Ala Gly Phe Gly260 265 270acc gcc gca ccg gcc cgc acc cgg ctg tgg gag gag ttc cag cgc gac 864Thr Ala Ala Pro Ala Arg Thr Arg Leu Trp Glu Glu Phe Gln Arg Asp275 280 285cgc gac aag cag ggc atg ggc cgc tcc tcc ttc ggc aag ccc gga atg 912Arg Asp Lys Gln Gly Met Gly Arg Ser Ser Phe Gly Lys Pro Gly Met290 295 300ccg ctg ggc aat ccg gcc cgg ggc gcg gtg ggc act ccg cac cag ata 960Pro Leu Gly Asn Pro Ala Arg Gly Ala Val Gly Thr Pro His Gln Ile305 310 315 320cgc gac ttc ctg cgg ctg cac gag gag gcc gga ctg gac cag gcg atc 1008Arg Asp Phe Leu Arg Leu His Glu Glu Ala Gly Leu Asp Gln Ala Ile325 330 335ttc ctc gtc cag ggc ggt ggc acc cgg cac gag cac atc cgc gaa tcg 1056Phe Leu Val Gln Gly Gly Gly Thr Arg His Glu His Ile Arg Glu Ser340 345 350ctg gag ctc ttc gcc aat gag gtg atg ccc gag ttc aag gag cgc gat 1104Leu Glu Leu Phe Ala Asn Glu Val Met Pro Glu Phe Lys Glu Arg Asp
355360 365gag gcc gcc gta cgg ctg aag acg gcc cgg ctc cag ccc gcc atc gac 1152Glu Ala Ala Val Arg Leu Lys Thr Ala Arg Leu Gln Pro Ala Ile Asp370 375 380gcc gcc atg gcc cgg cgc gag ccg cca cgg acg gcc gac ccc gac tac 1200Ala Ala Met Ala Arg Arg Glu Pro Pro Arg Thr Ala Asp Pro Asp Tyr385 390 395 400atc atc ccc gcc cgg agc cag agc 1224Ile Ile Pro Ala Arg Ser Gln Ser405<210>24<211>408<212>PRT<213>Streptomyces hygroscopicus<400>24Met Lys Phe Gly Leu Leu Tyr Gly Ala Gln Leu Pro Arg Pro Trp Thr1 5 10 15Gln Asp Ser Glu His Arg Leu Phe Asn Glu Met Leu Asp Glu Ile Glu20 25 30Leu Ala Asp Arg Leu Gly Phe Asp His Val Trp Cys Pro Glu His His35 40 45Phe Leu Glu Glu Tyr Ser His Met Ser Ala Pro Glu Ala Phe Leu Gly50 55 60Ala Val Ser Gln Arg Thr Ser Arg Ile Arg Ile Gly His Ala Val Ala65 70 75 80Leu Met Pro Pro Ala Phe Asn Pro Thr Ala Arg Val Ala Glu Arg Ile85 90 95Ala Thr Leu Asp Leu Leu Ser Asp Gly Arg Val Asp Phe Gly Thr Gly100 105 110Glu Ser Thr Thr Pro Thr Glu Leu Gly Gly Phe Gly Val Glu Arg Ser115 120 125Val Lys Arg Asp Gln Trp Ala Glu Ala Val Asp Ala Val Ala Arg Met130 135 140Phe Val Glu Glu Pro Phe Ala Gly Tyr Glu Gly Lys Tyr Val Ser Ala145 150 155 160Pro Ile Arg Asn Val Leu Pro Lys Thr Arg Gln Lys Pro His Pro Pro165 170 175Met Trp Met Ala Cys Gly Asn Arg Asp Ala Ile Arg Thr Ala Ala Ala180 185 190Lys Gly Leu Gly Ala Leu Asn Phe Ser Phe Phe Gly Pro Ala Glu Thr195 200 205Lys Lys Trp Val Asp Ala Tyr Tyr Ser Gly Ile Glu Ser Ala Asp Cys210 215 220Val Pro Ala Ala Phe Ala Val Asn Ala Gln Ile Ala Ala Thr Ile Pro225 230 235 240Met Phe Cys His Arg Asp Glu Thr Thr Ala Val Glu Arg Ala Val Asp245 250 255Gly Val Gln Phe Phe Asn Phe Gly Leu Gly Phe Tyr Ala Gly Phe Gly260 265 270Thr Ala Ala Pro Ala Arg Thr Arg Leu Trp Glu Glu Phe Gln Arg Asp275 280 285Arg Asp Lys Gln Gly Met Gly Arg Ser Ser Phe Gly Lys Pro Gly Met290 295 300Pro Leu Gly Asn Pro Ala Arg Gly Ala Val Gly Thr Pro His Gln Ile305 310 315 320Arg Asp Phe Leu Arg Leu His Glu Glu Ala Gly Leu Asp Gln Ala Ile325 330 335Phe Leu Val Gln Gly Gly Gly Thr Arg His Glu His Ile Arg Glu Ser340 345 350Leu Glu Leu Phe Ala Asn Glu Val Met Pro Glu Phe Lys Glu Arg Asp355 360 365Glu Ala Ala Val Arg Leu Lys Thr Ala Arg Leu Gln Pro Ala Ile Asp370 375 380Ala Ala Met Ala Arg Arg Glu Pro Pro Arg Thr Ala Asp Pro Asp Tyr385 390 395 400Ile Ile Pro Ala Arg Ser Gln Ser405<210>25<211>1239<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(1239)<223><400>25gtg tcc ggg cgc cacttc gaa caa gga gaa cgt ggt acc gcc atg gct 48Val Ser Gly Arg His Phe Glu Gln Gly Glu Arg Gly Thr Ala Met Ala1 5 10 15gac acc ccc gaa gaa gaa ctc cgc atc ctc gac ccg cag tcc gtc gcg 96Asp Thr Pro Glu Glu Glu Leu Arg Ile Leu Asp Pro Gln Ser Val Ala20 25 30cag gag ctg cgc aag cac ggc ccg cct cgg cag atc acg atg cac ggc 144Gln Glu Leu Arg Lys His Gly Pro Pro Arg Gln Ile Thr Met His Gly35 40 45acc acg gcg tgg ctc gtc tcc cgg tac gag gag gtc cgg gac tgt ctc 192Thr Thr Ala Trp Leu Val Ser Arg Tyr Glu Glu Val Arg Asp Cys Leu50 55 60gga cac ccc gga atg agc ccg gcc gcc gcc tac gcc gcc tcc cag ggc 240Gly His Pro Gly Met Ser Pro Ala Ala Ala Tyr Ala Ala Ser Gln Gly65 70 75 80cag acc aat ccg gtg agc ggg ttg ttc gag gac acg gtg gcc ggt acc 288Gln Thr Asn Pro Val Ser Gly Leu Phe Glu Asp Thr Val Ala Gly Thr85 90 95aat ccg ccc cag cac acc cgg ctg cgc agg ctg ctg gcc aag gcg ttc 336Asn Pro Pro Gln His Thr Arg Leu Arg Arg Leu Leu Ala Lys Ala Phe100 105 110acg gta cgc aga gtg gag agt ctg cgg cca cgg gtg cag gag atc acc 384Thr Val Arg Arg Val Glu Ser Leu Arg Pro Arg Val Gln Glu Ile Thr115 120 125gac aca ctg ctg gac cgg atc gcc gtc gac ggc cgg gcc gac ctc gtc 432Asp Thr Leu Leu Asp Arg Ile Ala Val Asp Gly Arg Ala Asp Leu Val130 135 140agc gcg ctg gcc att ccg ctg ccc atg cag gtg atc tgc gaa ctc ctc 480Ser Ala Leu Ala Ile Pro Leu Pro Met Gln Val Ile Cys Glu Leu Leu145 150 155 160ggt gtg ccc atc gcc gac cgc acc gaa ttc cac cag tgg gcc gat ctg 528Gly Val Pro Ile Ala Asp Arg Thr Glu Phe His Gln Trp Ala Asp Leu165 170 175atg ctc acg ccc ccg ctg gac ccg gac acc gcc gcg cgt tcc cag gac 576Met Leu Thr Pro Pro Leu Asp Pro Asp Thr Ala Ala Arg Ser Gln Asp180 185 190gcc tcc gcc aag ctg tgg acg tat atg gag gac ctc gcc gag gcc agg 624Ala Ser Ala Lys Leu Trp Thr Tyr Met Glu Asp Leu Ala Glu Ala Arg195 200 205cgg aag gcc ccg gag gac gac ctg atc agc gat ctg atg tcc gca cac 672Arg Lys Ala Pro Glu Asp Asp Leu Ile Ser Asp Leu Met Ser Ala His210 215 220gag gac gac cgg ctc agc cac cgc gag gtg gtc gcc acc gcc cgg atg 720Glu Asp Asp Arg Leu Ser His Arg Glu Val Val Ala Thr Ala Arg Met225 230 235 240atg ctg atc gcg ggg tac gag ctg acc ggc agc ttc atc agc aac gcg 768Met Leu Ile Ala Gly Tyr Glu Leu Thr Gly Ser Phe Ile Ser Asn Ala245 250 255gtt ttc tcg ctg ctg tcc cag ccc gac cag atg gaa ctg ctg cgc aag 816Val Phe Ser Leu Leu Ser Gln Pro Asp Gln Met Glu Leu Leu Arg Lys260 265 270gac ccc gag ctg gcc ggg cgc ggt ctg gag gag ctg ctc cgg cac gcc 864Asp Pro Glu Leu Ala Gly Arg Gly Leu Glu Glu Leu Leu Arg His Ala275 280 285ggg ccg ggc att ctc atc gtg cgt ttc gcc aac gag gac gtg gag atc 912Gly Pro Gly Ile Leu Ile Val Arg Phe Ala Asn Glu Asp Val Glu Ile
290 295300ggc tcc gta tcc atc cgc gcc ggc gac cag gtg ctc ctg gac atg gac 960Gly Ser Val Ser Ile Arg Ala Gly Asp Gln Val Leu Leu Asp Met Asp305 310 315 320gcc gca cac tcc gac ccg gcg cac ttc acc gac ggc gag cgg ctg gac 1008Ala Ala His Ser Asp Pro Ala His Phe Thr Asp Gly Glu Arg Leu Asp325 330 335ctc acg agg gac tcg gcc gta cac ctc cag ttc ggc cat ggc atc cac 1056Leu Thr Arg Asp Ser Ala Val His Leu Gln Phe Gly His Gly Ile His340 345 350tac tgc atc ggc gcg ccg ctg gcc agg gtg gag ggg cag atc gcc ctg 1104Tyr Cys Ile Gly Ala Pro Leu Ala Arg Val Glu Gly Gln Ile Ala Leu355 360 365gag agc ctg gtg cgg cgg ttc ccc ggg ctt cgg ctg agc gtt ccc gcc 1152Glu Ser Leu Val Arg Arg Phe Pro Gly Leu Arg Leu Ser Val Pro Ala370 375 380gcc gag atc agc cat agc aag aac ccg ttc atc cgc tcg ctg acc gcg 1200Ala Glu Ile Ser His Ser Lys Asn Pro Phe Ile Arg Ser Leu Thr Ala385 390 395 400ctg ccc gtc gag ttc gag gct cag cag ccc gta gcg ggg 1239Leu Pro Val Glu Phe Glu Ala Gln Gln Pro Val Ala Gly405 410<210>26<211>413<212>PRT<213>Streptomyces hygroscopicus<400>26Val Ser Gly Arg His Phe Glu Gln Gly Glu Arg Gly Thr Ala Met Ala1 5 10 15Asp Thr Pro Glu Glu Glu Leu Arg Ile Leu Asp Pro Gln Ser Val Ala20 25 30Gln Glu Leu Arg Lys His Gly Pro Pro Arg Gln Ile Thr Met His Gly35 40 45Thr Thr Ala Trp Leu Val Ser Arg Tyr Glu Glu Val Arg Asp Cys Leu50 55 60Gly His Pro Gly Met Ser Pro Ala Ala Ala Tyr Ala Ala Ser Gln Gly65 70 75 80Gln Thr Asn Pro Val Ser Gly Leu Phe Glu Asp Thr Val Ala Gly Thr85 90 95Asn Pro Pro Gln His Thr Arg Leu Arg Arg Leu Leu Ala Lys Ala Phe100 105 110Thr Val Arg Arg Val Glu Ser Leu Arg Pro Arg Val Gln Glu Ile Thr115 120 125Asp Thr Leu Leu Asp Arg Ile Ala Val Asp Gly Arg Ala Asp Leu Val130 135 140Ser Ala Leu Ala Ile Pro Leu Pro Met Gln Val Ile Cys Glu Leu Leu145 150 155 160Gly Val Pro Ile Ala Asp Arg Thr Glu Phe His Gln Trp Ala Asp Leu165 170 175Met Leu Thr Pro Pro Leu Asp Pro Asp Thr Ala Ala Arg Ser Gln Asp180 185 190Ala Ser Ala Lys Leu Trp Thr Tyr Met Glu Asp Leu Ala Glu Ala Arg195 200 205Arg Lys Ala Pro Glu Asp Asp Leu Ile Ser Asp Leu Met Ser Ala His210 215 220Glu Asp Asp Arg Leu Ser His Arg Glu Val Val Ala Thr Ala Arg Met225 230 235 240Met Leu Ile Ala Gly Tyr Glu Leu Thr Gly Ser Phe Ile Ser Asn Ala245 250 255Val Phe Ser Leu Leu Ser Gln Pro Asp Gln Met Glu Leu Leu Arg Lys260 265 270Asp Pro Glu Leu Ala Gly Arg Gly Leu Glu Glu Leu Leu Arg His Ala275 280 285Gly Pro Gly Ile Leu Ile Val Arg Phe Ala Asn Glu Asp Val Glu Ile290 295 300Gly Ser Val Ser Ile Arg Ala Gly Asp Gln Val Leu Leu Asp Met Asp305 310 315 320Ala Ala His Ser Asp Pro Ala His Phe Thr Asp Gly Glu Arg Leu Asp325 330 335Leu Thr Arg Asp Ser Ala Val His Leu Gln Phe Gly His Gly Ile His340 345 350Tyr Cys Ile Gly Ala Pro Leu Ala Arg Val Glu Gly Gln Ile Ala Leu355 360 365Glu Ser Leu Val Arg Arg Phe Pro Gly Leu Arg Leu Ser Val Pro Ala370 375 380Ala Glu Ile Ser His Ser Lys Asn Pro Phe Ile Arg Ser Leu Thr Ala385 390 395 400Leu Pro Val Glu Phe Glu Ala Gln Gln Pro Val Ala Gly405 410<210>27<211>678<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(678)<223><400>27atg aac gcc ctg atc ccc cgt cca cgc ctc gag gtg gcc ccc ggc gcc 48Met Asn Ala Leu Ile Pro Arg Pro Arg Leu Glu Val Ala Pro Gly Ala1 5 10 15gtc cat gtg ccg agc tgg ctc acc ctc gaa cag cag cgg gag ctg gtc 96Val His Val Pro Ser Trp Leu Thr Leu Glu Gln Gln Arg Glu Leu Val20 25 30ctc gcc tgc cgg ggc tgg gcc acc ggc ccg gtc ccg atc cgg cac acc 144Leu Ala Cys Arg Gly Trp Ala Thr Gly Pro Val Pro Ile Arg His Thr35 40 45aag ctg ccg cgc ggg ggc gtc atg tcg gtg cgc acg gtg tgc atc ggc 192Lys Leu Pro Arg Gly Gly Val Met Ser Val Arg Thr Val Cys Ile Gly50 55 60tgg cac tgg cag ccc tac gcc tac acc cgc acc gcc gac gat gtg aac 240Trp His Trp Gln Pro Tyr Ala Tyr Thr Arg Thr Ala Asp Asp Val Asn65 70 75 80ggc gcc cgg gtc gcc gaa ttc ccc gac tgg atg gtc gag ttg ggc cgt 288Gly Ala Arg Val Ala Glu Phe Pro Asp Trp Met Val Glu Leu Gly Arg85 90 95cgc gcc ctg gtc gac gcg tac gac gac gag acg gcc ggt gag ggg tac 336Arg Ala Leu Val Asp Ala Tyr Asp Asp Glu Thr Ala Gly Glu Gly Tyr100 105 110acc ccc gac acc gcg ctc atc aac ttc tac gac gcc cag gcg aag ctg 384Thr Pro Asp Thr Ala Leu Ile Asn Phe Tyr Asp Ala Gln Ala Lys Leu115 120 125ggc atg cac cag gac aag gac gag agg tca tcc gcc ccg gtg gtc tcg 432Gly Met His Gln Asp Lys Asp Glu Arg Ser Ser Ala Pro Val Val Ser130 135 140ctc acc atc ggc gac agc tgt gtc ttc cgc ttc ggc aac acc gag acc 480Leu Thr Ile Gly Asp Ser Cys Val Phe Arg Phe Gly Asn Thr Glu Thr145 150 155 160cgt acc aag ccg tac acc gac ctc gaa ctc gct tcc ggg gat ctg ttc 528Arg Thr Lys Pro Tyr Thr Asp Leu Glu Leu Ala Ser Gly Asp Leu Phe165 170 175gtc ttc gga ggc ccc tcc cgc tac gcc tat cac gcc gtc ccc agg atc 576Val Phe Gly Gly Pro Ser Arg Tyr Ala Tyr His Ala Val Pro Arg Ile180 185 190ctg ccc gga acc ggt gac ccg gcc acc gga ctg aag tcc ggg cgg ctg 624Leu Pro Gly Thr Gly Asp Pro Ala Thr Gly Leu Lys Ser Gly Arg Leu195 200 205aac atc acc atg cgg gtc acc ggt ctg gcc gat ccc cag tcg tca gtc 672Asn Ile Thr Met Arg Val Thr Gly Leu Ala Asp Pro Gln Ser Ser Val210 215 220gtc ccg 678Val Pro225<210>28<211>226<212>PRT<213>Streptomyces hygroscopicus<400>28Met Asn Ala Leu Ile Pro Arg Pro Arg Leu Glu Val Ala Pro Gly Ala1 5 10 15Val His Val Pro Ser Trp Leu Thr Leu Glu Gln Gln Arg Glu Leu Val20 25 30Leu Ala Cys Arg Gly Trp Ala Thr Gly Pro Val Pro Ile Arg His Thr35 40 45Lys Leu Pro Arg Gly Gly Val Met Ser Val Arg Thr Val Cys Ile Gly50 55 60Trp His Trp Gln Pro Tyr Ala Tyr Thr Arg Thr Ala Asp Asp Val Asn65 70 75 80Gly Ala Arg Val Ala Glu Phe Pro Asp Trp Met Val Glu Leu Gly Arg85 90 95Arg Ala Leu Val Asp Ala Tyr Asp Asp Glu Thr Ala Gly Glu Gly Tyr100 105 110Thr Pro Asp Thr Ala Leu Ile Asn Phe Tyr Asp Ala Gln Ala Lys Leu115 120 125Gly Met His Gln Asp Lys Asp Glu Arg Ser Ser Ala Pro Val Val Ser130135 140Leu Thr Ile Gly Asp Ser Cys Val Phe Arg Phe Gly Asn Thr Glu Thr145150 155 160Arg Thr Lys Pro Tyr Thr Asp Leu Glu Leu Ala Ser Gly Asp Leu Phe165 170 175Val Phe Gly Gly Pro Ser Arg Tyr Ala Tyr His Ala Val Pro Arg Ile180 185 190Leu Pro Gly Thr Gly Asp Pro Ala Thr Gly Leu Lys Ser Gly Arg Leu195 200 205Asn Ile Thr Met Arg Val Thr Gly Leu Ala Asp Pro Gln Ser Ser Val210 215 220Val Pro225<210>29<211>726<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(726)<223><400>29atg agc acc acg aac gac acc gca cgc atc cat cag cgc gtg gcc gcg 48Met Ser Thr Thr Asn Asp Thr Ala Arg Ile His Gln Arg Val Ala Ala1 5 10 15gcc gac tgg cca cag ctg gcc gag gag ctg gac acc tac ggg tgc gcg 96Ala Asp Trp Pro Gln Leu Ala Glu Glu Leu Asp Thr Tyr Gly Cys Ala20 25 30ctc act cca cgg ctg ctg acc ccc gcc cag tgc gcc cgc atc gcc ggg 144Leu Thr Pro Arg Leu Leu Thr Pro Ala Gln Cys Ala Arg Ile Ala Gly35 40 45ctg tac ggg cag gac gag cag ttc agg aac acg atc gac atg gcc cgc 192Leu Tyr Gly Gln Asp Glu Gln Phe Arg Asn Thr Ile Asp Met Ala Arg50 55 60cac cgc ttc ggc tcc gga cag tac cgc tac ttc acc cat gac ctg ccc 240His Arg Phe Gly Ser Gly Gln Tyr Arg Tyr Phe Thr His Asp Leu Pro65 70 75 80gaa ccg gtg gcc gag ctg cgc gcc gcg ctc tat ccg cgg ctg ctg acc 288Glu Pro Val Ala Glu Leu Arg Ala Ala Leu Tyr Pro Arg Leu Leu Thr85 90 95atc gcg cgt gac tgg gcg gag cgg ctc ggc cgc ccg gcg ccc tgg ccg 336Ile Ala Arg Asp Trp Ala Glu Arg Leu Gly Arg Pro Ala Pro Trp Pro100 105 110gac agc ctc gag aag tgg ctg gcc atg tgt cat gag gcc gga cag gac 384Asp Ser Leu Glu Lys Trp Leu Ala Met Cys His Glu Ala Gly Gln Asp115 120 125cgc tcc gcg cag atc ctg ctg cgc tac ggc ccc ggc gac tgg aac gcc 432Arg Ser Ala Gln Ile Leu Leu Arg Tyr Gly Pro Gly Asp Trp Asn Ala130 135 140ctg cac cgg gac gta ttc ggc gac atg ctc ttc ccg ctc cag gtg gtg 480Leu His Arg Asp Val Phe Gly Asp Met Leu Phe Pro Leu Gln Val Val145 150 155 160atc ggg ctc gac gcg tac ggc acg gac tac acg ggc ggg gag ttc ctg 528Ile Gly Leu Asp Ala Tyr Gly Thr Asp Tyr Thr Gly Gly Glu Phe Leu165 170 175ctg gtc gag cag cgg ccc cgc gcc cag tcc cgg ggc acc acg acc gtc 576Leu Val Glu Gln Arg Pro Arg Ala Gln Ser Arg Gly Thr Thr Thr Val180 185 190ctc cag cag ggc cac ggc ctg atc ttc acc acc cgt gac cgt ccc gtg 624Leu Gln Gln Gly His Gly Leu Ile Phe Thr Thr Arg Asp Arg Pro Val195 200 205gcc acc aag cgc ggc tgg tcg gcc ggt gtg atg cgg cac ggg gtc agc 672Ala Thr Lys Arg Gly Trp Ser Ala Gly Val Met Arg His Gly Val Ser210 215 220acg gtg cgt tcc ggg cgc cgc cac gca ttg ggg ctg gtc ttc cac gac 720Thr Val Arg Ser Gly Arg Arg His Ala Leu Gly Leu Val Phe His Asp225 230 235 240gcc gcc 726Ala Ala<210>30<211>242<212>PRT<213>Streptomyces hygroscopicus<400>30Met Ser Thr Thr Asn Asp Thr Ala Arg Ile His Gln Arg Val Ala Ala1 5 10 15Ala Asp Trp Pro Gln Leu Ala Glu Glu Leu Asp Thr Tyr Gly Cys Ala20 25 30Leu Thr Pro Arg Leu Leu Thr Pro Ala Gln Cys Ala Arg Ile Ala Gly35 40 45Leu Tyr Gly Gln Asp Glu Gln Phe Arg Asn Thr Ile Asp Met Ala Arg50 55 60His Arg Phe Gly Ser Gly Gln Tyr Arg Tyr Phe Thr His Asp Leu Pro65 70 75 80Glu Pro Val Ala Glu Leu Arg Ala Ala Leu Tyr Pro Arg Leu Leu Thr85 90 95Ile Ala Arg Asp Trp Ala Glu Arg Leu Gly Arg Pro Ala Pro Trp Pro100 105 110Asp Ser Leu Glu Lys Trp Leu Ala Met Cys His Glu Ala Gly Gln Asp115 120 125Arg Ser Ala Gln Ile Leu Leu Arg Tyr Gly Pro Gly Asp Trp Asn Ala130 135 140Leu His Arg Asp Val Phe Gly Asp Met Leu Phe Pro Leu Gln Val Val145 150 155 160Ile Gly Leu Asp Ala Tyr Gly Thr Asp Tyr Thr Gly Gly Glu Phe Leu165 170 175Leu Val Glu Gln Arg Pro Arg Ala Gln Ser Arg Gly Thr Thr Thr Val180 185 190Leu Gln Gln Gly His Gly Leu Ile Phe Thr Thr Arg Asp Arg Pro Val195 200 205Ala Thr Lys Arg Gly Trp Ser Ala Gly Val Met Arg His Gly Val Ser210 215 220Thr Val Arg Ser Gly Arg Arg His Ala Leu Gly Leu Val Phe His Asp225 230 235 240Ala Ala<210>31<211>504<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1).. (504)<223><400>31atg acg gtc cac acg acg atc gac agc ccg ctc ggc gag ctg ctg ctg 48Met Thr Val His Thr Thr Ile Asp Ser Pro Leu Gly Glu Leu Leu Leu1 5 10 15gtg ggc gag gag tcc gcc acc gcg ccg ggg ggc acc gca ctc atc tcc 96Val Gly Glu Glu Ser Ala Thr Ala Pro Gly Gly Thr Ala Leu Ile Ser20 25 30ctg tcc gtg ccc ggc cag aag ggc ggg gcc gtc gtc cag gac ggt tgg 144Leu Ser Val Pro Gly Gln Lys Gly Gly Ala Val Val Gln Asp Gly Trp35 40 45agc gag gat gcc gag gcg ttc acc gag atc gtc tcc cag ttg cgc tcc 192Ser Glu Asp Ala Glu Ala Phe Thr Glu Ile Val Ser Gln Leu Arg Ser50 55 60tac ttc gac ggc gag cgc acc cgc ttc gac atc gag tgc gtc gag ggc 240Tyr Phe Asp Gly Glu Arg Thr Arg Phe Asp Ile Glu Cys Val Glu Gly65 70 75 80ggt acg gac ttc cag cgc agg gtc tgg cag gcg ctg gag gcc att ccg 288Gly Thr Asp Phe Gln Arg Arg Val Trp Gln Ala Leu Glu Ala Ile Pro85 90 95tac ggc acc act gtc agc tac ggc gac atc gcc cgg cag atc ggc gcc 336Tyr Gly Thr Thr Val Ser Tyr Gly Asp Ile Ala Arg Gln Ile Gly Ala100 105 110ccg cgc acg gcc gtc cgc tcc gtc ggc acc gcg arc ggc cgc aat cca 384Pro Arg Thr Ala Val Arg Ser Val Gly Thr Ala Ile Gly Arg Asn Pro115 120 125ctg ctg gtc gtg cgg ccc tgc cac cgg gtc atc ggc gcc acc ggc gca 432Leu Leu Val Val Arg Pro Cys His Arg Val Ile Gly Ala Thr Gly Ala130 135 140ctg acc ggc tat gcg ggc gga ctg gag cgc aag cag cga ctc ctc gtt 480Leu Thr Gly Tyr Ala Gly Gly Leu Glu Arg Lys Gln Arg Leu Leu Val145150 155 160cac gag ggc gcc ctc cag acc gcc 504His Glu Gly Ala Leu Gln Thr Ala165<210>32<211>168<212>PRT<213>Streptomyces hygroscopicus<400>32Met Thr Val His Thr Thr Ile Asp Ser Pro Leu Gly Glu Leu Leu Leu1 5 10 15Val Gly Glu Glu Ser Ala Thr Ala Pro Gly Gly Thr Ala Leu Ile Ser20 25 30Leu Ser Val Pro Gly Gln Lys Gly Gly Ala Val Val Gln Asp Gly Trp35 40 45Ser Glu Asp Ala Glu Ala Phe Thr Glu Ile Val Ser Gln Leu Arg Ser50 55 60Tyr Phe Asp Gly Glu Arg Thr Arg Phe Asp Ile Glu Cys Val Glu Gly65 70 75 80Gly Thr Asp Phe Gln Arg Arg Val Trp Gln Ala Leu Glu Ala Ile Pro85 90 95Tyr Gly Thr Thr Val Ser Tyr Gly Asp Ile Ala Arg Gln Ile Gly Ala100 105 110Pro Arg Thr Ala Val Arg Ser Val Gly Thr Ala Ile Gly Arg Asn Pro115 120 125Leu Leu Val Val Arg Pro Cys His Arg Val Ile Gly Ala Thr Gly Ala130 135 140Leu Thr Gly Tyr Ala Gly Gly Leu Glu Arg Lys Gln Arg Leu Leu Val145 150 155 160His Glu Gly Ala Leu Gln Thr Ala165<210>33<211>618<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(618)<223><400>33atg cac gag gga cac ggc cac cag gag tac atc gtc acg tcc gac ccc 48Met His Glu Gly His Gly His Gln Glu Tyr Ile Val Thr Ser Asp Pro1 5 10 15gag gcg gtg gcc cgt gtc cgg gcc tcc ttg ctg cgc acc ctg cca gtg 96Glu Ala Val Ala Arg Val Arg Ala Ser Leu Leu Arg Thr Leu Pro Val20 25 30gcc gca tgg gcc ggg gtg gcc agt gcc gtg gtc atc gtc tcg gcc gtg 144Ala Ala Trp Ala Gly Val Ala Ser Ala Val Val Ile Val Ser Ala Val35 40 45gcc ctc gtc ctc ttc gcc ctc ggc cac agc gcc tcc cgg ctg tgg gtc 192Ala Leu Val Leu Phe Ala Leu Gly His Ser Ala Ser Arg Leu Trp Val50 55 60ctg gtg ttc gcc tgg ccc gcg gcg ttc ctc ggc tat gac gcc agg cgc 240Leu Val Phe Ala Trp Pro Ala Ala Phe Leu Gly Tyr Asp Ala Arg Arg65 70 75 80cga ttc gcc gat ata cgg cgg ctg aag cgg acc tgg gcg gcg aaa gag 288Arg Phe Ala Asp Ile Arg Arg Leu Lys Arg Thr Trp Ala Ala Lys Glu85 90 95gtg tcc ccg gtg gcg atg cgc ctc tcc gcc gag ggc ctg cgc tgc gcc 336Val Ser Pro Val Ala Met Arg Leu Ser Ala Glu Gly Leu Arg Cys Ala100 105 110atc gac tcc gcc ccg gag ccc gtt ttc ctc ccc tgg tcc gcg atc gcc 384Ile Asp Ser Ala Pro Glu Pro Val Phe Leu Pro Trp Ser Ala Ile Ala115 120 125cag gtg cgg gtg acg ggc cag ggc ctc agc acg gtg cgg gtc gat ctc 432Gln Val Arg Val Thr Gly Gln Gly Leu Ser Thr Val Arg Val Asp Leu130 135 140gcc ccc ggc gtg tcc gcc acc acc ccc ggg gtc agc ggg ctg gag cag 480Ala Pro Gly Val Ser Ala Thr Thr Pro Gly Val Ser Gly Leu Glu Gln145 150 155 160ccc gag gcc cgg atg cgc atg cgg cgc gcc tgg aac ggc ggg atg cgg 528Pro Glu Ala Arg Met Arg Met Arg Arg Ala Trp Asn Gly Gly Met Arg165 170 175ctg cgc ttc acc gtc tac gcc ctc cgc cag ccg atc agc gag atc gac 576Leu Arg Phe Thr Val Tyr Ala Leu Arg Gln Pro Ile Ser Glu Ile Asp180 185 190cag gct ctc ggc cac ttc tcg aac ggg cgg atc ggt atc cgc 618Gln Ala Leu Gly His Phe Ser Asn Gly Arg Ile Gly Ile Arg195 200 205<210>34<211>206<212>PRT<213>Streptomyces hygroscopicus<400>34Met His Glu Gly His Gly His Gln Glu Tyr Ile Val Thr Ser Asp Pro1 5 10 15Glu Ala Val Ala Arg Val Arg Ala Ser Leu Leu Arg Thr Leu Pro Val20 25 30Ala Ala Trp Ala Gly Val Ala Ser Ala Val Val Ile Val Ser Ala Val35 40 45Ala Leu Val Leu Phe Ala Leu Gly His Ser Ala Ser Arg Leu Trp Val50 55 60Leu Val Phe Ala Trp Pro Ala Ala Phe Leu Gly Tyr Asp Ala Arg Arg65 70 75 80Arg Phe Ala Asp Ile Arg Arg Leu Lys Arg Thr Trp Ala Ala Lys Glu85 90 95Val Ser Pro Val Ala Met Arg Leu Ser Ala Glu Gly Leu Arg Cys Ala100 105 110Ile Asp Ser Ala Pro Glu Pro Val Phe Leu Pro Trp Ser Ala Ile Ala115 120 125Gln Val Arg Val Thr Gly Gln Gly Leu Ser Thr Val Arg Val Asp Leu130 135 140Ala Pro Gly Val Ser Ala Thr Thr Pro Gly Val Ser Gly Leu Glu Gln145 150 155 160Pro Glu Ala Arg Met Arg Met Arg Arg Ala Trp Asn Gly Gly Met Arg165 170 175Leu Arg Phe Thr Val Tyr Ala Leu Arg Gln Pro Ile Ser Glu Ile Asp180 185 190Gln Ala Leu Gly His Phe Ser Asn Gly Arg Ile Gly Ile Arg195 200 205<210>35<211>2721<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(2721)<223><400>35atg gga gga cgt gct cgt ccg gct cgg cga cgg ctg ggg ccc ctg tcg 48Met Gly Gly Arg Ala Arg Pro Ala Arg Arg Arg Leu Gly Pro Leu Ser1 5 10 15tat acg cga agc gtc gcc ggg cag gcg ttc atc ttg cag ctt ctg ctg 96Tyr Thr Arg Ser Val Ala Gly Gln Ala Phe Ile Leu Gln Leu Leu Leu20 25 30atc ctg gtt ctg gtg gcc gcg gcg gtg gtg gcc gtc gca gcg gat gcc 144Ile Leu Val Leu Val Ala Ala Ala Val Val Ala Val Ala Ala Asp Ala35 40 45cgg agc cac agc acg acc gac gct cgc cgg cga tcc ctc gcg gtc gcc 192Arg Ser His Ser Thr Thr Asp Ala Arg Arg Arg Ser Leu Ala Val Ala50 55 60gag acc ttg gca cac tcc ccc gga atg gcc cgg gcc ctg acc agc gac 240Glu Thr Leu Ala His Ser Pro Gly Met Ala Arg Ala Leu Thr Ser Asp65 70 75 80cgg ccg acg tcg ctg ctg gag tcg cat gcg gag gcg gcg cgg aag aga 288Arg Pro Thr Ser Leu Leu Glu Ser His Ala Glu Ala Ala Arg Lys Arg85 90 95rca ggc gtc gac agc gtc gtg gtg ttc aac act cat ggc atc cgc ctc 336Ser Gly Val Asp Ser Val Val Val Phe Asn Thr His Gly Ile Arg Leu100 105 110acc cac ccc gag aag gca ttg arc ggc aag cgg arc gtc gga ccg gcc 384Thr His Pro Glu Lys Ala Leu Ile Gly Lys Arg Ile Val Gly Pro Ala115 120 125ggg ctg gtg cgg gac gag ctg aaa ggc aag acg atc acg gag tcc ttc 432Gly Leu Val Arg Asp Glu Leu Lys Gly Lys Thr Ile Thr Glu Ser Phe130 135 140cag gcc agc cag ggc ccg tcc gtg gtc tcg gcg gtc ccc gtc acc agg 480Gln Ala Ser Gln Gly Pro Ser Val Val Ser Ala Val Pro Val Thr Arg145 150 155 160gcc gac ggc acc ttc ctc ggc ggt gtg tcc gtc ggg gtc aag atc gcg 528Ala Asp Gly Thr Phe Leu Gly Gly Val Ser Val Gly Val Lys Ile Ala165 170 175agc gtg aac agc gag gtg gac cgt cgg cta ccg ctg ctg ctc ggc agt 576Ser Val Asn Ser Glu Val Asp Arg Arg Leu Pro Leu Leu Leu Gly Ser180 185 190ggc acc ggg gca ctg gcc ctg gcc tcg ggc ggg gcg gcg ctg atg agc 624Gly Thr Gly Ala Leu Ala Leu Ala Ser Gly Gly Ala Ala Leu Met Ser195 200 205agg cgg gtg cgg cgg cag acc cac ggc ctg ggc gcc gcg gag atg acg 672Arg Arg Val Arg Arg Gln Thr His Gly Leu Gly Ala Ala Glu Met Thr210 215 220cgg atg tac gag cac cat gac gcg gtg ttg cgc tcg gtc cgc gaa ggg 720Arg Met Tyr Glu His His Asp Ala Val Leu Arg Ser Val Arg Glu Gly225 230 235 240gtg ctg gtc ctg acc gcg ggc ggg cgg ctg ctg gtg gtc aac gac gag 768Val Leu Val Leu Thr Ala Gly Gly Arg Leu Leu Val Val Asn Asp Glu245 250 255gcc cgg gaa ctg ctc ggg ctg gct ccg gac gcg gag ggg cgg cgc atc 816Ala Arg Glu Leu Leu Gly Leu Ala Pro Asp Ala Glu Gly Arg Arg Ile260 265 270gac gag ctc ggc ctc gaa ccg cac ctg acg caa ctg ctg gcg tcg gga 864Asp Glu Leu Gly Leu Glu Pro His Leu Thr Gln Leu Leu Ala Ser Gly275 280 285cgg cgc gtc acc gac gag gtg cac ccc cgc ggg gat cga cta ctg gcg 912Arg Arg Val Thr Asp Glu Val His Pro Arg Gly Asp Arg Leu Leu Ala290 295 300gtc aat atg cgg tcc acg gac cgt gcg ggc gat ccc gcc gga aac gtg 960Val Asn Met Arg Ser Thr Asp Arg Ala Gly Asp Pro Ala Gly Asn Val305 310 315 320gtg acg ctg agg gac acc acc gcg ctg cgg gtg ctg tcc gac cgg gcc 1008Val Thr Leu Arg Asp Thr Thr Ala Leu Arg Val Leu Ser Asp Arg Ala325 330 335gag caa gcc ggt gag cgg ctg aag ctg ctg tcc gac gcc ggg gtg cgg 1056Glu Gln Ala Gly Glu Arg Leu Lys Leu Leu Ser Asp Ala Gly Val Arg340 345 350atc agc tcc agc ctg gag ctg acg ggc acc gcg gag aag ctg gtg gac 1104Ile Ser Ser Ser Leu Glu Leu Thr Gly Thr Ala Glu Lys Leu Val Asp355 360 365gtg gcc gtc ccc cgg ttc gcc gac atc gtc tcg gtc gaa ctg ctg gag 1152Val Ala Val Pro Arg Phe Ala Asp Ile Val Ser Val Glu Leu Leu Glu370 375 380ccc gtg ctg cgc ggc gag gag ccc gag ccg ccg tac gag cca ctg gcg 1200Pro Val Leu Arg Gly Glu Glu Pro Glu Pro Pro Tyr Glu Pro Leu Ala385 390 395 400ccg cac cgg acc gcc gtc ggc gga gat ccc ccc gac ggc ctc gtc ttc 1248Pro His Arg Thr Ala Val Gly Gly Asp Pro Pro Asp Gly Leu Val Phe405 410 415cgc gtg ggc gag cga gtc gtc tac gca ccc tcc aca ccg cag agc cgg 1296Arg Val Gly Glu Arg Val Val Tyr Ala Pro Ser Thr Pro Gln Ser Arg420 425 430gcc gtg aag gcc gga gcc gcc gtc ctc ctg acc gat ctg acg ggc ccc 1344Ala Val Lys Ala Gly Ala Ala Val Leu Leu Thr Asp Leu Thr Gly Pro435 440 445ggc gag tcg ccg agc gac cac tcc gcc ccg tac cag tcc ccc ggg caa 1392Gly Glu Ser Pro Ser Asp His Ser Ala Pro Tyr Gln Ser Pro Gly Gln450 455 460tcg gcc acg tac agt gcc gag acc cgg cgc ctc ctc gac cgc ggg gtc 1440Ser Ala Thr Tyr Ser Ala Glu Thr Arg Arg Leu Leu Asp Arg Gly Val465 470 475 480cac tcg ctg atc acc gtc ccg ctg cgg ttc cgc ggg gtc acc ctc ggc 1488His Ser Leu Ile Thr Val Pro Leu Arg Phe Arg Gly Val Thr Leu Gly485 490 495ctg gcc acc ttc tgg cgg acc cgg ccc ggt gag ccg ttc gac gag gcg 1536Leu Ala Thr Phe Trp Arg Thr Arg Pro Gly Glu Pro Phe Asp Glu Ala500 505 510gat ctg gcg atc gcc ggg gag ctg gcc gtg cgc acc gcc gta tgt gtc 1584Asp Leu Ala Ile Ala Gly Glu Leu Ala Val Arg Thr Ala Val Cys Val515 520 525gac aac gcc cgc cgc tac gcc cgc gaa cac acc atg gtc acc acc ttg 1632Asp Asn Ala Arg Arg Tyr Ala Arg Glu His Thr Met Val Thr Thr Leu530 535 540cag cgc acc ctc ctc ccc agc ggt ctg ccc gat cag gac gcc gtg cgg 1680Gln Arg Thr Leu Leu Pro Ser Gly Leu Pro Asp Gln Asp Ala Val Arg545 550 555 560gtg gcg tcc cgc tat ctg ccc gca cag ggc gag acg ggc gga tcc tgg 1728Val Ala Ser Arg Tyr Leu Pro Ala Gln Gly Glu Thr Gly Gly Ser Trp565 570 575ttc gat gtg atc cct ctc ccc ggg gcc cgg gtc gcg ctg gtc gtc ggg 1776Phe Asp Val Ile Pro Leu Pro Gly Ala Arg Val Ala Leu Val Val Gly580 585 590aag gtg gcc ggg cag ggc ctg cac gcc gcg gcc acg atg ggg cgg ctg 1824Lys Val Ala Gly Gln Gly Leu His Ala Ala Ala Thr Met Gly Arg Leu595 600 605cgc acc gcg gtg cag aac ttc tcg gcc ctg gac gtg ccc ccg gat gag 1872Arg Thr Ala Val Gln Asn Phe Ser Ala Leu Asp Val Pro Pro Asp Glu610 615 620ctc ctc tcc cat ctg gac gag ctg gtc acc cgt ctc gac ctg gag cgc 1920Leu Leu Ser His Leu Asp Glu Leu Val Thr Arg Leu Asp Leu Glu Arg625 630 635 640gag gcc gat tcg gac gac gtc cgg atc acg ggc gcc acc tgc ctg tac 1968Glu Ala Asp Ser Asp Asp Val Arg Ile Thr Gly Ala Thr Cys Leu Tyr645 650 655gcg atc cac gac tcg gtg tcc ggc cac tgc gcc atg gcc cgg gcc ggc 2016Ala Ile His Asp Ser Val Ser Gly His Cys Ala Met Ala Arg Ala Gly660 665 670gat ccg ggc atc gcc gtg acc cac ccg gac ggc acc gtg gac ctc cct 2064Asp Pro Gly Ile Ala Val Thr His Pro Asp Gly Thr Val Asp Leu Pro675 680 685gcg gta ccc atc ggc ccg gcc ctg ggc atg ggc ggg gag ccg ttc gag 2112Ala Val Pro Ile Gly Pro Ala Leu Gly Met Gly Gly Glu Pro Phe Glu690 695 700gcg gtc ggc ctc tcg ctg ccc gcc gca agc cgg ctg gtg ctg tac acc 2160Ala Val Gly Leu Ser Leu Pro Ala Ala Ser Arg Leu Val Leu Tyr Thr705710 715 720aac ggc ctt ctt gaa ggg gaa ggc caa gcc gcc gac acc ggc ctc gac 2208Asn Gly Leu Leu Glu Gly Glu Gly Gln Ala Ala Asp Thr Gly Leu Asp725 730 735ctg ctg cgc cgc acc ctc gcg gcc gag ccg gac ctc ggc ccg gac gag 2256Leu Leu Arg Arg Thr Leu Ala Ala Glu Pro Asp Leu Gly Pro Asp Glu740 745 750acc tgc cgg agc ctt ttc gac acc gtg ctt ccg gcc cac ccg agc gac 2304Thr Cys Arg Ser Leu Phe Asp Thr Val Leu Pro Ala His Pro Ser Asp755 760 765gat gtg gcg ctg ctg gtg gcc cgg acc cgc ctg ctc gcc ccg gag aac 2352Asp Val Ala Leu Leu Val Ala Arg Thr Arg Leu Leu Ala Pro Glu Asn770 775 780gtg gcc gag tgg gat gtg ccg ttc gac ctg gcg gcg gtc gcc ccg ctg 2400Val Ala Glu Trp Asp Val Pro Phe Asp Leu Ala Ala Val Ala Pro Leu785 790 795800cgc gcc acc tgc acc cgg aaa ctg cgg gcg tgg ggc ctg gag gac gcc 2448Arg Ala Thr Cys Thr Arg Lys Leu Arg Ala Trp Gly Leu Glu Asp Ala805 810 815gcg tac acc gcc gag ctg atc atc agt gaa ctg atc acc aac gcc ctg 2496Ala Tyr Thr Ala Glu Leu Ile Ile Ser Glu Leu Ile Thr Asn Ala Leu820 825 830cgg tac ggc tcc cct ccc gta cgc ata cgg ctg ctg cgc ggc cgc ggc 2544Arg Tyr Gly Ser Pro Pro Val Arg Ile Arg Leu Leu Arg Gly Arg Gly835 840 845ctg atc ttc gag gtc tcc gac ggc agc agc acc gca ccc cat ctg cgg 2592Leu Ile Phe Glu Val Ser Asp Gly Ser Ser Thr Ala Pro His Leu Arg850 855 860cgg gcc gcg atc acc gac gag ggc ggc cgc ggg ctg ttc ctc gtc gcc 2640Arg Ala Ala Ile Thr Asp Glu Gly Gly Arg Gly Leu Phe Leu Val Ala865 870 875 880cag ttc gcc cag cgc tgg ggc acc cgc tac acc ccg cac ggc aag gtc 2688Gln Phe Ala Gln Arg Trp Gly Thr Arg Tyr Thr Pro His Gly Lys Val885 890 895atc tgg gcc gag gcg gcc ctg gac ggc ggc ctc 2721Ile Trp Ala Glu Ala Ala Leu Asp Gly Gly Leu900 905<210>36<211>907<212>PRT<213>Streptomyces hygroscopicus<400>36Met Gly Gly Arg Ala Arg Pro Ala Arg Arg Arg Leu Gly Pro Leu Ser1 5 10 15Tyr Thr Arg Ser Val Ala Gly Gln Ala Phe Ile Leu Gln Leu Leu Leu20 25 30Ile Leu Val Leu Val Ala Ala Ala Val Val Ala Val Ala Ala Asp Ala35 40 45Arg Ser His Ser Thr Thr Asp Ala Arg Arg Arg Ser Leu Ala Val Ala50 55 60Glu Thr Leu Ala His Ser Pro Gly Met Ala Arg Ala Leu Thr Ser Asp65 70 75 80Arg Pro Thr Ser Leu Leu Glu Ser His Ala Glu Ala Ala Arg Lys Arg85 90 95Ser Gly Val Asp Ser Val Val Val Phe Asn Thr His Gly Ile Arg Leu100 105 110Thr His Pro Glu Lys Ala Leu Ile Gly Lys Arg Ile Val Gly Pro Ala115 120 125Gly Leu Val Arg Asp Glu Leu Lys Gly Lys Thr Ile Thr Glu Ser Phe130 135 140Gln Ala Ser Gln Gly Pro Ser Val Val Ser Ala Val Pro Val Thr Arg145 150 155 160Ala Asp Gly Thr Phe Leu Gly Gly Val Ser Val Gly Val Lys Ile Ala165 170 175Ser Val Asn Ser Glu Val Asp Arg Arg Leu Pro Leu Leu Leu Gly Ser180 185 190Gly Thr Gly Ala Leu Ala Leu Ala Ser Gly Gly Ala Ala Leu Met Ser195 200 205Arg Arg Val Arg Arg Gln Thr His Gly Leu Gly Ala Ala Glu Met Thr210 215 220Arg Met Tyr Glu His His Asp Ala Val Leu Arg Ser Val Arg Glu Gly225 230 235 240Val Leu Val Leu Thr Ala Gly Gly Arg Leu Leu Val Val Asn Asp Glu245 250 255Ala Arg Glu Leu Leu Gly Leu Ala Pro Asp Ala Glu Gly Arg Arg Ile260 265 270Asp Glu Leu Gly Leu Glu Pro His Leu Thr Gln Leu Leu Ala Ser Gly275 280 285Arg Arg Val Thr Asp Glu Val His Pro Arg Gly Asp Arg Leu Leu Ala290 295 300Val Asn Met Arg Ser Thr Asp Arg Ala Gly Asp Pro Ala Gly Asn Val305 310 315 320Val Thr Leu Arg Asp Thr Thr Ala Leu Arg Val Leu Ser Asp Arg Ala325 330 335Glu Gln Ala Gly Glu Arg Leu Lys Leu Leu Ser Asp Ala Gly Val Arg340 345 350Ile Ser Ser Ser Leu Glu Leu Thr Gly Thr Ala Glu Lys Leu Val Asp355 360 365Val Ala Val Pro Arg Phe Ala Asp Ile Val Ser Val Glu Leu Leu Glu370 375 380Pro Val Leu Arg Gly Glu Glu Pro Glu Pro Pro Tyr Glu Pro Leu Ala385 390 395 400Pro His Arg Thr Ala Val Gly Gly Asp Pro Pro Asp Gly Leu Val Phe405 410 415Arg Val Gly Glu Arg Val Val Tyr Ala Pro Ser Thr Pro Gln Ser Arg420 425 430Ala Val Lys Ala Gly Ala Ala Val Leu Leu Thr Asp Leu Thr Gly Pro435 440 445Gly Glu Ser Pro Ser Asp His Ser Ala Pro Tyr Gln Ser Pro Gly Gln450 455 460Ser Ala Thr Tyr Ser Ala Glu Thr Arg Arg Leu Leu Asp Arg Gly Val465 470 475 480His Ser Leu Ile Thr Val Pro Leu Arg Phe Arg Gly Val Thr Leu Gly485 490 495Leu Ala Thr Phe Trp Arg Thr Arg Pro Gly Glu Pro Phe Asp Glu Ala
500 505 510Asp Leu Ala Ile Ala Gly Glu Leu Ala Val Arg Thr Ala Val Cys Val515 520 525Asp Asn Ala Arg Arg Tyr Ala Arg Glu His Thr Met Val Thr Thr Leu530 535 540Gln Arg Thr Leu Leu Pro Ser Gly Leu Pro Asp Gln Asp Ala Val Arg545 550 555 560Val Ala Ser Arg Tyr Leu Pro Ala Gln Gly Glu Thr Gly Gly Ser Trp565 570 575Phe Asp Val Ile Pro Leu Pro Gly Ala Arg Val Ala Leu Val Val Gly580 585 590Lys Val Ala Gly Gln Gly Leu His Ala Ala Ala Thr Met Gly Arg Leu595 600 605Arg Thr Ala Val Gln Asn Phe Ser Ala Leu Asp Val Pro Pro Asp Glu610 615 620Leu Leu Ser His Leu Asp Glu Leu Val Thr Arg Leu Asp Leu Glu Arg625 630 635 640Glu Ala Asp Ser Asp Asp Val Arg Ile Thr Gly Ala Thr Cys Leu Tyr645 650 655Ala Ile His Asp Ser Val Ser Gly His Cys Ala Met Ala Arg Ala Gly660 665 670Asp Pro Gly Ile Ala Val Thr His Pro Asp Gly Thr Val Asp Leu Pro675 680 685Ala Val Pro Ile Gly Pro Ala Leu Gly Met Gly Gly Glu Pro Phe Glu690 695 700Ala Val Gly Leu Ser Leu Pro Ala Ala Ser Arg Leu Val Leu Tyr Thr705 710 715 720Asn Gly Leu Leu Glu Gly Glu Gly Gln Ala Ala Asp Thr Gly Leu Asp725 730 735Leu Leu Arg Arg Thr Leu Ala Ala Glu Pro Asp Leu Gly Pro Asp Glu740 745 750Thr Cys Arg Ser Leu Phe Asp Thr Val Leu Pro Ala His Pro Ser Asp755 760 765Asp Val Ala Leu Leu Val Ala Arg Thr Arg Leu Leu Ala Pro Glu Asn770 775 780Val Ala Glu Trp Asp Val Pro Phe Asp Leu Ala Ala Val Ala Pro Leu785 790 795 800Arg Ala Thr Cys Thr Arg Lys Leu Arg Ala Trp Gly Leu Glu Asp Ala805 810 815Ala Tyr Thr Ala Glu Leu Ile Ile Ser Glu Leu Ile Thr Asn Ala Leu820 825 830Arg Tyr Gly Ser Pro Pro Val Arg Ile Arg Leu Leu Arg Gly Arg Gly835 840 845Leu Ile Phe Glu Val Ser Asp Gly Ser Ser Thr Ala Pro His Leu Arg
850 855 860Arg Ala Ala Ile Thr Asp Glu Gly Gly Arg Gly Leu Phe Leu Val Ala865 870 875 880Gln Phe Ala Gln Arg Trp Gly Thr Arg Tyr Thr Pro His Gly Lys Val885 890 895Ile Trp Ala Glu Ala Ala Leu Asp Gly Gly Leu900 905<210>37<211>969<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1).. (969)<223><400>37gtg aga aca gct cgc cgt acc agg aga cgt ggc cgg ttg acc gcc gcg 48Val Arg Thr Ala Arg Arg Thr Arg Arg Arg Gly Arg Leu Thr Ala Ala1 5 10 15gtg tcc ggt ctg ttc atc acg gca gcc ctc gcg aca gtc ggt acg agt 96Val Ser Gly Leu Phe Ile Thr Ala Ala Leu Ala Thr Val Gly Thr Ser20 25 30gcg gcc gct tcc tcc gcg atg acc gcc acg tcc gcg ccc agt gcc acc 144Ala Ala Ala Ser Ser Ala Met Thr Ala Thr Ser Ala Pro Ser Ala Thr35 40 45gcc acg ccc ccg tcc gta tcc acg ccc gtg tcc ggc gcc gcc acg ccc 192Ala Thr Pro Pro Ser Val Ser Thr Pro Val Ser Gly Ala Ala Thr Pro50 55 60gtg tcc ggc gcc gcc tcg tcc gtg tcc ggc gcc gcc tcg gct gtg gca 240Val Ser Gly Ala Ala Ser Ser Val Ser Gly Ala Ala Ser Ala Val Ala65 70 75 80tcc ctg gat gtc ccg ggc acc gcc tgg acc gtg gac gag cgc acc gga 288Ser Leu Asp Val Pro Gly Thr Ala Trp Thr Val Asp Glu Arg Thr Gly85 90 95acg ctg cga gtc ctc gtc ggt tcc acg gcc cgg gaa gcc gat ctg gcc 336Thr Leu Arg Val Leu Val Gly Ser Thr Ala Arg Glu Ala Asp Leu Ala100 105 110agg ctc gac cgc acc gcc gag cgc ttc ggc ggc acg atc acc gtg gag 384Arg Leu Asp Arg Thr Ala Glu Arg Phe Gly Gly Thr Ile Thr Val Glu115 120 125cgg ctc gac ggt ccg ctg cgg acc ctg ctc tcc ggt ggc gac ggg atc 432Arg Leu Asp Gly Pro Leu Arg Thr Leu Leu Ser Gly Gly Asp Gly Ile130 135 140cac tcc acc acg ggg ctg cgc tgc tcc gcg ggg gtc aat gtg caa agc 480His Ser Thr Thr Gly Leu Arg Cys Ser Ala Gly Val Asn Val Gln Ser145 150 155 160ggc acc acg tat tac ttc gtc acg gcc ggc cac tgc acc gac gcc gcc 528Gly Thr Thr Tyr Tyr Phe Val Thr Ala Gly His Cys Thr Asp Ala Ala165 170 175ccc acc tgg tac acc ggc tcc gat gcg acc acc ccg gtc ggt tcg acg 576Pro Thr Trp Tyr Thr Gly Ser Asp Ala Thr Thr Pro Val Gly Ser Thr180 185 190acc gcc acc agc ttc ccg ggc aat gac tac ggc gtc gtc cgg tac acc 624Thr Ala Thr Ser Phe Pro Gly Asn Asp Tyr Gly Val Val Arg Tyr Thr195 200 205aac acg gcc gtt ccg cac ccc ggg acc gtg gga acc gtg gac atc acc 672Asn Thr Ala Val Pro His Pro Gly Thr Val Gly Thr Val Asp Ile Thr210215 220ggg acc gcc acc gcc tac gtc ggc cag cag gtc tgc cgc cgg ggt gcc 720Gly Thr Ala Thr Ala Tyr Val Gly Gln Gln Val Cys Arg Arg Gly Ala225 230 235 240acg acc ggc gtc cgg tgc ggt cag gtc atc gcg ctc aac gcc acc gtc 768Thr Thr Gly Val Arg Cys Gly Gln Val Ile Ala Leu Asn Ala Thr Val245 250 255aac tac ggc ggc ggt gat gtc gtc tcc ggc ctg atc cag acc aat atc 816Asn Tyr Gly Gly Gly Asp Val Val Ser Gly Leu Ile Gln Thr Asn Ile260 265 270tgc gcc gag ccg ggc gac agc ggc ggt ccg ctc tac gcg ggc gac aag 864Cys Ala Glu Pro Gly Asp Ser Gly Gly Pro Leu Tyr Ala Gly Asp Lys275 280 285atc atc ggc att ctc tcg ggc ggc tcc ggg gac tgc gcg acc gga ggc 912Ile Ile Gly Ile Leu Ser Gly Gly Ser Gly Asp Cys Ala Thr Gly Gly290 295 300acc acc ttc tac cag ccg atc cag gag gtg ctg agc gcc tac ggc ctc 960Thr Thr Phe Tyr Gln Pro Ile Gln Glu Val Leu Ser Ala Tyr Gly Leu305 310 315 320acc gtc tac 969Thr Val Tyr<210>38<211>323<212>PRT<213>Streptomyces hygroscopicus<400>38Val Arg Thr Ala Arg Arg Thr Arg Arg Arg Gly Arg Leu Thr Ala Ala1 5 10 15Val Ser Gly Leu Phe Ile Thr Ala Ala Leu Ala Thr Val Gly Thr Ser20 25 30Ala Ala Ala Ser Ser Ala Met Thr Ala Thr Ser Ala Pro Ser Ala Thr35 40 45Ala Thr Pro Pro Ser Val Ser Thr Pro Val Ser Gly Ala Ala Thr Pro50 55 60Val Ser Gly Ala Ala Ser Ser Val Ser Gly Ala Ala Ser Ala Val Ala65 70 75 80Ser Leu Asp Val Pro Gly Thr Ala Trp Thr Val Asp Glu Arg Thr Gly85 90 95Thr Leu Arg Val Leu Val Gly Ser Thr Ala Arg Glu Ala Asp Leu Ala100 105 110Arg Leu Asp Arg Thr Ala Glu Arg Phe Gly Gly Thr Ile Thr Val Glu115 120 125Arg Leu Asp Gly Pro Leu Arg Thr Leu Leu Ser Gly Gly Asp Gly Ile130 135 140His Ser Thr Thr Gly Leu Arg Cys Ser Ala Gly Val Asn Val Gln Ser145 150 155 160Gly Thr Thr Tyr Tyr Phe Val Thr Ala Gly His Cys Thr Asp Ala Ala165 170 175Pro Thr Trp Tyr Thr Gly Ser Asp Ala Thr Thr Pro Val Gly Ser Thr180 185 190Thr Ala Thr Ser Phe Pro Gly Asn Asp Tyr Gly Val Val Arg Tyr Thr195 200 205Asn Thr Ala Val Pro His Pro Gly Thr Val Gly Thr Val Asp Ile Thr210 215 220Gly Thr Ala Thr Ala Tyr Val Gly Gln Gln Val Cys Arg Arg Gly Ala225 230 235 240Thr Thr Gly Val Arg Cys Gly Gln Val Ile Ala Leu Asn Ala Thr Val245 250 255Asn Tyr Gly Gly Gly Asp Val Val Ser Gly Leu Ile Gln Thr Asn Ile260 265 270Cys Ala Glu Pro Gly Asp Ser Gly Gly Pro Leu Tyr Ala Gly Asp Lys275 280 285Ile Ile Gly Ile Leu Ser Gly Gly Ser Gly Asp Cys Ala Thr Gly Gly290 295 300Thr Thr Phe Tyr Gln Pro Ile Gln Glu Val Leu Ser Ala Tyr Gly Leu305 310 315 320Thr Val Tyr<210>39<211>1659<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1).. (1659)<223><400>39gtg gca cca acg ccc cgt cat ctg gaa cag gcg gcc ccg acg gcg acc 48Val Ala Pro Thr Pro Arg His Leu Glu Gln Ala Ala Pro Thr Ala Thr1 5 10 15gag tcg gcc gat ccg gcg ctg tcc tgg ccg aag ggc gtc cct gtg ccg 96Glu Ser Ala Asp Pro Ala Leu Ser Trp Pro Lys Gly Val Pro Val Pro20 25 30ctg gtg gtg tcc ggc cga ggc gcc gcg gcg ctc gcc gcc cag gcg caa 144Leu Val Val Ser Gly Arg Gly Ala Ala Ala Leu Ala Ala Gln Ala Gln35 40 45cgg cta cgg acc ttc gta gcc gac gag ccg caa ctc gac ttg agc gaa 192Arg Leu Arg Thr Phe Val Ala Asp Glu Pro Gln Leu Asp Leu Ser Glu50 55 60ctc ggc tac gcg ttg ggt tgt ggt cgg gcg ggg ttg tcg gat cgt ggg 240Leu Gly Tyr Ala Leu Gly Cys Gly Arg Ala Gly Leu Ser Asp Arg Gly65 70 75 80gtg gtg gtg gcg ggt ggt cgt gag gag ttg ttg gtg ggg ttg ggt ggg 288Val Val Val Ala Gly Gly Arg Glu Glu Leu Leu Val Gly Leu Gly Gly85 90 95ttg gtg cgg ggt gag ggg ggt gtg ggt gtg gtg tcg ggt tcg gtg gtg 336Leu Val Arg Gly Glu Gly Gly Val Gly Val Val Ser Gly Ser Val Val100 105 110cgt ggt cgg ttg ggg gtg ttg ttt gct ggt cag ggg tgt cag cgg gtg 384Arg Gly Arg Leu Gly Val Leu Phe Ala Gly Gln Gly Cys Gln Arg Val115 120 125ggg atg ggg cgt ggg ttg tat gag gtg ttc ccg gtg ttc cgg gat gcc 432Gly Met Gly Arg Gly Leu Tyr Glu Val Phe Pro Val Phe Arg Asp Ala130 135 140ttc gac gcg gtg tgt gag gtg ttg gat cgg gag ttg ggt gcg ggt ggt 480Phe Asp Ala Val Cys Glu Val Leu Asp Arg Glu Leu Gly Ala Gly Gly145 150 155 160gtg gtg ggt tcg gtg cgg gag gtg gtg ttc ggg ggt ggg ggg ttg ttg 528Val Val Gly Ser Val Arg Glu Val Val Phe Gly Gly Gly Gly Leu Leu165 170 175gag cgg acg gtg ttt gct cag gcg ggg ttg ttc gcc gtg gag gtg ggg 576Glu Arg Thr Val Phe Ala Gln Ala Gly Leu Phe Ala Val Glu Val Gly180 185 190ttg ttc cgg ttg gtg gag tcg tgg ggt gtg gtg gtg gat gtg gtg ggt 624Leu Phe Arg Leu Val Glu Ser Trp Gly Val Val Val Asp Val Val Gly195 200 205ggg cat tcg gtg ggt gag gtg acg gcg gcg tat gtg gcg ggt gtg ttg 672Gly His Ser Val Gly Glu Val Thr Ala Ala Tyr Val Ala Gly Val Leu210 215 220tcg ttg gag gat gcg gcg gtg ttg gtg gcg gcg cgg ggt cgg ttg atg 720Ser Leu Glu Asp Ala Ala Val Leu Val Ala Ala Arg Gly Arg Leu Met225 230 235 240gag gcg ttg ccg gag ggt ggg gcg atg gtg gcg gtg gct gcg ggt gag 768Glu Ala Leu Pro Glu Gly Gly Ala Met Val Ala Val Ala Ala Gly Glu245 250 255gag gtg gtg cgg cct ttg ctg gtg tcg gcg gtg gat att gcg gcg gtg 816Glu Val Val Arg Pro Leu Leu Val Ser Ala Val Asp Ile Ala Ala Val260 265 270aac ggg ccc gaa gcg gtg gtg ctc tcc ggt gat gag gag ccg gta cta 864Ash Gly Pro Glu Ala Val Val Leu Ser Gly Asp Glu Glu Pro Val Leu275280 285cgg gtt gcg cgc gat ttg tcg gat cag ggg tgt cgg acg agg cgt ttg 912Arg Val Ala Arg Asp Leu Ser Asp Gln Gly Cys Arg Thr Arg Arg Leu290 295 300gcg gtt tcg cat gcg ttc cat tcc gcc cgt atg gag ccg atg ctg gag 960Ala Val Ser His Ala Phe His Ser Ala Arg Met Glu Pro Met Leu Glu305 310 315 320gag ttc cgg gag gcg atc gcc gat ctg tcg ttc tcg gcg ccg gtg att 1008Glu Phe Arg Glu Ala Ile Ala Asp Leu Ser Phe Ser Ala Pro Val Ile325 330 335cct ctg gtg tcg aat gtg acc ggg cgg ttg gcg gat gcg gag acc gtg 1056Pro Leu Val Ser Asn Val Thr Gly Arg Leu Ala Asp Ala Glu Thr Val340 345 350tgt tcg ccg gag tac tgg gtg gag cat gtg cgt tcg gcc gtg cgg ttc 1104Cys Ser Pro Glu Tyr Trp Val Glu His Val Arg Ser Ala Val Arg Phe355 360 365gcg gac ggt gtg cgg gcg ctc gct gac tac ggt gtg ggc acc tat ctg 1152Ala Asp Gly Val Arg Ala Leu Ala Asp Tyr Gly Val Gly Thr Tyr Leu370 375 380gag ttg gcg ccg gat gcg gtg ttg tcc gcg atg gtt ggt gat tgt cra 1200Glu Leu Ala Pro Asp Ala Val Leu Ser Ala Met Val Gly Asp Cys Leu385 390 395 400ccg gaa ggg tcg gct gct gag agt gtg gtg gtg ccg tcg ctg cgg cgg 1248Pro Glu Gly Ser Ala Ala Glu Ser Val Val Val Pro Ser Leu Arg Arg405 410 415gag ggc gac gag ccc cgt gcg ctg atg acc gcc atc gct cag ctg cat 1296Glu Gly Asp Glu Pro Arg Ala Leu Met Thr Ala Ile Ala Gln Leu His420 425 430gtg gca ggc gta ccc atc gac ttc ggt gcc ctg ttc ggt gcc acg gtt 1344Val Ala Gly Val Pro Ile Asp Phe Gly Ala Leu Phe Gly Ala Thr Val435 440 445ctg ccc acc cat att tcg gct ctg ccg acg tat gcg ttc cag cgg gag 1392Leu Pro Thr His Ile Ser Ala Leu Pro Thr Tyr Ala Phe Gln Arg Glu
450 455 460cat tac tgg ttg gtg ggg gac ggg cgt gga gcc ggc gat gtg gcg tcc 1440His Tyr Trp Leu Val Gly Asp Gly Arg Gly Ala Gly Asp Val Ala Ser465 470 475 480gcc ggg ctg gcg ggg gtg gag cat cca ttc ctg ggc gcg atg acg gag 1488Ala Gly Leu Ala Gly Val Glu His Pro Phe Leu Gly Ala Met Thr Glu485 490 495gtg ccc ggg tcg ggt gag gtg ttg ttc tcc tcg cgg ttg tcg ttg ggg 1536Val Pro Gly Ser Gly Glu Val Leu Phe Ser Ser Arg Leu Ser Leu Gly500 505 510tct cat ccg tgg ctg gcc gat cat gtg gct gcg ggt gcg gtg ttg ttg 1584Ser His Pro Trp Leu Ala Asp His Val Ala Ala Gly Ala Val Leu Leu515 520 525ccg ggt gcg gcg ttt gtg gag ttg gtg gtg cgg agc tgg acg atg agg 1632Pro Gly Ala Ala Phe Val Glu Leu Val Val Arg Ser Trp Thr Met Arg530 535 540tgg gct gcg gtg ggg tgg agg agc tgg 1659Trp Ala Ala Val Gly Trp Arg Ser Trp545 550<210>40<211>553<212>PRT<213>Streptomyces hygroscopicus<400>40Val Ala Pro Thr Pro Arg His Leu Glu Gln Ala Ala Pro Thr Ala Thr1 5 10 15Glu Ser Ala Asp Pro Ala Leu Ser Trp Pro Lys Gly Val Pro Val Pro20 25 30Leu Val Val Ser Gly Arg Gly Ala Ala Ala Leu Ala Ala Gln Ala Gln35 40 45Arg Leu Arg Thr Phe Val Ala Asp Glu Pro Gln Leu Asp Leu Ser Glu50 55 60Leu Gly Tyr Ala Leu Gly Cys Gly Arg Ala Gly Leu Ser Asp Arg Gly65 70 75 80Val Val Val Ala Gly Gly Arg Glu Glu Leu Leu Val Gly Leu Gly Gly85 90 95Leu Val Arg Gly Glu Gly Gly Val Gly Val Val Ser Gly Ser Val Val100 105 110Arg Gly Arg Leu Gly Val Leu Phe Ala Gly Gln Gly Cys Gln Arg Val115 120 125Gly Met Gly Arg Gly Leu Tyr Glu Val Phe Pro Val Phe Arg Asp Ala130 135 140Phe Asp Ala Val Cys Glu Val Leu Asp Arg Glu Leu Gly Ala Gly Gly145 150 155 160Val Val Gly Ser Val Arg Glu Val Val Phe Gly Gly Gly Gly Leu Leu165 170 175Glu Arg Thr Val Phe Ala Gln Ala Gly Leu Phe Ala Val Glu Val Gly180 185 190Leu Phe Arg Leu Val Glu Ser Trp Gly Val Val Val Asp Val Val Gly195 200 205Gly His Ser Val Gly Glu Val Thr Ala Ala Tyr Val Ala Gly Val Leu210 215 220Ser Leu Glu Asp Ala Ala Val Leu Val Ala Ala Arg Gly Arg Leu Met225 230 235 240Glu Ala Leu Pro Glu Gly Gly Ala Met Val Ala Val Ala Ala Gly Glu245 250 255Glu Val Val Arg Pro Leu Leu Val Ser Ala Val Asp Ile Ala Ala Val260 265 270Asn Gly Pro Glu Ala Val Val Leu Ser Gly Asp Glu Glu Pro Val Leu275 280 285Arg Val Ala Arg Asp Leu Ser Asp Gln Gly Cys Arg Thr Arg Arg Leu290 295 300Ala Val Ser His Ala Phe His Ser Ala Arg Met Glu Pro Met Leu Glu305 310 315 320Glu Phe Arg Glu Ala Ile Ala Asp Leu Ser Phe Ser Ala Pro Val Ile325 330 335Pro Leu Val Ser Asn Val Thr Gly Arg Leu Ala Asp Ala Glu Thr Val340 345 350Cys Ser Pro Glu Tyr Trp Val Glu His Val Arg Ser Ala Val Arg Phe355 360 365Ala Asp Gly Val Arg Ala Leu Ala Asp Tyr Gly Val Gly Thr Tyr Leu370 375 380Glu Leu Ala Pro Asp Ala Val Leu Ser Ala Met Val Gly Asp Cys Leu385 390 395 400Pro Glu Gly Ser Ala Ala Glu Ser Val Val Val Pro Ser Leu Arg Arg405 410 415Glu Gly Asp Glu Pro Arg Ala Leu Met Thr Ala Ile Ala Gln Leu His420 425 430Val Ala Gly Val Pro Ile Asp Phe Gly Ala Leu Phe Gly Ala Thr Val435 440 445Leu Pro Thr His Ile Ser Ala Leu Pro Thr Tyr Ala Phe Gln Arg Glu450 455 460His Tyr Trp Leu Val Gly Asp Gly Arg Gly Ala Gly Asp Val Ala Ser465 470 475 480Ala Gly Leu Ala Gly Val Glu His Pro Phe Leu Gly Ala Met Thr Glu485 490 495Val Pro Gly Ser Gly Glu Val Leu Phe Ser Ser Arg Leu Ser Leu Gly500 505 510Ser His Pro Trp Leu Ala Asp His Val Ala Ala Gly Ala Val Leu Leu515 520 525Pro Gly Ala Ala Phe Val Glu Leu Val Val Arg Ser Trp Thr Met Arg530 535 540Trp Ala Ala Val Gly Trp Arg Ser Trp545 550<210>41<211>3339<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(3339)<223><400>41gtg ggc gcc gta ccg ctc cag gaa ccg ctc ggc gta ggc ggg gcc gaa 48Val Gly Ala Val Pro Leu Gln Glu Pro Leu Gly Val Gly Gly Ala Glu1 5 10 15cca ggg gtc ctc gtc gat ctc cag ctc gcg ggc ggc cag ggc gat gtc 96Pro Gly Val Leu Val Asp Leu Gln Leu Ala Gly Gly Gln Gly Asp Val20 25 30ggc gtg gcg gtc ggc gac ccc gag gcg gcc gac gtc gat cac gcc ggt 144Gly Val Ala Val Gly Asp Pro Glu Ala Ala Asp Val Asp His Ala Gly35 40 45gac ccg gca ggt ccc ggg gtc gag cag gac gtt gtt ggg gca cag gtc 192Asp Pro Ala Gly Pro Gly Val Glu Gln Asp Val Val Gly Ala Gln Val50 55 60gcc atg gca gac gac cag gtc ctc ctt ctc ggg acg ggt gcg gtc gag 240Ala Met Ala Asp Asp Gln Val Leu Leu Leu Gly Thr Gly Ala Val Glu65 70 75 80ctc cgc cag gag ctg gtc gcc ggt cca ccc ggc ccg ctc ctc ctg cag 288Leu Arg Gln Glu Leu Val Ala Gly Pro Pro Gly Pro Leu Leu Leu Gln85 90 95gtc gtc gag gtc cac cag gcc ctc ggc gac gtt ccg ccg ggc ctc ggc 336Val Val Glu Val His Gln Ala Leu Gly Asp Val Pro Pro Gly Leu Gly100 105 110gac cgc cgc gtc gag gcg ccg gtc gaa ggg gca gtc ctc cac ggg cag 384Asp Arg Arg Val Glu Ala Pro Val Glu Gly Ala Val Leu His Gly Gln115 120 125ctc gtg gag ggc gcg ggc cag ctc cgc cat cgc ctc gac cac ggc gaa 432Leu Val Glu Gly Ala Gly Gln Leu Arg His Arg Leu Asp His Gly Glu130 135 140ccg ctg gtg ctc ggg cca ctc ctc ggc cgc cgc gac gcc ggg gac ggc 480Pro Leu Val Leu Gly Pro Leu Leu Gly Arg Arg Asp Ala Gly Asp Gly145 150 155 160ctc cgt gac gag cca cgc ggc ggt gtc gtc ggc acc gcg ctc gac gac 528Leu Arg Asp Glu Pro Arg Gly Gly Val Val Gly Thr Ala Leu Asp Asp165 170 175gcg ggg gac ggg gat cgg gtg gat gtg gtg cag ccg gtg tcg ttt gcg 576Ala Gly Asp Gly Asp Arg Val Asp Val Val Gln Pro Val Ser Phe Ala180 185 190gtg atg gtg ggg ttg gcg cgg gtg tgg ttg gcg gct ggt gtg gtg ccg 624Val Met Val Gly Leu Ala Arg Val Trp Leu Ala Ala Gly Val Val Pro195 200 205tcg gtg gtg gtg ggt cat tcg cag ggg gag att gcg gct gcg tgt gtg 672Ser Val Val Val Gly His Ser Gln Gly Glu Ile Ala Ala Ala Cys Val210215 220gcg ggt ggg ttg tcg ttg gag gac gcg gtg cgg gtg gtg gtg ttg cgg 720Ala Gly Gly Leu Ser Leu Glu Asp Ala Val Arg Val Val Val Leu Arg225 230 235 240agt cgt gcg gtg gcg gct ggg ctc tcg ggc cgt ggc ggg atg gtg tcg 768Ser Arg Ala Val Ala Ala Gly Leu Ser Gly Arg Gly Gly Met Val Ser245 250 255ttg gcg gtg ggt gtg gcg gag gcg gag ggg ttg gtt gag cgg tgg tcg 816Leu Ala Val Gly Val Ala Glu Ala Glu Gly Leu Val Glu Arg Trp Ser260 265 270ggg cgt atc gag gtg gcg gcg gtg aat ggg ccg ttg tcg gtg gtg gtg 864Gly Arg Ile Glu Val Ala Ala Val Asn Gly Pro Leu Ser Val Val Val275 280 285gct ggt gag ccg gat gcc ttg cgg ggg ttg gtg gcg gag tgt gag ggc 912Ala Gly Glu Pro Asp Ala Leu Arg Gly Leu Val Ala Glu Cys Glu Gly290 295 300gcg ggg gtg cgg gcg cgg tgg gtt gat gtg gat tac gcc tcg cat acg 960Ala Gly Val Arg Ala Arg Trp Val Asp Val Asp Tyr Ala Ser His Thr305 310 315 320gcg cag gtg gag gcg gtc gag ggg gag ttg gct cgg tcg ttg gcg caa 1008Ala Gln Val Glu Ala Val Glu Gly Glu Leu Ala Arg Ser Leu Ala Gln325 330 335att cgt ccg gtg tcc tca cgt att ccg ttc ttt tcg acg gtg gag gct 1056Ile Arg Pro Val Ser Ser Arg Ile Pro Phe Phe Ser Thr Val Glu Ala340 345 350ggg tgg ctg gac acg gcc gag ctg gac gcc ggg tac tgg tac cgg aat 1104Gly Trp Leu Asp Thr Ala Glu Leu Asp Ala Gly Tyr Trp Tyr Arg Asn355 360 365ctg cgg agc acc gtg cgc ttc gcg ccg tcg atc gac cgg ttg atc gag 1152Leu Arg Ser Thr Val Arg Phe Ala Pro Ser Ile Asp Arg Leu Ile Glu370 375380gaa ggc ttt gcg gcg ttt gtc gaa gtg agc gcg cat ccg gtg ctg acg 1200Glu Gly Phe Ala Ala Phe Val Glu Val Ser Ala His Pro Val Leu Thr385 390 395 400atg ggc atc gag gcg gcg gcg gag cgg gcg gac gtt ggg ccg gtc gtg 1248Met Gly Ile Glu Ala Ala Ala Glu Arg Ala Asp Val Gly Pro Val Val405 410415gtg acc ggg acg ctc cgc cgg gat cag ggt gat atg cgt cgt gtg ctc 1296Val Thr Gly Thr Leu Arg Arg Asp Gln Gly Asp Met Arg Arg Val Leu420 425 430act tcc ctg gcc gag gtg tac gta cgc ggt gtc ccc gtg aac tgg acc 1344Thr Ser Leu Ala Glu Val Tyr Val Arg Gly Val Pro Val Asn Trp Thr435 440 445acc ctg ctg ggc gac atc ccg gcg cgc gcc gcg ttg gat ctg ccg acg 1392Thr Leu Leu Gly Asp Ile Pro Ala Arg Ala Ala Leu Asp Leu Pro Thr450 455 460tac gcc ttc cag cat cag cac tac tgg ctg aag aac gcc att ccc acc 1440Tyr Ala Phe Gln His Gln His Tyr Trp Leu Lys Asn Ala Ile Pro Thr465 470 475 480gat gcg gga gcc atc gac gat cag ctt ccg ggc ctg gtc gaa ctg ccc 1488Asp Ala Gly Ala Ile Asp Asp Gln Leu Pro Gly Leu Val Glu Leu Pro485 490 495gcc gag acc ggc gcc ttg acc gct cgc ctt ctt ggg gag tcc acg cag 1536Ala Glu Thr Gly Ala Leu Thr Ala Arg Leu Leu Gly Glu Ser Thr Gln500 505 510gaa cag gaa cgc atc ctg ctc aag acc gtt cgc cag gag acc gcg agc 1584Glu Gln Glu Arg Ile Leu Leu Lys Thr Val Arg Gln Glu Thr Ala Ser515 520 525gtc ttg ggc cac tcc tcg ctg gac gcc att gaa ccg gac atg gtg ttc 1632Val Leu Gly His Ser Ser Leu Asp Ala Ile Glu Pro Asp Met Val Phe530 535 540aac cag atc ggc ttc gac tcg gcc acc gca gta cag ctg cga aac cgt 1680Asn Gln Ile Gly Phe Asp Ser Ala Thr Ala Val Gln Leu Arg Asn Arg545 550 555 560ctg aac gcg ctc acc gac cgg act ctg ccg acc acc ctg ctc ttc gac 1728Leu Asn Ala Leu Thr Asp Arg Thr Leu Pro Thr Thr Leu Leu Phe Asp565 570 575tac ccc acg ccc ctg atc ctc gcc gac ttc ctg cgt gac gaa ctc atc 1776Tyr Pro Thr Pro Leu Ile Leu Ala Asp Phe Leu Arg Asp Glu Leu Ile580 585 590ggg gac acg gcg gcc ccg gag ggg gtg ccg gaa gcg aca gcg gcg ccg 1824Gly Asp Thr Ala Ala Pro Glu Gly Val Pro Glu Ala Thr Ala Ala Pro595 600 605ggg gat gtg tcg acc gag ccg gtg gcg atc gtg ggt atg gcg tgc cgg 1872Gly Asp Val Ser Thr Glu Pro Val Ala Ile Val Gly Met Ala Cys Arg610 615 620ctg ccg ggt ggc gtc tcc acc ccg gaa gag cta tgg gac ctg gtg ctt 1920Leu Pro Gly Gly Val Ser Thr Pro Glu Glu Leu Trp Asp Leu Val Leu625 630 635 640cag ggg cgg gac ggg gtc agc gac ttc ccc gtg aac cgt ggc tgg gat 1968Gln Gly Arg Asp Gly Val Ser Asp Phe Pro Val Asn Arg Gly Trp Asp645 650 655ctg gag aat ctg ttc cac ccg gac ccg gac cac ccc gct acc agc tat 2016Leu Glu Asn Leu Phe His Pro Asp Pro Asp His Pro Ala Thr Ser Tyr660 665 670gcg cac caa ggc gga ttt ctg cac gac gcc ggg gag ttt gac gcg ggt 2064Ala His Gln Gly Gly Phe Leu His Asp Ala Gly Glu Phe Asp Ala Gly675 680 685ttc ttc ggg atc tca cca cgc gag gca ctg gcc gtg gac ccg caa cag 2112Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Val Asp Pro Gln Gln690 695 700cgt ctg atg ctg gaa acc tcg tgg gaa gcg ctg gaa cgc gcc ggg atc 2160Arg Leu Met Leu Glu Thr Ser Trp Glu Ala Leu Glu Arg Ala Gly Ile705 710 715 720gac ccg acc acg ctg cgg ggc aag gac gtc ggt gtc ttc tcc ggt gtg 2208Asp Pro Thr Thr Leu Arg Gly Lys Asp Val Gly Val Phe Ser Gly Val725 730 735acg tac cac aac tac ggc tcg ggc gtg gag ccg gtt ccc gcc gag ctc 2256Thr Tyr His Asn Tyr Gly Ser Gly Val Glu Pro Val Pro Ala Glu Leu740 745 750gaa ggc atg ctg ggg ctc ggc gcc tcg gcg agc gtg ctg tca ggg cgg 2304Glu Gly Met Leu Gly Leu Gly Ala Ser Ala Ser Val Leu Ser Gly Arg755 760 765gtg tcg tat gcg ctg ggc ttc gag ggg ccg tcg gtc gcg gtg gac acg 2352Val Ser Tyr Ala Leu Gly Phe Glu Gly Pro Ser Val Ala Val Asp Thr770 775 780gcg tgc tcc tcg tcc ctg gtg gcg ttg cac ttg gcg gcg cag gcg ttg 2400Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Ala Gln Ala Leu785 790 795 800cga gca ggc gag tgc tcg atc gcc ctt gcc ggt ggg gtc acg gtg atg 2448Arg Ala Gly Glu Cys Ser Ile Ala Leu Ala Gly Gly Val Thr Val Met805 810 815ccg act ccc ggt atc ttc atc gcc ttc tca cgg cag cgc ggc atg tcg 2496Pro Thr Pro Gly Ile Phe Ile Ala Phe Ser Arg Gln Arg Gly Met Ser820 825 830gtc gat ggc cgg tgc aag tcg ttc tcg gcg tcg gcg gac ggt acg ggg 2544Val Asp Gly Arg Cys Lys Ser Phe Ser Ala Ser Ala Asp Gly Thr Gly835 840 845tgg gcc gag ggt gtg ggt gtg ctg gcg ctg gag cgg ctg tcg gac gcg2592Trp Ala Glu Gly Val Gly Val Leu Ala Leu Glu Arg Leu Ser Asp Ala850 855 860gag cga aac ggc cat cgg gtg ttg gcg gtg gtg cgg ggc agt gcg gtg 2640Glu Arg Asn Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val865 870 875 880aat cag gac ggt gcg tcg aat ggg ttg acg gcg ccg aat ggt ccg tcg 2688Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser885 890 895cag cag cgt gtc att cgg cag gcg ctg gcc agt gcg ggt gtg tcg gct 2736Gln Gln Arg Val Ile Arg Gln Ala Leu Ala Set Ala Gly Val Ser Ala900 905 910gcc gag gtg gat gtg gtc gag gca cat ggc acg ggt acg gcg ctg ggc 2784Ala Glu Val Asp Val Val Glu Ala His Gly Thr Gly Thr Ala Leu Gly915 920 925gat ccc att gag gcg cag gcg gtg ttg gcc acg tat ggc cag gat cgt 2832Asp Pro Ile Glu Ala Gln Ala Val Leu Ala Thr Tyr Gly Gln Asp Arg930 935 940gat cgg cct ttg ttg atg ggg tcg ttg aag tcg aat atc ggt cat gcg 2880Asp Arg Pro Leu Leu Met Gly Ser Leu Lys Ser Asn Ile Gly His Ala945 950 955 960cag gcg gcc gcg ggt gtg gct ggt gtg atc aag atg gtg ttg gcg ctg 2928Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Leu Ala Leu965 970 975cgg cat ggc atc gct cct cgg acg ttg cat gtg gac gag ccg acc tcg 2976Arg His Gly Ile Ala Pro Arg Thr Leu His Val Asp Glu Pro Thr Ser980 985 990cag gtg gat tgg tcg acg ggt gcg gtg gag ctg ttg acc gag gag cgg 3024Gln Val Asp Trp Ser Thr Gly Ala Val Glu Leu Leu Thr Glu Glu Arg995 10001005gtg tgg cct gag gtg ggt cgt cct cgc cgg gct gga gtg tcc gcg 3069Val Trp Pro Glu Val Gly Arg Pro Arg Arg Ala Gly Val Ser Ala101010151020ttc ggg gtc agt ggc acc aac gcc ccg tca tct gga aca ggc ggc 3114Phe Gly Val Ser Gly Thr Asn Ala Pro Ser Ser Gly Thr Gly Gly102510301035ccc gac ggc gac cga gtc ggc cga tcc ggc gct gtc ctg gcc gaa 3159Pro Asp Gly Asp Arg Val Gly Arg Ser Gly Ala Val Leu Ala Glu104010451050ggg cgt ccc tgt gcc gct ggt ggt gtc cgg ccg agg cgc cgc ggc 3204Gly Arg Pro Cys Ala Ala Gly Gly Val Arg Pro Arg Arg Arg Gly105510601065gct cgc cgc cca ggc gca acg gct acg gac ctt cgt agc cga cga 3249Ala Arg Arg Pro Gly Ala Thr Ala Thr Asp Leu Arg Ser Arg Arg107010751080gcc gca act cga ctt gag cga act cgg cta cgc gtt ggg ttg tgg 3294Ala Ala Thr Arg Leu Glu Arg Thr Arg Leu Arg Val Gly Leu Trp108510901095tcg ggc ggg gtt gtc gga tcg tgg ggt ggt ggt ggc ggg tgg tcg 3339Ser Gly Gly Val Val Gly Ser Trp Gly Gly Gly Gly Gly Trp Ser110011051110<210>42<211>1113<212>PRT<213>Streptomyces hygroscopicus<400>42Val Gly Ala Val Pro Leu Gln Glu Pro Leu Gly Val Gly Gly Ala Glu1 5 10 15Pro Gly Val Leu Val Asp Leu Gln Leu Ala Gly Gly Gln Gly Asp Val20 25 30Gly Val Ala Val Gly Asp Pro Glu Ala Ala Asp Val Asp His Ala Gly35 40 45Asp Pro Ala Gly Pro Gly Val Glu Gln Asp Val Val Gly Ala Gln Val50 55 60Ala Met Ala Asp Asp Gln Val Leu Leu Leu Gly Thr Gly Ala Val Glu65 70 75 80Leu Arg Gln Glu Leu Val Ala Gly Pro Pro Gly Pro Leu Leu Leu Gln85 90 95Val Val Glu Val His Gln Ala Leu Gly Asp Val Pro Pro Gly Leu Gly100 105 110Asp Arg Arg Val Glu Ala Pro Val Glu Gly Ala Val Leu His Gly Gln115 120 125Leu Val Glu Gly Ala Gly Gln Leu Arg His Arg Leu Asp His Gly Glu130 135 140Pro Leu Val Leu Gly Pro Leu Leu Gly Arg Arg Asp Ala Gly Asp Gly145 150 155 160Leu Arg Asp Glu Pro Arg Gly Gly Val Val Gly Thr Ala Leu Asp Asp165 170 175Ala Gly Asp Gly Asp Arg Val Asp Val Val Gln Pro Val Ser Phe Ala180 185 190Val Met Val Gly Leu Ala Arg Val Trp Leu Ala Ala Gly Val Val Pro195 200 205Ser Val Val Val Gly His Ser Gln Gly Glu Ile Ala Ala Ala Cys Val210 215 220Ala Gly Gly Leu Ser Leu Glu Asp Ala Val Arg Val Val Val Leu Arg225 230 235240Ser Arg Ala Val Ala Ala Gly Leu Ser Gly Arg Gly Gly Met Val Ser245 250 255Leu Ala Val Gly Val Ala Glu Ala Glu Gly Leu Val Glu Arg Trp Ser
260 265 270Gly Arg Ile Glu Val Ala Ala Val Asn Gly Pro Leu Ser Val Val Val275 280 285Ala Gly Glu Pro Asp Ala Leu Arg Gly Leu Val Ala Glu Cys Glu Gly290 295 300Ala Gly Val Arg Ala Arg Trp Val Asp Val Asp Tyr Ala Ser His Thr305 310 315 320Ala Gln Val Glu Ala Val Glu Gly Glu Leu Ala Arg Ser Leu Ala Gln325 330 335Ile Arg Pro Val Ser Ser Arg Ile Pro Phe Phe Ser Thr Val Glu Ala340 345 350Gly Trp Leu Asp Thr Ala Glu Leu Asp Ala Gly Tyr Trp Tyr Arg Asn355 360 365Leu Arg Ser Thr Val Arg Phe Ala Pro Ser Ile Asp Arg Leu Ile Glu370 375 380Glu Gly Phe Ala Ala Phe Val Glu Val Ser Ala His Pro Val Leu Thr385 390 395 400Met Gly Ile Glu Ala Ala Ala Glu Arg Ala Asp Val Gly Pro Val Val405 410 415Val Thr Gly Thr Leu Arg Arg Asp Gln Gly Asp Met Arg Arg Val Leu420 425 430Thr Ser Leu Ala Glu Val Tyr Val Arg Gly Val Pro Val Asn Trp Thr435 440 445Thr Leu Leu Gly Asp Ile Pro Ala Arg Ala Ala Leu Asp Leu Pro Thr450 455 460Tyr Ala Phe Gln His Gln His Tyr Trp Leu Lys Asn Ala Ile Pro Thr465 470 475 480Asp Ala Gly Ala Ile Asp Asp Gln Leu Pro Gly Leu Val Glu Leu Pro485 490 495Ala Glu Thr Gly Ala Leu Thr Ala Arg Leu Leu Gly Glu Ser Thr Gln500 505 510Glu Gln Glu Arg Ile Leu Leu Lys Thr Val Arg Gln Glu Thr Ala Ser515 520 525Val Leu Gly His Ser Ser Leu Asp Ala Ile Glu Pro Asp Met Val Phe530 535 540Asn Gln Ile Gly Phe Asp Ser Ala Thr Ala Val Gln Leu Arg Asn Arg545 550 555 560Leu Asn Ala Leu Thr Asp Arg Thr Leu Pro Thr Thr Leu Leu Phe Asp565 570 575Tyr Pro Thr Pro Leu Ile Leu Ala Asp Phe Leu Arg Asp Glu Leu Ile580 585 590Gly Asp Thr Ala Ala Pro Glu Gly Val Pro Glu Ala Thr Ala Ala Pro595 600 605Gly Asp Val Ser Thr Glu Pro Val Ala Ile Val Gly Met Ala Cys Arg
610 615 620Leu Pro Gly Gly Val Ser Thr Pro Glu Glu Leu Trp Asp Leu Val Leu625 630 635 640Gln Gly Arg Asp Gly Val Ser Asp Phe Pro Val Asn Arg Gly Trp Asp645 650 655Leu Glu Asn Leu Phe His Pro Asp Pro Asp His Pro Ala Thr Ser Tyr660 665 670Ala His Gln Gly Gly Phe Leu His Asp Ala Gly Glu Phe Asp Ala Gly675 680 685Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Val Asp Pro Gln Gln690 695 700Arg Leu Met Leu Glu Thr Ser Trp Glu Ala Leu Glu Arg Ala Gly Ile705 710 715 720Asp Pro Thr Thr Leu Arg Gly Lys Asp Val Gly Val Phe Ser Gly Val725 730 735Thr Tyr His Asn Tyr Gly Ser Gly Val Glu Pro Val Pro Ala Glu Leu740 745 750Glu Gly Met Leu Gly Leu Gly Ala Ser Ala Ser Val Leu Ser Gly Arg755 760 765Val Ser Tyr Ala Leu Gly Phe Glu Gly Pro Ser Val Ala Val Asp Thr770 775 780Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Ala Gln Ala Leu785 790 795 800Arg Ala Gly Glu Cys Ser Ile Ala Leu Ala Gly Gly Val Thr Val Met805 810 815Pro Thr Pro Gly Ile Phe Ile Ala Phe Ser Arg Gln Arg Gly Met Ser820 825 830Val Asp Gly Arg Cys Lys Ser Phe Ser Ala Ser Ala Asp Gly Thr Gly835 840 845Trp Ala Glu Gly Val Gly Val Leu Ala Leu Glu Arg Leu Ser Asp Ala850 855 860Glu Arg Asn Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val865 870 875 880Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser885 890 895Gln Gln Arg Val Ile Arg Gln Ala Leu Ala Ser Ala Gly Val Ser Ala900 905 910Ala Glu Val Asp Val Val Glu Ala His Gly Thr Gly Thr Ala Leu Gly915 920 925Asp Pro Ile Glu Ala Gln Ala Val Leu Ala Thr Tyr Gly Gln Asp Arg930 935 940Asp Arg Pro Leu Leu Met Gly Ser Leu Lys Ser Asn Ile Gly His Ala945 950 955 960Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Leu Ala Leu
965 970 975Arg His Gly Ile Ala Pro Arg Thr Leu His Val Asp Glu Pro Thr Ser980 985 990Gln Val Asp Trp Ser Thr Gly Ala Val Glu Leu Leu Thr Glu Glu Arg995 10001005Val Trp Pro Glu Val Gly Arg Pro Arg Arg Ala Gly Val Ser Ala101010151020Phe Gly Val Ser Gly Thr Asn Ala Pro Ser Ser Gly Thr Gly Gly102510301035Pro Asp Gly Asp Arg Val Gly Arg Ser Gly Ala Val Leu Ala Glu104010451050Gly Arg Pro Cys Ala Ala Gly Gly Val Arg Pro Arg Arg Arg Gly105510601065Ala Arg Arg Pro Gly Ala Thr Ala Thr Asp Leu Arg Ser Arg Arg107010751080Ala Ala Thr Arg Leu Glu Arg Thr Arg Leu Arg Val Gly Leu Trp108510901095Ser Gly Gly Val Val Gly Ser Trp Gly Gly Gly Gly Gly Trp Ser110011051110<210>43<211>1479<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(1479)<223><400>43gtg gcc gct gct gcc gcg ctg agc gcg tgc ggc aca ccg gaa gca cac 48Val Ala Ala Ala Ala Ala Leu Ser Ala Cys Gly Thr Pro Glu Ala His1 5 10 15gga aga ccc acg ggg gtg gcg atg gag ccg gcg gca ccg gcg cag tac 96Gly Arg Pro Thr Gly Val Ala Met Glu Pro Ala Ala Pro Ala Gln Tyr20 25 30gta ctg atc act cag tgc ttg cag aac gac ttc ttc ctc aac ctg gac 144Val Leu Ile Thr Gln Cys Leu Gln Asn Asp Phe Phe Leu Asn Leu Asp35 40 45tgc cag ttg tcc ctg ccg gac agc gcc gtc tcc aag ctg ctg ctg gac 192Cys Gln Leu Ser Leu Pro Asp Ser Ala Val Ser Lys Leu Leu Leu Asp50 55 60agc gag agc ggt gcg tcc ctc cac acg gag ggc cac cgc agg gtc ctg 240Ser Glu Ser Gly Ala Ser Leu His Thr Glu Gly His Arg Arg Val Leu65 70 75 80tcc gag tcg gag ctg cgc cgt tcg ccc ctg gcc cgt ttc ctc gac gcc 288Ser Glu Ser Glu Leu Arg Arg Ser Pro Leu Ala Arg Phe Leu Asp Ala85 90 95acc gtg ggc tcc cgt acg cgc gga cac ggg gac ggg gtt ctg cat ctg 336Thr Val Gly Ser Arg Thr Arg Gly His Gly Asp Gly Val Leu His Leu100 105 110atc aac atc cgt gac tgg cat gtc ccg gga gag aca tac gac ctg gag 384Ile Asn Ile Arg Asp Trp His Val Pro Gly Glu Thr Tyr Asp Leu Glu115 120 125cgc agg cag tac ggg gcc cat tgc gag gcc gac acc tgg ggg gcg gcg 432Arg Arg Gln Tyr Gly Ala His Cys Glu Ala Asp Thr Trp Gly Ala Ala130 135 140tac gtc gac ggg ctc acg gac ctg ctg gcc ccg gat gag cgc gcg ccc 480Tyr Val Asp Gly Leu Thr Asp Leu Leu Ala Pro Asp Glu Arg Ala Pro145 150 155 160gcg gac ggc gag ggc ggc tgg ggc ggg aaa ctc cat gtc cac cat gtg 528Ala Asp Gly Glu Gly Gly Trp Gly Gly Lys Leu His Val His His Val165 170 175cgg tcc aac acc ctc ttc gac ttc cag cac agc gcc ggc gga cgt ccc 576Arg Ser Asn Thr Leu Phe Asp Phe Gln His Ser Ala Gly Gly Arg Pro180 185 190gac ctc agc gaa ccg gcg ccg ctg acc aca ctg ctg gac ggt ctg ctg 624Asp Leu Ser Glu Pro Ala Pro Leu Thr Thr Leu Leu Asp Gly Leu Leu195 200 205ggc gat gga cgt cag gag acg acg cat gtc gcg gtg gtc ggc gtc ctc 672Gly Asp Gly Arg Gln Glu Thr Thr His Val Ala Val Val Gly Val Leu210 215 220acc gat atc aag gtc cag ctg ctg ctg acc ggt atc cgc tcc cgc tac 720Thr Asp Ile Lys Val Gln Leu Leu Leu Thr Gly Ile Arg Ser Arg Tyr225 230 235 240gac gta cgg cag ctc gtc gtc tcc gac gcg ctc acc gcc agc agg acc 768Asp Val Arg Gln Leu Val Val Ser Asp Ala Leu Thr Ala Ser Arg Thr245 250 255ctg gag cgc cat ctg acg gcg ctg gac ttc tgc cag cgt gtg ctg cgc 816Leu Glu Arg His Leu Thr Ala Leu Asp Phe Cys Gln Arg Val Leu Arg260 265 270acc gag gtg atg atc ggc ctg gcg gag ctg gcc cgt ttc ctg ggc tcc 864Thr Glu Val Met Ile Gly Leu Ala Glu Leu Ala Arg Phe Leu Gly Ser275 280 285cgg ccg gac gac gac cgg ctg tcc cgt ggc ggg gac gag gag ttc gtg 912Arg Pro Asp Asp Asp Arg Leu Ser Arg Gly Gly Asp Glu Glu Phe Val290 295300ggc tac tcc tca tac atc cag gac aag cag ggc atc ctg tcg tac gag 960Gly Tyr Ser Ser Tyr Ile Gln Asp Lys Gln Gly Ile Leu Ser Tyr Glu305 310 315 320gac gcc agg atg cgg gac tat cgc atc cag acc tcg gaa cgc ctc cgg 1008Asp Ala Arg Met Arg Asp Tyr Arg Ile Gln Thr Ser Glu Arg Leu Arg325 330 335cgg acg cag cac acg gtc ggc ttc gcc agc aag ttc ctg ctg ggg ctg 1056Arg Thr Gln His Thr Val Gly Phe Ala Ser Lys Phe Leu Leu Gly Leu340 345 350ggc acc tgt ctg ctg gtc agc gcc ctt gtg ctg tcg ctc gtc ggc gtc 1104Gly Thr Cys Leu Leu Val Ser Ala Leu Val Leu Ser Leu Val Gly Val355 360 365ttc ctc ccg ggc cgt atc ggg tgg cag agc ccc gcc gtg ctc ggg gcg 1152Phe Leu Pro Gly Arg Ile Gly Trp Gln Ser Pro Ala Val Leu Gly Ala370 375 380ctc ggg gtg ggg cag atc gtc acg ttg ttc ttc acc cgg ccg gtc aga 1200Leu Gly Val Gly Gln Ile Val Thr Leu Phe Phe Thr Arg Pro Val Arg385 390 395 400tcg gtg cag gac gcg ctg gcg gag gag acc atc tac cgg atg atc ctg 1248Ser Val Gln Asp Ala Leu Ala Glu Glu Thr Ile Tyr Arg Met Ile Leu405 410 415gag agc cgc agc ctg aag gtg gcc ctg gcg cgg ttc cac atc acc acg 1296Glu Ser Arg Ser Leu Lys Val Ala Leu Ala Arg Phe His Ile Thr Thr420 425 430gcc acc gcg ctc cga cgg cat gac gat gtg aac ggc caa tcc gac gcc 1344Ala Thr Ala Leu Arg Arg His Asp Asp Val Asn Gly Gln Ser Asp Ala435 440 445ctg gca cgc cag ttg gag atc ctg gag aag atc gac acg gcc gac ttc 1392Leu Ala Arg Gln Leu Glu Ile Leu Glu Lys Ile Asp Thr Ala Asp Phe450 455 460gaa cgg ctg aaa cag ctg ggg gtg acc ccg cgg gcc gaa tcg tcc ggg 1440Glu Arg Leu Lys Gln Leu Gly Val Thr Pro Arg Ala Glu Ser Ser Gly465 470 475 480acg ggg cgg ccc cgc aga aga atc cgc tca cag gtt tcc 1479Thr Gly Arg Pro Arg Arg Arg Ile Arg Ser Gln Val Ser485 490<210>44<211>493<212>PRT<213>Streptomyces hygroscopicus<400>44Val Ala Ala Ala Ala Ala Leu Ser Ala Cys Gly Thr Pro Glu Ala His1 5 10 15Gly Arg Pro Thr Gly Val Ala Met Glu Pro Ala Ala Pro Ala Gln Tyr20 25 30Val Leu Ile Thr Gln Cys Leu Gln Asn Asp Phe Phe Leu Asn Leu Asp35 40 45Cys Gln Leu Ser Leu Pro Asp Ser Ala Val Ser Lys Leu Leu Leu Asp50 55 60Ser Glu Ser Gly Ala Ser Leu His Thr Glu Gly His Arg Arg Val Leu65 70 75 80Ser Glu Ser Glu Leu Arg Arg Ser Pro Leu Ala Arg Phe Leu Asp Ala85 90 95Thr Val Gly Ser Arg Thr Arg Gly His Gly Asp Gly Val Leu His Leu100 105 110Ile Asn Ile Arg Asp Trp His Val Pro Gly Glu Thr Tyr Asp Leu Glu115 120 125Arg Arg Gln Tyr Gly Ala His Cys Glu Ala Asp Thr Trp Gly Ala Ala130 135 140Tyr Val Asp Gly Leu Thr Asp Leu Leu Ala Pro Asp Glu Arg Ala Pro145 150 155160Ala Asp Gly Glu Gly Gly Trp Gly Gly Lys Leu His Val His His Val165 170 175Arg Ser Asn Thr Leu Phe Asp Phe Gln His Ser Ala Gly Gly Arg Pro180 185 190Asp Leu Ser Glu Pro Ala Pro Leu Thr Thr Leu Leu Asp Gly Leu Leu195 200 205Gly Asp Gly Arg Gln Glu Thr Thr His Val Ala Val Val Gly Val Leu210 215 220Thr Asp Ile Lys Val Gln Leu Leu Leu Thr Gly Ile Arg Ser Arg Tyr225 230 235 240Asp Val Arg Gln Leu Val Val Ser Asp Ala Leu Thr Ala Ser Arg Thr245 250 255Leu Glu Arg His Leu Thr Ala Leu Asp Phe Cys Gln Arg Val Leu Arg260 265 270Thr Glu Val Met Ile Gly Leu Ala Glu Leu Ala Arg Phe Leu Gly Ser275 280 285Arg Pro Asp Asp Asp Arg Leu Ser Arg Gly Gly Asp Glu Glu Phe Val290 295 300Gly Tyr Ser Ser Tyr Ile Gln Asp Lys Gln Gly Ile Leu Ser Tyr Glu305 310 315 320Asp Ala Arg Met Arg Asp Tyr Arg Ile Gln Thr Ser Glu Arg Leu Arg325 330 335Arg Thr Gln His Thr Val Gly Phe Ala Ser Lys Phe Leu Leu Gly Leu340 345 350Gly Thr Cys Leu Leu Val Ser Ala Leu Val Leu Ser Leu Val Gly Val355 360 365Phe Leu Pro Gly Arg Ile Gly Trp Gln Ser Pro Ala Val Leu Gly Ala370 375 380Leu Gly Val Gly Gln Ile Val Thr Leu Phe Phe Thr Arg Pro Val Arg385 390 395 400Ser Val Gln Asp Ala Leu Ala Glu Glu Thr Ile Tyr Arg Met Ile Leu405 410 415Glu Ser Arg Ser Leu Lys Val Ala Leu Ala Arg Phe His Ile Thr Thr420 425 430Ala Thr Ala Leu Arg Arg His Asp Asp Val Asn Gly Gln Ser Asp Ala435 440 445Leu Ala Arg Gln Leu Glu Ile Leu Glu Lys Ile Asp Thr Ala Asp Phe450 455 460Glu Arg Leu Lys Gln Leu Gly Val Thr Pro Arg Ala Glu Ser Ser Gly465 470 475 480Thr Gly Arg Pro Arg Arg Arg Ile Arg Ser Gln Val Ser485 490<210>45<211>1521<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(1521)<223><220><221>misc_feature<222>(48,431)<223>r=a或g<400>45atg tca aca cca cct atc gcc ggt gac gac cag acg ccg cgc cgg ctr 48Met Ser Thr Pro Pro Ile Ala Gly Asp Asp Gln Thr Pro Arg Arg Xaa1 5 10 15agg ctg cgc cgc cgc agg gcc gac gcc gac cgc ggg cgc cgg ggc ggg 96Arg Leu Arg Arg Arg Arg Ala Asp Ala Asp Arg Gly Arg Arg Gly Gly20 25 30cgg gca tcc gca cgg cgg ttc ccc gat ggc gcc ctg ccg cag ccc gag 144Arg Ala Ser Ala Arg Arg Phe Pro Asp Gly Ala Leu Pro Gln Pro Glu35 40 45ccc gtc gcg tcg gat gtc atc cgg gcc ggt gac agc acc tgg ctc cgg 192Pro Val Ala Ser Asp Val Ile Arg Ala Gly Asp Ser Thr Trp Leu Arg50 55 60gac cgg gcg cgc aag cac ggc gcg tcg gcg gcc acc cgg aag gtc ttc 240Asp Arg Ala Arg Lys His Gly Ala Ser Ala Ala Thr Arg Lys Val Phe65 70 75 80gac ccc tgg gtc ctg gcc ggc ccg gac cgg gtg ccc tac ttc gcc gaa 288Asp Pro Trp Val Leu Ala Gly Pro Asp Arg Val Pro Tyr Phe Ala Glu85 90 95ctg gcc agt ctg cgc aac cgg gtc aag cac cgg ctc gcc gag gag cat 336Leu Ala Ser Leu Arg Asn Arg Val Lys His Arg Leu Ala Glu Glu His100 105 110gcg cga gcc gag gag gac ggc gcg ctg gag gcg agc cgg gtc agg gcg 384Ala Arg Ala Glu Glu Asp Gly Ala Leu Glu Ala Ser Arg Val Arg Ala115 120 125gcc gcc acc gcg gcc gga gag cgg ctg gag cgg gcc ggg cag cgg crg 432Ala Ala Thr Ala Ala Gly Glu Arg Leu Glu Arg Ala Gly Gln Arg Xaa130 135 140gtc gtc ctg gag cgg cag cag acg gtc acc acc gcc cag ctg gac cgg 480Val Val Leu Glu Arg Gln Gln Thr Val Thr Thr Ala Gln Leu Asp Arg145 150 155 160ctg gcg cgg cgg gcc gac cgg tgg cag acc ttc cgc gac acc gtg cgg 528Leu Ala Arg Arg Ala Asp Arg Trp Gln Thr Phe Arg Asp Thr Val Arg165 170 175ggc ggt ttc gag cgc cgg tgg ctg cgc gcc cgt atg cct gcc gac ggc 576Gly Gly Phe Glu Arg Arg Trp Leu Arg Ala Arg Met Pro Ala Asp Gly180 185 190agc gac ggg acc gac ccc gga cgg cag ggc gcc acc cgg cgc gag gac 624Ser Asp Gly Thr Asp Pro Gly Arg Gln Gly Ala Thr Arg Arg Glu Asp195 200 205gag ccg gag acc acc ggc cac gcc agc tgg cag gcg gtg tcc gaa ccc 672Glu Pro Glu Thr Thr Gly His Ala Ser Trp Gln Ala Val Ser Glu Pro210 215 220gat ccg gtg gcg gag gcg gac gcg gcc gac cgc gcc ctg tcc acc agg 720Asp Pro Val Ala Glu Ala Asp Ala Ala Asp Arg Ala Leu Ser Thr Arg225 230 235 240gcg gcg tgg gag ggc gcg gcg gcg cgc ccc ggg atg ccg cgc tgg atg 768Ala Ala Trp Glu Gly Ala Ala Ala Arg Pro Gly Met Pro Arg Trp Met245 250 255aag ctc ggt gtg ctg gcc gcg ttg gtc gtg gtg gaa ctg ccc gtc tac 816Lys Leu Gly Val Leu Ala Ala Leu Val Val Val Glu Leu Pro Val Tyr260 265 270tac tcg gtg ttc gag aat ctg cac ggt gtc ggg cgc ttc gcc gat ctg 864Tyr Ser Val Phe Glu Asn Leu His Gly Val Gly Arg Phe Ala Asp Leu275 280 285ctc tcc tac agc ctc atg gtg gcc gtg gcg gtg gcg atg atc ctc gcc 912Leu Ser Tyr Ser Leu Met Val Ala Val Ala Val Ala Met Ile Leu Ala290 295 300ccg cat atc gcg ggc tgg ata ctg cgg cgg cgc tcc gcc acc ggt gcg 960Pro His Ile Ala Gly Trp Ile Leu Arg Arg Arg Ser Ala Thr Gly Ala305 310 315 320gtc cgg ctg tcg gcc gtg ccc gcc ctc gcc ctg ctg ggc gtg tgg gcg 1008Val Arg Leu Ser Ala Val Pro Ala Leu Ala Leu Leu Gly Val Trp Ala325 330 335tac ggc gcc tgg gcg ctg ggg gat ctg cgg gcc aag gtg gcg ttc cgg 1056Tyr Gly Ala Trp Ala Leu Gly Asp Leu Arg Ala Lys Val Ala Phe Arg340 345 350gag gag cct ccg ctg gat ctg ccg ccc gat gtg gcc gcg gac gtg ggc 1104Glu Glu Pro Pro Leu Asp Leu Pro Pro Asp Val Ala Ala Asp Val Gly355 360 365gac agc gtg cgc aac ccg ccg agc ctc ctg gag tcc ctg cat ctg gac 1152Asp Ser Val Arg Asn Pro Pro Ser Leu Leu Glu Ser Leu His Leu Asp370 375 380gcg cag agc gtg acc tgg atg ttc gtc gcg ctg ctg ctg ctc tcc ggc 1200Ala Gln Ser Val Thr Trp Met Phe Val Ala Leu Leu Leu Leu Ser Gly385 390 395 400ggg atc gcc ttc ctg atc ggg ctg ggc gag gag cat ccg tat ctc gcg 1248Gly Ile Ala Phe Leu Ile Gly Leu Gly Glu Glu His Pro Tyr Leu Ala405 410 415gcg tac cgg acc acg gcc gag cgg ctg cgg gag ctg gag cgg gac atg 1296Ala Tyr Arg Thr Thr Ala Glu Arg Leu Arg Glu Leu Glu Arg Asp Met420 425 430gag acg gat ctc gcg ggt tcc gag cgt gcc aag gag gcc gag gcc acc 1344Glu Thr Asp Leu Ala Gly Ser Glu Arg Ala Lys Glu Ala Glu Ala Thr435 440 445ctg ggt gcc cgc gcg gag gcc cgc cgc gcg gcc cat gag gcg cgg ctc 1392Leu Gly Ala Arg Ala Glu Ala Arg Arg Ala Ala His Glu Ala Arg Leu450 455 460tac gcg gtc gac gat ctc tac gaa gcc gcg gcc cac gcc tat ctg gac 1440Tyr Ala Val Asp Asp Leu Tyr Glu Ala Ala Ala His Ala Tyr Leu Asp465 470 475 480ggg gtg gcc atg gag tcc agc gat ccg gcg gtc acg gag gcc gcc atg 1488Gly Val Ala Met Glu Ser Ser Asp Pro Ala Val Thr Glu Ala Ala Met485490 495cgg ctg tcc aag cag tgg ccg ctg ctg ccg cgc 1521Arg Leu Ser Lys Gln Trp Pro Leu Leu Pro Arg500 505<210>46<211>507<212>PRT<213>Streptomyces hygroscopicus<220><221>misc_feature<222>(16)<223>Xaa=Leu.<220><221>misc_feature<222>(144)<223>Xaa=Arg或Gln.<400>46Met Ser Thr Pro Pro Ile Ala Gly Asp Asp Gln Thr Pro Arg Arg Xaa1 5 10 15Arg Leu Arg Arg Arg Arg Ala Asp Ala Asp Arg Gly Arg Arg Gly Gly20 25 30Arg Ala Ser Ala Arg Arg Phe Pro Asp Gly Ala Leu Pro Gln Pro Glu35 40 45Pro Val Ala Ser Asp Val Ile Arg Ala Gly Asp Ser Thr Trp Leu Arg50 55 60Asp Arg Ala Arg Lys His Gly Ala Ser Ala Ala Thr Arg Lys Val Phe65 70 75 80Asp Pro Trp Val Leu Ala Gly Pro Asp Arg Val Pro Tyr Phe Ala Glu85 90 95Leu Ala Ser Leu Arg Asn Arg Val Lys His Arg Leu Ala Glu Glu His100 105 110Ala Arg Ala Glu Glu Asp Gly Ala Leu Glu Ala Ser Arg Val Arg Ala115 120 125Ala Ala Thr Ala Ala Gly Glu Arg Leu Glu Arg Ala Gly Gln Arg Xaa130 135 140Val Val Leu Glu Arg Gln Gln Thr Val Thr Thr Ala Gln Leu Asp Arg145 150 155 160Leu Ala Arg Arg Ala Asp Arg Trp Gln Thr Phe Arg Asp Thr Val Arg165 170 175Gly Gly Phe Glu Arg Arg Trp Leu Arg Ala Arg Met Pro Ala Asp Gly180 185 190Ser Asp Gly Thr Asp Pro Gly Arg Gln Gly Ala Thr Arg Arg Glu Asp195 200 205Glu Pro Glu Thr Thr Gly His Ala Ser Trp Gln Ala Val Ser Glu Pro210 215 220Asp Pro Val Ala Glu Ala Asp Ala Ala Asp Arg Ala Leu Ser Thr Arg225 230 235 240Ala Ala Trp Glu Gly Ala Ala Ala Arg Pro Gly Met Pro Arg Trp Met245 250 255Lys Leu Gly Val Leu Ala Ala Leu Val Val Val Glu Leu Pro Val Tyr260 265 270Tyr Ser Val Phe Glu Asn Leu His Gly Val Gly Arg Phe Ala Asp Leu275 280 285Leu Ser Tyr Ser Leu Met Val Ala Val Ala Val Ala Met Ile Leu Ala290 295 300Pro His Ile Ala Gly Trp Ile Leu Arg Arg Arg Ser Ala Thr Gly Ala305 310 315 320Val Arg Leu Ser Ala Val Pro Ala Leu Ala Leu Leu Gly Val Trp Ala325 330 335Tyr Gly Ala Trp Ala Leu Gly Asp Leu Arg Ala Lys Val Ala Phe Arg340345 350Glu Glu Pro Pro Leu Asp Leu Pro Pro Asp Val Ala Ala Asp Val Gly355 360 365Asp Ser Val Arg Asn Pro Pro Ser Leu Leu Glu Ser Leu His Leu Asp370 375 380Ala Gln Ser Val Thr Trp Met Phe Val Ala Leu Leu Leu Leu Ser Gly385 390 395 400Gly Ile Ala Phe Leu Ile Gly Leu Gly Glu Glu His Pro Tyr Leu Ala405 410 415Ala Tyr Arg Thr Thr Ala Glu Arg Leu Arg Glu Leu Glu Arg Asp Met420 425 430Glu Thr Asp Leu Ala Gly Ser Glu Arg Ala Lys Glu Ala Glu Ala Thr435 440 445Leu Gly Ala Arg Ala Glu Ala Arg Arg Ala Ala His Glu Ala Arg Leu450 455 460Tyr Ala Val Asp Asp Leu Tyr Glu Ala Ala Ala His Ala Tyr Leu Asp465 470 475 480Gly Val Ala Met Glu Ser Ser Asp Pro Ala Val Thr Glu Ala Ala Met485 490 495Arg Leu Ser Lys Gln Trp Pro Leu Leu Pro Arg500 505<210>47<211>1791<212>DNA<213>Streptomyces hygroscopicus<220><221>misc_feature<222>(671,1039,1088)<223>s=c或g<220><221>misc_feature<222>(771,774)<223>n=a或t或c或g<220><221>misc_feature<222>(775,778,781,794)<223>m=a或c<220><221>misc_feature<222>(977,1029,1105)<223>k=g或t<220><221>misc_feature<222>(983,1016,1034,1709)<223>r=a或g<400>47atg atc aaa gac gcc agg ccc ccg gaa ccg ttc cag tat gac ccg gcg 48Met Ile Lys Asp Ala Arg Pro Pro Glu Pro Phe Gln Tyr Asp Pro Ala1 5 10 15tca ggc atc tac gag ggc gtt ctc cgg ttg act tcc ggg cgt ttt cag 96Ser Gly Ile Tyr Glu Gly Val Leu Arg Leu Thr Ser Gly Arg Phe Gln20 25 30gag cgg gcc cta tgg gga gca ttc ccg ggt acc acc tca ccg ata cgg 144Glu Arg Ala Leu Trp Gly Ala Phe Pro Gly Thr Thr Ser Pro Ile Arg35 40 45tct gac aga gaa tcc aat cga cat cca cat cgg cat cga caa cgg cat 192Ser Asp Arg Glu Ser Asn Arg His Pro His Arg His Arg Gln Arg His50 55 60cca cat cgg cgt cgg cta cat cgg ccg cga acc ctt tgc ggg aga aag 240Pro His Arg Arg Arg Leu His Arg Pro Arg Thr Leu Cys Gly Arg Lys65 70 75 80cgg aat acc act gtc cgc aat gcg gct gtc cgg tgc ggg aat ttc cgt 288Arg Asn Thr Thr Val Arg Asn Ala Ala Val Arg Cys Gly Asn Phe Arg85 90 95acc ggg gaa atc ggg gga tcc att tcc atg atc aca tct gac agt gtc 336Thr Gly Glu Ile Gly Gly Ser Ile Ser Met Ile Thr Ser Asp Ser Val100 105 110aac ggg gtg gtg cgc cgc ggc agg ctc ggc cgt acc gcc cgc ttc gcg 384Asn Gly Val Val Arg Arg Gly Arg Leu Gly Arg Thr Ala Arg Phe Ala115 120 125gcc cgc tgg cgg ggc aag cgc gac ggc gcg cgc ggc gtc ccc cgc atc 432Ala Arg Trp Arg Gly Lys Arg Asp Gly Ala Arg Gly Val Pro Arg Ile130 135 140gtg ctc ccg gag ccg tcc ggg gag cag cgg agc aag acg ccg ccg ccc 480Val Leu Pro Glu Pro Ser Gly Glu Gln Arg Ser Lys Thr Pro Pro Pro145 150 155 160atc gag cca ccc gct ccc gaa ctg ctg atc acc cct tac gtg atg gag 528Ile Glu Pro Pro Ala Pro Glu Leu Leu Ile Thr Pro Tyr Val Met Glu165 170 175gtg cgg acc ggc gtc cgc cga acc acc gag cag atg cgc tcc gcc ctc 576Val Arg Thr Gly Val Arg Arg Thr Thr Glu Gln Met Arg Ser Ala Leu180 185 190atc ggg cgg gag cac gcc ctg ctc agc agg ttg cgc gcc gag tcg gtg 624Ile Gly Arg Glu His Ala Leu Leu Ser Arg Leu Arg Ala Glu Ser Val195 200 205cgc gtg gtc acc cag tac gac gtc cgc gag gac ccc cgg ccc gcg gsg 672Arg Val Val Thr Gln Tyr Asp Val Arg Glu Asp Pro Arg Pro Ala Xaa
210 215 220ctc gcg cgc tac ggc cac tgg gtg ggt cag tgg cgc acc agc gtg gac 720Leu Ala Arg Tyr Gly His Trp Val Gly Gln Trp Arg Thr Ser Val Asp225 230 235 240cgg tgc cga tcg cat gcc cat gcc gtg gtg gac cag gcc aat cag cga 768Arg Cys Arg Ser His Ala His Ala Val Val Asp Gln Ala Asn Gln Arg245 250 255ctn ssn mtg mta mtg gga cgc ggt gmg cga gac cca ccc cca gct ctc 816Xaa Xaa Xaa Xaa Xaa Gly Arg Gly Xaa Arg Asp Pro Pro Pro Ala Leu260 265 270ccg cct ccc ccg gcg ccc gcc cgg gga ctg gct gcc cgg ccg ggt gga 864Pro Pro Pro Pro Ala Pro Ala Arg Gly Leu Ala Ala Arg Pro Gly Gly275 280 285gct gga ccg gtc ctg gta cca gcc cga cgt ctg gct gct ggc cga cga 912Ala Gly Pro Val Leu Val Pro Ala Arg Arg Leu Ala Ala Gly Arg Arg290 295 300cga cag cac gcg gac ggc cac ctc ccg ggc gct gca cat act cga acg 960Arg Gln His Ala Asp Gly His Leu Pro Gly Ala Ala His Thr Arg Thr305 310 315 320gca gaa cac cga ccg ckt cga crg gag gac cgc gtg atg acc gtc cac 1008Ala Glu His Arg Pro Xaa Arg Xaa Glu Asp Arg Val Met Thr Val His325 330 335act ccc gyt ccg gag cgc cck gcc gyc cgg sgg cac gga aac cgg cgg 1056Thr Pro Xaa Pro Glu Arg Xaa Ala Xaa Arg Xaa His Gly Asn Arg Arg340 345 350cac gga aac cgg cgg cgc gcg ctg ccc gcc gsg ctg gtg ctc gct ctc 1104His Gly Asn Arg Arg Arg Ala Leu Pro Ala Xaa Leu Val Leu Ala Leu355 360 365kcg gcg gcc gcc acg gcc tgc ggc tcc gac gag ccg tca cgc tac tcg 1152Xaa Ala Ala Ala Thr Ala Cys Gly Ser Asp Glu Pro Ser Arg Tyr Ser370 375 380cag aca tgt ggt gtc gtg gtc gac ggc tcc ggc tcg gcc gac gcc tcc 1200Gln Thr Cys Gly Val Val Val Asp Gly Ser Gly Ser Ala Asp Ala Ser385 390 395 400cgg acc ggc ttc gac gcg gag gcc aag ctc aag gcc acc ctc cag acg 1248Arg Thr Gly Phe Asp Ala Glu Ala Lys Leu Lys Ala Thr Leu Gln Thr405 410 415ttc ctg tcg gac aag aag tgc cgc aag acg tcc ttc gcc ccc ata acc 1296Phe Leu Ser Asp Lys Lys Cys Arg Lys Thr Ser Phe Ala Pro Ile Thr420 425 430aag gtt tcc gag gcg tcg aag tgc cag gtc agc ccg ctc gac ctg gac 1344Lys Val Ser Glu Ala Ser Lys Cys Gln Val Ser Pro Leu Asp Leu Asp435 440 445ccg gac acc tcg aag acc gcc gac cgc gag cgg acc cgc acc gcc atg 1392Pro Asp Thr Ser Lys Thr Ala Asp Arg Glu Arg Thr Arg Thr Ala Met450 455 460cgt gcc gtc gcc ctc tcc aac gcc ctg aag ctg ctg cgc tgc gcc cag 1440Arg Ala Val Ala Leu Ser Asn Ala Leu Lys Leu Leu Arg Cys Ala Gln465 470 475 480aag gag gag ccc ggc tcc gat gtg ctc ggc ggg ctg tcg cgc atc gcg 1488Lys Glu Glu Pro Gly Ser Asp Val Leu Gly Gly Leu Ser Arg Ile Ala485 490 495ctg tcc aag ccg agc ggt gac gac gcg tcg ttc gac gtc ctg gtg gtc 1536Leu Ser Lys Pro Ser Gly Asp Asp Ala Ser Phe Asp Val Leu Val Val500 505 510agc gac ttc gac cag ggc gac acc gac ttc cgg ctc ggg cgg cag gac 1584Ser Asp Phe Asp Gln Gly Asp Thr Asp Phe Arg Leu Gly Arg Gln Asp515 520 525ctg tcc acc gcc acc agc cgc cgg acc gtc atc gac gac ttc ctc aag 1632Leu Ser Thr Ala Thr Ser Arg Arg Thr Val Ile Asp Asp Phe Leu Lys530 535 540tcg cac ggc aaa ccg aag ctg tcc ggc gcc gat gtc tac ccg gtg ggc 1680Ser His Gly Lys Pro Lys Leu Ser Gly Ala Asp Val Tyr Pro Val Gly545 550 555 560tac ggc atg aag tac cac acc gac acc tyc cgg tac gag cag ttc aac 1728Tyr Gly Met Lys Tyr His Thr Asp Thr Xaa Arg Tyr Glu Gln Phe Asn565 570 575gcc ttc tgg acg gag ctt ctg gag ggg agg gtc aag gca cat gtc aac 1776Ala Phe Trp Thr Glu Leu Leu Glu Gly Arg Val Lys Ala His Val Asn580 585 590acc acc tat cgc cgg 1791Thr Thr Tyr Arg Arg595<210>48<211>597<212>PRT<213>Streptomyces hygroscopicus<220><221>misc_feature<222>(224)<223>Xaa=Gly或Ala.<220><221>misc_feature<222>(257)<223>Xaa=Leu.<220><221> misc_feature<222>(258)<223>Xaa=Gly或Ala或Arg或Pro.<220><221>misc_feature<222>(259)<223>Xaa=Met或Leu.<220><221>misc_feature<222>(260)<223>Xaa=Ile或Leu.<220><221>misc_feature<222>(261)<223>Xaa=Met或Leu.<220><221>misc_feature<222>(265)<223>Xaa=Glu或Ala.<220><221>misc feature<222>(326)<223>Xaa=Arg或Leu.<220><221>misc_feature<222>(328)<223>Xaa=Arg或Gln.<220><221>misc_feature<222>(339)<223>Xaa=Ala或Val.<220><221>misc_feature<222>(343)<223>Xaa=Pro.<220><221>misc_feature<222>(345)<223>Xaa=Ala或Val.<220><221>misc_feature<222>(347)<223>Xaa=Gly或Arg.<220><221>misc_feature<222>(363)<223>Xaa=Gly或Ala.<220><221>misc_feature<222>(369)<223>Xaa=Ala或Ser.<220><221>misc_feature<222>(570)<223>Xaa=Ser或Phe.<400>48Met Ile Lys Asp Ala Arg Pro Pro Glu Pro Phe Gln Tyr Asp Pro Ala1 5 10 15Ser Gly Ile Tyr Glu Gly Val Leu Arg Leu Thr Ser Gly Arg Phe Gln20 25 30Glu Arg Ala Leu Trp Gly Ala Phe Pro Gly Thr Thr Ser Pro Ile Arg35 40 45Ser Asp Arg Glu Ser Asn Arg His Pro His Arg His Arg Gln Arg His50 55 60Pro His Arg Arg Arg Leu His Arg Pro Arg Thr Leu Cys Gly Arg Lys65 70 75 80Arg Asn Thr Thr Val Arg Asn Ala Ala Val Arg Cys Gly Asn Phe Arg85 90 95Thr Gly Glu Ile Gly Gly Ser Ile Ser Met Ile Thr Ser Asp Ser Val100 105 110Asn Gly Val Val Arg Arg Gly Arg Leu Gly Arg Thr Ala Arg Phe Ala115 120 125Ala Arg Trp Arg Gly Lys Arg Asp Gly Ala Arg Gly Val Pro Arg Ile130 135 140Val Leu Pro Glu Pro Ser Gly Glu Gln Arg Ser Lys Thr Pro Pro Pro145 150 155 160Ile Glu Pro Pro Ala Pro Glu Leu Leu Ile Thr Pro Tyr Val Met Glu165 170 175Val Arg Thr Gly Val Arg Arg Thr Thr Glu Gln Met Arg Ser Ala Leu180 185 190Ile Gly Arg Glu His Ala Leu Leu Ser Arg Leu Arg Ala Glu Ser Val195 200 205Arg Val Val Thr Gln Tyr Asp Val Arg Glu Asp Pro Arg Pro Ala Xaa210 215 220Leu Ala Arg Tyr Gly His Trp Val Gly Gln Trp Arg Thr Ser Val Asp225 230 235 240Arg Cys Arg Ser His Ala His Ala Val Val Asp Gln Ala Asn Gln Arg245 250 255Xaa Xaa Xaa Xaa Xaa Gly Arg Gly Xaa Arg Asp Pro Pro Pro Ala Leu260 265 270Pro Pro Pro Pro Ala Pro Ala Arg Gly Leu Ala Ala Arg Pro Gly Gly275 280 285Ala Gly Pro Val Leu Val Pro Ala Arg Arg Leu Ala Ala Gly Arg Arg290295 300Arg Gln His Ala Asp Gly His Leu Pro Gly Ala Ala His Thr Arg Thr305 310 315 320Ala Glu His Arg Pro Xaa Arg Xaa Glu Asp Arg Val Met Thr Val His325 330 335Thr Pro Xaa Pro Glu Arg Xaa Ala Xaa Arg Xaa His Gly Asn Arg Arg340 345 350His Gly Asn Arg Arg Arg Ala Leu Pro Ala Xaa Leu Val Leu Ala Leu355 360 365Xaa Ala Ala Ala Thr Ala Cys Gly Ser Asp Glu Pro Ser Arg Tyr Ser370 375 380Gln Thr Cys Gly Val Val Val Asp Gly Ser Gly Ser Ala Asp Ala Ser385 390 395 400Arg Thr Gly Phe Asp Ala Glu Ala Lys Leu Lys Ala Thr Leu Gln Thr405 410 415Phe Leu Ser Asp Lys Lys Cys Arg Lys Thr Ser Phe Ala Pro Ile Thr420 425 430Lys Val Ser Glu Ala Ser Lys Cys Gln Val Ser Pro Leu Asp Leu Asp435 440 445Pro Asp Thr Ser Lys Thr Ala Asp Arg Glu Arg Thr Arg Thr Ala Met450 455 460Arg Ala Val Ala Leu Ser Asn Ala Leu Lys Leu Leu Arg Cys Ala Gln465 470 475 480Lys Glu Glu Pro Gly Ser Asp Val Leu Gly Gly Leu Ser Arg Ile Ala485 490 495Leu Ser Lys Pro Ser Gly Asp Asp Ala Ser Phe Asp Val Leu Val Val500 505 510Ser Asp Phe Asp Gln Gly Asp Thr Asp Phe Arg Leu Gly Arg Gln Asp515 520 525Leu Ser Thr Ala Thr Ser Arg Arg Thr Val Ile Asp Asp Phe Leu Lys530 535 540Ser His Gly Lys Pro Lys Leu Ser Gly Ala Asp Val Tyr Pro Val Gly545 550 555 560Tyr Gly Met Lys Tyr His Thr Asp Thr Xaa Arg Tyr Glu Gln Phe Asn565 570 575Ala Phe Trp Thr Glu Leu Leu Glu Gly Arg Val Lys Ala His Val Asn580 585 590Thr Thr Tyr Arg Arg595<210>49<211>705<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(705)<223><220><221>misc_feature<222>(556,561)<223>r=a或g<220><221>misc-feature<222>(557)..(558)<223>m=a或c<220><221>misc_feature<222>(590)<223>w=a或t<400>49gtg gag aac gtc cca gag cgc gca gag ccc acg ctc cgg atc agt cag 48Val Glu Asn Val Pro Glu Arg Ala Glu Pro Thr Leu Arg Ile Ser Gln1 5 10 15aca cac ttc ccg gtg gag acc ctg ggt ccc ggg cgg cgc ctg gcc gtc 96Thr His Phe Pro Val Glu Thr Leu Gly Pro Gly Arg Arg Leu Ala Val20 25 30tgg tcg cag ggg tgc gga ctg gcc tgc gcc ggc tgt atg tcc cgg cac 144Trp Ser Gln Gly Cys Gly Leu Ala Cys Ala Gly Cys Met Ser Arg His35 40 45acc tgg gat ccg cga ggc ggc gcc tct cgt acg gtg tcg tcc ctg ctc 192Thr Trp Asp Pro Arg Gly Gly Ala Ser Arg Thr Val Ser Ser Leu Leu50 55 60ggg ctg tgg cgc gag gcg ttg gcg cgc ggc gcg gac ggg ctg acg atc 240Gly Leu Trp Arg Glu Ala Leu Ala Arg Gly Ala Asp Gly Leu Thr Ile65 70 75 80agc ggc ggg gag ccg ctc gac cag ccc gcc gct ctg gag gcc ctg ctg 288Ser Gly Gly Glu Pro Leu Asp Gln Pro Ala Ala Leu Glu Ala Leu Leu85 90 95gcc ggg gcg gtg cgg gcc cgt gcg gag gcg gtg gca tcg ggc ggc ccg 336Ala Gly Ala Val Arg Ala Arg Ala Glu Ala Val Ala Ser Gly Gly Pro100 105 110gcg gcg ggc cgt gag atc gac atc ctc ctc tac acg ggg tac gag gag 384Ala Ala Gly Arg Glu Ile Asp Ile Leu Leu Tyr Thr Gly Tyr Glu Glu115 120 125gac gaa gtg gag cgt gac gcg gcg cgc tcc gcc gcc gtc cgc cac gcc 432Asp Glu Val Glu Arg Asp Ala Ala Arg Ser Ala Ala Val Arg His Ala130 135 140gat gcg ctg gtg acc gga cgc ttc cgg gtg gcc gag ccc acc gcg ctg 480Asp Ala Leu Val Thr Gly Arg Phe Arg Val Ala Glu Pro Thr Ala Leu145 150 155 160gtg tgg cgc ggc tcg gcg aac cag cgc ata cgg ccg cgt acg gcg cgc 528Val Trp Arg Gly Ser Ala Asn Gln Arg Ile Arg Pro Arg Thr Ala Arg165 170 175ggg tgg gcg cgc tac cag gag cat ctg rmm cgr acg gag agc ggg ccg 576Gly Trp Ala Arg Tyr Gln Glu His Leu Xaa Arg Thr Glu Ser Gly Pro180 185 190cgt cta cag gtg gwc gag ggg gag ggc gat gtg cgg ctc tac gga gtg 624Arg Leu Gln Val Xaa Glu Gly Glu Gly Asp Val Arg Leu Tyr Gly Val195 200 205ccg cgg cgc ggc gaa ctg gtc gag ctg gag cgt cgg ttg cgg cgg gcg 672Pro Arg Arg Gly Glu Leu Val Glu Leu Glu Arg Arg Leu Arg Arg Ala210 215220ggg atc gcc ctc acc ggt gcg agc tgg cgc ccc 705Gly Ile Ala Leu Thr Gly Ala Ser Trp Arg Pro225 230 235<210>50<211>235<212>PRT<213>Streptomyces hygroscopicus<220><221>misc_feature<222>(186)<223>Xaa=Glu或Asp或Ala或Lys或Asn或Thr.<220><221>misc_feature<222>(197)<223>Xaa=Asp或Val.<400>50Val Glu Asn Val Pro Glu Arg Ala Glu Pro Thr Leu Arg Ile Ser Gln1 5 10 15Thr His Phe Pro Val Glu Thr Leu Gly Pro Gly Arg Arg Leu Ala Val20 25 30Trp Ser Gln Gly Cys Gly Leu Ala Cys Ala Gly Cys Met Ser Arg His35 40 45Thr Trp Asp Pro Arg Gly Gly Ala Ser Arg Thr Val Ser Ser Leu Leu50 55 60Gly Leu Trp Arg Glu Ala Leu Ala Arg Gly Ala Asp Gly Leu Thr Ile65 70 75 80Ser Gly Gly Glu Pro Leu Asp Gln Pro Ala Ala Leu Glu Ala Leu Leu
85 90 95Ala Gly Ala Val Arg Ala Arg Ala Glu Ala Val Ala Ser Gly Gly Pro100 105 110Ala Ala Gly Arg Glu Ile Asp Ile Leu Leu Tyr Thr Gly Tyr Glu Glu115 120 125Asp Glu Val Glu Arg Asp Ala Ala Arg Ser Ala Ala Val Arg His Ala130 135 140Asp Ala Leu Val Thr Gly Arg Phe Arg Val Ala Glu Pro Thr Ala Leu145 150 155 160Val Trp Arg Gly Ser Ala Asn Gln Arg Ile Arg Pro Arg Thr Ala Arg165 170 175Gly Trp Ala Arg Tyr Gln Glu His Leu Xaa Arg Thr Glu Ser Gly Pro180 185 190Arg Leu Gln Val Xaa Glu Gly Glu Gly Asp Val Arg Leu Tyr Gly Val195 200 205Pro Arg Arg Gly Glu Leu Val Glu Leu Glu Arg Arg Leu Arg Arg Ala210 215 220Gly Ile Ala Leu Thr Gly Ala Ser Trp Arg Pro225 230 235<210>51<211>1218<212>DNA<213>Streptomyces hygroscopicus<220><221>CDS<222>(1)..(1218)<223><220><221>misc_feature<222>(118)<223>n=a或g或t或c<220><221>misc_feature<222>(257)<223>y=c或t<220><221>misc_feature<222>(274)<223>s=c或g<400>51atg tgc ggc tct acg gag tgc cgc ggc gcg gcg aac tgg tcg agc tgg 48Met Cys Gly Ser Thr Glu Cys Arg Gly Ala Ala Asn Trp Ser Ser Trp1 5 10 15agc gtc ggt tgc ggc ggg cgg gga tcg ccc tca ccg gtg cga gct ggc 96Ser Val Gly Cys Gly Gly Arg Gly Ser Pro Ser Pro Val Arg Ala Gly20 25 30gcc cct gag cgg ggg cgc ccg nct cgg gtg gca ggg cgc gcc gcg acc 144Ala Pro Glu Arg Gly Arg Pro Xaa Arg Val Ala Gly Arg Ala Ala Thr35 40 45ccg gaa gcc gtg gcc tcg gcg gct gtg gtg ctt gcg gca gcg gac ctt 192Pro Glu Ala Val Ala Ser Ala Ala Val Val Leu Ala Ala Ala Asp Leu50 55 60gtg gcg gtg gcc ttg gcg gct gtg gtc cct atg gct ggg tgc tcg gcg 240Val Ala Val Ala Leu Ala Ala Val Val Pro Met Ala Gly Cys Ser Ala65 70 75 80gcg atg gcc tcg gcg gyt gtg gtc ctt gcg gca sgg gcc gtt gtg gca 288Ala Met Ala Ser Ala Xaa Val Val Leu Ala Ala Xaa Ala Val Val Ala85 90 95gag cgc cct gtg gcg gtg gtc tcg gcg gct gcg atc ctc tac gcc gga 336Glu Arg Pro Val Ala Val Val Ser Ala Ala Ala Ile Leu Tyr Ala Gly100 105 110cgc atc gtg gcc ggc atc acc ggc gcc aca ggt gcg gtt gct ggc gcc 384Arg Ile Val Ala Gly Ile Thr Gly Ala Thr Gly Ala Val Ala Gly Ala115 120 125tat atc gcc gac atc acc gat ggg gaa gat cgg gct cgc cac ttc ggg 432Tyr Ile Ala Asp Ile Thr Asp Gly Glu Asp Arg Ala Arg His Phe Gly130 135 140ctc atg agc gct tgt ttc ggc gtg ggt atg gtg gca ggc ccc gtg gcc 480Leu Met Ser Ala Cys Phe Gly Val Gly Met Val Ala Gly Pro Val Ala145 150 155 160ggg gga ctg ttg ggc gcc atc tcc ttg cat gca cca ttc ctt gcg gcg 528Gly Gly Leu Leu Gly Ala Ile Ser Leu His Ala Pro Phe Leu Ala Ala165 170 175gcg gtg ctc aac ggc ctc aac cta cta ctg ggc tgc ttc cta atg cag 576Ala Val Leu Asn Gly Leu Asn Leu Leu Leu Gly Cys Phe Leu Met Gln180 185 190gag tcg cat aag gga gag cgt cga ccg atg ccc ttg aga gcc ttc aac 624Glu Ser His Lys Gly Glu Arg Arg Pro Met Pro Leu Arg Ala Phe Asn195 200 205cca gtc agc tcc ttc cgg tgg gcg cgg ggc atg act atc gtc gcc gca 672Pro Val Ser Ser Phe Arg Trp Ala Arg Gly Met Thr Ile Val Ala Ala210 215 220ctt atg act gtc ttc ttt atc atg caa ctc gta gga cag gtg ccg gca 720Leu Met Thr Val Phe Phe Ile Met Gln Leu Val Gly Gln Val Pro Ala225 230 235 240gcg ctc tgg gtc att ttc ggc gag gac cgc ttt cgc tgg agc gcg acg 768Ala Leu Trp Val Ile Phe Gly Glu Asp Arg Phe Arg Trp Ser Ala Thr245 250 255atg atc ggc ctg tcg ctt gcg gta ttc gga atc ttg cac gcc ctc gct 816Met Ile Gly Leu Ser Leu Ala Val Phe Gly Ile Leu His Ala Leu Ala260 265 270caa gcc ttc gtc act ggt ccc gcc acc aaa cgt ttc ggc gag aag cag 864Gln Ala Phe Val Thr Gly Pro Ala Thr Lys Arg Phe Gly Glu Lys Gln275 280 285gcc att atc gcc ggc atg gcg gcc gac gcg ctg ggc tac gtc ttg ctg 912Ala Ile Ile Ala Gly Met Ala Ala Asp Ala Leu Gly Tyr Val Leu Leu290 295 300gcg ttc gcg acg cga ggc tgg atg gcc ttc ccc att atg att ctt ctc 960Ala Phe Ala Thr Arg Gly Trp Met Ala Phe Pro Ile Met Ile Leu Leu305 310 315 320gct tcc ggc ggc atc ggg atg ccc gcg ttg cag gcc atg ctg tcc agg 1008Ala Ser Gly Gly Ile Gly Met Pro Ala Leu Gln Ala Met Leu Ser Arg325 330 335cag gta gat gac gac cat cag gga cag ctt caa gga tcg ctc gcg gct 1056Gln Val Asp Asp Asp His Gln Gly Gln Leu Gln Gly Ser Leu Ala Ala340 345 350ctt acc agc cta act tcg atc att gga ccg ctg atc gtc acg gcg att 1104Leu Thr Ser Leu Thr Ser Ile Ile Gly Pro Leu Ile Val Thr Ala Ile355 360 365tat gcc gcc tcg gcg agc aca tgg aac ggg ttg gca tgg att gta ggc 1152Tyr Ala Ala Ser Ala Ser Thr Trp Asn Gly Leu Ala Trp Ile Val Gly370 375 380gcc gcc cta tac ctt gtc tgc ctc ccc gcg ttg cgt cgc ggt gca tgg 1200Ala Ala Leu Tyr Leu Val Cys Leu Pro Ala Leu Arg Arg Gly Ala Trp385 390 395 400agc cgg gcc acc tcg acc 1218Ser Arg Ala Thr Ser Thr405<210>52<211>406<212>PRT<213>Streptomyces hygroscopicus<220><221>misc_feature<222>(40)<223>Xaa=Thr或Ala或Pro或Ser.<220><221>misc_feature<222>(86)<223>Xaa=Ala或Val.<220><221>misc_feature<222>(92)<223>Xaa=Gly或Arg.<400>52Met Cys Gly Ser Thr Glu Cys Arg Gly Ala Ala Asn Trp Ser Ser Trp1 5 10 15Ser Val Gly Cys Gly Gly Arg Gly Ser Pro Ser Pro Val Arg Ala Gly20 25 30Ala Pro Glu Arg Gly Arg Pro Xaa Arg Val Ala Gly Arg Ala Ala Thr35 40 45Pro Glu Ala Val Ala Ser Ala Ala Val Val Leu Ala Ala Ala Asp Leu50 55 60Val Ala Val Ala Leu Ala Ala Val Val Pro Met Ala Gly Cys Ser Ala65 70 75 80Ala Met Ala Ser Ala Xaa Val Val Leu Ala Ala Xaa Ala Val Val Ala85 90 95Glu Arg Pro Val Ala Val Val Ser Ala Ala Ala Ile Leu Tyr Ala Gly100 105 110Arg Ile Val Ala Gly Ile Thr Gly Ala Thr Gly Ala Val Ala Gly Ala115 120 125Tyr Ile Ala Asp Ile Thr Asp Gly Glu Asp Arg Ala Arg His Phe Gly130 135 140Leu Met Ser Ala Cys Phe Gly Val Gly Met Val Ala Gly Pro Val Ala145 150 155 160Gly Gly Leu Leu Gly Ala Ile Ser Leu His Ala Pro Phe Leu Ala Ala165 170 175Ala Val Leu Asn Gly Leu Asn Leu Leu Leu Gly Cys Phe Leu Met Gln180 185 190Glu Ser His Lys Gly Glu Arg Arg Pro Met Pro Leu Arg Ala Phe Asn195 200 205Pro Val Ser Ser Phe Arg Trp Ala Arg Gly Met Thr Ile Val Ala Ala210 215 220Leu Met Thr Val Phe Phe Ile Met Gln Leu Val Gly Gln Val Pro Ala225 230 235 240Ala Leu Trp Val Ile Phe Gly Glu Asp Arg Phe Arg Trp Ser Ala Thr245 250 255Met Ile Gly Leu Ser Leu Ala Val Phe Gly Ile Leu His Ala Leu Ala260 265 270Gln Ala Phe Val Thr Gly Pro Ala Thr Lys Arg Phe Gly Glu Lys Gln275280 285Ala Ile Ile Ala Gly Met Ala Ala Asp Ala Leu Gly Tyr Val Leu Leu290 295 300Ala Phe Ala Thr Arg Gly Trp Met Ala Phe Pro Ile Met Ile Leu Leu305 310 315 320Ala Ser Gly Gly Ile Gly Met Pro Ala Leu Gln Ala Met Leu Ser Arg
325 330 335Gln Val Asp Asp Asp His Gln Gly Gln Leu Gln Gly Ser Leu Ala Ala340 345 350Leu Thr Ser Leu Thr Ser Ile Ile Gly Pro Leu Ile Val Thr Ala Ile355 360 365Tyr Ala Ala Ser Ala Ser Thr Trp Asn Gly Leu Ala Trp Ile Val Gly370 375 380Ala Ala Leu Tyr Leu Val Cys Leu Pro Ala Leu Arg Arg Gly Ala Trp385 390 395 400Ser Arg Ala Thr Ser Thr40權(quán)利要求
1.吸水鏈霉菌17997生物合成格爾德霉素的基因簇,其特征是該基因簇全部負(fù)責(zé)格爾德霉素的生物合成,其組成包括1)gdnM,基因大小為819bp,編碼273個(gè)氨基酸;2)gdnQ,基因大小為1233bp,編碼411個(gè)氨基酸;3)gdnS,基因大小為630bp,編碼210個(gè)氨基酸;4)gdnP,基因大小為993bp,編碼331個(gè)氨基酸;5)gdnO,基因大小為1130bp,編碼377個(gè)氨基酸;6)gdnA,基因大小為1152bp,編碼384個(gè)氨基酸;7)gdnE,基因大小為444bp,編碼148個(gè)氨基酸;8)gdnK,基因大小為882bp,編碼294個(gè)氨基酸;9)gdnT,基因大小為774bp,編碼258個(gè)氨基酸;10)dnB,基因大小為2115bp,編碼705個(gè)氨基酸;11)gdnF,基因大小為1026bp,編碼342個(gè)氨基酸;12)gdnG,基因大小為1224bp,編碼408個(gè)氨基酸;13)gdnH,基因大小為1239bp,編碼413個(gè)氨基酸;14)orf1,基因大小為678bp,編碼226個(gè)氨基酸;15)orf2,基因大小為726bp,編碼242個(gè)氨基酸;16)orf3,基因大小為504bp,編碼168個(gè)氨基酸;17)orf4,基因大小為618bp,編碼206個(gè)氨基酸;18)orf5,基因大小為2721bp,編碼907個(gè)氨基酸;19)orf6,基因大小為969bp,編碼323個(gè)氨基酸;20)gdnC,基因大小為1659bp,編碼553個(gè)氨基酸;21)gdnD,基因大小為3339bp,編碼1113個(gè)氨基酸;22)gdn1,基因大小為1479bp,編碼493個(gè)氨基酸;23)gdn2,基因大小為1521bp,編碼507個(gè)氨基酸;24)gdn3,基因大小為1791bp,編碼597個(gè)氨基酸;25)gdn4,基因大小為705bp,編碼235個(gè)氨基酸;26)gdn5,基因大小為1218bp,編碼406個(gè)氨基酸。
2.格爾德霉素生物合成基因簇的克隆方法,其特征是利用AHBA生物合成基因保守序列設(shè)計(jì)引物上游引物 5’-AGAGGATCCTTCGAGCRSGAGTTCGC-3’BamH1下游引物 5’-GCAGGATCCGGAMCATSGCCATGTAG-3’以吸水鏈霉菌17997基因組DNA為模板,在LATaq酶作用下進(jìn)行PCR反應(yīng),獲得755bp產(chǎn)物,以此為探針,與17997基因文庫(kù)進(jìn)行菌落雜交和分子雜交,并對(duì)陽(yáng)性克隆進(jìn)行大規(guī)模DNA測(cè)序。
3.格爾德霉素生物合成基因簇序列在提高格爾德霉素發(fā)酵產(chǎn)量和優(yōu)化改造其結(jié)構(gòu)中的應(yīng)用。
全文摘要
本發(fā)明涉及從抗生素產(chǎn)生菌中克隆并獲得抗生素生物合成基因簇,具體是以安莎類(lèi)化合物生物合成基因保守序列(AHBA)基因克隆相關(guān)基因,以此為探針,克隆并獲得格爾德霉素生物合成基因簇,從而為提高格爾德霉素發(fā)酵產(chǎn)量和優(yōu)化改造其結(jié)構(gòu)奠定基礎(chǔ)。
文檔編號(hào)C12P19/34GK1388252SQ0212595
公開(kāi)日2003年1月1日 申請(qǐng)日期2002年8月6日 優(yōu)先權(quán)日2002年8月6日
發(fā)明者王以光, 高群杰 申請(qǐng)人:中國(guó)醫(yī)學(xué)科學(xué)院醫(yī)藥生物技術(shù)研究所