專利名稱：生物合成糖肽類抗生素a40926的基因及蛋白的制作方法
背景技術(shù)：
放線菌因其產(chǎn)生結(jié)構(gòu)多樣并且具有生物學(xué)活性的次生代謝物而廣為人知，這些次生代謝物中，許多用于商業(yè)用途(例如抗生素)。重要的代謝物不僅由鏈霉菌屬物種(Streptomyces spp.)(研究最為詳細(xì))產(chǎn)生，而且也由了解較少的放線菌屬產(chǎn)生例如，分別使用擬無枝酸菌屬(Amycolatopsis)、游動放線菌屬(Actinoplanes)和糖多孢菌屬(Saccharopolyspora)的物種工業(yè)化生產(chǎn)利福霉素、游壁菌素和紅霉素?？刂拼紊x物生物合成的遺傳因子組織在基因簇中，所述基因簇中含有代謝物合成、調(diào)節(jié)和抗性所需的所有基因。
許多不同的次生代謝物享有共同的生物合成路徑，相似的酶介入其中。聚酮化合物(Katz和McDaniel，1999)、非核糖體合成肽(Marahiel，1997)和脫氧糖(Rodriguez等人，2000)具有充分證明資料。然而，盡管具有這種相似性，但參與給定微生物中特定次生代謝物合成的基因簇的組織，并不能夠推測確定。事實(shí)上，非常相似的次生代謝物的合成可以由不同組織的簇控制，特別是當(dāng)相應(yīng)的生產(chǎn)性菌株不屬于相同屬的時(shí)候。這類實(shí)例可見于大環(huán)內(nèi)酯類抗生素中(Katz和McDaniel 1999)。另外，在放線菌內(nèi)，限定相同途徑酶的多重簇的出現(xiàn)，使生產(chǎn)性菌株內(nèi)所需的簇的鑒定變得復(fù)雜。這一點(diǎn)已顯示于聚酮化合物(例如Ruan等人，1997)和肽(例如Sosio等人，2000a)中，并通過基因組測序得到證實(shí)(Omura等人，2001；Bentley等人，2002)。因此，一個(gè)人不能與已知簇比較而推測得知新簇的組織、核苷酸序列、或者一致性程度。
糖肽，也因其作用機(jī)制而被稱為dalbaheptides(Parenti和Cavalleri，1989)，它與萬古霉素和游壁菌素是目前臨床使用中重要的抗生素種類，其干擾細(xì)菌細(xì)胞壁的交聯(lián)。它們往往是治療危及生命的感染最后的抗生素選擇。另一方面，腸道球菌中對糖肽抗性的出現(xiàn)、以及對該高水平抗性可能最終在二甲氧基苯青霉素抗性的金黃色葡萄球菌(Staphylococcus aureus)中廣泛傳播的恐懼促進(jìn)了對該類第二代藥物的搜索。隨著具有改善的活性、加廣的抗細(xì)菌譜或更優(yōu)的藥物代謝動力學(xué)的半合成衍生物的發(fā)展，已獲得了有希望的結(jié)果(Malabarba和Ciabatti2001)。
因此，存在經(jīng)處理天然存在的化合物而獲得改進(jìn)的糖肽的潛力和效用。然而，糖肽是結(jié)構(gòu)復(fù)雜的分子，它們的化學(xué)可及性限制在分子內(nèi)很少的位置。例如，盡管很容易從糖肽中將糖化學(xué)地去除而產(chǎn)生相應(yīng)的糖苷配基，不同的糖通過化學(xué)方法與特定位置的區(qū)域選擇性附著卻極為困難。已有顯示糖肽中的氯化程度影響抗生素活性。類似地，糖肽中芳環(huán)的化學(xué)脫氯易于實(shí)現(xiàn)，而結(jié)構(gòu)中所需環(huán)的選擇的鹵化則相對復(fù)雜。作為最后的實(shí)例，游壁菌素家族的糖肽含有連接到葡糖胺上的酰基鏈，所述葡糖胺在4位與芳基氨基酸附著，而萬古霉素類化合物不含有?；?。糖肽的?；兔擋；延谢瘜W(xué)或通過生物轉(zhuǎn)化的報(bào)導(dǎo)(Lancini和Cavalleri，1997)，但是通常全面導(dǎo)致低產(chǎn)量。根據(jù)上文，為了獲得難以或不可能通過化學(xué)方法制備的衍生物，有必要擁有可以在糖肽形成中用于改變這些步驟方向的基因和酶。由于已顯示氯化程度影響糖肽生物學(xué)活性，而且可以通過改變糖肽的糖基化或酰化模式獲得改進(jìn)的衍生物，這一點(diǎn)格外有意義(Malabarba和Ciabatti，2001)。主要的化學(xué)限制之一是改變肽主鏈中存在的氨基酸的類型或順序?；瘜W(xué)上，已顯示以相對低產(chǎn)量僅僅干預(yù)氨基酸1和3是可能的(Malabarba等人，1997)。因此非常需要使用精確設(shè)計(jì)的菌株直接通過發(fā)酵過程設(shè)計(jì)新的糖肽衍生物的通用方法。
具有吸引力的備選方法將通過設(shè)計(jì)天然存在的糖肽的生物合成過程而產(chǎn)生改進(jìn)的抗生素。這類實(shí)例已有報(bào)導(dǎo)。事實(shí)上，可以從萬古霉素和chloroeremomycin基因簇表達(dá)糖基轉(zhuǎn)移酶后，在體外和體內(nèi)選擇性糖基化糖肽糖苷配基(Solenberg等人，1997；Loosey等人，2001)。然而，迄今為止沒有一個(gè)得到說明的酶能夠在所需位置附著于葡糖胺殘基。類似地，balhimycin產(chǎn)生者地中海擬無枝酸菌(A.mediterranei)內(nèi)所選基因的失活導(dǎo)致balhimycin衍生物的獲得(Pelzer等人，1999)。然而，對于產(chǎn)生游壁菌素家族糖肽的菌株，沒有對這類實(shí)驗(yàn)進(jìn)行說明。
抗生素A40926屬于糖肽游壁菌素家族(Parenti和Cavalleri，1989)。它由密切相關(guān)分子的復(fù)合物組成，其核心結(jié)構(gòu)可以重導(dǎo)為具有剛性支架結(jié)構(gòu)的七肽骨架，該剛性支架結(jié)構(gòu)由氨基酸1-3、2-4和4-6之間的醚鍵以及氨基酸5-7之間的C-C鍵決定。另外，分子上存在兩個(gè)糖殘基和兩個(gè)氯原子。A40926復(fù)合物成分的結(jié)構(gòu)以下面顯示的分子式代表，其中R代表[C9-C12]烷基，以因子A1(R＝正癸基)，因子B0(R＝9-甲基癸基)以及因子B1(R＝正十一烷基)為主要成分。
最近將生產(chǎn)性菌株(以前認(rèn)為是馬杜拉放線菌屬物種(Actinomadura sp.)ATCC39727)重新分類為野野村菌屬物種(Nonomuria sp.)ATCC39727(Zhang等，1998)。除了顯示固有的抗細(xì)菌活性之外，A40926也是半合成的糖肽dalbavancin的前體(以前認(rèn)為是BI397或MDL 62397；Malabarba和Ciabatti，2001)。因此，其它處理A40926結(jié)構(gòu)及增加其產(chǎn)量的工具將是非常需要的。然而，來自野野村菌屬的所述簇尚無實(shí)例。因此，野野村菌屬內(nèi)調(diào)節(jié)A40926形成所需的基因也可以用于使生產(chǎn)過程最優(yōu)化。
最近，參與糖肽chloroeremomycin(van Wageningen等人，1998)、balhimycin(Pelzer等人，1999)、補(bǔ)體結(jié)合抑制素(Chiu等人，2001)以及A47934(Pootoolal等人，2002)形成的基因簇得到說明。這些分別被指定為cep、bal、com和sta的簇，分別獲得于東方擬無枝酸菌(Amycolatopsis orientalis)、地中海擬無枝酸菌(Amycolatopsis mediterranei)、淡紫灰鏈霉菌(Streptomyceslavendulae)和豐加鏈霉菌(Streptomyces toyocaensis)。這些簇為處理糖肽途徑提供了幾個(gè)有用的基因。然而，某些步驟不能以所述簇執(zhí)行。例如，可利用的基因簇不編碼能改變糖氧化狀態(tài)、附著脂肪酸鏈或在氨基酸3的芳族部分提供氯原子的功能。本發(fā)明中也說明了所有這些功能。
抗生素生產(chǎn)的工業(yè)過程的設(shè)計(jì)相對成功，實(shí)現(xiàn)了抗生素滴度達(dá)到每升幾克水平的大量發(fā)酵。這主要通過根據(jù)經(jīng)驗(yàn)的、反復(fù)試驗(yàn)方法實(shí)現(xiàn)，缺乏理論基礎(chǔ)。這樣，新方法的發(fā)展和現(xiàn)有技術(shù)的改進(jìn)仍然耗時(shí)并可能導(dǎo)致不穩(wěn)定、操作不一致以及累積不必要的副產(chǎn)物的細(xì)菌培養(yǎng)物。近幾年，合理的方法成功地應(yīng)用于增加鏈霉菌屬物種產(chǎn)生的抗生素水平，這些方法往往涉及目的基因簇之內(nèi)關(guān)鍵調(diào)節(jié)元件的處理或途徑中限速步驟的超表達(dá)。因此，編碼這類簇相關(guān)調(diào)節(jié)物或合成限制步驟的基因可以成為產(chǎn)量改善的有效工具。然而，迄今為止在放線菌內(nèi)鑒定的簇相關(guān)調(diào)節(jié)物屬于幾個(gè)不同的蛋白家族(Chater和Bibb1997)。即使在一個(gè)家族之內(nèi)，序列一致性也有相當(dāng)大的變化。因此，不能通過與其他簇的比較而預(yù)測簇相關(guān)調(diào)節(jié)物的存在、性質(zhì)、數(shù)量和序列，甚至那些限定相關(guān)抗生素的簇。作為舉例，泰樂菌素基因簇編碼四個(gè)不同的調(diào)節(jié)物，而沒有一個(gè)出現(xiàn)在限定相關(guān)的大環(huán)內(nèi)酯類抗生素紅霉素的簇內(nèi)(Bate等人，1999)。類似地，不能預(yù)先確定生物合成途徑中限速步驟的性質(zhì)和原因。
發(fā)明概述本發(fā)明提供在微生物內(nèi)生物合成糖肽A40926所需的一組分離的多核苷酸分子。在本發(fā)明的一種形式中，多核苷酸分子選自毗鄰的DNA序列(SEQ ID NO1)，該序列代表分離自野野村菌屬物種ATCC39727的dbv基因簇，由37個(gè)ORF組成，這些ORE編碼A40926形成所需的多肽。在SEQ ID NO2至38中提供了由上述37個(gè)ORF編碼的多肽的氨基酸序列。
本發(fā)明提供分離的核酸，該核酸包括選自下列的核苷酸序列a)dbv基因簇(SEQ ID NO1)，該基因簇編碼A40926合成所需的多肽；b)核苷酸序列，該核苷酸序列與dbv基因簇(SEQ ID NO1)編碼相同多肽，而不同于dbv基因簇本身的核苷酸序列；
c)dbv ORF 1至37中的任何核苷酸序列，該核苷酸序列編碼多肽SEQ ID NO2至38；d)核苷酸序列，該核苷酸序列與dbv ORF 1至37中任何一個(gè)ORF編碼相同多肽(SEQ ID NO2至38)，而不同于所述ORF的核苷酸序列。
本發(fā)明的另一個(gè)目的是提供分離的核酸，該核酸包括選自下列的核苷酸序列e)dbv ORF 3至4、6至10、18至20、22至23、29至30、以及36中的任何一個(gè)核苷酸序列，該序列編碼SEQ ID NO4至5、7至11、19至21、23至24、30至31、以及37中指定的多肽；f)核苷酸序列，該核苷酸序列與dbv ORF 3至4、6至10、18至20、22至23、29至30、以及36中的任何一個(gè)編碼相同的多肽(SEQID NO4至5、7至11、19至21、23至24、30至31、以及37)，而不同于所述dbv ORF的核苷酸序列；g)核苷酸序列，該核苷酸序列編碼的多肽與dbv ORF 3、6至9、18至20、22至23、29至30、以及36中的任何一個(gè)編碼的多肽(SEQID NO4、7至10、19至21、23至24、30至31、以及37)在氨基酸序列上具有至少80％、優(yōu)選86％、更優(yōu)選90％、最優(yōu)選95％或以上的同一性；h)核苷酸序列，該核苷酸序列編碼的多肽與dbv ORF 4和10中的任何一個(gè)編碼的多肽(SEQ ID NO5和11)在氨基酸序列上具有至少87％、優(yōu)選90％、更優(yōu)選95％或以上的同一性。
在一個(gè)實(shí)施方案中，本發(fā)明中分離的核酸包括選自O(shè)RF 1至37(SEQID NO2至38)的ORF組合，其編碼合成A40926中4-羥苯甘氨酸(4-hydroxyphenylglycine，HPG)殘基所需的多肽。在另一個(gè)實(shí)施方案中，核酸包括選自O(shè)RF 1至37(SEQ ID NO2至38)的ORF組合，其編碼合成A40926中3，5-羥苯甘氨酸(3，5-dihydroxyphenylglycine，DPG)殘基所需的多肽。在另一個(gè)實(shí)施方案中，核酸包括選自O(shè)RF 1至37(SEQ ID NO2至38)的ORF組合，其編碼合成A40926中七肽骨架所需的多肽。根據(jù)另一個(gè)實(shí)施方案，在本發(fā)明的核酸中，提供選自O(shè)RF 1至37(SEQ ID NO2至38)的ORF組合，其編碼A40926中氨基酸3和6的芳族殘基氯化所需的多肽。在另一個(gè)實(shí)施方案中，提供包括選自O(shè)RF 1至37(SEQ ID NO2至38)的ORF組合的核酸，其編碼A40926中氨基酸6的酪氨酸殘基β-羥化所需的多肽。在另一個(gè)實(shí)施方案中，提供包括選自O(shè)RF 1至37(SEQ IDNO2至38)的ORF組合的核酸，其編碼A40926中2和4、4和6、1和3、以及5和7位氨基酸的芳族殘基交聯(lián)所需的多肽。根據(jù)另一個(gè)實(shí)施方案，在本發(fā)明的核酸中，提供選自O(shè)RF 1至37(SEQ ID NO2至38)的ORF組合，其編碼添加和形成N-酰基葡糖醛酸胺(N-acylglucuronamine)殘基所需的多肽。在另一個(gè)實(shí)施方案中，提供包括選自O(shè)RF 1至37(SEQ ID NO2至38)的ORF組合的核酸，其編碼甘露糖殘基附著所需的多肽。在另一個(gè)實(shí)施方案中，提供包括選自O(shè)RF 1至37(SEQ ID NO2至38)的ORF組合的核酸，其編碼A40926N-甲基化所需的多肽。根據(jù)另一個(gè)實(shí)施方案，提供包括選自O(shè)RF 1至37(SEQ ID NO2至38)的ORF組合的核酸，其編碼A40926輸出及抗性所需的多肽。在另一個(gè)實(shí)施方案中，提供包括選自O(shè)RF 1至37(SEQID NO2至38)的ORF組合的核酸，其編碼調(diào)節(jié)dbv基因簇表達(dá)所需的多肽。在另一個(gè)實(shí)施方案中，提供包括選自SEQ ID NO1的一個(gè)或多個(gè)DNA片段的核酸，以增強(qiáng)選自O(shè)RF 1至37(SEQ ID NO2至38)中的ORF的表達(dá)水平。
本領(lǐng)域技術(shù)人員理解，提供編碼A40926生物合成途徑多肽的核苷酸序列的本發(fā)明，也提供編碼衍生自這些多肽的片段的核苷酸。另外，本領(lǐng)域技術(shù)人員理解，由于遺傳密碼的簡并，在SEQ ID NO2至38中指定的相同多肽可以由ORF 1至37的天然或人工變體編碼，即，由不同于ORF 1至37指定的基因組核苷酸序列，但是編碼相同多肽的核苷酸序列編碼。另外也應(yīng)理解，可以出現(xiàn)SEQ ID NO2至38中指定的多肽的天然發(fā)生或人工制造的變體，所述變體與上述初始多肽具有相同功能，但是含有非折疊或催化功能所必需的氨基酸的添加、缺失或置換，或者必需氨基酸的保守性置換。
本領(lǐng)域技術(shù)人員也理解，提供了A40926生物合成所需的整個(gè)簇的核苷酸序列后，本發(fā)明也提供存在于所述簇中的基因表達(dá)所需的核苷酸序列。這類調(diào)節(jié)序列包括但是不限于啟動子和增強(qiáng)子序列、反義序列、轉(zhuǎn)錄終止子和抗終止子序列。這些序列用于調(diào)節(jié)存在于dbv基因簇中的基因的表達(dá)。攜帶所述核苷酸序列的細(xì)胞也在本發(fā)明范圍內(nèi)，攜帶的所述核苷酸序列獨(dú)立于其它核苷酸序列，或與其它核苷酸序列融合。
一方面，本發(fā)明提供分離的核酸，該核酸包括編碼ORF 9多肽(SEQID NO10)、或者所述多肽天然存在的變體或衍生物的核苷酸序列，該多肽用于向糖肽抗生素前體核心結(jié)構(gòu)附著N-?；咸前窔埢?。另一方面，本發(fā)明提供核酸，該核酸包括編碼ORF23多肽(SEQ ID NO24)、或者所述多肽天然發(fā)生的變體或衍生物的核苷酸序列，該多肽用于向糖肽抗生素前體核心結(jié)構(gòu)附著脂肪酸殘基。另一方面，本發(fā)明提供核酸，該核酸包括編碼ORF 29多肽(SEQ ID NO30)、或者所述多肽天然發(fā)生的變體或衍生物的核苷酸序列，該多肽用于附著于糖肽抗生素前體的糖基的氧化。另一方面，本發(fā)明提供核酸，該核酸包括編碼ORF 10多肽(SEQ ID NO11)、或者所述多肽天然發(fā)生的變體或衍生物的核苷酸序列，該多肽用于核心糖肽抗生素前體中b-羥基酪氨酸和DPG殘基的氯化。在另一方面，本發(fā)明提供核酸，該核酸包括編碼ORF20多肽(SEQ ID NO21)、或者所述多肽天然發(fā)生的變體或衍生物的核苷酸序列，該多肽用于向糖肽抗生素前體附著甘露糖殘基。
另一方面，本發(fā)明提供核酸，該核酸包括編碼由ORF 7、18、19、24和35所編碼的多肽(SEQ ID NO8、19、20、25和36)、或者所述多肽天然發(fā)生的變體或衍生物的核苷酸序列，該多肽用于糖肽抗生素或糖肽抗生素前體向細(xì)胞外的輸出，以及賦予抗性。另一方面，本發(fā)明提供核酸，該核酸包括編碼ORF 7多肽(SEQ ID NO8)、或者所述多肽天然或人工發(fā)生的變體或衍生物的核苷酸序列，該多肽用于賦予生產(chǎn)性菌株對糖肽抗生素或糖肽抗生素前體的抗性。另一方面，本發(fā)明提供核酸，該核酸包括編碼ORF 3、4、6、22和36多肽(SEQ IDNO4、5、7、23和37)、或者所述多肽天然或人工發(fā)生的變體或衍生物的核苷酸序列，該多肽用于增加糖肽抗生素前體的產(chǎn)量。
在一個(gè)實(shí)施方案中，本發(fā)明提供攜帶核苷酸序列額外拷貝的糖肽生產(chǎn)性菌株，該核苷酸序列指定了至少一個(gè)選自O(shè)RF 1至37((SEQ IDNO2至38)的任何一個(gè)中的ORF。在一個(gè)優(yōu)選的實(shí)施方案中，這類糖肽生產(chǎn)性菌株是屬于放線菌目(Actinomycetales)的任何菌株。在另一個(gè)優(yōu)選的實(shí)施方案中，這類糖肽生產(chǎn)性菌株是野野村菌屬成員。在更深一個(gè)方面，本發(fā)明提供野野村菌屬菌株，該菌株在SEQ ID NO1中指定的核苷酸序列中含有一個(gè)或多個(gè)變異，這類變異引起ORF 1至37(SEQ ID NO2至38)中一個(gè)或多個(gè)的表達(dá)的增加或降低。
在一個(gè)優(yōu)選的實(shí)施方案中，本發(fā)明提供核酸，該核酸包括由SEQ IDNO1指定的核苷酸序列或其部分，由一個(gè)或多個(gè)載體攜帶，用于由另一個(gè)細(xì)胞產(chǎn)生A40926、一個(gè)或多個(gè)其前體或衍生物。在一個(gè)優(yōu)選的實(shí)施方案中，所述核苷酸序列或其部分在單獨(dú)的載體上攜帶。在另一個(gè)優(yōu)選的實(shí)施方案中，這類載體是細(xì)菌人工染色體。另一方面，所述細(xì)菌人工染色體是ESAC載體(如WO99/63674中所說明)。在另一個(gè)優(yōu)選的實(shí)施方案中，本發(fā)明提供不同于野野村菌屬物種ATCC 39727的重組放線菌菌株，其含有SEQ ID NO1指定的基因簇，所述基因簇在ESAC載體中攜帶，該載體整合到所述重組放線菌菌株染色體中。
一方面，本發(fā)明提供用于提高A40926生產(chǎn)的方法，所述方法包括下列步驟(1)以重組DNA載體轉(zhuǎn)化通過生物合成途徑方法產(chǎn)生A40926或A40926前體的微生物，所述載體包括選自O(shè)RF 1至37(SEQ ID NO2至38)的任何一個(gè)的DNA序列，該序列編碼所述途徑中的限速活性；(2)在適合細(xì)胞生長、表達(dá)所述基因以及生產(chǎn)所述抗生素或抗生素前體的條件下培養(yǎng)使用所述載體轉(zhuǎn)化的微生物。
另一方面，本發(fā)明提供產(chǎn)生A40926衍生物的方法，所述方法包括下列步驟(1)將選自由SEQ ID NO1限定的核苷酸序列的片段克隆到適宜載體中，所述片段含有至少ORF 1至37(SEQ ID NO2至38)中之一的部分，所述ORF編碼多肽，該多肽催化想要繞過的生物合成步驟；(2)通過去除或置換一個(gè)或多個(gè)密碼子滅活所述ORF，所述密碼子指定對所述多肽的活性所必需的氨基酸；(3)使用所述重組DNA載體轉(zhuǎn)化通過生物合成途徑方法產(chǎn)生A40926或A40926前體的微生物；(4)篩選產(chǎn)生的轉(zhuǎn)化體中所述DNA序列被突變拷貝置換從而產(chǎn)生斷裂基因的那些重組體；以及(5)在適合細(xì)胞生長、所述途徑的表達(dá)以及所述途徑類似物的生產(chǎn)的條件下，培養(yǎng)所述突變細(xì)胞。
另一方面，本發(fā)明提供產(chǎn)生新糖肽的方法，所述方法包括下列步驟(1)使用重組DNA載體轉(zhuǎn)化通過生物合成途徑方法產(chǎn)生不同于A40926及其前體的糖肽或糖肽前體的微生物，所述載體包括選自O(shè)RF1至37(SEQ ID NO2至38)的一個(gè)或多個(gè)ORF，編碼修飾所述糖肽或糖肽前體的一個(gè)或多個(gè)多肽的表達(dá)；(2)在適于細(xì)胞生長、表達(dá)所述基因以及產(chǎn)生所述抗生素或抗生素前體的條件下培養(yǎng)用所述載體轉(zhuǎn)化的微生物。
適于采用該方法產(chǎn)生糖肽或糖肽前體的微生物實(shí)例是屬于鏈霉菌屬、擬無枝酸菌屬、游動放線菌屬、野野村菌屬等的菌株。
另一方面，本發(fā)明提供另一個(gè)產(chǎn)生新糖肽的方法，所述方法包括下列步驟(1)使用重組DNA載體轉(zhuǎn)化微生物，所述載體包括選自O(shè)RF1至37(SEQ ID NO2至38)的一個(gè)或多個(gè)ORF，編碼一個(gè)或多個(gè)修飾糖肽或糖肽前體的多肽(活性多肽)，且所述微生物選自不產(chǎn)生糖肽或糖肽前體、并且可以有效表達(dá)引入的ORF的微生物；(2)在適于活性多肽存在的條件下，制備所述微生物的細(xì)胞提取物或細(xì)胞級分，所述細(xì)胞提取物或細(xì)胞級分至少含有所述活性多肽；(3)向所述細(xì)胞提取物或細(xì)胞級分添加糖肽或糖肽前體，在所述活性多肽可以修飾所述糖肽或糖肽前體的條件下溫育所述混合物。
適于采用該方法的微生物的實(shí)例是屬于淺青紫鏈霉菌(Streptomyces lividans)、天藍(lán)色鏈霉菌(Streptomycescoelicolor)、大腸桿菌(Escherichia coli)、枯草芽孢桿菌(Bacillus subtilis)等的菌株。
本發(fā)明的另一個(gè)方面包括分離的多肽，該多肽包括參與A40926生物合成途徑的多肽序列，選自a)由dbv ORF 1至37(SEQ ID NO2至38)中任何一項(xiàng)編碼的ORF多肽，或者是與由dbv ORF 1至37(SEQ ID NO2至38)中任何一項(xiàng)編碼，優(yōu)選由dbv ORF3至4、6至10、18至20、22至23、29至30(SEQ ID NO4至5、7至11、19至21、23至24、30至31和37)中任何一項(xiàng)編碼的多肽氨基酸序列相同的多肽；b)多肽，該多肽與dbv ORF 3、6至9、18至20、22至23、29至30以及36(SEQ ID NO4、7至10、19至21、23至24、30至31以及37)中任何一項(xiàng)編碼的多肽的氨基酸序列具有至少80％、優(yōu)選86％、更優(yōu)選90％、最優(yōu)選95％或以上的同一性；以及c)多肽，該多肽與dbv ORF 4和10(SEQ ID NO5至11)中任何一項(xiàng)編碼的多肽的氨基酸序列具有至少87％、優(yōu)選90％、更優(yōu)選95％或以上的同一性。
定義術(shù)語“分離的核酸”指天然或合成來源的DNA分子，是基因組DNA或互補(bǔ)DNA(cDNA)，可以是單鏈或雙鏈。該術(shù)語也指天然或合成來源的RNA分子。
術(shù)語“核苷酸序列”指ORF的全部長度或部分長度的序列，以及在此公開的基因間區(qū)域。本發(fā)明示于序列表中的任何一個(gè)核苷酸序列是(a)編碼序列，(b)從(a)轉(zhuǎn)錄產(chǎn)生的RNA分子，(c)利用密碼子簡并性編碼相同多肽的編碼序列，或(d)含有啟動子、增強(qiáng)子、終止子和抗終止子序列的基因間區(qū)域。
術(shù)語“基因簇”、“簇”和“生物合成簇”均指定為含有所有次生代謝物合成所需基因的微生物基因組的毗鄰片段。
術(shù)語“dbv”指負(fù)責(zé)野野村菌屬物種ATCC39727中A40926生物合成的遺傳因子。
術(shù)語“ORF”指編碼一個(gè)多肽的基因組核苷酸序列。在本發(fā)明上下文中，術(shù)語ORF與“基因”同義。
術(shù)語“ORF多肽”指由ORF編碼的多肽。
術(shù)語“dbv ORF”指包括于dbv基因簇之內(nèi)的ORF。
術(shù)語“NRPS”指非核糖體肽合成酶，該酶是負(fù)責(zé)將氨基酸整合到次生代謝物寡肽骨架中的酶學(xué)活性的復(fù)合物。有功能的NRPS是催化一個(gè)或多個(gè)氨基酸整合到寡肽中的酶。
術(shù)語“NRPS模塊”或“模塊”指指導(dǎo)一個(gè)氨基酸向寡肽的活化、整合及可能的修飾的NRPS片段。
術(shù)語“NRPS基因”指編碼NRPS的基因。
術(shù)語“次生代謝物”指通過基因簇指定的一組基因的表達(dá)、由微生物產(chǎn)生的生物活性物質(zhì)。
術(shù)語“生產(chǎn)性宿主”是由供體生物衍生的基因簇指導(dǎo)次生代謝物形成的微生物。
術(shù)語“ESAC”指“大腸桿菌-鏈霉菌屬人工染色體”，即在大腸桿菌宿主內(nèi)攜帶及保持大的DNA插入片段、并可以引入及保持于放線菌屬生產(chǎn)性宿主中的重組載體。ESAC的實(shí)例于WO99/67374中給出。
附圖簡述

圖1.分離的DNA片段衍生于野野村菌屬物種ATCC39727染色體。粗線表示在SEQ ID NO1中說明的片段。攜帶所述分離的DNA片段的粘粒指定為11A5、7F3、7E9、1B1、7A2、11B9和7C7。
圖2.dbv簇的基因組織。各個(gè)ORF以箭標(biāo)代表，并如表1中編碼。方向與圖1中相同?？潭染€上的數(shù)字顯示序列坐標(biāo)(以kb為單位)。
發(fā)明詳述A.野野村菌屬dbv基因A40926是由野野村菌屬物種ATCC39727產(chǎn)生的密切相關(guān)糖肽抗生素的復(fù)合物。本發(fā)明提供核酸序列以及A40926生物合成的基因簇的表征。A40926基因簇以及側(cè)翼DNA序列的物理組織報(bào)告于圖1中，該圖說明了野野村菌屬物種ATCC39727基因組的90kb基因組片段以及一組限定這些片段的粘粒的物理圖譜。控制A40926生物合成的DNA片段，指定為dbv簇，其遺傳組成顯示于圖2中，其核苷酸序列如SEQID NO1所報(bào)告。
可以通過與其他糖肽簇的比較及從其基因產(chǎn)物功能確定該簇的精確邊界。因此，在左端(圖1)，dbv簇由dbv ORF 1劃界，其編碼參與HPG合成的酶HmoS(SEQ ID No2)。在右側(cè)，dbv簇由attL位點(diǎn)的殘余部分劃界，該部分與tRNA基因的3’末端相似，跨越SEQ ID NO1的核苷酸71065至71138。dbv簇跨越約71,100個(gè)堿基對，含有37個(gè)ORF，指定為dbv ORF1至dbv ORF37。SEQ ID NO1(71138堿基對)的毗鄰核苷酸序列編碼列于SEQ ID NO2至38中的37個(gè)推導(dǎo)的蛋白。ORF1(SEQ ID NO2)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸1140至40推導(dǎo)的366個(gè)氨基酸。ORF2(SEQ ID NO3)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸2329至1259推導(dǎo)的356個(gè)氨基酸。ORF3(SEQ ID NO4)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸5161至2558推導(dǎo)的867個(gè)氨基酸。ORF4(SEQ ID NO5)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸6231至5266推導(dǎo)的321個(gè)氨基酸。ORF5(SEQ ID NO6)代表從翻譯SEQ ID NO1核苷酸7183至8292推導(dǎo)的369個(gè)氨基酸。ORF6(SEQ ID NO7)代表從翻譯SEQID NO1核苷酸8320至8973推導(dǎo)的217個(gè)氨基酸。ORF7(SEQ ID NO8)代表從翻譯SEQ ID NO1核苷酸9069至9659推導(dǎo)的196個(gè)氨基酸。ORF8(SEQ ID NO9)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸10667至9708推導(dǎo)的319個(gè)氨基酸。ORF9(SEQ ID NO10)代表從翻譯SEQID NO1互補(bǔ)鏈上核苷酸11896至10670推導(dǎo)的408個(gè)氨基酸。ORF10(SEQ ID NO11)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸13419至11950推導(dǎo)的489個(gè)氨基酸。ORF11(SEQ ID NO12)代表從翻譯SEQID NO1互補(bǔ)鏈上核苷酸14741至13479推導(dǎo)的420個(gè)氨基酸。ORF12(SEQ ID NO13)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸16019至14823推導(dǎo)的398個(gè)氨基酸。ORF13(SEQ ID NO14)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸17163至16009推導(dǎo)的384個(gè)氨基酸。ORF14(SEQ ID NO15)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸18366至17185推導(dǎo)的393個(gè)氨基酸。ORF15(SEQ ID NO16)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸18671至18462推導(dǎo)的69個(gè)氨基酸。ORF16(SEQ ID NO17)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸24259至18668推導(dǎo)的1863個(gè)氨基酸。ORF17(SEQ ID NO18)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸36529至24278推導(dǎo)的4083個(gè)氨基酸。ORF18(SEQ ID NO19)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸39021至36760推導(dǎo)的753個(gè)氨基酸。ORF19(SEQ ID NO20)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸39851至39152推導(dǎo)的232個(gè)氨基酸。ORF20(SEQ ID NO21)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸41732至40125推導(dǎo)的535個(gè)氨基酸。ORF21(SEQ ID NO22)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸42584至41772推導(dǎo)的270個(gè)氨基酸。ORF22(SEQ ID NO23)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸44130至42868推導(dǎo)的420個(gè)氨基酸。ORF23(SEQ IDNO24)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸46355至44226推導(dǎo)的709個(gè)氨基酸。ORF24(SEQ ID NO25)代表從翻譯SEQ ID NO1核苷酸46632至48578推導(dǎo)的648個(gè)氨基酸。ORF25(SEQ ID NO26)代表從翻譯SEQ ID NO1核苷酸48575至54868推導(dǎo)的2097個(gè)氨基酸。ORF26(SEQ ID NO27)代表從翻譯SEQ ID NO1核苷酸54865至58056推導(dǎo)的1063個(gè)氨基酸。ORF27(SEQ ID NO28)代表從翻譯SEQ ID NO1核苷酸58152至58985推導(dǎo)的277個(gè)氨基酸。ORF28(SEQ ID NO29)代表從翻譯SEQ ID NO1核苷酸59046至60641推導(dǎo)的531個(gè)氨基酸。ORF29(SEQ ID NO30)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸62445至60874推導(dǎo)的523個(gè)氨基酸。ORF30(SEQ IDNO31)代表從翻譯SEQ ID NO1核苷酸62887至63312推導(dǎo)的141個(gè)氨基酸。ORF31(SEQ ID NO32)代表從翻譯SEQ ID NO1核苷酸63469至64587推導(dǎo)的372個(gè)氨基酸。ORF32(SEQ ID NO33)代表從翻譯SEQ ID NO1核苷酸64599至65240推導(dǎo)的213個(gè)氨基酸。ORF33(SEQ ID NO34)代表從翻譯SEQ ID NO1核苷酸65237至66541推導(dǎo)的434個(gè)氨基酸。ORF34(SEQ ID NO35)代表從翻譯SEQID NO1核苷酸66538至67335推導(dǎo)的265個(gè)氨基酸。ORF35(SEQ IDNO36)代表從翻譯SEQ ID NO1核苷酸67332至68618推導(dǎo)的428個(gè)氨基酸。ORF36(SEQ ID NO37)代表從翻譯SEQ ID NO1互補(bǔ)鏈上核苷酸69423至68685推導(dǎo)的251個(gè)氨基酸。ORF37(SEQ ID NO38)代表從翻譯SEQ ID NO1核苷酸69608至70894推導(dǎo)的428個(gè)氨基酸。
dbv簇表現(xiàn)出與其他糖肽簇基本不同的組織。五個(gè)bal、cep、com、sta和dbv簇之間的比較概括于表1中。
表1
a+符號表示在其他說明的糖肽基因簇中存在直向同源物(ortholog)b當(dāng)其他糖肽基因簇中不存在直向同源物時(shí)，報(bào)告在GeneBank中Blast搜索結(jié)果c在存在于其他糖肽簇中以及GeneBank中Blast搜索聯(lián)合結(jié)果的基礎(chǔ)上，提議的dbv ORF功能。
d該列報(bào)告了與其他糖肽基因簇的最佳匹配的百分比序列一致性及其起源的簇e具有最高分值的GeneBank條目的編號(Accession number)f從Blast搜索獲得的概率分值g前列GeneBank條目的生物及提議的功能?？s寫為S.，鏈霉菌屬；M.，中間根瘤菌屬(Mesorhizobium)；A.，擬無枝酸菌屬h由Blast搜索報(bào)告的保守結(jié)構(gòu)域*存在于其他糖肽簇中，但是具有較高一致性的序列存在于數(shù)據(jù)庫其它地方實(shí)際上，編碼七個(gè)NRPS模塊的基因組織為兩個(gè)背馳轉(zhuǎn)錄的區(qū)域，由12kb的片段分隔(圖2)。這與bal、cep、com和sta簇的組織形成對照，在這些簇中，NRPS基因的七個(gè)模塊存在于一個(gè)緊湊的區(qū)域，全部以相同方向翻譯。另外，盡管在bal、cep、com和sta簇中，除了一個(gè)之外所有ORF以相同方向轉(zhuǎn)錄，但37個(gè)dbv ORF中僅有22個(gè)以一個(gè)方向轉(zhuǎn)錄，而余下的15個(gè)以相反的方向轉(zhuǎn)錄。這說明了dbv簇的轉(zhuǎn)錄復(fù)雜性。
dbv簇也以幾個(gè)ORF的存在為特征，這些ORF在bal、cep、com和sta簇中沒有發(fā)現(xiàn)同系物。這些ORF包括dbv ORF 3、6至8、18至20、22、23、29、30和36(SEQ ID NO4、7至9、19至21、23、24、30、31和37)。五個(gè)bal、cep、com、sta和dbv簇之間的比較總結(jié)于表1中?？傊?，如此處所說明的dbv簇的遺傳組成，基本上有別于參與其它糖肽合成的其他簇。因此，它代表了具有這類基因組成的簇的第一個(gè)實(shí)施例。
B.dbv基因的功能本發(fā)明特別公開了編碼NRPS的DNA序列，NRPS負(fù)責(zé)A40926七肽前體的合成。dbv NRPS由四個(gè)多肽組成，每個(gè)多肽含有1至3個(gè)模塊。將這些多肽指定為dbv ORF 16、ORF 17、ORF 25和ORF26(SEQ ID NO17、18、26和27)。使用模塊系統(tǒng)由NRPS進(jìn)行肽合成，其中，裝載模塊尾隨以一系列延長模塊。在NRPS中，每個(gè)延長模塊以存在至少3個(gè)結(jié)構(gòu)域?yàn)樘卣?，所述結(jié)構(gòu)域?yàn)橄佘账峄?A)結(jié)構(gòu)域，負(fù)責(zé)底物識別和激活；硫醇化作用(T)結(jié)構(gòu)域，作為硫酯使氨基酸與延長肽共價(jià)結(jié)合；以及縮合(C)結(jié)構(gòu)域，催化肽鍵形成。除了這些核心結(jié)構(gòu)域之外，最后一個(gè)模塊含有硫酯酶(Te)結(jié)構(gòu)域，將連接完整肽與NRPS的酯鍵水解。有些模塊通過差向異構(gòu)化(E)結(jié)構(gòu)域的作用將L-氨基酸轉(zhuǎn)化為D型。dbv NRPS由七個(gè)模塊組成，總共為七個(gè)A結(jié)構(gòu)域、七個(gè)T結(jié)構(gòu)域、六個(gè)C結(jié)構(gòu)域、三個(gè)E結(jié)構(gòu)域以及一個(gè)Te結(jié)構(gòu)域。特定地，dbv ORF 26(SEQID NO27)編碼NRPS模塊1和2，限定了結(jié)構(gòu)域A-T-C-A-E-T的序列，且是HPC和Tyr殘基(頭兩個(gè)氨基酸)整合到A40926的七肽核心中所必需的；dbv ORF 25(SEQ ID NO26)編碼NRPS模塊3，限定了結(jié)構(gòu)域C-A-T的序列，且負(fù)責(zé)DPG殘基的整合；dbv ORF 17(SEQ ID NO18)編碼NRPS模塊4至6，限定了結(jié)構(gòu)域C-A-E-T-C-A-E-T-C-A-T的序列，且負(fù)責(zé)A40926七肽核心中兩個(gè)HPG和Tyr殘基的整合；dbvORF16(SEQ ID NO17)編碼NRPS模塊7，限定了結(jié)構(gòu)域C-A-T-C*-T-Te的序列(C*表示未知功能的非典型縮合結(jié)構(gòu)域)，且是最后一個(gè)DPG殘基整合以及A40926的七肽前體釋放所必需的。
存在于dbv簇中的其他基因代表用于增加A40926生產(chǎn)或合成新代謝物的新的遺傳因子。其中，dbv ORF9(SEQ ID NO10)編碼糖基轉(zhuǎn)移酶，該酶在七肽中向4位HPG殘基的酚式羥基添加N-?；?葡糖胺殘基(分子式I)?？梢詫⒃摶蚩寺〔⒃诋愒此拗髦斜磉_(dá)，以產(chǎn)生能夠?qū)-?；?葡糖胺殘基添加到其他糖肽糖苷配基上的活性酶。作為選擇，可以在生產(chǎn)性菌株中將dbv ORF9滅活，導(dǎo)致A40926糖苷配基的形成。雖然可以通過化學(xué)方法獲得該糖苷配基(Malabarba和Ciabatti，2001)，但通過單獨(dú)的發(fā)酵過程產(chǎn)生該糖苷配基可以滿足需要，不需要化學(xué)的干涉。
本發(fā)明的其他優(yōu)選核酸分子包括dbv ORF10(SEQ ID NO11)，它編碼鹵化酶(halogenase)，負(fù)責(zé)氯原子在A40926氨基酸3和氨基酸6的加成。dbv ORF 10代表新的遺傳因子，有別于存在于cep、com、sta和bal簇中的鹵化酶基因。事實(shí)上，A40926氯化模式在這些糖肽中相當(dāng)獨(dú)特?？梢詫⒃摶蚩寺〔⒃诋愒此拗髦斜磉_(dá)，以產(chǎn)生能夠氯化糖肽芳族殘基3和6的活性酶。
本發(fā)明的其他優(yōu)選核酸分子包括dbv ORF 23(SEQ ID NO24)，它編碼?；D(zhuǎn)移酶，負(fù)責(zé)以脂肪酸在氨基酸4葡糖胺殘基的N-?；bv ORF 23代表新的遺傳因子，不存在于cep、com、sta和bal簇中?？梢詫⒃摶蚩寺〔⒃诋愒此拗髦斜磉_(dá)，以產(chǎn)生能夠?qū)Σ煌请牡奶腔糠諲-?；幕钚悦浮?br> 本發(fā)明的其他優(yōu)選核酸分子包括dbv ORF 29(SEQ ID NO30)，它編碼已糖氧化酶，負(fù)責(zé)附著于A40926中氨基酸4的D-葡糖胺殘基向氨基葡糖醛酸的氧化。dbv ORF 29代表新的遺傳因子，不存在于cep、com、sta和bal簇中?？梢詫⒃摶蚩寺〔⒃诋愒此拗髦斜磉_(dá)，以產(chǎn)生能夠氧化附著到糖肽的D-葡糖胺的活性酶。
本發(fā)明的其他優(yōu)選核酸分子包括dbv ORF 36(SEQ ID NO37)，它編碼硫酯酶，負(fù)責(zé)水解來自NRPS的異常中間肽。與其他以不同于NRPS的多肽存在的硫酯酶相似(Kotowska等，2002)，dbv ORF 36的產(chǎn)物通過水解NRPS上的所有不進(jìn)一步加工入七肽的硫酯而負(fù)責(zé)為A40926的生物合成保持有效的NRPS。它因此代表新的遺傳因子，不存在于cep、sta、com和bal簇中?？梢詫⒃摶蚩寺〔⒃诹硗獾奶请纳a(chǎn)性菌株中表達(dá)，以增加形成的產(chǎn)物產(chǎn)量。宿主菌株包括但是不限于屬于放線菌目，屬于鏈孢囊菌科(Streptosporangiaceae)、小單孢菌科(Micromonosporaceae)、假諾卡氏菌科(Pseudonocardiaceae)和鏈霉菌科(Streptomycetaceae)，屬于野野村菌屬(Nonomureae)、游動放線菌屬、擬無枝酸菌屬、鏈霉菌屬等的菌株。
本發(fā)明的其他優(yōu)選核酸分子包括dbv ORF 20(SEQ ID NO21)，它編碼甘露糖基轉(zhuǎn)移酶，負(fù)責(zé)向氨基酸7添加甘露糖殘基。它因此代表新的遺傳因子，不存在于cep、sta、com和bal簇中?？梢詫⒃摶蚩寺〔⒃诹硗獾奶请纳a(chǎn)性菌株中表達(dá)，以產(chǎn)生攜帶有添加至氨基酸7的甘露糖殘基的糖肽。作為選擇，可以在生產(chǎn)性菌株中將dbv ORF20滅活，導(dǎo)致去甘露糖A40926的形成。雖然可以通過其他方法獲得該化合物(Lancini和Cavalleri，1997)，但通過單獨(dú)的發(fā)酵過程產(chǎn)生該化合物可以滿足需要。
dbv簇也包括許多基因，這些基因負(fù)責(zé)非蛋白原性氨基酸HPG和DPG的合成。對于前者的合成，需要dbv ORF 1、2、5和37(SEQ IDNO2、3、6和38)的產(chǎn)物。DPG的合成，除了ORF 37(SEQ ID NO38)之外，需要dbv ORF 31至34(SEQ ID NO32至35)的參與。它們的功能概括于表1。由于HPG和DPG是非蛋白原性氨基酸，所以經(jīng)由NRPS的七肽合成依賴于它們的有效性。因此，這些酶的活性是糖肽生物合成中的限速步驟。由此可以通過增加這些ORF的表達(dá)而獲得增加的糖肽產(chǎn)量?？梢栽贏40926生產(chǎn)性菌株中，單獨(dú)或以其任何組合超表達(dá)這些基因，以增加A40926的產(chǎn)量。
dbv簇也包括許多基因，這些基因負(fù)責(zé)將糖肽中間物或終產(chǎn)物輸出到細(xì)胞質(zhì)外、以及負(fù)責(zé)賦予生產(chǎn)性細(xì)胞抗性。這些基因包括dbv ORF 7、18至19、24和35(SEQ ID NO8、19至20、25和36)。dbv ORF 7編碼羧肽酶，負(fù)責(zé)從生長中的肽聚糖去除末端D-丙氨酸部分。它代表新的遺傳因子，不存在于cep、com、sta和bal簇中。dbv ORF 18至19和24編碼ABC類轉(zhuǎn)運(yùn)蛋白(van Veen和Konings，1998)，負(fù)責(zé)A40926或其中間物的依賴ATP的分泌。dbv ORF 35編碼Na/K離子反向轉(zhuǎn)運(yùn)蛋白，負(fù)責(zé)逆質(zhì)子梯度輸出A40926或其中間物?？梢栽诹硪粋€(gè)糖肽生產(chǎn)性菌株中，單獨(dú)或以其任何組合克隆并表達(dá)這些基因，以增加形成的產(chǎn)物產(chǎn)量。宿主菌株包括但不限于屬于屬于放線菌目，屬于鏈孢囊菌科、小單孢菌科、假諾卡氏菌科和鏈霉菌科，屬于野野村菌屬、游動放線菌屬、擬無枝酸菌屬、鏈霉菌屬等的菌株。作為選擇，可以在A40926生產(chǎn)性菌株中單獨(dú)或以其任何組合超表達(dá)這些基因，以增加A40926產(chǎn)量。
dbv簇也包括許多調(diào)節(jié)基因，這些基因在A40926生產(chǎn)中負(fù)責(zé)直接或間接激活生物合成和抗性基因的表達(dá)。這些基因包括dbv ORF 3、4、6和22(SEQ ID NO4、5、7和23)。dbv ORF 3與存在于吸水鏈霉菌(Streptomyces hygroscopicus)的基因簇中的正調(diào)節(jié)基因HygR高度相關(guān)(Ruan等，1997)。它代表新的遺傳因子，不存在于cep、com、bal和sta簇中。dbv ORF 4與存在于其他糖肽簇中的相似調(diào)節(jié)基因高度相關(guān)。dbv ORF 6和22一起編碼雙組分信號轉(zhuǎn)導(dǎo)體系?？梢栽诹硪粋€(gè)糖肽生產(chǎn)性菌株中單獨(dú)或以其任何組合將這四個(gè)基因克隆并表達(dá)，以增加形成產(chǎn)物的產(chǎn)量。宿主菌株包括但不限于屬于放線菌目，屬于鏈孢囊菌科、小單孢菌科、假諾卡氏菌科和鏈霉菌科，屬于野野村菌屬、游動放線菌屬、擬無枝酸菌屬、鏈霉菌屬等的菌株。作為選擇，可以在A40926生產(chǎn)性菌株中單獨(dú)或以其任何組合將這些基因克隆或超表達(dá)，以增加A40926產(chǎn)量。
C.dbv簇的用途本發(fā)明也提供表達(dá)完整A40926分子、其任何前體或其任何衍生物的核酸。這類核酸包括分離的基因簇，該基因簇包括編碼糖肽的ORF，所述糖肽足以指導(dǎo)A40926裝配。在一個(gè)實(shí)例中，可以將完整的dbv簇(SEQ ID NO1)引入合適的載體中，并用于轉(zhuǎn)化所需的生產(chǎn)性宿主。一方面，將該DNA片段引入能夠攜帶大DNA片段的合適的載體。這類載體的實(shí)例包括但是不限于細(xì)菌人工染色體(BAC)載體或特定衍生物，例如ESAC載體(Shizuya等人，1992；Ioannou等人，1994；Sosio等人，2000b)。另一方面，將dbv簇以兩個(gè)分離的片段克隆到兩個(gè)不同載體中，這兩個(gè)載體可以在所需的生產(chǎn)性宿主中相容。在另一方面，可以將dbv簇細(xì)分為三個(gè)片段，將每一個(gè)克隆到分離的相容載體中。單、雙或三載體系統(tǒng)用途的實(shí)例在文獻(xiàn)中得到說明(例如Xue等人，1999)。
一旦將dbv簇合適地克隆到一個(gè)或多個(gè)載體中，可以將其引入許多合適的生產(chǎn)性宿主中，在合適的生產(chǎn)性宿主中，可以發(fā)生具有比天然宿主中更高效率的糖肽抗生素的生產(chǎn)。優(yōu)選的宿主細(xì)胞是那些可以有效表達(dá)放線菌類基因的物種或菌株。這類宿主包括但是不限于放線菌目、鏈孢囊菌科、小單孢菌科、假諾卡氏菌科和鏈霉菌科、野野村菌屬、游動放線菌屬、擬無枝酸菌屬和鏈霉菌屬等。作為選擇，可以將克隆到一個(gè)或多個(gè)合適載體中的dbv簇的第二個(gè)拷貝，引入A40926生產(chǎn)性菌株中，dbv基因的第二個(gè)拷貝將在此增加A40926產(chǎn)量。
生產(chǎn)能力向得到充分表征的宿主的轉(zhuǎn)移，可以基本改善通向最優(yōu)化和發(fā)展過程的幾個(gè)部分可以更有效地增加生產(chǎn)性菌株中天然產(chǎn)物的滴度；可以在已知可能的干擾活動背景下進(jìn)行天然產(chǎn)物的純化；可以更有效地控制復(fù)合物的組成；可以通過操縱發(fā)酵條件或通過途徑工程更有效地產(chǎn)生天然產(chǎn)物改變的衍生物。
作為選擇，可以將生物合成基因簇修飾、插入宿主細(xì)胞，并用于合成或化學(xué)修飾多種代謝物例如，可以重編排、修飾可讀框，并將其與其他糖肽生物合成基因簇組合。
利用此處提供的信息，可以使用常規(guī)和廣為人知的方法實(shí)現(xiàn)A40926核酸的克隆與表達(dá)。
在另一個(gè)可能的用途中，通過使用常規(guī)分子生物學(xué)技術(shù)從dbv基因簇分離選擇的ORF，并滅活選擇的ORF。將克隆入合適的載體(所述載體含有在野野村菌屬物種ATCC39727染色體中在側(cè)面與所述ORF相接的DNA片段)的突變ORF引入所述野野村菌屬菌株中，在此兩個(gè)同源重組的雙交換事件導(dǎo)致所述ORF在生產(chǎn)菌株中的失活。該方法可以以有效的方式用于A40926前體或衍生物的生產(chǎn)。
在另一個(gè)可能的用途中，從dbv基因簇分離選擇的ORF，并將其置于所需啟動子的控制之下。然后，無論通過前述的置換初始ORF、還是作為所述ORF的額外拷貝，將經(jīng)過設(shè)計(jì)、克隆到合適載體中的ORF引入野野村菌屬物種ATCC 39727中。該方法可以用于增加或降低ORF的表達(dá)水平，該ORF對于A40926分子、其前體或衍生物的生產(chǎn)是關(guān)鍵的。
實(shí)施例下列實(shí)施例供以闡明鑒定A40926基因簇的原理和方法學(xué)、以及鑒定和分析dbv基因的原理和方法學(xué)。這些實(shí)施例供以闡明本發(fā)明的原理和方法學(xué)，但是并不意味限制其范圍。
普通方法除非另外指出，細(xì)菌菌株和克隆載體均從公共保藏或商業(yè)來源獲得。對分子生物學(xué)使用標(biāo)準(zhǔn)方法(例如Sambrook等人，1989；Kieser等人，2000)。在HT瓊脂(Kieser等人，2000)和Rare3培養(yǎng)基(10g/l葡萄糖，4g/l酵母提取物，10g/l麥芽汁，2g/l蛋白胨，2g/lMgCl2，0.5％甘油)中培養(yǎng)野野村菌屬。按照發(fā)表的方法分離糖肽(Lancini和Cavalleri，1997)。使用來自Wisconsin package，9.1版本(Accelrys)的程序進(jìn)行序列分析。使用Blast或Fasta程序在公共站點(diǎn)(http//www.ncbi.nlm.nih.gov/blast/index.html和http//www.ebi.ac.uk/fasta33)進(jìn)行數(shù)據(jù)庫搜索。
實(shí)施例1-A40926生物合成基因的分離使用粘粒載體Supercos(Stratagene，La Jolla，CA 92037)中來自野野村菌屬ATCC39727的DNA建立基因組文庫。為了將片段大小量優(yōu)化于40kb范圍之內(nèi)，使用Sau3AI部分消化野野村菌屬ATCC39727的總DNA。使用堿性磷酸酶處理經(jīng)部分消化的DNA，并與事先以BamHI消化的Supercos連接。體外包裝連接混合物，并將其用于轉(zhuǎn)染大腸桿菌XL1Blue細(xì)胞。通過與兩個(gè)探針雜交篩選產(chǎn)生的粘粒文庫，所述探針從bal簇片段的PCR擴(kuò)增獲得，PCR擴(kuò)增使用地中海擬無枝酸菌DSM 5908基因組DNA為模板。這些探針是bgtfA，從使用寡核苷酸(oligos)5′-ATGCGCGTGTTGATCTCG-3′(SEQ ID NO39)和5′-CGGCTGACCGCGGCGAAC-3′(SEQ ID NO40)的擴(kuò)增獲得；以及dpgA，從使用寡核苷酸5′-CGTGGGGGTGGATGTATCGA-3′(SEQ ID NO41)和5′-TCACCATTGGATCAGCG-3′(SEQ ID NO42)的擴(kuò)增獲得。從保存于GenBank的編號Y16952的序列設(shè)計(jì)所有寡核苷酸。使用寡核苷酸Pep8(Sosio等人，2000a)進(jìn)行進(jìn)一步雜交。分離對一個(gè)或多個(gè)這樣的探針陽性的粘粒，使用限制酶繪制物理圖譜。通過這些實(shí)驗(yàn)鑒定報(bào)告于圖1中的粘粒。由此從野野村菌屬物種ATCC39727基因組鑒定的片段含有負(fù)責(zé)抗生素A40926合成的dbv基因簇。
上文的實(shí)施例供以闡明分離dbv簇的原理和方法學(xué)。本領(lǐng)域技術(shù)人員將想到，可以將dbv簇克隆到多種載體中。然而，本領(lǐng)域技術(shù)人員理解，假定72kb大小的dbv簇，優(yōu)選的載體是能夠攜帶大的插入片段的那些，例如λ、粘粒和BAC載體。本領(lǐng)域技術(shù)人員理解，其它探針可以用于這類文庫中dbv簇的鑒定。由SEQ ID NO1中報(bào)告的序列，可以從野野村菌屬物種ATCC39727 DNA PCR擴(kuò)增任何片段，并將該片段用于篩選以此類DNA建立的文庫。可以鑒定所述文庫的一個(gè)或多個(gè)克隆，所述克隆包括由SEQ ID NO10覆蓋的任何片段。另外，通過使用異源探針，例如從cep、bal、com和sta簇衍生的那些，利用表1中提供的信息，來鑒定dbv簇也是可能的。作為選擇，其他指導(dǎo)次生代謝物合成的基因簇，含有關(guān)于使得能夠進(jìn)行異源雜交充分與dbv基因相關(guān)的基因。所有這些變化在本發(fā)明范圍之內(nèi)。
實(shí)施例2-A40926基因簇的序列分析通過鳥槍法對dbv簇測序，dbv簇如實(shí)施例1中所述進(jìn)行鑒定。在此將dbv簇序列作為SEQ ID NO1提供。使用Codonpreference[GCG，(Genetic Computer group，Madison，WI 53711)版本9.1]分析產(chǎn)生的DNA序列，以鑒定相似的編碼序列。接下來，使用程序Tfasta(GCG，版本9.1)，通過對bal、cep、com和sta簇的比較，分析以這種方法鑒定的每個(gè)編碼序列。然后使用程序Blast對GenBank、或使用Fasta對SwissProt搜索沒有確定與這些簇中任何一個(gè)相匹配的編碼序列。最后，通過使用程序Pileup(GCG，版本9.1)對相關(guān)序列多重比對，或者通過搜索上游核糖體結(jié)合位點(diǎn)，確定每個(gè)ORF的精確起始密碼子?？偣茶b定了37個(gè)ORF，命名為dbv ORF 1至dbv ORF 37。這些分析的結(jié)果概括于表1，在此作為SEQ ID No2至SEQ ID No38提供于序列表中。下面提供細(xì)節(jié)。
2A.特化氨基酸HPG和DPG的合成七個(gè)由dbv簇編碼的蛋白參與特化氨基酸HPG和DPG的合成即，ORF 1和ORF 2(SEQ ID NO2和3)參與形成A40926所需的HPG殘基的合成，它們分別編碼對-羥基扁桃酸酯氧化酶和對-羥基扁桃酸酯合成酶。在其它糖肽簇中可以發(fā)現(xiàn)這些ORF的同系物(表1)，其功能經(jīng)實(shí)驗(yàn)方法得以確定(Li等人，2001；Hubbard等人，2000)。ORF 31至34(SEQ ID NO32至35)參與形成A40926所需的DPG殘基的合成。在其它糖肽簇中可以發(fā)現(xiàn)這些ORF的同系物，其指導(dǎo)含有DPG殘基的七肽的合成(表1)，相應(yīng)基因產(chǎn)物的參與經(jīng)實(shí)驗(yàn)方法得以確定(Pfeifer等人，2001；Chen等人，2001)。ORF37(SEQ ID NO38)編碼對-羥苯乙醛酸和3，5-二羥苯乙醛酸的轉(zhuǎn)氨作用所需的氨基轉(zhuǎn)移酶，以分別產(chǎn)生HPG和DPG。其功能經(jīng)實(shí)驗(yàn)方法得以確定(Pfeifer等人，2001；Hubbard等人，2000)，它優(yōu)先利用酪氨酸作為氨基供體(Hubbard等人，2000)。該反應(yīng)導(dǎo)致對-羥苯丙酮酸酯的形成，對-羥苯丙酮酸酯然后可以通過ORF 2(SEQ ID NO3)基因產(chǎn)物的作用轉(zhuǎn)化為對羥扁桃酸酯。
在dbv簇中也發(fā)現(xiàn)有其它間接參與HPG和DPG合成的ORF，即ORF5和ORF 30(SEQ ID NO6和31)。ORF 5(SEQ ID NO6)編碼預(yù)苯酸酯脫氫酶，該酶參與對-羥苯丙酮酸酯的合成，對羥苯丙酮酸酯是ORF 2(SEQ ID NO3)產(chǎn)物的底物。該ORF因此編碼引發(fā)將酪氨酸轉(zhuǎn)化為HPG的循環(huán)的酶。因此，該ORF的表達(dá)水平對于為形成A40926提供充分水平的HPG而言是重要的。ORF 30(SEQ ID NO31)編碼多肽，該多肽與由細(xì)菌基因組序列鑒定的未知功能的假定多肽高度相似，最佳匹配由來自天藍(lán)色鏈霉菌的NP626911.1代表(表1)。然而，所有這些蛋白都表現(xiàn)4-羥苯甲酰輔酶A硫酯酶特有的保守結(jié)構(gòu)域(Benning等人1998)。因此，ORF 30(SEQ ID No31)的產(chǎn)物也許在這個(gè)小的聚酮化合物的合成中促進(jìn)DPG或其前體之一的釋放。ORF 30(SEQ ID NO31)是dbv簇所特有的(表1)。
2B.A40926七肽前體的合成由ORF 16、17、25和26(SEQ ID NO17、18、26和27)編碼的四個(gè)蛋白參與A40926七肽核心的合成。所有這些顯示與其他NRPS的顯著相似性。以與其他NRPS系統(tǒng)的比對為基礎(chǔ)，由這四個(gè)ORF編碼的蛋白的建議結(jié)構(gòu)域組成和特異性報(bào)告于表2中。
表2.dbv NRPS的結(jié)構(gòu)域組成及功能
不能根據(jù)dbv NRPS基因在dbv簇內(nèi)的遺傳定位來預(yù)測其特定功能的分配。事實(shí)上，盡管對于至今為止所有報(bào)導(dǎo)的糖肽簇，在模塊的基因順序和相應(yīng)氨基酸整合入多肽的順序之間存在共線性，但對于dbv簇，情況并非如此(圖2)，因?yàn)槠銷RPS基因被背弛轉(zhuǎn)錄。然而，可以在下列觀察的基礎(chǔ)上預(yù)測其功能和特異性i)由ORF16(SEQ ID NO17)指定的蛋白的結(jié)構(gòu)域組成，及其以硫酯酶結(jié)構(gòu)域終止的事實(shí)，與DPG殘基的識別和七肽最后一個(gè)肽鍵的形成、繼之為酶結(jié)合硫酯的切割的功能最為一致(表2)；ii)ORF 17(SEQ ID NO18)的模塊組織和結(jié)構(gòu)域組成，與所述含有模塊4至6的多肽最為一致，模塊4至6是七肽氨基酸4至6的識別及其整合所需的，如在其他糖肽NRPS系統(tǒng)所見的(vanWageningen等人，1998；Pelzer等人，1999；Chiu等人，2001；Pootoolal等人，2002)；iii)由于ORF 25(SEQ ID NO26)編碼兩個(gè)NRPS模塊但是僅一個(gè)C結(jié)構(gòu)域，所以該ORF產(chǎn)物的結(jié)構(gòu)域組織與其起始七肽合成和催化第一個(gè)肽鍵形成的功能最為一致(表2)；iv)ORF 26(SEQ ID NO27)的結(jié)構(gòu)域組織與含有負(fù)責(zé)識別和整合七肽中第三個(gè)氨基酸的模塊3的多肽最為一致，這是因?yàn)樵撃K不含有E結(jié)構(gòu)域(模塊2、4和5的功能所需)，且分別存在或不存在C和Te結(jié)構(gòu)域(表2)，分別排除了該ORF編碼模塊1和7。
在dbv簇中也發(fā)現(xiàn)其它間接參與A40926七肽前體合成的ORF，即ORF 15和ORF 36(SEQ ID NO16和37)。ORF 15(SEQ ID NO16)編碼功能未知的短肽。許多編碼NRPS系統(tǒng)的簇中發(fā)現(xiàn)該基因產(chǎn)物的同系物。ORF 36(SEQ ID NO37)編碼II型硫酯酶，該蛋白通常由其它含有NRPS或聚酮化合物合酶基因的簇編碼。這些硫酯酶被提議的功能是，通過去除與酶共價(jià)附著的異常中間物而增強(qiáng)NRPS和PKS系統(tǒng)運(yùn)轉(zhuǎn)的效率(Heathcote等人，2001)。其它已知糖肽簇不編碼該蛋白的直向同源物(表1)。
2C.七肽中芳族殘基的交聯(lián)由ORF 11至14(SEQ ID NO12至15)編碼的四個(gè)蛋白參與將A40926七肽前體的芳族殘基連接在一起的交聯(lián)反應(yīng)。這四個(gè)蛋白顯示與P450單加氧酶的顯著同源性(表1)。在與其它糖肽簇中發(fā)現(xiàn)的P450單加氧酶一致性水平的基礎(chǔ)上，以及在對由存在于bal簇中基因所編碼的P450單加氧酶所預(yù)測功能的基礎(chǔ)上(Bischoff等人，2001)，可以作出下列預(yù)測。即，ORF 14(SEQ ID NO15)的產(chǎn)物可能參與氨基酸2和4的芳族殘基的交聯(lián)；ORF 12(SEQID-NO13)的產(chǎn)物可能參與氨基酸4和6的芳族殘基的交聯(lián)；以及ORF 11(SEQID NO12)的產(chǎn)物可能參與氨基酸5和7的芳族殘基的交聯(lián)。ORF 13(SEQ ID NO14)的直向同源物不存在于bal、cep和com簇中，但是見于sta簇中(表1)。由于在與A40926相似的A47934結(jié)構(gòu)中，在氨基酸1和3的芳族殘基之間含有額外的交聯(lián)，ORF13(SEQ ID NO14)的產(chǎn)物可能參與該交聯(lián)反應(yīng)。
2D.β-羥基酪氨酸的形成以及芳族殘基的氯化由ORF10和ORF28(SEQ ID NO11和29)編碼的兩個(gè)蛋白參與β-羥基向作為氨基酸6存在于七肽中的酪氨酸殘基的加成，以及氨基酸2和6的族組殘基的氯化。在與其它糖肽簇中發(fā)現(xiàn)的編碼鹵化酶的基因的一致性水平的基礎(chǔ)上，以及在對存在于bal簇中的鹵化酶基因所預(yù)測功能的基礎(chǔ)上(Puk等人，2002)，ORF 10(SEQ ID NO11)的產(chǎn)物可能參與氯原子向氨基酸3和6的芳族殘基的引入。ORF28(SEQ IDNO29)的產(chǎn)物是高度相關(guān)的蛋白家族，含有非血紅素鐵雙加氧酶特有的基序。從sta簇預(yù)測了一個(gè)這樣的蛋白(Pootoolal等人，2002)，提示該蛋白參與酪氨酸的β-羥基化作用。該羥基化反應(yīng)的精確的時(shí)間選擇目前尚未知。由于它發(fā)生在balhimycin的合成中，所以它可能出現(xiàn)在氨基酸6整合入七肽之前(Bischoff等人，2001)；它可能出現(xiàn)在七肽合成期間、或七肽骨架完成之后。
2E.糖的加成和修飾，以及N-甲基化由ORF 9、20、23、27和29(SEQ ID NO10、21、24、28和30)編碼的五個(gè)蛋白參與A40926生物合成中一些晚期步驟。它們的預(yù)測功能如下。ORF 9(SEQ ID NO10)與由其它糖肽簇編碼的蛋白高度相關(guān)(表1)，已證實(shí)它們參與糖向存在于4位的氨基酸殘基芳環(huán)對羥基的附著(Solenberg等人，1997)。ORF9(SEQ ID NO10)特定地編碼糖基轉(zhuǎn)移酶，該酶參與N-酰基葡糖胺殘基向A40926糖苷配基的附著。沒有其它得到說明的糖肽簇編碼具有這種特異性的糖基轉(zhuǎn)移酶。
在其它得到說明的糖肽簇中沒有發(fā)現(xiàn)ORF 20(SEQ ID NO21)的同系物。該蛋白含有甘露糖基轉(zhuǎn)移酶蛋白家族的特征基序(表1)。另外，在天藍(lán)色鏈霉菌基因組中(表1)、以及指定抗生素雷冒拉寧(ramoplanin)合成的游動放線菌屬物種的簇中(WO0231155)，鑒定了該ORF的同系物。由于雷冒拉寧含有附著于肽核心的甘露糖殘基，附著所有這些數(shù)據(jù)指向ORF20(SEQ ID NO21)在甘露糖殘基附著至氨基酸7羥基中的功能。在下面的實(shí)施例4中也證實(shí)了這種假設(shè)的功能。
在其它得到說明的糖肽簇中沒有發(fā)現(xiàn)ORF 23(SEQ ID NO24)的同系物。該蛋白含有?；D(zhuǎn)移酶家族3的特征基序(表1)。由于A40926含有附著于氨基糖殘基NH2基的?；?，所以所述ORF的產(chǎn)物可能直接或間接參與A40926前體的?；a(chǎn)生表征A40926復(fù)合物的化合物家族。
在bal和cep簇中發(fā)現(xiàn)ORF 27(SEQ ID NO28)的同系物(表1)。已經(jīng)證實(shí)，來自cep簇的ORF 27同系物參與chloroeremomycin中間物的末端亮氨酸殘基的N-甲基化。A40926的N-末端位置存在HPG殘基。因而，ORF 27(SEQ ID NO28)的產(chǎn)物可能催化糖肽前體中HPG殘基的N-甲基化，并且因此被賦予了與其它得到說明的甲基轉(zhuǎn)移酶不同的特異性。
在其它得到說明的糖肽簇中沒有發(fā)現(xiàn)ORF 29(SEQ ID NO30)的同系物(表1)。該蛋白含有FAD結(jié)合特有的基序，顯示出與己糖氧化酶相當(dāng)大的匹配(表1)。由于A40926含有附著于氨基酸4的葡糖醛酸胺殘基，所以由ORF 29(SEQ ID NO30)編碼的蛋白可能參與葡糖胺殘基的氧化。由于該蛋白也含有分泌到細(xì)胞質(zhì)外的蛋白的特征性假定信號肽序列，所以所述氧化可能發(fā)生在細(xì)胞質(zhì)外，使用附著到糖肽核心的葡糖胺殘基為底物2F.輸出和抗性由ORF 7、18、19、24和35(SEQ ID NO8、19、20、25和36)編碼的五種蛋白參與A40926或其某些前體向細(xì)胞質(zhì)外的輸出、以及賦予生產(chǎn)菌株抗性。其預(yù)測功能如下。
在其它得到說明的糖肽簇中沒有發(fā)現(xiàn)ORF 7(SEQ ID NO8)的同系物。所述蛋白含有羧肽酶VanY家族的特征基序(表1)。該家族在某些萬古霉素抗性腸道球菌中研究最為充分，在腸道球菌中，該家族參與末端丙氨酰殘基從初生肽聚糖中某些五肽鏈的去除，從而降低結(jié)合到其分子靶標(biāo)的糖肽的程度(Evers等人，1996)。ORF 7(SEQ IDNO8)因此可能參與在生產(chǎn)性菌株野野村菌屬物種ATCC38727中賦予對A40926的某種水平的抗性。
在其它糖肽簇中存在ORF 24和ORF 35(SEQ ID NO25和36)的同系物(表1)。預(yù)測它們分別編碼ABC型和依賴離子的跨膜轉(zhuǎn)運(yùn)蛋白。因此，它們可能參與A40926或其某些前體的輸出或區(qū)室化。在其它得到說明的糖肽簇中沒有發(fā)現(xiàn)ORF 18和ORF 19(SEQ ID NO19和20)的同系物(表1)。預(yù)測它們編碼另外的ABC-型運(yùn)輸?shù)鞍?，其中，僅ORF 18(SEQ ID NO19)經(jīng)預(yù)測為跨膜蛋白。因此，它們可能參與A40926或其某些前體的輸出或區(qū)室化。
2G.調(diào)節(jié)由ORF 3、4、6和22(SEQ ID NO4、5、7和23)編碼的四個(gè)蛋白參與一個(gè)或多個(gè)dbv基因表達(dá)的調(diào)節(jié)。在其它得到說明的糖肽簇中沒有發(fā)現(xiàn)ORF 3(SEQ ID NO4)的同系物。所述蛋白含有LuxR家族正調(diào)節(jié)物的特征基序，且與從吸水鏈霉菌PKS簇中發(fā)現(xiàn)的一個(gè)正調(diào)節(jié)物最為相關(guān)(Ruan等人，1997)。在其它糖肽簇中存在ORF 4(SEQID NO5)的同系物(表1)，它們屬于LysR型正轉(zhuǎn)錄因子調(diào)節(jié)物家族。因此，ORF 3和4(SEQ ID NO4和5)可能為一個(gè)或多個(gè)dbv基因的表達(dá)所需。ORF 6和ORF 22(SEQ ID NO7和23)編碼細(xì)菌雙組分信號轉(zhuǎn)導(dǎo)系統(tǒng)的兩個(gè)成員。前一個(gè)蛋白是可能的反應(yīng)調(diào)節(jié)物，與天藍(lán)色鏈霉菌CutR蛋白具有最佳匹配(表1)。后一個(gè)蛋白是可能的跨膜組氨酸激酶，與吸水鏈霉菌的假定傳感器蛋白激酶最為相關(guān)(表1)。因此，ORF 6和22(SEQ ID NO23)可能參與感受觸發(fā)dbv簇中一個(gè)或多個(gè)基因表達(dá)的信號。
實(shí)施例3-dbv簇在ESAC載體中的分離使用實(shí)施例2中提供的信息，如下所述在ESAC載體中分離dbv簇。以在pPAC-S1載體中的野野村菌屬ATCC39727 DNA建立基因組文庫(Sosio等人，2000b)。按照說明將來自野野村菌屬ATCC39727的DNA預(yù)先置入瓊脂糖填料中(Sosio等人，2000b；WO99/67374)，并且以Sau3AI部分消化以最優(yōu)化片段大小在100-200kb范圍內(nèi)。簡單地，按照說明將產(chǎn)生的DNA片段走PFGE凝膠，從瓊脂糖凝膠回收并釋放(Sosio等人，2000b；WO99/67374)。按照說明進(jìn)行因而發(fā)生的步驟，包括載體制備、連接和大腸桿菌DH10B感受態(tài)細(xì)胞的電穿孔(Sosio等人，2000b；WO99/67374)。將產(chǎn)生的菌落排列在尼龍濾器上，并使用兩個(gè)探針通過雜交進(jìn)行篩選，探針來自野野村菌屬ATCC39727基因組DNA的PCR擴(kuò)增。使用寡核苷酸5′-TCAGGAGACGAACCCCGC-3′(SEQID NO43)和5′-GTGCACGAAAGTCCCGTC-3′(SEQ ID NO44)獲得探針A；使用5′-ATGGACTCCCACGTTCTC-3′(SEQ ID NO45)和5′-TCAGGGGAGACATGCGGT-3′(SEQ ID NO46)獲得探針B。所有這些序列衍生自SEQ ID NO1。然后分離對所有這些探針陽性的ESAC克隆，并以EcoRI和EcoRV消化繪制物理圖譜。從一個(gè)這類實(shí)驗(yàn)中，分離含有約84kb插入片段的ESAC克隆NmES1。NmES1跨過整個(gè)dbv簇(SEQID NO1)，并延伸至SEQ ID NO1的核苷酸1的5’約5kb，以及SEQ ID NO1的核苷酸71138的3’約8kb。
上述實(shí)施例用以闡明可以在ESAC載體中獲得dbv簇的原理和方法學(xué)。本領(lǐng)域技術(shù)人員將想到，pPAC-S1載體僅是可以用于此目的的ESAC載體的一個(gè)實(shí)例。其它用于克隆整個(gè)dbv基因簇并轉(zhuǎn)移到適宜放射菌類宿主中的載體已有說明(Sosio等人，2000b；WO99/67374)。另外，用于制備野野村菌屬物種ATCC39727 DNA的大插入片段文庫的其它方法也在本發(fā)明范圍內(nèi)，這些方法包括但是不限于部分消化、片段分離和回收、載體制備、連接和大腸桿菌細(xì)胞的轉(zhuǎn)化。本領(lǐng)域技術(shù)人員也將想到，一旦如在SEQ ID NO1中那樣確定了dbv簇的邊界，可以使用除上述探針A和B之外的任何探針或探針的聯(lián)合，來篩選以野野村菌屬物種ATCC39727 DNA建立的文庫，以鑒定插入片段跨越整個(gè)dbv簇的克隆。作為選擇，使用SEQ ID NO1和表1中提供的信息，可以從其它基因簇獲得有用的探針，這些基因簇含有與dbv基因足夠相關(guān)的基因，以允許異源雜交。所有這些變異在本發(fā)明范圍內(nèi)。
實(shí)施例4-使用基因置換的A40926途徑操作使用實(shí)施例2中提供的信息，如下所述在ORF 20中構(gòu)建框內(nèi)缺失。通過以寡核苷酸5′-TTTTGAATTCTCAGGCGATCCGTCCGTCT-3′(SEQ IDNO47)和5′-TTTTCTAGAGCCCGGACACCCGGGGGCTGA-3′(SEQ ID NO48)擴(kuò)增獲得片段A；通過以寡核苷酸5′-TTTTCTAGAAGTCATGGTGATGTGCGACAT-3′(SEQ ID NO49)和5′-TTTTAAGCTTATGTTGCAGGACGCCGACCG-3′(SEQ ID NO50)擴(kuò)增獲得片段B。然后，使用EcoRI和XbaI消化片段A，使用XbaI和HindIII消化片段B，二者都連接到事先以EcoRI和HindIII消化的pSET152(Bierman等人，1992)中。大腸桿菌DH5α細(xì)胞轉(zhuǎn)化之后，產(chǎn)生的質(zhì)粒指定為pSM4，根據(jù)EcoRI和HindIII消化后存在4kb和1.5kb片段而識別該質(zhì)粒。將pSM4的等分試樣轉(zhuǎn)移到大腸桿菌ET12567(pUB307)(Kieser等人，2000)細(xì)胞內(nèi)，產(chǎn)生菌株SM4。然后，將來自LB中過夜培養(yǎng)物的SM4細(xì)胞約108CFU與在Rare3培養(yǎng)基中生長約80小時(shí)的野野村菌屬ATCC39727約107CFU混和。將產(chǎn)生的混合物涂布于HT盤上，其于28℃溫育約20小時(shí)。用水溫和洗滌去除過量大腸桿菌細(xì)胞后，使用3ml軟瓊脂將盤覆蓋，軟瓊脂中含有200mg萘啶酮酸和15mg/ml阿泊拉霉素。另外于28℃溫育3-5周后，將野野村菌屬接合后體在含有阿泊拉霉素的新鮮培養(yǎng)基上劃線。進(jìn)一步處理一個(gè)名為菌株SS18的這類接合后體。在不含阿泊拉霉素的HT培養(yǎng)基中將菌株SS18培養(yǎng)數(shù)代，將適宜的稀釋物涂布于不含阿泊拉霉素的HT瓊脂上。使用寡核苷酸5′-TTTTGAATTCTCAGGCGATCCGTCCGTCT-3′(SEQ ID NO47)和5′-TTTTAAGCTTATGTTGCAGGACGCCGACCG-3′(SEQ ID NO50)，通過PCR分析單菌落。根據(jù)存在1.5kb條帶，識別含有缺失的ORF 20等位基因的菌落。在HT培養(yǎng)基中培養(yǎng)一個(gè)指定為SSM18的這類菌落，通過與可信標(biāo)準(zhǔn)物比較確認(rèn)去甘露糖基-A40926的形成(Malabarba和Ciabatti，2001)。
上述實(shí)施例用以闡明能夠在A40926生產(chǎn)性菌株野野村菌屬物種ATCC39727中由突變的拷貝置換ORF的原理和方法學(xué)，所述ORF選自任何由SEQ ID NO2至38指定的ORF。本領(lǐng)域技術(shù)人員將想到，ORF20(SEQ ID NO21)僅是用于在SEQ ID NO1指定的簇中產(chǎn)生框內(nèi)缺失的方法學(xué)的一個(gè)實(shí)例。本領(lǐng)域技術(shù)人員也理解框內(nèi)缺失僅是用于生成突變的一種方法，在任何由SEQ ID NO2至38指定的ORF中，也可以使用其它方法產(chǎn)生無義突變型，這些方法包括但是不限于移碼突變、插入和定點(diǎn)突變。本領(lǐng)域技術(shù)人員也理解，確立了在任何由SEQ IDNO1指定的ORF中產(chǎn)生突變的方法后，這些相同的方法學(xué)可以應(yīng)用于改變這些相同ORF的表達(dá)水平。這一點(diǎn)如何實(shí)現(xiàn)的實(shí)例包括但是不限于所述ORF的多拷貝在野野村菌屬物種ATCC39727基因組中任何位置的整合、控制所述ORF表達(dá)水平的啟動子中的改變、干擾其表達(dá)的反義RNA或轉(zhuǎn)錄終止子的去除。
最后，在用于將突變的等位基因引入野野村菌屬物種ATCC39727的載體中、在供體和受體菌株的接合和培養(yǎng)條件中、在選擇和篩選接合后體及其衍生物的方法中的所有變化均在本發(fā)明范圍內(nèi)。
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ccgcacgtgc gggggcaggc ggaaccggtt gcggatgtca cgtggcctgc ggcccatcca 660cggcacatcg agcgtgagca tcaacgcccg gcaccccgcg tcctcggccc ggcggatcag 720gccgagggtg gcggcgtgct cgcgaaggca gtagagctgg aaccagacgt gtccccccag 780ggcggtgacg tcctccaccg ggacgctgct caaggtgctg acggtgaacg ggaccccggc 840gtcccgcgcc gcccgggccg tcgccagctc accgtcggga tgcacgagcc ggtggtaggc 900gacgggggcc accgccaccg gcatcgtcgc ggggtggccc agcagcgtcg cacgggtgga 960gcacgccgac acgtcctgga gcacccgcgg caccaggaac acccggtcga aggcggcccg1020attcgcacgg agggtctgct cgcggccgct cccgccgtcg atgaagtccc ggacgtcggc1080ggggaggacc ttggcggcga tctcctcgta ctcggcgagg cagacgggac tttcgtgcac1140gctgtcagga cgctcgggcc cgctgccggg acgctcgggc ccgctgccgg gacgctcggg1200cccgctgccg ggacgctcgg gcccgctgcc gggacgctcc cgcacgctgc tgggacgctc1260atgcacgctg ctgggacctc gccacctcga cggcctcgta gagggccttg atgttggcgc1320ctccgaaggt gcgggctccc tgccgctcga tgacctcgaa gaagagggtc tcgcgcggat1380gggtggacgc cgtgaagatc tggaagagct gtccgccgtg atcctcgtca gcgagcagtc1440ccgtcgcgcg caactggtcc accgtgtgac cccggatctg gatccgtgat tcgagcaggt1500cgtagtagct gcccggcgtg ctgaggaagc ggacgccccg ctcggacagg gtgttcacgg1560cgtgcacggc gtccgaggag gagaaggcga cgtgctgcac cccggcaccg gcgtgccgtt1620cgaggaacat gtcgatctgg ccggcctcgg ccatcgggtc gggttcgatg agtgtcagcg1680tgacggcgcc ggaggcgctc tgcaccacct tggactccat ggcctgggtg ccgacctcga1740tgcgttcctt gaaggtctcg ctgaagccga gggtggcgac gtagaagtcg gtgatgatgt1800cgaggtcacc cgtgggcagg cacacggcga agtggtcgat gtcgagcagc tccgccgcgt1860ccgcaccgga ctcggcggcg gacggagcct cggagaagcc gaccggcagg ccggggtcgt1920
cgccggggtc ccgctggacg agggtgtgga ccacgtcgcc gaagccgccg atcgcggcgg1980agcaggccgg cccggggccg gggtgccggg acggggaccg tacgggccgg gcgccggcgg2040ccacggcatg ggtgaagacg acgtcgacgt cgggggtccg cagggcgatg tcggcgaccc2100cgtcgccgtg cgtccgcaca taggccgaag ccggatggcc gtcggacgtg gcctgggtga2160ggacgagggt gatgcggccc tgccggagcg cgacgctgcg atggtcgctg gcgttcgccg2220tgcccacgac ggcgaagcgg tattcgtcgg tccaagggag agtggcgacc ttcagatccg2280ctacgtacat ttcgacgtaa tcaacggcga gaggcggaag cgattccata ttccgacgct2340acggccgggc ggggaggttc gcaccgtgtc cattggacgc gctcgcaggc cgcgctcaca2400gcagattccg gtacattccc gaggcctttt caggccggcg tggacggtcg gcggatcagg2460cttcataaaa agcctgccct ggcgtattct cgggttaatc aaccccgatg gatatcctgc2520ccgaggccgg cgaattcggc ttgtcgaact cttcgctcta cagccgcact gcctcacgcg2580gctcgcggcc ggctgtggcc gtcgccttat cggcgatgtc cgcggcgaag aggttgccca2640ggtcaccccg agtctgtacg tggagtttcc gatagatcct ggtgagatgc tgctcgaccg2700tgctgcgcgt gatgtagagc gcctcggcga tctcacgatt ggtgtgccca cgggcggcga2760gcacggcgac ccgccgttcg gcgccgctca acggtgcggt ctcaccatga tcgtgctgtg2820cggcgagcct cctcatcaag ggcttcgcgt tgcactcgcg ggccagctcc tgcgcccgca2880cccagtaggc ccgggcctcg tccttgccgc ccttgagctg tggggtcccg gcgaggtcgc2940agagggaaag ggccagctgg tagcgatcct gggcggcctc cagcgcgtcc acggactgca3000tcagcaaccg ctggcgctgt gcgggcttgc tcagctgcgc gtgcaggcgg agggcgaccc3060cgtacgtccg caggtcaccg gaggaggtgt gggcgatctg ggccgtgacc agatcggccg3120ccctgcgacg ccagcccagt tgcaggcacg ctcgcgccgc gccgaggcgc caggggacca3180cgtcggacag gctgctgccc cagcgctgga ccgcctgccc gcatgccagg aagccggcga3240
aggcggcgcg aggctgctcc gtgaccaggt ggtagtgcgc cctcgcgagc tcgtagccga3300tcccgaaggc ggtctccgcc gtctcgcggg gcatcggcac cgccacggtc gccttcgcct3360cgtcgaggtg gcccatcgcg gtctgggcat ggagcagggt gctgagtggc gcgccgatcg3420cgacgcccca gccgctgggc tgcagtatgg tcagcgcctc ctgcgcatgg gcctcggccc3480ccgccaggtc gcccttgcgc cacgccgtct ccgcccggat ggcggagatg atcgccttcc3540aggtgggcgc cttcgtcacc ccgggctcct tgaggagcgt ctcgcaggag gccgccacct3600ccgacactcc gcccagcagc agtgccatca gagccgagat gatgctgtcc atcgcctcat3660ccgtcggctc cgcctgacgc aggatccggc gcgcgtcctc gactgtctgg cccatcgagc3720cgcgggcgga ccggggcaat ctgtcgagaa gcaccgggtg gacgtggcac atcgcgatca3780aggacgcgtc ggcgtccctg tcggcgacgc tcggcctcag ccgatcgatc agctccgccg3840cgtcggcgaa ccggccgtac cacagcagct ggcggaacag ctccatcccg tgagatccac3900gcaacgcacc cgagcgcgtg gcgtcgagca gatcgggcac gtgacgtgcc gccactgccg3960ggtcgacgcg ccactccgcc gcggcgagca tcaccttcac gtccagccgg cgaggcgtgc4020cccagccgga cgccagggcg agccgtaagc acttcatgac agcgacgaaa tcaccctcgt4080cgaacgcctg ccttcccgct tcgacgagga cgtcgaaagc ccactcctca cccgaccagc4140ccgcctccag caagcgcgtg gccacagccg acggtgggcc tccccgccga tggaggatct4200ccgcggcccg ccggaggatc tccatcctgc cgtaggaggt catgcgcccg agtacggcca4260ggcggcccgc ctcatgacga aagcgccccc cggccaggag cccggcgcgc tccagcatcc4320ccatcgagcg tgtcgcggca ggaggggcga tgcccacgag ctcgcccacc gcgtccggcg4380tggcgtgctc gccgaggacg gccaccgcct ccgcgacgcg gacggcctcc ggctcgcagc4440catgaacgca cgctgccacc gcgctcatga aggagtcgcc gaccacgagc ccgggcgcgc4500cggcctcctg atcctcgatc agcgcccgga ccagcagcgg gctgccgccg ctgaagcggt4560
agaggtcgtc ggcgagctgg tcggccgtct cggccccgag gtgctcggtg gcgaactgcc4620tgaccgccgg acggggcagg agcggcagct cgaccagctc gatgccgggc aggcgcagca4680aggactcggc gacatggggg agaggggccg gcggccggtc ctggcagatc gtgacggcga4740tcatcatcct ggtgtccgtc agcaggggcg tcatggacag gatggccagc agggacggat4800cgtcggcgag atccacgtcg tcgatcgtca ggaggatcgg gttcgcctcg gccatctgga4860acagggagac gcagacgtcc tcgaccgcgt caccgcccct gcgcgcggtc agccgctccg4920ctgccccgcg gcccaggatc tggtcggcga ccccccagtc cagcgactgc tccgccggcg4980tgcagcgggc cgtgaccagc cggatgccgg ccgcgatgga tcgcatgccg agctcgtgga5040ggatggcggt cttgccgccg accacaggcc ccgtgatgac ggccactcca ccgcggccgg5100ccgcggtgga atcgagcaac ctcgtcagac tcttcagttc acgatctcgc ccgaacagca5160ctcttgctcg tcccccaagc ggttcgtcga cttggtttgc cgtgtgcctg atctggtcct5220ggtcccgtcg ctctacatac ggccgcccgg ctcatccact cgtgctcatc cagcggccag5280atcggtcgcc cgcccctcca ggcgatccgc gaacgctgcc cagatctggg catgatccct5340ggcgcatctc gcgacaacgg tgccccaatg cggcggcact ccgcgcaaga tcctttccca5400ttcctgcccg tcgatggagt gcaatgatag cattcgcaac aaaattcggc cggtttcggt5460cagacgtaat gcgggatcgg ccttgagcct ttccagcacg gcttggcggt ctcggccgtc5520gacgtggccg aaatcctgtt ctgcccgacg cagtaattcc ggcttggtcc ttaatctccg5580gctcccgtcc ggaatcgggc tctcaccgtg ctccaaccgg cctctcacat cccggaccgt5640ctccggggag atgccgacct gtttggcgac ctggcggagc gaaaggtccg gatggctgcg5700gatgagctcg gcggcgagtc tcctcccctc tgagctgtcc accggacgga tgcgcccgtc5760ccgcccgatt ctggcctcgt caccgccttg tcctctgcgc ctgcgcaggt cggccaccgt5820gccggcggag atgccggtcg ccgaggccac ccgtcgatca gaccactgcg gatgtgtccc5880
gatgatccgg acggccgcac gcttgcggtc ggccagtgag agcggcagcc cgtgccgcac5940gttcgcctcg acggccagga cgaaggcgtc cgattcggtg ccgtcgatca gcctcaccga6000gattgttgtt tcacccctga cccgcgccac cttcaaccgg tgcaggccgt cgatcacccg6060catcgttgga cggtggacga gaatgggcgg aagctcccct tgtgccgaca acagggtctc6120gacgtgctct ggatcctcgc ccgaagtccg gggtgagtac acagaggaca gccgggacag6180ctcgatttcg acgacaggga gagtggctat gtcaactccc gtcgggtcca cctagcctcc6240gattcgatta gcgtcatatc ggagccgggg gcgttcaaaa aacaacccag ccgcgtgcgc6300cgcgcgcacc ttcgacgatt ccccgtcgcg cctgcagcat ctggtcccgg gcaagcctgg6360acttcccggc gcgagctgca taaatcgatc ggccaagtgc tctgtcgaga gaatgcgtcg6420catcctcttt tcttcggcaa ctccacgcgg caaagaattg gacgctgtcg ccgcgaatcc6480gtagccgtct acctcatcga attgcagaac gcttcccgtt agcattccga tcactccgac6540tttcggttag gccttcctcc ggaaggttaa aggaggctgt gcaggtcgaa ccacccccta6600tcccggacat ccacccccct agtttcggat aagaccgatg cgcggggttg cgcctctgtc6660gcgaagcgga gtatccggtg ctggaccgcc cgaatcgagc ggtcaccatg cgtgtcaatc6720cgtgtgtatt ggcatgcgcc gtcggcgcga gcccggcggg gccgcggcgg tcccacggtt6780tcgctcatga caccgtctcc aggtgagggt gatcgcggta gccggccacg ggcgcgctgc6840cgcagcggcg gccatgctga tctgcccatg gaccagcagg ccgacggtga ggtcccgccg6900gacggccggc tcccggtaca acgtacgtca gttcttctcg gcgatctagg ggagtgggcg6960gggtgccttc gccgggcatg cgggcggcct gtcctttggc aattgacagg cgtgaatgca7020gaaaggagcg cggccacctc tgacctgccg agtaagggaa tggattactc atcaatggcg7080ccggtggcca cggaactcgc ccggcgatcc ggcgtgtcca aatggcgcgg tgcccaggcc7140cgccgatgga caccgcccgg tgcgcgggct taagaagtag ccgtgaccct ggagaggacg7200
ctcatcgtcg gcaccggtct gatcggcacc tccgccgcgc tcgcccttcg cgagaagggg7260gtggcggtct acctgtccga cgtcgacgca catgccgtac ggctggcgcg agcgctcggc7320gcgggccagg agtggaccgg tcagcgcgtg gacctggcat tgatcgccgt gcccccgccc7380agcgtggggc agcggctggc cgatctgcag cagcggcggg ccgcgcgggc gtacaccgat7440gtgaccagcg tcaaggtcga tccgatcgcc gacgcggagc ggctcggctg cgacctgacc7500tcctatgtcc ccggacaccc gctcgccggc cgggagcggt ccggcccggc cgccgcccgt7560gccgatctgt tcctgggacg tccctgggcg ctctgccccc gccctgagac gggtgcggat7620gccgtgcggc tggccaggga gctggtctcg atgtgcgggg cggagcccta caccgtgagt7680gcgggcgagc acgacacggc ggtggcgctg gtgtcgcacg ccccgcacgt ggccgcgtcc7740gcggtggcgg cgcggctgag ggacggcgac gacgtcgcgc tggccctggc ggggcagggg7800ctgcgcgacg tgacgcggat cgccgcaggg gaccccctgc tgtggcggat gattctcgcc7860gcgaacgccc tgccggtggc cggggtgctg gagcggatcg cggccgatct cgccgcggcg7920gcctcggcgc tgcggtccgg cgatctcgac gatgtgacgg atctgctgcg gcgcggcgtg7980gacggccacg gccggatccc cgacaagcac ggcggcccgg cgcgtgacta cacggtgatc8040caggtggtgc tgcaggatcg gccgggagag ctggcgaggc tcttcaacgc ggcggggctc8100gcggacgtca acatcgagga catccgcctg gagcactcgg ccggcctgcc ggtcggggtg8160gtcgaggtct ccgtgcgccc ggaggacacc ggccggctca ccgaggcact gcgcttccac8220ggctggcacg tcccgcccgt ccccgacggc aactcgagga tcgaccggac gcgagctatg8280gtgtcagact gacagccccc gatcgagacg gcgacacgaa tgcgcgttct ggtggtggag8340gaccaagtcg acctggccga ctcggtggcg cgggtgctgc gtcgcgaggg catggccgtc8400gatgtcagtc atgacggcga tgacgcacag gagcgcctct ccgtgatcga ctacgacgtc8460gtggtgcttg atcgggatat tcccggcgtc catggcgacg agctgtgcgc tgagatcgcc8520
gtggacgatc gcaggacccg ggtgctgatg ctcaccgcgt ccgggacgac cgctgaccgg8580gtggcgggcc tgagcctggg cgccgacgac tatctgccga agccgttcgc cttcgccgag8640ctggtggcgc gcatccgcgc cctgggcagg cgcgcgcatc ctcccgcgcc gccgatcctg8700gtccacggcg acctgcggct cgatccggcg caacgggtgg cgatcagggg cggcatgcgg8760ctgccgctga ccaccaagga gctggcggtc ctggagcatc tgctgaccgc gcgcggccgg8820gtggtgtcgg ccgaggagct gctcgaacgg gtctgggacg agcaagccga cccgttcacc8880accaccgtga aggcgacgat caaccggctg cgctcgaagc tcggccagcc gccggtgatc8940gaaaccgtcc cgcgcgaggg atatcgcatc tgatccgcgc ggtcacagag cggtcacacg9000ttctctgacc ctcgtgtcac cttctgctcc gtagaactgg tgtcagatca ccagactgga9060ggagagggat gaggagaagc gagggtgacg acgaaccacg cactctcccg cctcgggccc9120gggaccgggt gtacaccgcg gtcacgcggg tgctcgccgt gctcctgctg cccgtggcgt9180tcgtccgtca gcccggccgc gcccgcgagc tggcctgcgg ctgggcgttg aggatgcgat9240tcccggcaga ggacctcacc gggctcaccg acggcgccag ggcggcgttc accgcggcgc9300gggccgaggc gctgtggcgt cacggccagc tcgtcggtct cacttccgga taccgcgatc9360cccgggtcca gcagcggatg ttcgaggagg aggtgcgccg ctcagggtcc gtggccgccg9420cacggatgtt cgtggcgccg ccggccgagt ccaaccacgt caagggcatg gcgctggacg9480tacgcccgca cgagggcgcg cgctggctgg aggcgcacgg cgcccgctac gacctctacc9540gcatctacga caacgagtgg tggcacttcg aacaccgccc ggagtgcggt ggcacgccac9600cacggcggct accccaccca ggcgcggcct gggcgagccg gaacgggggc cgggtctagc9660tagggcacgg ggtcgccgcg gggatcggtc cccggccggc ttcggcgcta gggcagctcg9720atgcggccgc tccgctgata ccagtgacgg cccgccagca aatgggtgac gaccgccttc9780tccagcgtcg agcgctgcgg aagctcctcc agcggctggc cgttgtagcg gaagacgaac9840
tccaggatcg cgtcgtcccc gtcctgcggt tcggagtcga ggagcgtcca gccgcgtctg 9900agctgcagga tgtgggagtc ctcggcgaga tactcggcca gctgcggatc gagcagccac 9960gaggtgcctg tcgccgcccg ggcgccgtgc tcgggaaaat gccgttcgaa gaacgggcgg 10020gcacgacgga gcgagtcgta atagatgtcg gggatcagcg gcccgcccac ttcggggatg 10080tgcaggccga ggacgggcgt gccgtccttg gcgacggcca ggttgtactg gagccggccg 10140agccggtaga ccaggccgcg cacgagcagg gtgagccacc acggcatgtt cgtgccgccc 10200tcgccgtact tgcggcgatg gatggccacc gattccccca gctgcgtcag ggtctcccag 10260gtggtcgcct cggggatgtc ccgtgtcgcg tggaagcgcc gcaacgccgg aagcgtcgcg 10320aggaagacgt acacgtggaa gtagcgggcg gcggccccgg tctcgtacgg cagggtcggc 10380ccaccccgta ccttcacctt gtagtcgccc atgtgccgga cgagctcgtg gtgggcgcgt 10440tcgagcagcc accacagggc cgggtcgcga tccgggccgg gggtggccgc cacgatctcc 10500tcgacgtcgg gagccggcac ctccagccgg tgtaagagat cacgagcctc atcgccctga 10560ggcaggcgca ccggctcggg gggcggtccg agctcctcga gccgggagag ccacgccgtg 10620gcgttctctc ccagccgcag ctgcctgcgc acgctctcag catccatcgt cactccgttc 10680tgttccgccc ggccccggcg gccgtgtcga gcaggagttt cgcggccacg gccgccccgt 10740cggcgcggat cttcccggcc acgtcgatcg cccgcgcgcg ggtctcggga gccagcgccg 10800tggtgagcgc ggccgacagg ctctccacgg tcggcacccg cccgtcgtgt gccacgccga 10860tgcccagctc ggccacccgg ccggcgtggt acggctggtc ggtcatctgg ggcaccacga 10920cctggggagc gcccgcccgg gtgaccgcgg tcgtgatgcc cgcgctgccg gcgtggacga 10980cggcggccac ccggccgaac aacacctggt ggttcacctc gccgacggtc aggcagtcgc 11040tccggtcgtc gggcggggct aggccggccc agccacggga gacgatcacc cggtggccat 11100gggcccggat cgcctcgatg gccaccctcg cggcgtcggt gggggcgggc ccgctgccga 11160
actccacgtg caccggtggc gggccggcct ccaggaacgc ctccacctcg gcgggcaggg 11220gccgttcgtc gggcatgatc cacgcaccgg tctgcacgac gtcgaggtcc gtccgctgca 11280gcggggccag gaccgggtcc gcggccagga aggggcgatc ggtgtagccg tagctgaaga 11340tgtcgtccac cggcggcagg ccgatcgagg cccgccggct gttgagcgcg gcaccgaacc 11400gctggtaggc gccctggttg ttgcggtccc acagcacccg gttgtcggtc acgtcccgcg 11460cgggctgctc accgaggggt ggcggcggcg ggtagtacgg cgacggcaca tagatggggc 11520agtagaagac gtagacgtag gggatgccga gcttctcggc caccgaccgg acggcgaccg 11580ccgccgacag cacgccgctc accaccatca cctcgcaccc ctcggcggcc ggcaggacct 11640ggtcgagctg cgtggcgatg gcctcggcgt cgagccgggg cacgtcctcg agcgagggcg 11700gcctcttccc gtgcagcttc gcgcgcatcg aggtgccgac cggcaccagc ggcaccccgg 11760cctcggccag tctctccgcg cagtccggcg gggcgcacat ccgtgtctcc gcgcctagct 11820cacgcagctg gaccgccagg cccagcagcg gttcgacgtc cccgcgtgat ccggacgtcg 11880acaacaacac gcgcatgtcg tatccctgtt ccgtggattc tggtgcggat cgatcggaag 11940gccggagcct caggggtgat gtgtcagcca tctcatcccg tcgggtgagg tcaccagccc 12000gccggggaac agtggctgct cgggctcggc gtccgcaccg agcaccgccc tcatctgctc 12060ctgcccgccc tcctgcatca cctgtttgac cacctgtgac ttgaacagcg gcaccatgct 12120ggagtcgtcg ccgtcggcca tctgatcgac ggccgcggcg aactcggcgc tgcgctcggc 12180gatccgccct gaggtcgcca gcgccgtctc gccggaggac agaccgccca ccaggtccac 12240gaacgactcc agctcggtgt actccttgtt gttggtgacc ttcttggcgt gccagaaata 12300cgactcctcg ttcacgttca tctcgtagaa cgccagcagg aactcgtagt acacgctgta 12360ctcgcggcga tatcgcgcct cgaactcatg cagcgcgatc ttctcctcga cgtcaccggc 12420caggacgctg ttgatcgacc gggccgccag gaggccgctg taggtggcca ggtgcacccc 12480
ggaggagaac accgggtcca cgaagcacgc ggcatcgccc accaggatca tcccgggccg 12540ccagaacttc gtctggtggt aggagtagtc cttgcggacc cgcagctgcc cgtacttgcc 12600ggtcgtcacc cggcgcgccg gcgcgaggta ctccgagatc agcgggcact cggcgatcag 12660cgcggccagc gccttctccc gatcgccctg gatcttctcc gccatctccc ggcgcaccac 12720cgcgcccacg ctggtcagcg tgtcgctcag cgggatgtac cagaaccagc cgctgtcgaa 12780ggccacgctc aggatgttgc ccgagtacgg ctccgccagc cgcttgccgc cctcgaagta 12840accgaacagc gccaggctgc ggaagaactc cgaatagttc cgcgtgccac cgacgctgga 12900atacaaccgg ctcttgttgc ccgacgcgtc gatcacgaaa cgcgcggaca ccgcgtgctc 12960gccgccgtca ggatcgacgt aacgcaggcc ggtgacccga tcgccgtcct cgatcacctc 13020ggtgaccgag catccctcac gcaccaccac gcccttgcgt ctggcgttgc cgagcaggat 13080ctcgtcgaag cgtgcccgct ccacctggta ggcgaaagtc gtcggacccg tgatccgcgg 13140agagacggag aaggagaacg tccacggctc cggccgcgcc ccccaccgga aggtgccccc 13200gcgcttcacg ggaaaccccg ccgccgcgag ctcgtccgtc accccgagca tccggcacac 13260cccgtgcacg gtcgagggca gcaacgactc gccgatctga taccgcggaa agacttcctt 13320ctccaccagc agcacccgat gaccctgcat ggccaccagt gtcgccacgg tcgaaccgcc 13380agggccgccg ccggcgacca ccacatcgaa ctcttccacg gacttctcct ttttcgttgt 13440ggtcatgcga agtcgcccgg catttcggcc gcaggccgct accaggtgac cggcaactcg 13500tccgggcaat cgatgaacgc gttacggaac ttcacttcct cggcggacac cgccaggcgc 13560agcccgggaa accggcgcca caaactctga tacgccatgc gcagcagcgt cctggctatc 13620gccgcgccta tgcagtaatg gatgccgtgc ccgaacccga cgtgcgagcc gcagtcacgg 13680cgcacgtcga ggacgttggc attcggcgtc agcgcctcgt cgcgattcgc catcagaatc 13740gagcacagga cgtaatcccc ggccttgatc agctggccgt cgacgaccac gtcccggacg 13800
gcgagccgtg gattcggctg ctgcacgggc gacaggaacc gcagcagctc accgaccacc 13860cggtcggcct cctcgcgtcc ggcgaagaga gactgtcgct ggtcgggatg atccagcagc 13920gcgagaaccc cgaagccgat cgaccccgcg acggtttcga caccacccag gatcagcgcc 13980gtgagtacgc ccttcagctc ctcgtccgtg acatcgtctc cgtgctcccg caccagcatc 14040ccgatgaacc cctcgtcagg gtccttccgc tgccggatga tgaggccgtt cagataccgg 14100ttgaacgccg cgctgtcggc cgcccgggcc ttgaacccgc ggctgagatc gacgttctgc 14160ctgacacgcc ggatgaactc gatccgatca tcacgcggga tgccgagcag ctcacacagc 14220actcctccgc cgaccggatc ggcgaacagc gcctggacgt ccgcgggcgg ccccgcggcc 14280tccagctcgt cgatgcggtc atcgatgagg tcctgcatgg cgggctccag ccggcggatc 14340cggcgggccg tgaactccgg ggtcagcatc ccgcgcagcc gcgtgtgctc gggcggatca 14400tagaccgaca gctgaccgac cagattcggc ggtatgggct ctccggcgat cgatggcgcc 14460gaactccacc gggggcgcgt cgtgaagttc tcgtgatcgc cgagtattct gcgcacgacg 14520tcgtatccca aagcctgcca gacatagtcg acacgcagct gagtggccgc gtcaccgcct 14580atccggacca gtgggccatg cgccctgagc gcgaacatgt cctcatgcgg atcacagtgc 14640gtccgcatca tgtagttcgc cgtcggctgc aggaccggcg cgcccgcatc gatatcgtca 14700tccatacccg ggtcgaaact ccattcgctg tcgatccgca cgctcggctg atccgatcct 14760ggtcgcgggc ggaagatatt tccagcgtcg tcaaatggac gatgggaacg ggaattccgc 14820gatcaccagg cgaccatcag actggtcaat ccatacgcgg gagtggtcaa ccggaacgat 14880ggctcccgat cgggatccgc gagcctcagc gtgggaaaac gccgccacag ggcggtgtag 14940accgtgcgca gttcgaggcg ggccagagcg gctcccaggc aatgatggac gccgtgcccg 15000aacgcgacat gggggacggg ctcgcgccgg acatcgaggc ggccggcatc cggcagcagg 15060gcagggtcac ggttggccat gggcagagag caggagacgg tctctccctc cttgatcacc 15120
tggcccccga tggtgacgtc ctccatggcg acccggggcg tcggcgcata ggggacggtc 15180aggtagcgga tcagctcgtc gaccgcccga tccgccgact ggtcgtcgcc ctgcaacgcg 15240gcgatctgct cggggtgtct gagcagggcc agcacgccga gcccgatcat gccggagatg 15300ttgtcgtcgc cggccagcat cacctgaacg cagaagcccc gcagctcctc gtccgtggcc 15360gtgtcaccgt actcggcgag gacggctccg agcagcccct cgccgggatc cttccgctcc 15420ctggcgatca tggccagcag gtagcgggag aacgccgcgc cggcggccgc ccgcctcttc 15480tggctgcgcg aggcgtcgag atggccgtga cacagctgca tgaacatggc gcggtcgtcc 15540cgtggcaccc cgatcagctc gcacagcacg gcccctggca cctcgtcggc gacgagttcg 15600accagatccg caggggggcc cgcccgttcc agggcgtcga gccgttcggt cacgatctgt 15660tcgatgtacg gcttcagccg ccggatccgg cgcagggtga atcccggggt cagcttctgg 15720cggagccgcg tgtgctcagg cgggtcgtag tccatcaggt tcccgaccag ctcacgcggc 15780cggaagttgc ctcttccgcc gatctcgtcc cgttcgttcc agcggcgccg ggtgctgaac 15840cgccggtgat cgccgagcac ctgccgcacg acggtgtacc ccgtggccag ccaggtggtc 15900tccgcgtccg ctcctgatcc gatggtgatc ctcgtcagcg ttccggcggc gcgcagttcg 15960tccgccggat ccaggtcctg ccgccgagta tggaggggcc gcgcgccgtc accactcaac 16020gggaagctcc tccacggcga agggggccgg cttccccggt ttgaaccgca ggtcctctgc 16080cgggaccgcc agccgcagcg acgggaaccg gcggaccaac gccggcaacg ccacttgcgc 16140ctggagcctg gccagcggtg ccccgaggca gaagtggacg ccgtgcccga acgcgaggtg 16200ttcggggttg ccccgggtga ggtcgaagcg gtcctcgcgc gcacgattgc ccgccaggat 16260cgagcaggtc aggacatcac cggcgtggat gtcccgtccg gccaggcgcg tgtcgaccag 16320tgcggtccgg ggagaggggg tctcgacgat cgacgcgtag cggaacacct cctcggccgc 16380gctgtccgcg agctccggac gctcgcgcag cagcgccatc tggtcggggt gggtcacgag 16440
gaggagcacc gcgatcgcca gctgcgaggc catctgctcg accgccccga tcatgatccc 16500ctcgacgagc cccgccagct cctcgtcggt gacctcgcct ccgtgctcgc gcacgatgcc 16560gccgatcatc ccggtgccgg gatcgaggcg ttcgcgagcc gccagtttcc tggcgtagtc 16620gacgatgccc aggcccgaca cgttccgctg cctggggact cggctctccc ggctgtcccg 16680gaacatcctc gacagctcgg cctggtcgtc acgggggacg ccgaggaagt cgcaggcgat 16740cagcgccggg atgggccagg cggcgttcct gacgaagtcg accggcgacc ccatgctctc 16800cagatcggcc aagcagtcct cgacggtctc ttcgacgaca ggccgcaggc tctcgatccg 16860ccgggcggtg ttcgccctgg tcacggtcct gcgcaaccgg gtgtgatcgg gcgcgtcgta 16920cgactgcagg attcccggca gccaggcgcg ctccgcctcg tcctcgaccg ggcgcatcga 16980gctgaaccgg ttggcgtcgg cgagaatctc tctgatctcg ccatatccgg tgacgagcca 17040ctgcttgtgg ccgtccagcc ccggctcggt gtcgtactcg tgcagcggcc cgtcctcttg 17100caggtcgaag agcgccggca cgggatcgag cctcagccgc tgatgcggca gcggaaccac 17160catgattctc ctcagcttcc ggcgttacca gtcgagcagc agtgctttca cgtcgaacgg 17220cggcggcccc aatctgatct cttgttcggg ctcggccagc cggagtgcgg ggaagcggcg 17280tgccagagcc gggatcgccg accggaagat gagctcggcc aggggtctgc caagacagtg 17340atggatgccg tgcccgaacg cgacattcgg cgctctgtcg cgggtgaggt cgaactgatc 17400gtccgggccg gggaagtgcc gccggttcgc tcccagcaac gagcacgtga cggtgtcgcc 17460ggccttgacg atgcggtcac cgatgcgcac gtcctccagc gcgatccgcg gagtgagctt 17520ctcgtcgatg gtgagatagc gcaccatctc ctccagccag tcaggcacga cgtccggctt 17580gtcccgaagc agcgcgaact gctcggggac ctcggccatc agccacgcgc ccgccgcgag 17640gaaacgagcc acctggtcac cgcccgcgcc catgacgaac gcggccagcc ccgtcagctc 17700cgcgtcggtg atctcgtcac cgtgttcgcg caccacgacg ctgagcatgt cgtcgccggg 17760
atcacggcgc gtgcgagcca cgacctggcc catgtaggtc atgaacttgt tcccggcggc 17820tccgcgtctg ctggccgccc gctgggaccg gctggcgtgc aggctgcgtg acagctccgc 17880ctgatcatca cgtggaatgc cgaggaagtc gcaggtcgcc gtcgtcgcga tggaccaccc 17940gaaatgcggg acgaagtcca gcgggccacc gatggactcg atggcgtcca ggcagtcctc 18000gacgacctga tcgacctgcg ggcggaaccg ctccatccgc cggacggtga acgcgggcga 18060gaccacccgg cgcagtcgcg tgtgctccgg cgggtcgtac tgggtgatga agccgggaaa 18120gacgattccg gccgcggtcc cgccgtagag caacctggag ctgaacttgt ccgagcccag 18180cacctgccgg acctcgtcga acccggtggc gagccacgcg gtccgccctc cagggccttc 18240ctcggcgccc agctcggtca tcgggccctc ggccatgaag gaccgcagct gtggcaccgg 18300atcgaaccgg tccctccagt gcagctcccc gggcaggacg acgttgagct cctcgaacac 18360ttccacgtca caggtccttc cgcctcaacg gtggtctcag gccggtcgga cgggcgctgg 18420gcccgtccaa ccgtccacat caagcggctg gacaccctcg ctcaggcgcc ggcttccgcg 18480atgagactct tcggccggat gtccgtccag ttctcctcga cgtaggcgag gcattcctgg 18540cgggtggcca cgccgtggac gcgggtccag ccaggcggca cctccgcgaa cgagggccag 18600agcgagtgct gtccttcgtc gttgacgagc acgaggaagg agccgtcttc gttctcgaac 18660gggttggtca tcgctgtgtc ctttcaccgt ccggccgggg ccggagtttc tcggcgacga 18720cggccccgat ccgggccagc gccgcgggct gcagcatctg catgtggtcg atctcgatct 18780cgtgaggctc gacggttccg gtggtgaggg gtcgccagct ggcgatggcg tccgcgacgg 18840gcagatggga ggggcggttc actgtggcga cgaagagcag gatgtcgcag ccgaagctgc 18900gggaggtgtg cagcggcccg acccgggcga ggtgctccat gacctcgtcc aggcgcttcc 18960tggcgccggc ctccgtggcc accgcggcgg cgagctgcgc ctgctgctcc tgctgcctgt 19020cgaagtccgc ggcctcctga tcggccgcgt cgccgcgcgg gcgccggagc ctgcccacgt 19080
cggtgggata ggcgtcgagc agggcgagca ggccgacctg ctccccttgc tcctccagca 19140ccctggccat ctcctgcgcg atccgcccgc ccagtgacca cccgaggagg tggtacggcc 19200cggtcggctg cacggcgcgg atctgctcga cgtaatcggc cgccatctcc tcgacgccgg 19260ccgccagcgg ctccgtacga gccaggccgc gcgcctgcac gccgtagacc ggctggttgg 19320ggggcaggct ccgcagcagg ggcgcgtagt tccagctcag ccctccgctc gcatggacgc 19380agtacagcgg cggacggtta ccgccggctc gcagcggcag cagcacctcg aagtcgcccg 19440tgccggtctt caccgagccg ctcgatcccc gccgctcgcc gacgacgacc agggtgcccc 19500cggctgtcca gcgggcgagc aggcccgtgg gcagcatgcg ccgccccgtg gccccgaagg 19560ggcaggccag ggtccggtcg cccggctccg cgtccaccgc cgcgccggtg aggtagagct 19620cgccgacggc gacggcgggg cgcagccggt cgtcgagcac gagcgcgccg agcggaccgc 19680cctcggccag gtcggcggcc accgggggca cggcctcgga ccacttcgcc ggcgcctcgg 19740ccggacgttc gcgttcggcg tcgtccagca ggacgtccag gtcgctgacg cgccgctggg 19800gatcctccgc cacctgctcc aggaagctga ccagccgccg tgccagcgac tcggccgtgg 19860cctgatcgaa gaggtcggcg gcatagtgga gggtgccctc gatgccgtcc tcgtcgcggc 19920gctcggtgag cctgaacgcc agatccagct cgatggcctc cggcccgaca ggttcgacgc 19980tggtgcgcag ggcgggcagc tccgtcgcgt cccacgcgcc gaggtcctcc tcgtgcacct 20040ccaaccccac ctggaacacg ggatggcggg agagcgagac cggcaggtcg agcagctcga 20100cgatcctggc gaagggcacg tccaggtgct ggcgcgcgga ccggatcgcc tcctgcgccc 20160gggtgacgac ctccaggaag gtggggtcgc ccgagaggtc cgtgcgcagg gcgagcggcc 20220gggcgaaggg cccgatcatc ggctccaggt cgatgaggtc gtcgtcccgt ggcagcttcg 20280tgccgatcac caggtcgtgg cccgccccga gcctggtcag cagcatggcg agcgcggcat 20340gcacgatctg gaacgggtgc gcgccgatcg ggtccaccgc ctccaccagc ctggcgtgcg 20400
ggccggcgtc cagtcgcaac gacaccgtgc cggcccgccg cgacgcgacg gccgaccggg 20460ggcggtcgaa cgggagcacc gtctccccgt ggatgcccgc cagattgtcg cgccagaaca 20520ccagctgctc gttgatcagg ccgtccgcat cgcgctcgcc ttcgagcagg cgccgctccc 20580agatcgcgta gtcggcgaac tgcagtgtca ggggcgcccg ctccggtgcc cggccggcac 20640gccgcgcgcc gtacgccgcc gacaggtccc ggaggaacac atccagcgac tcgtcatcgg 20700cgaggatccg gtgcaccatc aggtgcagga cgtgttcccc gtcggagagc cggaacaggt 20760caccgcgcca cggcacctcc cgggtgaggt cgaagaccga ctcccgcagc tcggtgagca 20820gcccgggcag gctctcctcg gtggcgggaa ccggcgtcag gtcaaccggc gaggcgtcgt 20880gtacgtgctg gtgaacgctc tgcgcgtggc cggggaaggt cgtccggaga atctcgtgcc 20940gcgccgcgac gtcgccgagc gccgcctcca gcgcgggcac gtccagccgg ccgcgcaagc 21000gcagcgcgac cgagacgtgc aggccggcgg cctccccggg actcgccagc agccaggcgc 21060tgagctgctg ggcggtgagc ggtacccggc ccggccgttc ggcgggctcc agcgcggggc 21120gtgacttcgc ggccagcgcc cgggcgacac ccgcgggggt ggccgcggag aacagctgcc 21180ggatgggcag gtccgcaccg agctcctcac ggatccgcgc gatgagccgc atggccagtg 21240ccgaactgcc gccgagatca tggaaggcgt cgtcgacgcc cacccggtcg acgccgagga 21300tctcggcgaa gagcgcgcac agcaccttct cggtctcgct ctcctgtgcc ctgtccggcg 21360cacgtcccac gagatcgggg gcgggcagag ccaggcgatc caccttgccg ttgggcgtga 21420caggcagcgc gggcagggcg acgaccgcca ggggaaccat gtacgcgggc aggaccaggg 21480ccatctcccg ccggatctcc gccggccccg catcggttcc gtcggagatg aagtagccga 21540ccaggcgctt ctcgcccggc tggtcctccc gcgccacgac gaccgcctcg accacgccgc 21600gctgggccgc cagcacggcc tccacctcgc cgagctccac ccggtagccg cggatcttca 21660cctggtcgtc ggtgcggccg aggaacacca cctcgccgtc gcggttccag cgcgccaggt 21720
cgccggtgcg gtacatgcgc tcaccaggag aagggtccac ggaggccgga acggccacga 21780accgctctgc cgtcaggccc ggcccgccga gatacccgcg ggccagcccg gtgcccgcga 21840tgtacagctc gcccgccacc cccggcgcga ccgggcgcag gaaggcgtcc aggatgtaga 21900tcctgcggtt ggtcatggga cggccgatcg gcagctcccg cccgacctcc tcgccgggct 21960cgatcggctt ccacgtcgcg cacagggtgg tctcggtcgg tccgtacgtg ttgcgcaccc 22020gcaggccggg cacggcccgc cgcaggtgct ccacggactg cgccggaacc acgtcaccac 22080cggtcccgac ctcgaccagg cccgcgaaac actccgggga cgactccgcg agggcccgga 22140aggtaccggc ggtgagatgg acgaaggtca cgccccgttc gacggcctgt ctcatcccga 22200gcgcgtccag cactcccggc tcggtgagca cgacccggcc acccatggcg agcggcaccc 22260acatcgcgta gagcgaaggg tcgaagacgt gcgtcgcgtg catcagcacg gcgtcgcccg 22320ggccgatccg ccagccctcg tcgcccgcca ggccggccac ggccccatgg gggacgccca 22380cccccttcgg caggccggtg gagccggagg tgtacatcac gtacgccagg tcgtcggcgc 22440tcagccggat ctgcggcgcc gtggcggcac ccgcgtcgat ggccgcgcgg gtctccgggg 22500cgtcgatgac gatcgcgtcc gccggcgcca cttccctggt ggcccgggtg cacaggacgg 22560ccgagacacc ggagtcggcg agcacgaact cgatccgctc ggccgggtgc tcgacgtcca 22620ccgggacgta cgcggcgccc gccttccagc tcgccaggaa cgcgatcagc aggtcaggcg 22680acctgtccat gaccacgccg acgcggtcgc cacggccgat gccacgagcg gcgaggtggc 22740gggccagccg gttcgccgcc tggtcgacct cggcgtaggt caggtccgcg ccgccggcat 22800cggtgatcgc caccgcgtcc ggcgccgtgg ccacccgccg tccgaagaga tcgagcacgg 22860actgccccgg cgtggggccc gccgtcgcgt tccagtcctc caccaccagg gcgcgctcgg 22920cttcgctcag cagcgtcagc cggccgacga ggacgtcggg ctcggcgacc agccgctcaa 22980gcacgcgagc cagcgcgccc acgaccgatt cggcggccgc ctcgtcgaag aggccgcggt 23040
cgtagtcgag gatgagcggc atctgcgcgc cgggcccggt gatcagggtg aacgggtagt 23100gcgaggagtt gcgtccgcgc cgcaccggtc tcaggtccag gccgccgtcc tcttcggccc 23160ggccgagtcc ctggcgcggg aagttctcgt agatgacgag cgtgtcgaag accgccccgg 23220gcccgacggc ggcctgcatc tcctgcaggc cgagatgctg gtgcgccatg agtgccgact 23280ggctgcgctg cagctcggcg agcagctcga cgacccgccg gccgccttcg agccggaccc 23340gtaccggcag ggtgccgagc agctgcccga ccatcgactc cacaccggcc agctcggcgg 23400gccgccccga ggcggtcgcg ccgaacacca cgtcggtgcg gccggcgagc tgcgccagga 23460ccatggccca cgcaccctgg acgacggtgt tcaaggtgag gccgtggccg cgcgccagcc 23520gcgccagccc gtccgtcagc tccgcggaga gctcgatcac cgcggtgccc atgtccggca 23580cgcgggccgg atcggccggg gcgaccagcg tgggcgtgtc cagtccggcg agctcctgcc 23640gccaggccgc ccgggccgcc tccttgtcct gccggcccag ccaggcgagg tagtcccggt 23700aggacacggc ggcaggcagc ccggacgcgt cgccgcccgc cgcgtagatc gcggccagct 23760cgcggtgcag gatcggcatc gaccagccgt ccagcaggac atggtgcagg gtgtgcacga 23820gccggtggct ggccgggccg agccggatga ggtgcagctt catcagcggt gccgcatcga 23880gggggagccg ctcggccagc tcgtccgccg ccagccggtc cacctcgctg tcgaggaggt 23940cgtccggcag cccgtggaga tccgtttcac gccaggggat ctccgcctcc cgcgcgatga 24000cctgcaccat ctgcgcgccg ctgacatagc ggaaataggc ccgcagcgcg gcatgccggt 24060ccacgagcgc ctgccacgac gccctcagcc gcccggcgtc cagcgggccg tcgatgccgt 24120acacggtctg caccgtgtag gtgtcgggcc cgtcgtcgtc gagggcggtg tgatagagca 24180tgccctcctg cagcggcgag aggggccaga cgtcttccac gctggagcgc ggcttcgcac 24240gagtgtcgtc aatggtcacg atctgctcct tatggagtca tccgccggcc ggtccggcct 24300cgagttggtc cagctgatca ggcgaaagat ccacgagtgt gccggccggg ggctccggtt 24360
ccccggtgcc ctcgccgtcg gccgggagct ccttgacgac cgccgccagc cgttccgccg 24420tcttctcgtc gaacacctgc cacggggtga ggtccagccc cttccggcgg gccagggccg 24480acagctgcat cgaggtgatc gagtcgccgc cgagctcgaa gaagctgtcg ccggcgccca 24540cctcctccag gccgagcacc tccgcgaaca gctcgcacaa cttcgcctcc atggccgagc 24600gcgggtcgcg tcctgacgac gacctcgcga aatcgggggc ccgcagcgcc cgatgatcga 24660ccttgccgtt cggggtcagg ggcatcgtgt ccagcgggac gaacgccgcc ggcctcatgt 24720gctccggcag gcgtccggcc gcgctctcgc ggagggcgga gatcaacgcg ccgtcctgcc 24780cggcctcgga gggagcgccg gccacctgct cggccgcggg gacgacatac gccaccaggt 24840acttctggcc cggaccgtcc tcgcgggcga cgaccgccac ctgggcgacc cccggatggt 24900ccgccagcac ggcctcgatc tcacccggct cgatccgata gccgcgcacc ttgacctgcg 24960cgtcggcccg gccggtgaag accagctcac cgtcccgggt ccagcgggcc cggttgccgg 25020tgcggtacat gcgctcacca ggacgggcag ggctcaccga ggccggcacc gcgacgaacc 25080gctccgctgt caggcccgga cggccgaggt agccgcgggc gagcccggcc cccgccacat 25140agagctcgcc ggtcacacct ggcggcacgg gctgcaggaa ggcgtcgagc acataggctc 25200gcaggccggt gatcggccgg ccgatgggca ccacgtcgcg tcccggagac agcggggagc 25260tcatcgtcgc gcagacggtc gtctcggtgg gcccgtaggc gttgatcatc cggcggcccg 25320gcgaccagcg gtccaccagc gcgggcgggc aggcctcgcc ggccacgacc agggtctcca 25380ggctgtccgg caggtcgtcc tcgacggccg gcacgctcgg cggcacggtc acgtgggtga 25440tgccccaccg gcgtaccgcg tcgcccagcg acacccgggg cggcatgctc tccgcgtcgg 25500ccagcaccac ggtcccgccc gacaacaggg ccatgcacag ctcggagacg gcggcgtcga 25560agccgagagc ggcgaactgc aggatccgcg aggcggacgt gacgccgaag cgctcgatct 25620gcgcgctcgc cagattgccg agcccggcat gggggacgag gactcccttg ggcacgcccg 25680
tcgaccccga ggtgtagatc acatacgccc cgtcacccgc ctccacccgg ggcagcgcag 25740tgcgcggatc ggcggcgagc ggcgcgtcca gcgccaccac cgcgcccgcg aactcctccg 25800ggacggcctg cctggtctcg ctcgtgcaca gcagcacctc cggcgcggaa tccgccagga 25860tgaagctgat gcgctcgcgc ggataatcgg gatccatcgg gacgaacacc ccgcccgccg 25920aggacacccc gagcagtgcc accaccagct cggccgagcg tcccacgagc acgcccaccc 25980gcgtctcacg gcgcacgccc agccccacca gcagccgcgc cagctcctcc gcctcgtcca 26040gcagtccgct gtacgacagg ctccgggccg cgtccaccac cgccaccgca tccggcgagc 26100gctccacctg ccggcggaac agcatcggca ccggctccgc ggcgggcggc acgccggtcc 26160tgttccactc ctccaccacc aggcggcgct gctcaggacc gatcaggccc acgcgcccga 26220ccggcacgcg cggctcggcc accacctgct ccagtgcccg gaggatcgac gcgagcatct 26280cctcggcctc ggcccgatcg accacgtccg gccggtagat gaactcaccg tggacgcggc 26340ccgccacgga cgcgcgcatg gacagcggat agtgccctgt gtcgttcggg atgcccgcgg 26400gccgcatgac gagcgcgtcg gggccttcgg gccgaggcgg cgggggcggg tagttctcga 26460acaccacgat cgtgtcgaac gccgcgcccg gaccggcgag ctggttgatc tcgctcagcc 26520ccacgtgctg gtgcggcatg cacgcgacct gccgttcctg aaggtctgtc agcatgtcga 26580ggaacggctc cgcaccggcc aggcgagccc ggaccggcaa catgttcatg aacaggccga 26640cggcggactc cacaccgggg atctcgggcg ggcgcccggc caccgcggcg ccgaagacca 26700cgtcgtcgcg tccggtcagc cgggccaggt gcagtgccca gatcccctgg aagagcgtgt 26760tcgccgtcac gccgtgacga ccggtgaact ccaccacgcg ccggctcagc gcctcgtcga 26820gttcgaaccc gacacgttcg ggctccaggg gagtggtgat cgtctccggc ggcacgacgt 26880gggtcgcctc gtcgagcccc gccagctcgg cccgccacgc ctctcgggcg gccgccttgt 26940cctggcgggc gatccaggcg agatagtcgc ggtacgacgt cgcggccgga agggcccggc 27000
cgtcaccgcc ggactcgtac acggtcagca cgtcctcggt gatcagcggc agggaccagc 27060cgtcggccac gatgtgatgc gaggtcagga ccagccggtg ccggcgttcg ccgaggcgca 27120ccaggtgcag ccgcagctgc ggcgcccggg tcaggtcgaa ccgctcggtg tgcagctgct 27180ccgcgaggcg gtcgaactcc gccagcgcct cgtcctcggg cagccgggac agatcggtct 27240cctgccagtc cagcggcacc tcgcgagcga tcgcctgcac ggccgcgccg gacccgagct 27300ggtggaagct cgcccgcagg gcggggtgcc ggtcgagcag agcctgccag gaggcgcgga 27360accgggcgac gtccaacgga ccgtcgaggg cgagcttgcg catccccgcg tagacgtccg 27420ggccgcgctc gtcggcggcg tggaacagca ggccctcctg gagcggagac agcggccaga 27480tgtcgagcag ggtcggtacg gcggcctcga cctccgccac gtcctgctgc gtcagcgaga 27540tgagcgggaa gtccgacggc gtgtgcccgc cggcgccgcc gccaccgacg tgtgccgcaa 27600ggccggtcag catggccagc caggcctgcg cgagcgactc cgcctcggcc tcgccgagca 27660gccgccccgc ccaggtcacg gtcaggctca gctcaggtcc tgccgcaccg tccagcacgg 27720ccgcgtcgat ctccacggcg tgccgcaacg ccgtgtcctg ctccgccgtg ccgccgatgg 27780tgcccagcag ctgccagggc tccggggcgc ccgcggaccg ggacgggaag cggccgaggt 27840agttgaaccc gatctccggc ttcggcgccg ccgcgagagc ctgccccgtc ccggcgttga 27900gatagcgcag gatcccgtag ccgagcccgc cgtcgggcac ggcccgcacg ttctccttga 27960cctgcttcag caggtgaccg gccgcaccgc cacccgcgat cacttcggcc ggatcgatcc 28020ctgtcacatc cagccggagc ggatgcacgt cggtgaacca gccgaccgtc cgcgacaggt 28080ccagctcgtc gatgggccgg cggccgtgac cttcgacgtc caccacgacc gcggtgccgc 28140cgcgccagtg ggccaccgcg cctgccagcg tcgccagcaa cacctcgtgg acaccgcagt 28200ggaaggcgga ggtggcctgc tccacgagca cgcccgcccg gtcatgcggc agcgtccacg 28260atgtgcgtcc cgcggtcgag acggtgtcgc gcgccgggtc gagctcgccc agccgcgatc 28320
gcgccccgtc gaggatctcc gtccacgtct ccagctccgt ggcccgtgtc accgcctgat 28380cggccagcgt tcgcgcccag cgccggaacg agacgtcgac ggggtcgagc accggccgcc 28440ggccggcggc cacggcttcg caggccacct gcaggtccgg cagcaggatt cgccacgaca 28500cgacgtccac cacgagatgg tgcgccgcca cgacgagccg tcccacccgc cctggccccg 28560cgtccaccca gaccgcccgg atcatcacgc cggcgtgggg atccagccgt gcggccgcgt 28620cgcgggcgca gcgatccgcg atctcatcca cgtcaccggt gccggcctcg acccgttcga 28680ccagcgtcgc cgcgtccacc gctccgcggc cggccacgac cagccggggc tgcgcagccc 28740cggtgcggac gatccggctg cgcagcatgt catgcgcgtc gatgaccgcg cccaatccgg 28800ccgccagcac gtccaccgac aggtcgtcgg gcgcaccggc ggtcacccac tgggacaggg 28860cgccccgggt catcgcgtcg ggatcgcgtt cgagcagtgc ccggatcacc ggcgtcgaca 28920tcacctcacc gacgccgtcg tcgaggctcg cccgcgtcgc accgccgcgt tcggcgacca 28980tcgcgatccc ggcgggcgtc ttgcgctcga agacgtcctt cgcgccgaag acgagctcct 29040cacgtcgcgc gcgggcggcc aaccgcatgg agaggatcga gtcgccgccc agctcgaaga 29100agctgtcctc ggctccggct cgcgccacgc ccaggacctc ggcgaacagt tcgcacaaca 29160cccgctcggc ctcggtacgc ggctcccggc cggccgcctt cccggtgaac tcggggacgg 29220gcagcgcggc acggtcgatc ttcccgttgg gcgtcagcgg gacgccgtcc agcagcacca 29280ccgccgccgg caccatgaac tccggcagcc gtcccgcgag gtgctcgcgt accgcgtcgg 29340gatccaggcc cgagccctcc tccgcggtca cgtaggcgat gagtctcttc tcgccgggac 29400ggtcctcccg cgccacgacg accgcctgcg cgacgtgcgg aacctcggcc agcgccgcct 29460cgatctcccc tggctcgacg cggtagcccc ggatcttcac ctgggagtcg gcccgcccgg 29520cgaacagcag ctcgcctcgg tccgtccagc gcgccaggtc gccggtgcgg tacatccgct 29580caccggaggc cgcggggttc accgaagcgg gcaccgcgat gaaccgctcc gaggtcgccg 29640
cgggggcgcc caggtaaccg tgtgccaggc ccgcgccggc gaggtagagc tcaccggtga 29700cgttcggcgc caccggctgg aggaaggcat ccaggacgta cacctgccgg ccggccagcg 29760gacggccgat gggcaaggtg tcgcccgttt ccgtgtgcgg ctcgatgagg tgccaggtgg 29820cgcagagcgt gacctcggtg gggccgtaca actcccggac ccggacctcc gggcatgccc 29880ggcgcacccg tgcgacggac tcgagcggca ccacgtcccc gccggtgagg acctcgcgca 29940gcccgctgaa ggagtccggc gactcctccg ccagcacccg gaaggtcccc gccgtcagat 30000ggacggtggt cgcgccccgt gcgatcacgt cccgcagccg ctgcgcgtcg atcgcgcccg 30060gttccgcgac catcacgcag gctccgctga ccagcggcac ccagatctcg agcagcgacg 30120cgtcgaacgc gtgcgacgcg tgcatcaaca cgcggtcgcc ggcgccctgc gaccagcccg 30180ggtcgccggc cagagccgcg gcgctcccat gcggcaccgc gacgcccttc ggcaccccgg 30240tcgatccgga cgtgtacatc acgtaggcca cgtcatgcgc tccgaccgcg agcggtggcg 30300cctcgtgccg ctccgcctcg gtcgcgggtg cgtccatgac caccggctcg atcccgtccg 30360ggaccgcgtg ccgggtcgct cccgcgcaca ccgccaccga cgcgccggcg tcggccagca 30420tccgctcgat gcgctccgcc gggtagtcca cgttcaccgg gacttgcgcg gcccccgcct 30480tccagaccgc gagcagggcg acgatcaggt ccgcgccgcg ttccatcagc acgccgacgc 30540ggtcgccgcg ccgcacgccc ctcctggcca ggtgccccgc cagccggtcc gattcccggt 30600cgaggccggc gtaggacagg gtgcgtccgt cgccgatgac cgccgtcgcg tccggcgccg 30660cgtcggcctg gcgccggaac agctccggca ccgatgaacc gccggccgcc gcaccggtcg 30720agttccagcg ctccgtcacg gagccgcggg tggatcggct ggtcacggcc aggcggccga 30780cgggaagcga gggctccgcc accatccggg ccaggacccg cacgacctgc ccggtgatct 30840cggcggccag gtccccgccg atccagtcgg gccggtagtc cagctggatc tgcaggcgcg 30900cgcccgggat gacgctcacg gacagcggat aggtggtgcc ggtccgcgtg cggatcgagc 30960
tgatcgccac gccaccgtcg tcgagaccgt cggcgtccag cgggtagttg acgatcatca 31020ggatcgtgtc gaagatcgag cccggccccg ccgccttctg gatctccggc agccccaggt 31080gctgatgctc cgtcaaggac gactggcgcc gctgcaggtc ctggagcagg tccagcaccg 31140gaacagcccc gtcgaggcgc acccggaccg gaacggtgtt gatgaacatc cccaccatcc 31200gctcgacatc cggcaacgcg tccgccggac gcccggacac gaccgtgccg aacaccacat 31260ccgtccgtct cgccagccgc gccagcacca gggcccaggc gccctgcacg accgtgctca 31320acgtcagccc atgaccacgg gcgaagccgg tgagggcgcg ggtcgcctcc tcggacagcc 31380attcggcatg cccgtccggc atcaccggcg ccttgcccgc gtcgaggccc accacggtcg 31440gttcgtccag cccggcgagc tcggcccgcc acgccgatcg tgccgcgtcc tcgtcctgac 31500ggctcagcca cgccacgtag tcccggtagg agggcggcgc cggcgagacc cgtccgtcgg 31560cgtaggcggt cagcatctcg cccagcagga tcggcgtgga ccagccgtcc acgagcacat 31620ggtgcgacgt caccacgagc cggtgccgcg ccgcaccgag acggatcagc agcaaccgca 31680gcagcggcgc cctgctgacg tcgaaccgct ccgcctgatc cgccgcgagc aggcgttcca 31740cctccgcgtc cggctcatcg agccgcgaca ggtccgcctc acgccacagg acctcggcct 31800cgcccacgac gacctgcacc gtctcgccgg atcccagctg gtggaagccc gtccggagcg 31860tctcgtgccg gtcgatcacc gactgccacg ccgcgtgcag ccgttgcgcg tcgagcggcc 31920cgtcgaggtc caggatccgc tgggtctggt agacgtcgac gccgtcctcg tcgaaggctc 31980tctcgaagag gatgccctcc tggagcggcg acagtggcca gacgtccgtc aggccgggcg 32040ccacggcctc cagttcgtcc acgtcccgct gccgcacctc gaccagctcg aagtcggacg 32100gtgtgtgtcc gcccgcgccg ggagtgtcgg cgagagcggc gaggccggcc agcgtgtcca 32160gccacgcctc gccgagccgc tccaccgcgg cagggtcgag gtccctgccg tcgatggcga 32220gtctcagccg ggggccggcc ggcgtgtcct gaacgtccgc gccgacctcc agggcgtggg 32280
actggacgag gtccggcccg gccgcctgtc cgccgagagc cccttcgcac acctgccacg 32340cggtgtcctc ggaggcgacg ccggaccgtc cgagatagtt gaatccgatc tgggccgacg 32400gcagctccgc cagccgggcg ccggtttcgg ggttgaggta gcgcaacagc ccgtagccga 32460gcccgtcgcc cggcaccgct cgcgcctgtt ccttcacggc cttcagcaac tccccggccg 32520ccgcagctcc tggaccgaca ccggagacat cgaggcggac cggatgaacg ctggtgaacc 32580agcccacggt acgcagcaga tcctctccgt cggcggcatg gcggccgtgg ccttccacgt 32640ccaccaggat cccggcgtca gcaccgcgcc accgcgccac cgcacccgcc aggcccgcca 32700gcaggacgtc ctgaaccccg cagtggaagg ctgccggcac gcgcgccacc aggttgcgcg 32760cttgggcatc ggacagtgtc cgcgaccacg acgccgactg cccggggtgc cgctccagcg 32820gcaggtcgcc gccttcgagc acgccggccc aatggccggc ctcggccacg gtgctctcgc 32880tgagcgcctg cccggccagc cgccgcgccc attgccggta cgacgtcacc gcgggttcga 32940ggacgggggt tccgccggag accgcctcgt cgtaggccgc ccgcagatcc gacagcagga 33000tcgcccacga gaccgcgtcg acgaccaggt gatgcaccac caaggccaac cggcccggct 33060cggcgtcgcc cgcgtcgacc cacacggccc ggaccatgat cccttcggac gggtccagcg 33120tgcccgccgc cgtcctggcc tcgcgctcgg cgcgctcagc gaggttcccg ttcccggccg 33180ccacccgcgt caccaggccg gccgcgtcca cggcacccgg ctcggccacc atcagccgtc 33240cgtcgggctc cacccgcgtc cgtagcagat cgtgcacatc caggacggcc tgcagggcgg 33300tcaccagcgc gtccggggcg aagccggccg gggtgacgac gacccgcgcc tgcgcgaaac 33360cggggcgcac cgcgtcatcg ccgagggcac gcatcaccgg cgtcctcggg atctcgccca 33420cgcccggctc cactgaggag gctcgcctcc ccggggcctg ttgagccagc gccgccagcc 33480gctcgggcgt gcggtgctcg aacacctgtc ggggggtcag cgggataccc tggcgccgcg 33540cgcgggcggc gacctgcatc gacgagatcg agtccccgcc cagctcgaag aagctgtctg 33600
cgaccccgac ccgccccgcc cccaggacct cggcgaacac tccgcacagg atccgctcgg 33660cgtcggtggc cggctcccgg tccaccgccc cggcagcgaa gtccggctcg ggcagggccc 33720ggcggtccac ctttccgttg ccggtcagcg gcaacgcgtc cagcaccagc accgcggccg 33780gaaccatgaa ctcgggcagc gtcgcggcga gctgctcgcg tatccgcacc gggtcgaggt 33840ccccccctgt ttcggcgacc acgtaaccga tcaggcgctc ttcccgcgcg gacaccacgg 33900cctgaccgac acctggaagg ccggcgagga ccgcctcgat ctcgccgggc tccacccggt 33960acccgcggat cttcacctgg tcgtcggcac gcccggcgaa cgccagctca ccctgatccg 34020tccagcgcgc caggtctccg gtccggtaca tccgcccacc gggcacgaac ggctcggcga 34080cgaaccgctc ggccgtcaac gccgggcggc ccagatagcc ctgcgccacc ccggccccgg 34140cgacgtacag ctcgcccgtc acccccgggg gcacgggccg caggaacgcg tcgaggacat 34200agacccgccg ccccgcgagc ggacgcccga tcggcagcac cggccccgtc ggctcgcccg 34260gctgcagcag ccaccatgtc gcacacagcg tggcctccgt cgggccgtag agatgccgca 34320cgcggacgtc cgggcacgcc cgccgcaccc gttccaccgc cgcgagcggc accgcgtccc 34380caccggtcag cacctcgcgc agcccggcga ccgactccgg tgactcctcg gccagcaccc 34440ggaaggtccc cgccgtcagg tgagcgcagg tgacaccgcc ggccacgtac ccggccaggg 34500cctcgccgtc caccgcgccc ggctcggcga gcacgacccg ggcgcccgac agcagcggca 34560cccacagctc gaacagcgag atgtcgaacg cgtgcgaggc gtgcatcagc acggcgtcct 34620cgggccccag cccccatccc ggctcgccgg ccagcgccgc gacgttgccg tgcgagaccg 34680cgacgccctt cggcctgccc gtcgatcccg acgtgtacat cacgtacgcg aggtcgtccg 34740cgtgcgcacc cgcggagaga cgggcgtgct ccgccaccgc ccgcagcgtg tccgggtcgt 34800ccaggacgat cggatcgagc ccgccggccg gcacggcggc ctggcacgct cgctcggtca 34860ccactgccgc cggctccgcg tccgcgagca tgaactgcac gcgctccgcc gggtaggcgg 34920
gatccaccgg cacgaacgcc gctcccgcct tccacaccgc cagcagcgtc gcgatcaggc 34980cgggtgaccg gcccatcacc acggccaccc gatccccgcg ccggacgccc cggccgctca 35040ggtagccggc gagcctctcc gcgtgctcgg ccagctcacc gaacgagacc gcccgcttcc 35100cctcgacgac cgccacccgg tcacggccgc gctccacctg gcggtcgaag agatccggag 35160ccagctcgcc cggcgccacg cggggtgccg cactccatgc gttcaccacc agcgcacgct 35220cggccgcact cgtcacgtcg acctcggcca ccgtgaggtc gcccgcgccc gccagctgcc 35280gcagaatccc ggtgaatcgc tccaggatgg cgagcgcggc ttcccggtcg aagaggtccg 35340tcacatggtc gagattgagc agcatcgact cgccggggac ggcgaccagc gtcagcggat 35400aatgggcggc ttcccggccc tggtctattc gaatatcgaa ggctgccgcg gcatccgatg 35460ggcgaagctc acggggaaag ttctggaaaa cgagcaaggt gtcgaagacg gcgccggcgc 35520cggccgtcct ctgaatatcc gccaatccca tgtactggtg ggggatgagc gccgactgcc 35580gcttctgcaa atccgccagg aattcgatga ccggcgtcga accgctcagc cgcacgcgta 35640cggggacggt gttgaggaac aaccccacca tcccctcgac gccgggcaga tccggcgggc 35700gtgccgagac cgccgcaccg aacaccacgt ccgtccggcc cgcgagctgg gcgagcagca 35760acgcccacgc gccctgcacc actgtgttca gcgtcagccc atgggtgcga gccagctcgc 35820tcagggctcg cgtgaggtcc tcgggcagct cgaccgtgat gttctccggc atggcgggcg 35880cccggttcgc atcggcgggc gccaccagcg tcggctcctc gacaccccgc agctccgccg 35940cccatgccga cagcgtgcgc tccttgtcct gccggtccag ccacaccagg taatcccggt 36000acgacggcac cgcgggcagg tccagcgggc tcccgtcggc cgcgtacagc atcgacagct 36060cgtcgagcat gatgggcatc gaccagccat ccatgatcgc gtggtggcag gtcatcacca 36120ggcggtggtc gtcgccggcg agacggatca gggtcagccg cagcaacggc gccttcgcga 36180ggtcgaacct ccgcgtcctg tcctcctcgg ccaccgcgcg cacggcctcc tcgggctcgc 36240
tgaggtggga gaggtccacc acccgccacg gcagctccac ctgcctggcg atgagctgca 36300ccgtctcacc tgatttgcgc tgccgaaaac aagcccggag agcggcgtgc cgcgccagga 36360gcgcctccca tgcggcacgc agtctgtccg cttccaccgg accgttcagg ttcaggatcc 36420aatggcccac ataaaggccg ggccagtcgt cgtcataggt cgtgtggaag agcaaccctt 36480gctggagtgg tgacagcggc cagaaatctt cgatccgcga ctgagccatg gatgaatatc 36540tccctcaatc agcaaagcgg cccgagaggg aatcatccat tgatgggtct gacccggaca 36600atctgtccat ccgtgactgc cgtcaccgat ccgggtgggg tcgaaggagg ccgccgacgc 36660ggaacgtggc ggcttgcggg cgagcaacat ggctacggcg cgccatccac agctggatgg 36720cgcgccgtag ccaggttcac cgctcgatcg agcgcggcct cactcgaagg aaagccccgc 36780ggccggcgtc acccggacgg cccggcgtgc cgggagaaca ctggccagga gccccgccag 36840ggcggcgacg aggacgacga cggcgagcag tggccagggg acctgcatgg tggcgttgtc 36900gagagcctgc ttcacgaagg tctcgtaacc gacccaggcg aacccgatgc cgatcacggt 36960gccgagcacg gcggccacca gggagagcag cacggcctcg gcggccagca tccgccgcaa 37020ctgcctgcga gtgagcccga gcgcgcgcag cagcgcgtgt tcgcgaacac gctcgagaac 37080ggacaggccc agggtgttgg cgatcccgac gagggcgatc gccacggaga agccgagcag 37140cgcgacgatg gcccaggtga ggatcatcag cggcgcgttc tccgtctcac gggcctccag 37200ctggtcgttc acgttcgccc cggccgcggc cgccaggtcg cccagctcac cgacgagccg 37260cgtcgagtcg gcgtcggcgg atgcgcggat ccagacggca cgcggcgcgg cggagtcggt 37320gagccgggcc agcgtctccg gcgcgacgac ggcctgcagc ccccagccgg tggcgagcga 37380gacctgcagc acggcccgcc ggtcgccgac cgtgaccctg accttgtcac cggcccgcag 37440gcgcagctgg cggaatgcgg actcatcgag cctgagcacg cctggctcca cccgggcgaa 37500cgacccgccg tcgtgggcca cccgctgggc atccggcgcg gtgaccaccg ggatcggctt 37560
gtcgaggccg gagaccgtgg cgacggcgcc gtccaccgcg atggcctgat ccaccccgga 37620agtgccacgg accttgtcga ggaagtcggc ggagaacggc ttgccggtcg agaccagcgc 37680ggcgtcgatg gggtgctggc cgtcgagtct ctcgttcagc gcctcggagg tgatggcgac 37740gccggtcagg acggcggtga tcagggtgat accgaccagc agtgaggcgg cggtggtggc 37800ggtccggcgc gggttgcgca cggcgttctt cgtcgcgagc cgcccgatgg tgccgagccg 37860cgtaccggtg atctccagca gacgggggat gagcaccggc ccgaacagga gcacgccggt 37920gaacaacgaa ccgccgccgg ccagcatgag caccgtgctg tgccaagcca tcgccgacgc 37980gagcaggacg agcccggcga tcaacatgaa gacgccgagc accagccgtg cccgccccgt 38040ggctgtacgc gggtcggtcg cggtgtcggg acgcagtgcc gccagcgggc tcacccgcac 38100cacgcgccgg atcggcagcc aggccgcgac cagggtggcc gtcagcccga tggcgagccc 38160gcccagcagc cacggcgcgg gcggtgccgg ggcggcgatc ggggtgatcg gtgagagggt 38220cttgatcagg gcgatgagcc cgtagccgag tccggcgccg accagcacgc cggccagcga 38280cgacaggagg ccgacgacgg ccgcctcccg gcgtaccgaa ctcaccacct ggcggcgggt 38340cgcaccgacg cagcgcaaca gggcgaagtc gcgcatgcgc tgggccagca ggatggagaa 38400ggtgttcgcg atgaccagga tcgagacgaa cacggcgatg ccggcgaaga gcagcagcag 38460cagtgaccag gtgtccacgc cgttctggag ctgcgccgtc cgggccgcga tctcctgctc 38520cggggtctgc accttcgcgg tctcgggcac cggaccgacc gcgccgcgca ccgtcaccgt 38580gtagatgccg agggagggat cgtcggccca gcgcatgagc tgcggccagg tgacgtacac 38640cgacgcctgc gccacaggag aaggcgcccg cacgatgccg accacggtga agtcggctgc 38700cgtggcacgc tcacctatcc ggatgcggtc gccgacggcg acgtcccagt tctgggcgtc 38760ccacaggtcc accacggcct cgcccttgcg ctcggggaaa cggcccgagg tgagctgctg 38820ccagcgcagg tccttggact cggcgaccgg ccccacgccc atctcggggt aggaccggtc 38880
acccgcgcgc accgtcagca tggccctgcc gagcggtgac gcgttcgcgc catgacgctc 38940gacgagctcg aacgcatcct cgttcgtcag cttggacacc acgtggtcgg agttgcggaa 39000cggcgccccg aagccggcca tgatgccgct ctgcgccccg gaggtgagca cgccgacccc 39060gacgacgaag gccacggcga cggtgaccgc gatcgccgcc gcgacgtacc tgcggacatg 39120ggtgcgcagc gacgcgagaa agacggtgcg catcaggcga tccgtccgtc ttccagggtg 39180accacgccgt cggcgtaggc cgcggcctca cgctcgtggg tgaccatcac gacggtctgg 39240cccagctcgc gggtggattt gtgcaggtac cccaggacct ccgccgaggt ggtgctgtcg 39300aggtttccgg tgggctcgtc ggcgaacagc agatccggcc cggtgatcag agcccgggcg 39360atggccaccc gctgctgctg gccgccggac atctcggagg gccggtggcc gagccggtcg 39420gccatgccga gggtttcggc gagcacgtgc acgcgctcgg tcgccgcgtc gtcgatgcgc 39480cggccgccga gctcgagcgg gagcgtgatg ttctggaacg ccgtgagcat cggcagcagg 39540ttgaaagact ggaacacgaa gccgatgtgc tcacggcgga agaccgtgag ctcgttgtcg 39600tcgagtgatc cgagatcggt gccggccacg gtgacagtgc catcgctcgc ctgatcgagc 39660ccggccaggc agtgcatcaa cgtggacttg cccgatccgc tcgaccccat gatcgcggtg 39720aacttgccgc gcgggaggtc gaggtcgacg ccgcgcaggg catgcacgcg ggtttcaccc 39780tggccgtaca ccttggtcag gtttcgcgcg ctggccgcca cggtttccag agcggctcgc 39840tggccggtca tatagaagca cccttcgatt gtgcttgcgt acagtcggca tgcatgagca 39900gaaagccatc attgacggct tcatggcgct attcttcgcg ccaaggctgg tagtcgtgct 39960ggtactccgc aaagcgccac ccatcgtaga cgagcagtcg gccgggcacc aacggttcca 40020aattgaagca gggcgccgtg cggagtaata gtcaagactg tggatgccga gttccttggc 40080gactgtggga agggtgcttg caccggacgg gcggcattcc ctggtcagcc cccgggtgtc 40140cgggccgctg gtccggcgtt ggcgtcgaag gaactgccgc cgtacctggg gtcgagcacg 40200
gatgcggacc acgtggcggg cgcggccagc atggccgcga cgccgatggt gagcccggcg 40260ctgaccagcg aactacgacg gggcctgacc agccgcgcca gcgcgagcgc gacgacggcg 40320accacgccga gcgcgaccgc gccccacatc gcccacggca gaaaagtggg gtagaaggac 40380cacaaccaga cggcccaggc gagttcggcc acgatcgcga gcggaaatat ccacgccatc 40440ctgcctccgc tccgatacgc ccgccagaac attacaatgc cgattccgga caaagcggct 40500accggcggcg cgagtacggc cacatatgcg ctgtgcggga tgacaaagac cgcgctgtag 40560ggcagggcga aggtgagaag ccacacgccc cacatcacca ttccgccgcg tgccgggtcg 40620gtacgctcgg cccggcgcca ccaccacagc ccgcacagca gagccatcag cgcgagcgga 40680tacagccaac cggacgcgac gccgaggcgg ccgccgaaca gcttgcccca gccgccccca 40740tgctcgatgc ctatctcggg gatgaccatg ccagggcgtg gccggggcag ctgcgtcgat 40800ctcttcggag gcgccgggcc gatcaccgag cccatgtagt tgggcggcag ggcgccgggc 40860agattgatgc ccaggcgtcc gagaccgttg tacccgaaca ccatcgcggc ggcgctgctg 40920ttcgtggtgc cgctgatgta gggccggtcg gcggccggag tgacgtggta gagcgtgatc 40980cacgacagcg acaccacgag cgtcaccact ccggcgatcc ccaggtgctg cagccgacgg 41040cgcagtccga tcggcgcgct caggagataa ccgatcgcca gggcgggcag gatcatccac 41100gcctgcaaca tcttcgcctg gaaacccagc ccgacccaga cgccggccca gaccagcgac 41160cgcagccgtc cttccagcac ggcccgctga taggagtcga cggcgagcac caggcacatg 41220accagcgccc catcggccat gctgtgcccg aacatggacg cggccacggg ggtgatggtg 41280aagacggcgg cggcgagcag acctggcacc acgcccgccc atcgccgcac gatccggtac 41340atcaccagca ccgagatcac gccctcgatc acctgcggca aggcaagggc ccaggcgtgg 41400aagccgaaga tcttgaccga gatggcctgc ggcacgaagg ccccggcgag cttgtcgagc 41460gtgtaggtcg cctgcacgtc gacggtgccg tacaggaacg ccttccagtt ctcggacatg 41520
ctcttgacgg cgtccgagta tctcggtgcg tagtcgacca gcggcaggtt ccaggcgtag 41580agcaccgctg ccgtggccgc gatgcagagc agcgccggcc gggcccacca cggctggccg 41640ggcggcgagc gccacaccgc ccagcggggg aatctgccgg cgggtgcggg gtcccggcac 41700gcggacggcg gagtcatggt gatgtgcgac atgaggaact cccaggcgtt tccttcggca 41760gttccctgcc tttactcggc tgcgtagcga atgaccggcc aggtggtctc gttatatccg 41820ccgtccggtg cggcgttcct ggcatgctca tcgagtttgg cgaacaggtt cttgttcggc 41880ccgtcgagca ccgacaactg cgtcgcgtag tgcttcatcg cctggaattt ccgcgtccgc 41940gcctcctcat cgacgaaact cagctccgga gagccgagcc ggaggccgtc aggcaattca 42000gccaggtcct gggaatacgc cgcgtacggg agatcctgcc agagtcgcag cggaatacct 42060cgctcgcgtg cggcgagcag cgtggcatcc cgcgtggcct tgtggtcggg gtgtttcccg 42120atggccacac aggtgagaac gagcgtcgga tcgcactccg cgatcatgga ctcgatgtcc 42180tccctgatcg cggcgaccag gtcgtggttg ttcgccggcg actgctggcg gaccatcgag 42240ccttcgttgt ggtgcagcag ccactggcca tccggtgacc ttcgatagat ggcatcgaga 42300aaacggccat gccgatggcc cgcaccgagc tgatcgaggg cggcgatgtc ctcatttcgt 42360cggcgcagcg gcgcgtcctc ggtcggcgac agaccccagc gtgcgtggaa tcgctccgcc 42420gccggggaat aagggggcgc cgcgctgccg gcgaacaccg tgaagacggt tacttttcca 42480ccgtcctgct ccgcttgggc gaggctggct ccgacggaga ggacggcatc atccaaatga 42540ggggagattg ctaatatccg ggttcggtcg gcgtcctgca acatggttgt cagtctggtg 42600tcggccctgc cccgttgcaa taaagcggaa ctggacggga cctcgcacgc gtggagaatt 42660tccgggcggg ccgggcacca cgatgagtca cccggtcacg tcgcagtcac acgttctctg 42720accagcctgt caccgtctgc tgcgtacaac tggtgtcaac gccgacaccg ggcaggagaa 42780gatgagtggg aagagcgcag ccgcacgacc tcgcctcggt cgcatcgaac gacgccttcg 42840
ccgggctcac gtcggcgacc gcggcctcta ggatggcgcc agccggcgca gcgcgcgccg 42900catgaggggg aagtggatct ctaccgagag gccaccctgc gggcgcgcgt gcgcggtcaa 42960cgtggcgtcg tgggcgacgg cgatggcgcg gacgatggac agcccgaggc cgtggtggtc 43020gtcggcgcgg gtgcggtcga gccgctggaa gggctcgaag aggcggtgga cctgctcggg 43080gggcaccacc gggccggtgt tggcgatgga gacgacggcc ttcccggcct cggcccgggt 43140ggagagctcc acctggccgc caggcacgtt gtagcgcatg gcgttgtcca gaaggttggt 43200gatgagtcgt tcgaccagtg ccgggtcgcc cgtggtgggg gcatgagcga tcccggtcac 43260caatcggggg tgtgggcaac cggcccggag ggacttcccg tcggcccagg aatcggttgc 43320cgcgccggcc gtggggctgt tcccgtcagc cctccgatcg gcactcacgc cggccctggg 43380gttgttcccg tcagccccgg ggccggtccc ctccatcgtg cggatcgtgt gctcggcgat 43440ctccgccaga tccaggggct cgcggtgatc gaggccgccc tcgctcttgg ccagcgtcag 43500cagcgattcc agcaggcgcc cctgctgccg gctgaggtcg agcagccgct ccatgatcga 43560tcgcatggac ggggtgtcgg cgtcccgatg caggaggctc tcctccagca acgcgtgctc 43620cagggtgagc ggggtgcgca gctcgtgggc cgcgttggcg acgaagcgct tctgcgcgtc 43680gagggcgctg tggagacgtt ccagcagctc gtccaccgtg tcggcgaggt tgcgcagctc 43740gtcgcgcggg ccgggcaggg cgagccgctc gtggacgttg cgggcggaga tccgcttgag 43800cgtggtgttc atcgtccgta gcgggcgcag catcctgcct gccaccagcc agccgagcaa 43860gaacgagatg accgtcatca gggccagcgc gatcagcgat tggaacagca ggttctccag 43920aatggccgcc tgctgctgcc gcgcgaaggc gcggaacctg ccgccagggt caccgtccac 43980cagcacgaag ggtctggagc cgcggaagag caggtaggtg atggcgagca ggaccacccc 44040tgaggcggcg aacaacgcgc cgtagacgag cgtgaggcgc agccgtacgc tgcggaaggc 44100tgttgtcagg cgtcggagac gatgggccac tgttccgatg gtatgagacc aggaccggcc 44160
ggaggagccc acggcgccga cgatcgcggc cccgggccga ggccgagatg ccgcgagtcg 44220ggcgcctacc gagtcagcgc accgcgcacc gctgccgtga cctcgggcgc cagggtgcgg 44280gcgaaggtgg tggtgaggtg gctgcggtcg gagtaggcga tcaggccgcc gatgacgggg 44340ccgcaccgct cgccgcacac caggtgatcg acactcgcca cggagacgag gccggtgtcg 44400tcggcgcggg cggcggcggc gagcggatcc ggccggagca cgacgccggc cgggccgccg 44460caggagtcca gatcgtccgg gtgcttggcg atgcagtggg gcacgctgtc cggcatggcc 44520ggggtgtcac gcaggacgag caccggaagg ccggcgccgg tgaaggcccg gagcgtgtcg 44580cggtaggccc gctcggccgc ggcctgctgg ccggctggcg agacgccggc gagcggcaca 44640tgcgtacggt tggacatgat caccaggtcg tagccgccgt tcacgatgga cccgaccgcc 44700cacttgttga tcttctggca gttctccgag acccccgcgc cttcgaggac gagcggctga 44760tcgacggtgt agcacgccag ctgtacgtag gtggtgagct gccagcgctc gctccacagc 44820gccttctcca gggccgggac ccagtgtccc gcgtgggagt tcccgaccag ggcgatgcgc 44880ctgccggcgg cgtcaggtcc gtacgtgcac gtgttccggg cgatgaacgg ttccttgttc 44940acgcacccgt ccgcgtacac ggcgggcttg tccttcaacg cgacctgagg aggcatcagc 45000aggcccagat cctggcacgc cgggtcgcgc acgacgccgg cacccaggca tgaccctgcc 45060cgcgaggccg cggcctcgaa cgcggcactc tccgtacgct cggcggcgtc ggcgtaggcg 45120acgacgcccg ctcccgctcc tgcgacgacc accacgcacg acgcgagcat cgcgaacgtg 45180agcctgcggc tgcggaccag gaccgggtgc cagcgcagcc ggtcctcgac gaggtactgc 45240gagagcgcgg cgaggaccag ggtcagcgcg atcacgccca cggactcgat cacggtcagc 45300gagcggccca gcgcgtacgg gaggatcatg atcggcggcc aatgccacag gtacaccgcg 45360taggaggcgt tgccgagcca ctggaccggc cgccacgcca gcgcccgccc gggtccgccg 45420cgcagaccgt ccgcggccgc tgcgatcacc aggcaggccc ccactgtcgg caccagggcg 45480
gcggctccgg ggaaggccgt ctcggcgtcg aaccggacca cggcccaccc gatcatgccc 45540aggccggccc acgcgagccc ggcccggacc gcccgcgcgc gcggcatcgc gcgtacggtg 45600agaaccgcgg cgagcagacc gccgagcgcg agctcccaga agcgggtcgt cgacacgaag 45660tacgcggcgg ccggatcggt cgccgtcttc tgcaccgacc aggcgaggga cgcggccacg 45720accgcacccg tgaccaccac cgcgctccac ctcgtgaagt tctccggagg gcgacgcccc 45780cgtgccaccc gggcggccag ccaggccgcc gaccccagca gcagcggcca gccgaggtag 45840aactgttcct cgatggacag cgaccagtag tgctgcgcgg gccagtccgg ctggtcgacg 45900tcgaggtagt tcgcctgcgt gagcgcgagt ctcaggttct ccacgtacac cgtggcggcg 45960atcacctcac gcgccgccgt ccccagcacc gtgagcggca gccagaccac cgacgcggcg 46020agcgtgacca ggagcgcgag gctcgcggcc gggatgaggc ggcggacgcg gcgtgcccag 46080aagtccagca gtctcccgcc gccgtgtccc ggctgacgca gcaggtggct cgtgatgagg 46140tacccggaga tgacgaagaa gacgtctacc cccacgtacc cgccggtcgg cccgccgggc 46200cacaggtgga acgcgaccac cgccgccacc gcgatcgccc ggaggccctg aatgtccgtg 46260cgggactcgg agctccggcc gccggcgtgc tcgcttcgcg gcgcacacga cggggcgtgc 46320ggcgtcagcc cgcatgcgca ggtcggaagg gacatctgtt cggtgggtgc cgggcgctcc 46380atggcaactc ccgcgtcatc gaggtgctgc gcagccctcg aaggtcgcac ccgcggacga 46440gagcctgctt gatcgcaagc gtgctcaacg gactcgatgt ctacaagccg gtccaggtga 46500acgcttggtc accaccaccg gtgaacgcgt ccaagcgcgc gaactgttca gttggaccca 46560ctcgtggaca tcggctccgc tcagcacgat tgaggtcgct gacttgcgtg cgcgtgtgag 46620aggagtcccg catggccata gtgtcgccgt tcggaggttt gctgaagggc gacggagagg 46680atgatcccgc gccgtccagg atccgcccgg ggacgttgcg acgagtgctc ggatacttcc 46740gcccgcacgt cggcaaggtg gcgctcttcg ttctcgtcac cgcattggat tcgatcttcg 46800
tcgtcgcgtc tccgttgatg ttgaaggacc tggtggacaa gggggttctg gggaacgatc 46860tggagctcgt catcctgctg gcgtgcctgg ccgccggctt cgccgtgatg agcacgctgt 46920tgcagctcgt gtcggcctac atctccggcc ggatcgggca gggggtcagt tacgacctgc 46980gggttcaggc ccttgaccac gtccagcggc tgccgatcgc gttcttcacc cggacccaga 47040cgggcgtgct ggtcggccgg ctgcacacgg agctggtcat gacgcagatg gcgttcaccc 47100agatgctgac ggccgccgcc agcgcggtca cggtcctgct ggtgctggcc gagctgttct 47160acctgtcgtg gatcgtcgcc ctcctcacgc tggtgctgat cccggtgttc ctggtgccct 47220ggtcttacgt gggacggcgg atgcagcgct acaccagagg gctgatggag gagaacgccg 47280gcctggccgg gctgctgcag gagcggttca acgtccaggg ggcgatgctc tccaagctct 47340tcggccgtcc ggccgaggag atggccgagt acgagagcag ggccggccgg atccgcgggc 47400tcgccgtgag cgtcaccctc tacggccgga tggcccccgc catcttcgcg ctgatggccg 47460cgctcgccac ggcgctcgtc tacggggtcg gcggcgggct cgtgctctcg caggcgttcc 47520agctcggcac gctggtcgcc ctggccaccc tgctcgggcg gctgttcggg ccgatcaccc 47580agctggccag cattcaggag aacgcgctca cggtcctggt gagcttcgag cggatcttcg 47640agctgctcga tctgaagccg ctgatcgagg aacgccccga cgcggtcgcg ctcaaggccg 47700gcaaggcctc ggacgtccag ttcgagaacg tgtcgttccg ctaccccagc gcggacgagg 47760tctcgctgcc gtcgctggaa cagaacgtgc gcaccgggca ggagcgtggt gaagcgacgc 47820cggaggtgct gcgcgacgtg agcctgcacg tgccggccgg caccctcacc gcgctcgtgg 47880gcccgtccgg cgccgggaag agcaccctca cgcacctggt gtcccggctg tacgacccga 47940cctccggaac cgttcgcgtc ggcggacacg acctgcggga cctcaccttc gactcgctgc 48000gcgaaacggt gggggtggtc agccaggaca cctacctctt ccatgacacg attcgggcga 48060accttctcta cgcccgcccc gacgccaccg aggacgagct ggtcgaggcg tgccgagggg 48120
cgcagatctg ggacctgatc gcatccctgc cacgcgggct cgacaccgtc gtgggtgatc 48180gcggttatcg cctgtcaggc ggggagaagc aacggctggc gatcgcccgg ctgctgctga 48240aggcaccctc ggtcgtcgtt ctcgacgagg ccaccgccca cctggactcg gagtcggagg 48300ccgccgtcca gcgggcactg acgacagccc tgcgcagccg tacctccctg gtgatcgccc 48360accggttgtc cacgatccgc gaggccgacc acattctcgt gatcgacgac gggagggtca 48420gggagcgcgg gacgcacgag gagttgctgg cggaaggcgg tctctacgcc gacctgtacc 48480acacgcagtt cgccaagtca ggcgtcaacg ggacccggcc gggacagggc gacggggcgg 48540agcccgtgca agaggtggtc ggtggagggg aacgatgagc gccggaacgc gggccacacc 48600gacgacggtg ctggacctct tcgcccgcca ggtgggccgg gcacccgatg cggtggctct 48660ggtcgacggg gaccgggtcc tgacctaccg gcggctggac gagctcgccg gagcgctgtc 48720cgggcgcctg atcggccggg gtgtcggccg gggtgatcgc gtcgcggtga tgatggaccg 48780ctcggcggac ctggtggtga cgctgctcgc cgtgtggcag gcgggggcgg cctacgtgcc 48840ggtggacgcc gcccttcccg cccggcgggt ggcgttcatg gtggcggact ccggagcctg 48900cctgatggtg tgctcggagg cgacgcgcga tgcggtaccg caaggggtcg agtcgatcgc 48960gttgaccggc gagggcggat gcggcacgtc ggcggtcacg gtggacccgg gggatctggc 49020gtacgtgatg tacacgtccg gctcgacggg caccccgaag ggggtggccg tcccgcatcg 49080gagcgtcgcg gagctgacgg gaaaccccgg ctggggggtg gagcccggcg aggcggtgct 49140catgcacgcg ccctacacct tcgacgcctc cctgttcgag atctgggtgc cgctcgtgtc 49200gggcgcccgg gtggtgatcg ccgcaccggg tgcggtggac gcccggcgcc tgcgcgaggc 49260ggtcgccgcc ggggtgacga gggtgcacct gaccgcgggc agcttccgcg cggtggcgga 49320ggagtcgccg gagtcgttcg cgcacttccg tgaggtgctg accggtggtg acgtggtgcc 49380cgcgtacgca gtgcagaagg tgcgggcggc ctgccctcac gtgcggatcc ggcatctgta 49440
cggcccgacg gagacgaccc tgtgcgcgac gtggcagctg ctggagccgg gtgacgtcgt 49500ggggcccgtc ctgccgatcg gccgcccgct gccgggccgc cgggcctggg tgctcgacgc 49560gtcattgcgg ccggtggagc ccggggtggt cggtgacctg tacctttccg gcgccggtct 49620ggcggacggc tacctggacc gggcggggct gacggcggaa cggttcgtgg cggatccgtc 49680cgcggcgggg aggcggatgt atcggacggg ggatctggct cagtggaccg cggacggtga 49740gctgctgttc gcgggccggg ccgacgacca ggtgaaggtc cgcggattcc ggatcgagcc 49800gggcgaggtc gaggccgcgc tgaccgctca gccgcacgtc cgcgaggccg tggtggtggc 49860gatcgacggg cgcctgatcg gttacgtggt ggcggacggg gacgtggatc ccgtactgat 49920gcgccggcgg ctggcggcgt cgctgccgga gtacatgatc ccggccgctc tggtcacgct 49980ggacgcgttg ccgctgaccg gcagcggcaa ggtggacagg agggcgctgc ccgagcccga 50040tttcgcgtcg gccgcgccgc gccgcgaacc cggcaccgag ccggagcgcg tcctgtgcga 50100cctgttcgcg gagcttctgc aaccggaggg aaggggggta ggggtcgatg acggtttcgt 50160cgagctgggc ggggactcga tcgtcgcgat ccggctggca gcacgtgcgt ccagggtggg 50220gctgctggtg acgcccgccc agatcttcaa ggagaagact ccggcacggc tggcagccgt 50280cgcgggtgcc gtaccggccg gcagacccgc cgacggcccg ctgatcaccc tcacggcgga 50340ggaggaggcg gagctggcga ccgccgtccc gggggccgag gaggtctggc cactcgcacc 50400gctccaggaa gggctctact tccaggccac cctcgacgac gagggtcacg acatctacca 50460ggcgcaatgg atcctggagc tggcggggcc gctggacgcc gcccggctgc gggcctcgtg 50520ggaagcggtc ttcgcccggc accccgagct tcgcgtgagc ttccaccggc gcgcgtcagg 50580cacgatgctg caggtcgtcg ccgggcacgt cgtcctgccg tggcgagagg tggatctggc 50640ggatgcgggc gatatcgacg cggccgtggc ggccctgatc agtgaggaac aggagcagcg 50700gttcgacctc gccaaggcac cgctgttccg gctggtgctg gtccgtcacg gcgaggaccg 50760
gcaccgcctg ctggtcgtcc atcaccacat cctgaccgat ggctggtcgg tggcggtcat 50820cctcaacgag gtggctgagg cgtacacgaa cggcggccgt ctcccggacc gcacgggcgc 50880ggcctcctac cgggactacc tggcctggct ggaccggcag gacaaggacg ccgcacgtgc 50940cgcctggcag gcggagctgt ccggcctcga agggcccgcg ccgatcgcga aggccgccac 51000cacgaccggc gccgggacgg gctacgaata tcgcatcgcc ttcctgaccc ctgacctcca 51060cacgcggctg acggagctgg cccgcgacca cgggctgacg ctgaacaccc tggcacaggg 51120cgcatgggcg atggtgctgg cgcggctcgc gcggcgcact gacgtggtct tcggcaccac 51180ggtcgcctgc cgtcccgccg agctccccga ggtggagtcg gtgccgggtc tcatgatgaa 51240cacggttccg gtccgggtgc cgctgcaggg cgcgcaatcg gtcgtggacc tgctcaccgg 51300cctgcaggaa cggcaggcgg ccttgctgcc gcaccagcat ctggggctga cggagatcca 51360gcgggcggca ggacctggcg cgacgttcga cacgctgctg gtcttcgaga actacccgcg 51420ggacttcgcc ggccagttca cctacctggg cacgatcgag gggacccact acccgctgac 51480cctcggcatc atcccggggg atcacttcag gatccagctc gtctaccggc gcgggcaggt 51540cggggagagc gtcgccgagt cgatcctggg atggttcacc ggcgctctca tgacgatggc 51600cgctgatccg cacgggccgg tgggccggat cggtgtgggt gaggcccggg ccggcggctc 51660ggaccgggcg atggcggcgg gggagccgct gccggtgctg ctacggcggg tggtgaagga 51720ccggccggac gaggtggcgg tggtggacgg cgacggtgag ctgtcgttcg gggaattgtg 51780ggaacgggcg acggcgctgg cggccgagct gagggctcac gggatcgggc cggagagccg 51840ggtggccgtg atggtgggca ggtcggcgtg gtgggcggtc ggggtgctgg gcgtctgctt 51900ggcgggcggc gcgttcatgc cggtggatcc ggcgtatccg gctgagcgcg tcaggtggat 51960cctggccgac tccgacccac ggctggtgct gtgcgcgggg acgacgcggg aggcggtgcc 52020ggaggagttc gcagaccggc tggtggtggt cgacgagctg gacctcgcgg ggagcgacga 52080
tgcgggcttg ccacgggtga gcccggatga cgcggcttat gtgatctata cgtcgggatc 52140gacggggact cccaaggggg tcgtcgtctc gcacgcgggc ctcgggaatc tggcgatggc 52200gcagatcgac cggttcgccg tgtcgccgtc gtcgcgagtc ctgcagttcg cggcgctggg 52260cttcgacgcg atggtgtcgg agatgttgat ggcgctgttg tcgggggcga ggctggtgat 52320ggcgccggag ccggccctgc caccgcgggt gtcgctggcc gaggcgttgc ggcggtggga 52380ggtcacgcac gtcacggttc cgccgtcggt gctggccacc gccgatgcgc tgccggccgg 52440gctggagacg gtggtggtgg cgggggaggc ctgcccgccg ggcctggccg aacgctggtc 52500ggcgggacgg cggctggtca acgcgtacgg gccgaccgag gccacggtct gcgcggcgat 52560gagcaggccg ttgacgggca gccgggaggt ggtcccgatc gggacaccca tcgccggcgg 52620ccgttgctac gtgctggacg cgttcctgcg gccgttgccg ccggggatca ccggtgagct 52680gtacgtggcc gggatcgggt tggcgcgcgg ctatctgggt cgtgcgtcgt tgacggctga 52740gcggttcgtg gcggatccgt tcgtggctgg tgagcggatg tatcggacgg gggatctggc 52800gtattggacg ggtgagggcg agctggtgtt cgccgggcgg gatgacgacc aggtgaagat 52860ccgtgggtat cgggtggagc cgggtgaggt ggaggcggtg ctggcggggc agccgggggt 52920ggatcaggcg gtggtggtgg cgcgtgaggg gcggttgctg ggttatgtcg tctccggtgg 52980tggggtggat ccggtgcggt tgcgtgaggg ggtcgcgcgg gtgttgccgg agtacatggt 53040gccggcggcg gtggtggtgc tgggtgcggt gccggtgacg gcgaacggga aggtggatcg 53100ggaggcgttg ccggatccgg gcttcggcgg gcgggtttcg ggccgggagc cgcgtacgga 53160ggtcgagcgg gcgttgtgcg ggctcttcgc cgaggtgctc gggctgccgg gggtgacggc 53220ggtggggccg gacgacagct tcttcgagct gggcggggac tcgatcactt cgatgcagct 53280ggcgtcgcgg gctcgccgcg aggggatgct cttcggcgcg cgggaggtgt tcgagcgcaa 53340gacgcctgcg gggctcgcgg cgatcgtcga tgtgggcggc gagcttgcgg caggtccggc 53400
cgacggcgtg ggggagatcg cgtggacgcc gatcatgcgg gcgctcgggg acgggatcgt 53460ggggtcgcgg ttcgcccagt gggtggtgct gggtgcgccg ccggacctac gggcggacgt 53520ggtggccgcg ggattggcgg cggtggtgga cacgcacgac gtgttgcggc tgcgggtcgt 53580cgatgaccgg gcgggccgcc ggctggcagt gggcgagcgc gggtcggtgg acacggccgg 53640gctggtcacg cggctcgagt gcggcggccg tccgccggac gaggtcgtgg agcgcgcggt 53700gcgggaggcc gtggggcggt tggacccggt ggcgggtgtg atggcgcagg cggtctgggt 53760ggatgcgggg ccggcgcgga cggggcggtt ggtcgtcgtg gtgcatcatc tggcggtcga 53820cgggatgtcg tggcggatcc tggtgcccga cctgcggctg gcgtgtgagg cggtggccga 53880ggggcgggat ccggtgctgg agccggtgtg ggggtcgttc cggcgctggg cggctctgct 53940ggaggagtcg gcgctctcgc gggagcgggt cggggagctg cacacgtggc ggacgatcgt 54000cgatcaggag gatcggccgg tcggccggcg gcggctgagc gcaggggatg cggccggggg 54060cgtgcgttca cggtcgtggg tgatgtcggg ggatgaggcg tcgctcctgg tggggaaggt 54120tccggtggcg ttccactgcg gggtccacga ggtcctgctg gcgggcctgg cgggagcggt 54180ggcgcgctgg cacggtgacg acggggtcct ggtggatgtg gaaggccacg ggcgtcatcc 54240ggccgagggg atggatctgt ccaggacggt gggctggttc accagcatgc atccggtgcg 54300cctggatgtg gcggggatcg agctggcggc ggtgccggcc ggtggccgtg cggccgggca 54360gttgctgaag gcggtcaagg agcagtcgcg ggcggcgccc ggcgacgggc tcggttacgg 54420gttgctgcgc catctcaatc ccgagacggg ccccgttctg gcggccctgc cgtcaccgca 54480gatcgggttc aactacatgg gccggttcgt caccgtcgac cagggcggtg cgcggccgtg 54540gcagccggtc ggggggatcg gcggttcgct ggaccccggc atgggcctgc cgcatgcgct 54600ggaggtcaat gcgatcgtcc acgacaggct ggcgggcccg gagctggtgc tcacggtgga 54660ctggcgggac gacctgctgg aggagaccga catcgaacga ctgtgccagg tgtggctgga 54720
catgttgtcc ggattgtccc gccaagcgga ggatccttcc gcaggcggac acaccgcgtc 54780cgacttcgcc ctactcgacc tcgaccagga cgagatcgag ggcttcgaag ccatagcagc 54840ggaactctct ggaggccaga catcgtgaac acgccgagca cacccgccgg atcggcgctt 54900gaggaagtct ggccgctgtc accgatgcag gaggggatcc tctatcacgc cgcactcgat 54960gaggcccctg acctctacct catccagcag tcgcagatca tcgaaggacc cttggacacc 55020gagcggttcc gcctggcttg ggagagcctc ctcaaccggc atgcggcgct tcgcgcgtgc 55080ttccaccggc ggaagtccgg tgagtcggtc cagctcatcc cccgtaaggt gccgctcccg 55140tggtccgagc gcgacctgtc cggcctgtcc gaggaggacg cgctggccga ggcgagcgtg 55200atcgcggaga aggagcgcgc cacgagattc gacccggcca agcctccgct gctgcggcag 55260gtgctgatcc ggttcggtcc ggacaagcac tgtctggtga cgacgagcca tcacctggtc 55320atggacgggt ggtcgcgggc gatcctcgag tcggagctcc tcgagctcta cgccgcgggt 55380ggcgccgagc cggggctgcg gcccgccggc tcctaccggg actatctggc ctggctggag 55440cggcaggaca aggaggccgc ccgcgcggca tggcgtgcgg agctggcggg cgccgaccgt 55500tcgacactcg gcatccccga agcgtccagg aagacccagg ggcagcgggt gcgggaggtg 55560ctcggctacg cgccggactt cacctccgct ctggtggact tcgcccgccg ccatgggctg 55620acgctgaaca cgctggtgca gggggcgtgg gcgttggtgc tggcccggct cacgcgccgt 55680cgtgacgtgg tgttcggcgc ggtggtctcg ggacgtccgg cggaggtgcc cggcgtggag 55740caggccgtcg ggctgttcat caacaccgtg ccggtgcgcg tccggttgga cggcgggcag 55800ccggtcatcc agctgctgac ggagctgcag gagcggcagt ccacgctcat ctcgcatcag 55860catctcgggc tgcaggagat ccagaagctc tccggggtga gcttcgacac cgtcgtgtcg 55920ttcgagaact acgtcgatcc gggggcgggt ccgggctccg atcgcgagct gcgcctgaga 55980ctgaaggagt ttcaccagtc ggcgccgtac gcgctcctcc tcggcatcat gccaggtgag 56040
agcctccaga ccgacgtgga gtaccggccc gagctgctcg acgcccgcgt cgccaaggag 56100gccctccacg ggctcgcccg cgtcctcgag cggatgatcg ccgagccgga gaccgcagtg 56160ggccgcctgg acgtggtcgg tgacgcgggg cgcgagctgg tggtcgagcg gtggaacgag 56220acgggcgacg cgatcggtgc gccgtccgcg gtggacctgt tccggcgcca ggttgcacgg 56280gcacccgccg cgacggcggt gacggccggg gacctggcct ggtcgtacgc ggagctcgac 56340gagcggtccg gccggctggc gcgggcactg acggaacgcg gcgtgcgacg cggcgaccgg 56400gtgggcgtgg tgctggggcg gtcggcagag gtgctggcag cctggctcgg agtgtggaag 56460gcaggcgcgg cgttcgtgcc ggtcgacccg gactacccgg cggaccgggt ggcgttcatg 56520ctggccgact ccgccgtcgc gatggtggtg tgccaggagg cgacctcggg tgtggtgccc 56580ccgggctacc agcagctcct ggtgaacgac gccgacgacg gcgaggccgc cctggtcccg 56640atcggggcgg acgatctcgc ctacgtgatg tacacctccg gatcgaccgg gaccccgaag 56700ggcgtggcga tcccgcacgg cggcgtggcg gcgctggcgg gagatccggg atggggcgtc 56760ggacccggcg acgcggtgct gatgcacgcc ccgcacacct tcgacgcgtc gttgtacgac 56820gtgtgggtgc cgctcgtctc cggcgcgcgg gtcatgatca ccgagccggg ggtcgtcgac 56880gcggagcggc tcgccgggca tgtggccgac ggcctcaccg cggtcaactt caccgcgggg 56940cacttccgcg cgctggcgca ggagtcgccg gagtcgttct ccgggctgcg cgaggtggcg 57000gcgggtggcg acgtggtgcc gctcgatgtg gtggagcggg tacggcgggc gtgcccgcgg 57060ctccgggtct ggcacaccta cggcccgacc gagaccacgc tgtgcgcgac gtggaaggcg 57120atcgagcccg gtgacgaggt ggggccggtg ctgcccatcg gccgggcact gccgggccgg 57180cggctgtacg tgctggacgc gttcctgcgg ccgttgccgc cgggcatcgc gggtgatctc 57240tacctcgcag gcgccggagt ggcccacggc tatctgggtc gtgcgtcgtt gacggctgag 57300cggttcgtgg cggatccgtt cgtggctggt gagcggatgt atcggacggg ggatctggcg 57360
tattggacgg gtgagggcga gctggtgttc gccgggcggg atgacgacca ggtgaagatc 57420cgtgggtatc gggtggagcc gggtgaggtg gaggcggtgc tggcggggca gccgggggtg 57480gatcaggcgg tggtggtggc gcgtgagggg cggttgctgg gttatgtcgt ctccggtggt 57540ggggtggatc cggtgcggtt gcgtgagggg gtcgcgcggg tgttgccgga gtacatggtg 57600ccggcggcgg tggtggtgct gggtgcggtg ccggtgacgg cgaacgggaa ggtggatcgg 57660gaggcgttgc cggatccggg cttcggcggg cgggtttcgg gccgggagcc gcgtacggag 57720gtcgagcggg cgttgtgcgg gctcttcgcc gaggtgctcg ggctgccggg ggtgacggcg 57780gtggggccgg acgacagctt cttcgagctg ggcggggact ccatccattc ggtgaagctg 57840gcagcgcggg ccacgcgtgc cggcatgccc ttcaccgtgg tcgaggtgtt cgagcacaag 57900acgcctgcgg ggctcgcgac gatcgtcgac gtgggcggcg agcccgcggc aggtccggct 57960gatcccccat cggactccga cctgctcggc ctggcgcagg acgagatagc ggagttcgag 58020gccgaattcg acgacgaacg tcattctctg cgctgatcga aagcgggcgc cgcgcacggt 58080gtgccggcag cctgcgagtt gtccaacatc ctgtcgtgcc aatgacgtat gcccatgagt 58140aggttggctc aatgataagc aaagcaatgc atggaccgat tcggcccgcc cgcgcggata 58200ccctgctggc ctcggtaggc gagcgaggca ttctgtgtga cttttacgac gagaacgcct 58260cggaaatctt ccgtgatttg gaggcggacg cgggcggcac ggaagaagcc cacgggttcg 58320cggcgctcgt ccgcccggag tcgggggcga tcctggagct cggggccgga acaggcaggc 58380tgacgattcc gctcctggag ctcggctggg aggtgaccgc cctcgaactg tcgaccgcga 58440tgctcaccac cctgcggacg cggctggcgg acgcgccggc ggacctccgg gatcggtgca 58500ccctcgttca cgcggacatg accgccttca aactgggaga acgcttcgga acggcgattc 58560tcagcccgtc cacgatcgac ctcctggacg atgccgacag accagggctg tactcgtcgg 58620tccgtgagca tctgcggccc ggcgggagat tcctgctcgg catggccaac cccgacgcgt 58680
ccggcaggca ggagccgctg gagcgcaccc aggagttcac gggcaggagc ggccgccgat 58740acgtgctgca cgccaaggtc tacccgtcgg aggagatccg cgacgtgacc attcatcctg 58800cggatgaatc ggcggacccc ttcgtcatct gcgtcaatcg cttcagagtc atcaccccgg 58860atcagatagc acgagagctg gagcaagccg gattcgacgt ggtcgcgcgg accccactgc 58920ccggggtgcg taatcacgaa ctggtgctgg aagcgcaatg gggcagcgtg gaagacgcgc 58980attagagccc tccggggaaa gcgcttgtgt acttttctgc agtcattcga cagtgaggaa 59040cagaaatgag tgaggagctc ctcttcctcc ggcccgacac cattatcgaa ccgctggcca 59100accggttcta cgcctcgatg tacgcgacgg ctcccgtcac ggccgccatg aatctcgcct 59160tccgtaacct gccgatgctg gagtcctacc tcgcatcccc ggaatggcat ttcgcagccg 59220ctcgcgatcc gaagttccgc ggcggattct tcgtcaacat cgaggagcag cggaagaacg 59280aggtcgaggc gctgctcgct gcgatccggc gcgacagcgc ggacgtgctc cggttcgccg 59340aggcgatcgc ggaggccgag aagatcatcc gcgaggaagc gaccggatac gatctcaggc 59400cgctctaccc gaagctgcct cccgagctgt cgggtctggt ggagatcgcc tatgacaccg 59460gcaacgcggc ctcgctgcac ttcctggagc cgctcatcta caagagcaag gcctacgccg 59520aggactgcca gtccgttcag ctctccgtgg agaccgggat cgagcggccg ttcgtgatga 59580gcaccccgcg actgccctca cccgacgtgc tcgagctgaa catcccgttc cggcatccgg 59640gtctggagga gctcttcctg tccaggatcc ggcccaccac cctggccgcc ctccgcgagg 59700cgctggagct cggcgacgcg gaagcggcgc ggctcgccga cctgctggtc ccggagccct 59760cgctcgcctc cgaccgccat gtcgcggccg gagcccggat ccgctactgg gggcacgcct 59820gcctgctcat gcagacgccc gacgtggcca tcatgacgga cccgttcatc agcgcggata 59880ccgacgcgac cggccgctac acctacaacg acctgcctga ccgcctcgac tacgtcctca 59940tcacgcacgg gcattccgac catctggtgc ccgagacgct gcttcaactg cgcggccggg 60000
tgggcacgtt cgtcgtgccg cgaacctcgc gcggcaacct gtgcgatcct tcgctggcgc 60060tctatctcag aagcttcggg ctgcccgcga tcgaggtgga cgatttcgat gagatcgagt 60120tccccggcgg gaagatcgtc tccaccccgt tcttcggcga gcacgccgat ctcgacatcc 60180gggccaagtc gacgtattgg atcaacctcg gtggcaagtc gatctgggtg ggcgcggact 60240cctcaggcct cgatccggtt ctctaccgcc atatccgccg gcatctcggc gcggtcaaca 60300tcgccttcct cgggatggaa tgcgatggcg cgccgctgaa ctggcagtac cagccgttca 60360tcaccaaggc gttgccgaag aagatgagcg acagccgcaa gatgtccggc tccaacgcgg 60420agcaggcagg tgcgatcgtc accgagctgg gcgccgagga ggcgtacatc tacgccatgg 60480gggaggagag ctggctgggg catgtcatgg ccaccagcta caacgaggac tcctaccagc 60540tccagcagat cgccgagttc gaggcatggt gttcccgcaa gggtgtgaag gccgctcatc 60600tgctcgacca gcatgagtgg cactggtcgt catccaggtg atcgcggtgg cccgccggtc 60660ggccttcgct caggcgggca gggccgcggt cgcaagcagc tgccgaggcc gtgctcgccg 60720aggccgtgct cgccgaggcc gtgcccgtgc tcgcccaggc cgtgcccgtg ctcgccgacg 60780ccgtgctcgt cgaggccggt gccagagggc gcgtcaccgg cctctcagcg caaccggccg 60840cgtgaaccgc ccggcggttc ggatcgttcg atatcagggc cggatcgaca acgcgtggtg 60900gaagtggtta cgcgggtcgt aggcggcctt caccttgcgc agccgcgggt ggttcccctt 60960gtagtagagg tcgtgccacg gcacgcccga ggtgttcaag cccggatccg cgaggtcgct 61020gtcggggtaa ttgatgtacg ccccatcgct gacgtcgttc ggcaccggca ccccgccggt 61080ctcggcgtac acatcggcat agagcttgcg gacccacgtc agatgcttgg cctcgttgcc 61140gggattcgcc caaccggtga tgtagttcac cttgagtatc gcgtcgcgct gcggcagggc 61200ggtggccgcc gggtcgacgg tgttcacctt cccgccgtag ccgatcagcc agacggcgcc 61260gtagtcgatc ccgtccatgt gggtcatgtt ctcgtacacg gcctgaatct gccggtcggt 61320
cagccgcttg cgcaggtagc cggctttcgt cttcgacgcc gggcccctgc ctcctcgccc 61380cggcgtcgag gccagccacc tctgttcgat cggctcgggc acctcggccg gcgggacgcc 61440gtcgatcacc gcctcgatgt gcgcgtcgag cagtctccgg gcgtccggcc gggtggcgtc 61500cacctggatg ggcatcatga agccgctctc acccatgccc gggacctcgt tcccgatcat 61560gagctgactc cacagcccgg tgtacggcga gtcgggcccg ctgttccgct cgtaccactc 61620cccgtggttg cgcagcagcc gggagaacgc cgcctccgtc atccccgccc agtcgaaggt 61680caccgtgctc gtgagcaacg tcgcgggcgg cttcggcagc agccgctccg gattccggcc 61740gacgtcctcc ggcaccctca tccagtactt cgtgaccacc ccgaagttcc cgccgccacc 61800gccggtgtgc gcccaccaca ggtcgtgatg ggggtcgtcg cgctcacggg tcgccacgat 61860cacgcgtgcc ttcccctgtt tgttgacgac gacgacctcg accgcgtaca agtagtcgac 61920cacggagccg aactgccgtg acagcgggcc gtacccgcct ccgcagatgt gtccgccgac 61980gccgaccccg ccgcagaccc cacccggtat ggtcacgttc cagcccaggt agagcttttc 62040gtacacctct gagagcgtgt tgcccggctc gatcaggaac gcgttcatcg acgggtcgta 62100cgcgatctcc gtcagcagcg acatgtcgat gatgaccttg acgtcggggt tgtcgacgaa 62160gtcctcgaaa cagtgcccac cgctgcggac ggcgacccgc ttgccggtgc gcaccgtctc 62220ctcgacggca tcggccacct gctgggtgga gccgaccagg tggatgtagt cgggctcgcc 62280gttgaagcgg ctgttggcgc cacgcagctt caggttgagg tagcgcgggt cgtccggagt 62340caccttgacc gggccggccg gcggtaagca gcgctcgccc cgcagctccg gtcgcgtgga 62400cgaggcgccg gccgacgcgg cgtccgctcc ggtgccgccg gtcaccaccg ccgccgcgcc 62460cccggcaagg gaggcactca gcaatctacg tcggttcagt tttgtcatgg cggcgacgtt 62520actatcggtt cgattcgatc aactcgctgt ctgactggac gtaagcgatc tcttcacgcc 62580gtggccgtac gtggctgtcc atcgcctaca gatttccgat ctctgaaggt acggtcacct 62640
gttgaagaac gcgtccgtca gcgcattcca ggtgacgccg ccgcgaacgc gcgctcacgg 62700gaaaactcgc cgtcgaggcg ggtgacgacg gaatcgtggt gtccaaccac ggaggccgtc 62760agttggacgg tgccgtcctg agccagtttc tgccaaacga ctgggaacac catgggacat 62820ccacacgatc aagagcccga cggccaaatc cgtcctgcgg ctcagagccc ccgccggttg 62880gtcgagatga cgagcacctc cgggcggcac ctgtatcacc gccaggtgcg attctccgat 62940atcgacgccc acggccacgt caacaatgtg cgtttcctgg aatacctgga ggacgcctgg 63000atcgccctct atctcgacaa tgcgggcccg ccgcaggagg accgcgacgg attgcccgcc 63060gtggggttcg ccgtcgtgcg ccacgagatc ttctatcggc gcccgctcag gttccggcac 63120gggtcggtgc gggtcgagtc gtgggtgacc aaggtgaaca gggtgacctg cgagatggcc 63180gcgcagatct gctcggacgg ggaggtgttc gtcgaagccc gctcgatgat catggggttc 63240gacacgcaca ccgccaagcc gcggcgcctc accctgcacg agcgcacctt tctcaagcgt 63300tacctgcgct gatgtgactt ctccattgcc ggccgcggct ccgggcgttg gacgattttg 63360accgccgaga tcggccgagc ctaccttcac ggtgttcgct gcgaccggaa aggtgaattc 63420aatggccgcg tccgaggtca agcaagtgct ccggagcaag ctcaggacat gggggtggat 63480gtatcgatga cgaccagcat cgcgtcggca gaagaccttt ccgtcctcac cggactgagc 63540gagatcacca cgttcgccgg cgtggggaca gccgtttccg ccacgtccta ttcgcaagcc 63600gagctgctcg aaatcctcga catacgcgat cccaggatcc gatcgctgtt cctgaacagc 63660gcgatcgagc ggcgttttct cgcgcttccg ccccagggcc gggacgggga gcgcgtggcg 63720gaaccgcagg gtgatctcct ggacaagcac aaaaagctcg ccgtcgatat gggatgccgg 63780gccctcgagt cctgcctgaa gtcggcgggc gcgacgctct cggatgtccg ccacctgtgc 63840tgcgtcacct cgaccggttt tctcaccccc ggcctgagcg cactcatcat ccgcgagctc 63900gggctcgacc cgcattgcag ccgcgccgac atcgtcggca tgggatgcaa cgcggggctg 63960
aacgcgctca acctggtcgc gggctggtcc gcggcgcacc cgggcgagct cgccgtcgtt 64020ctgtgcagcg aggcgtgttc cgctgcttac gcactggacg gcaccatgcg caccgcggtg 64080gtcaacagcc tgttcggcga cggatccgcc gccctcgccg tcgtctccgg tgacgggcgc 64140gctgccggcc cgcgcgtcct gaagttcgcg agctacgtca tcaccgacgc gatcgaggcg 64200atgcgctacg actgggaccg cgaccaggac cggttcagct tcttcctcga tccgcagatc 64260ccctacgtgg tcggcgcgca cgccgagatc gtcgtcgaca agctgctgtc cggtacgggg 64320ctgcgccgca gcgacatcgg ccattggctg gtgcactccg gcggcaagaa ggtgatcgac 64380gccatcgtcg tcaacctcgg cctgagccgg catgacgtcc gccacacgac cgctgtgctc 64440cgcgactacg ggaacctctc cagcggctcc ttcctcttct cctacgaacg gctcgccggc 64500gagggcgtga ccaggcccgg agactacggg gtgctcatga ccatggggcc cggctccacg 64560atcgaaacgg cgctgatcca atggtgagtg gcagtgacat gaacggcgaa ctggagctga 64620gcctcgacgg cacccaggcg ctgaccgcgt cggtcgagga gctgaacggc ctctgcgacc 64680gcgccgagga ccatcgagca cccggcccgg tcatcgtcca cgtcaccggc gtgccgcgcc 64740ttggctggtc gaaggggctg acggtgggcc tggtctccaa gtgggagcgg gtggtgcgcc 64800ggttcgaacg gctcggccgg ctcaccgtcg ccgtggcgtc aggcgactgc gcgggaccct 64860ctctcgacct cctcctcgct gccgacgtgc ggatcgccgc tccggcgacc cggctgctgc 64920cctcctgggc cggcggcgcc gcgtggccgg ggatggccgt ctaccggctc acccagcagg 64980ccggtacggg cggcatccgg cgggccgtgc tgctcggggc acccatcgac gccgaccgcg 65040cgctcgccct caacctgatc gacgaggtgt ccgcggaccc ggcggcgtcc ctggccggcc 65100tggcgggtgc cggggacggc gcggagctgg cgattcgcag gcagctgatg ttcgaggcga 65160gctcaaccac tttcgaggac gcgctcggtg ctcacctggc cgcggtggac cgggccctac 65220gacgggagac cctctcgtga cgacggattg gccggcgctg ccgcccaggg cgccgctcgc 65280
cctctggacc ctgacggcgg aggcccagcg agtcgacgac ctgctcgccg ggctgccgga 65340gcctcctgcc agaacctccg cccagcgcga tgccgcggcc tcggcactcg acaaggtgag 65400gcggatgcgc gcggactaca tggaggcgca cgccgaggag atctacggcg agctcacctc 65460cggccgcacc cggcacctgc gcatcgacga gctcgtacgg gccgccgccc gcgcctaccc 65520cggcctggtg cccaccgatg agcagatggc ggccgagcgc gcgcggccac aggcggagaa 65580ggaagggcgc gagatcgatc agggcatctt cctgcgcggg gtcctgcgtg ccccgaaggc 65640gggcccgcac ctgctcgacg ccatgctccg gcccaccccc agggcccttg agctgctccc 65700tgaattcatc gagtccggcg aggtgcggat ggaggcggtc ctgctgcggc gccgtgacgg 65760tgtcgcgtac ctgaccctgt gccgggacga ctgcctcaac gccgaggacg cgcagcaggt 65820ggacgacatg gagaccgcag tcgacctggc gctgctcgac ccccaggtcc gggtggggct 65880cctgcggggc ggcgagatga gccatccccg gtaccggggg cgccgggtgt tctgcgcggg 65940cgtcaacctc aagaagctga gctcgggcga catctccctc gtcgacttcc tcctacggcg 66000cgagctgggc tacatccaca agatcgttcg cggcgtgtac acggacggtt cgtggcactc 66060gaagctgacc gacaagccct ggatggcggt cgtcgactcc ttcgccatcg gcggtggggc 66120tcagctcctc ctggtcttcg accaggtgct ggcggcgtcc gactcctaca tcagcctgcc 66180tgcggcgacg gaggggatca ttccgggggt cgcgaactac cggctcaccc ggttcaccgg 66240gccacgcgcg gcccggcaga tgatcctcgg cgggcggcgg atccgggcgg acgagccgga 66300cgcacggttg atgatcgacg aggtcgtccc gccggaggag atggacgcgg cgatcgatcg 66360cgcactggcc cgcctcgacg gagatgcggt gccggccaac cggcgcatgc tgaacctggc 66420cgaggagccg cccgaggcgt tcggccggta cctggccgag ttcgccctgc agcaggcact 66480gcgcatctac ggcagggacg tcatcggcaa ggtcggcagg ttcgcagcgg gatcggcatg 66540agcgagcctc gcgtgcgcta cgagaagaag gaacacgtcg cccatgtgac gatgaaccgg 66600
ccccacgtgc tgaacgcgat ggatcgccgg atgcacgagg agctcgccga gatctgggac 66660gacgtcgagg ccgacgacga cgtcaggacg gtcgtcctga ccggtgcggg aacgcgggcc 66720ttctccgtcg gccaggacct caaggaacgc gcgctgctgg acgaggcggg cacgcaggcc 66780tcgacgttcg gcagccgggg gcaggcaggt catccccggc tgaccgaccg cttcaccttg 66840tccaagccgg tggtcgcccg ggtgcacggc tacgcgctgg gtggcggctt cgagctggtg 66900ctcgcctgcg acctcgtcat cgcctccgag gaggcggtgt tcggcctgcc ggaggtccgg 66960ctcggcctga tccccggggc gggaggcgtg ttccggctgc cgcggcagct gccgcagaag 67020gtggcgatgg gccatctgct gaccgggcgc cggatggatg cggccacggc gttccggtac 67080ggattggtga acgaggtcgt accgcttgat gagctggatc ggtgcgtggc cggatggacc 67140gacgacctcg tacgcgccgc tccgctgtct gttcgcgcga tcaaggaggc cgccatgcgg 67200tcgctcgaca ttcccctgga ggaggcgttc accacgtcct acccatggga agagcgtcgt 67260cggcgtagcg gcgatgcgat cgagggcgtc cgggcgttcg tcgagaagag ggacccggtc 67320tggacgtcga gatgatcccc ccgcacacgt tgctggtctt cttcgttcag gctgcggccc 67380tcctgctgct cgcgttgctc ctgggccgcc tggccgtacg gctgggcctg gcggcggtcg 67440tcggcgaact gtgtgccggc gtcatcctcg gcccctccgt gctggggcag gtcgcgcccg 67500gggcggagca gtggctgttt ccctcgccgt cgtcacacat gctggacgcc gtcgggcagc 67560tcggcgtgtt gttgctgatc ggcttgacgg gcgcgcatct ggatctgcgg ctgatccggc 67620ggcagggcgc cacggcggtg cgggtgagcg ccttcgggtt ggtcgtgccg atggccctcg 67680gcatcggcgc cggcctgttg ctgccggccg agttccgcgg gaccggcggc tcggccgtct 67740tcgccctgtt cctgggggtg acgatgtgtg tcagctcgat ccccgtgatc gccaagacgc 67800tgatggacat gaacctgctc catcgcaacg tcggccagct cacgctgacc gccggcatga 67860tcgacgacgc cttcgggtgg gtgctgcttt cggtggtgac ggcgatggcc accgccggag 67920
ccggtgcggg gaccgtggtg ctgtcgatcg cgtcgctgct cggggtgatc gtcttcagcg 67980tcgtcatcgg caggccggcg gtccgggtgg cgttgcggac gacggaggat cagggggtga 68040tcgccggcca ggtcgtggtg ctggtgctcg cggccgcggc cgggacgcat gcgctgggcc 68100tcgaaccgat cttcggggcc ttcgtcgccg ggctgctggt gagcacggcc atgccgaatc 68160cggtcagact ggcaccgctg cgcacggtga cgctcggggt gctggctccc ctctatttcg 68220ccaccatggg cctgcgcgtc gatctcacgg ccctggcgcg gccggaggtg ctcgccgtgg 68280ggctgctggt cctggccctg gcgatcatcg gcaagttcct gggcgccttc ctgggcgcct 68340ggaccagccg gctcagccga tgggaggcct tggcgctggg ggcggggatg aacgcccgtg 68400gcgtcatcca gatgatcgtg gcgacggtcg gcctgcggct gggggtgatc actgacgaga 68460tcttcacgat catcatcgtg gtggcggtga tcacctctct gctcgccccg ccactcctgc 68520gcctggccat gaccaggatc gaggccaccg ccgaggagga ggcccgcctc ctcgcctacg 68580ggctgcgccc cggcgaggcc cgggaagacg tacggtgacg acggctcggg atcgtcgtgc 68640ccgacgacaa ggccggcagc cggacggtgg tggccggtgc cggctcagcc acagtgggcc 68700ggggtcgcga tgcccagccg cgcgtgcagg tgcgcccaca gagcagcctg ctcgtgcccc 68760aggaagaagt ggcctccggg caggacgtgg caggagaact cccgagccgt caactcggcc 68820catcgcgcga ccgcgtcgag ccgtacgacg ggatcgtccg caccggtgaa cgccgtgatc 68880ggcaccgtca ggggcggccc aggcgtgtgg cggtaggact ggacgagctg gaagtcgttg 68940cgcacgtagg ggagggcgaa cgcccggaac tccgcgctcg cgagcgcctc ggcatcggtg 69000ccgcccaaca ggcgcagcct gtcgatgagc gcctcctcgg aggccggcgc cacccgatgc 69060gcgagacggc cacggtcgtg cgcggccaca cctccggaga cgaagagatg agccggcggg 69120ataccggacc cggtgagaag ccgcgccgtc tcgtaagcga tcaaactgcc catactgtgc 69180ccgaacagcg ccaccggccg gtcgaggagc ggcctcagct cacgccccac cgactccgcg 69240
agccggtggg catcaccgac gaggggttcg tgcaaccggt cggcgcggcc cggatactga 69300accgcgtgca cttctatctc cggcgcggcc agccggtgcc aattccggta gaagaccgcc 69360gaaccgcccg cgtgcggaaa acagatcagc cgcatcgtgg cgagcggccg cctgtcgaaa 69420caccgaaacc aggtggacat gtagcctcgc ttcggcctca tatcatggtc ttgggtcaat 69480cctggtgacc tgactatatg cctgcaccgc cataaagtat gtccgtccac tcatcggcgg 69540gcatgcggca cgagtctgcc caggtcgcac ttgacgcctg gtcggcaaag ggaaaaccct 69600tgcttccatg gactcccacg ttctcgccca tcaattgagc aaggaaacgc tgcacggatc 69660gctgatggac ccggccatcg agtcgatgaa tctactgaac gagattgccg gcaactaccc 69720cgacgccatt tccatggccg cgggccggcc gtacgaggag ttcttcgacg tcggcctcat 69780ccacgactat ctggaggcct accgcgacca tctccgcaac gaccggcgga tggatgacgc 69840cgggatcagc cgcatgcttt tccaatacgg gaccacgaag gggatcatct ccgaccttgt 69900cgcccggcac ctcgccgagg acgagaacat cgaggccgac ccggcctccg tggtcatcac 69960tgtgggcttc caggaggcca tgttcctggt gcttcgcgcg ctgcgagcga acgagcggga 70020cgtcctgctc gcccccacgc ccacctacgt cggcctgacc ggagcggcgc tgctcaccga 70080cacccctgtc tggccggtcc agtccaccga caacggcatc gacctcgacc accttgagca 70140ccaactgaaa cgcgcccagg accagggcgc ccgggtccgg gcctgctacg tgaccccgaa 70200cttcgccaac cccaccggca ccagcatgga cctgcccgcc cgccatcgcc tcctggaggt 70260cgccgcggcc cacggcatcc tgatcctgga ggacaacgcg tacggactcc tcggccagga 70320ccgcctcccc acgctgaagt ccctcgacca tgcggcgacc gtcgtctacc tcggctcctt 70380cgccaagacc ggcatgcccg gcgcccgggt cggctacgtc gtggcggacc agcacgtagc 70440ggggggcggc tcgctcgccg acgagctcgc gaagctcaag ggcatgctca ccgtgaacac 70500ctcgcccatc gcccaggcgg tgatcgccgg caagctgctg cgccacgact tcagcctggc 70560
ccgggccaac gcccgcgaga ccgccatcta ccagcgcaac ctccacctca cgctggacga 70620actcacccgc cggctcggcg ccgtcccggg agtcacctgg aacgcgccga cgggcgggtt 70680cttcatcacc gtcaccgtgc ccttcgtcgt ggatgacgag ctgttggaac acgctgcccg 70740cgatcatggc gttttgttca cgccgatgca tcacttctat ggtgggaagg atgggttcaa 70800ccagcttcgg ctgtcgatca gcctgctcaa cccgcaactg atcgaggagg gtgtctcccg 70860gcttgccggg ctcgtcaccg catgtctccc ctgaaccatg cctggggcct tgagtcggac 70920ggccgggttg cgtgcggccg ggatgaaggt caaccacaag cgggtggtgc gcgagcacgg 70980cctcgccggg cggtggccag cgaccaaggc ctcgacaaac gccatcgccg accctcccga 71040gggaggatcg gcggttgaag atctgtgtgc cccctgcagg attcgaacct gcgcacccgg 71100ctccggaggc cggtgctcta tcccctgagc taaggggg 71138<210>2<211>366<212>PRT<213>野野村菌屬<400>2Met His Glu Ser Pro Val Cys Leu Ala Glu Tyr Glu Glu Ile Ala Ala1 5 10 15Lys Val Leu Pro Ala Asp Val Arg Asp Phe Ile Asp Gly Gly Ser Gly20 25 30Arg Glu Gln Thr Leu Arg Ala Ash Arg Ala Ala Phe Asp Arg Val Phe35 40 45Leu Val Pro Arg Val Leu Gln Asp Val Ser Ala Cys Ser Thr Arg Ala50 55 60
Thr Leu Leu Gly His Pro Ala Thr Met Pro Val Ala Val Ala Pro Val65 70 75 80Ala Tyr His Arg Leu Val His Pro Asp Gly Glu Leu Ala Thr Ala Arg85 90 95Ala Ala Arg Asp Ala Gly Val Pro Phe Thr Val Ser Thr Leu Ser Ser100 105 110Val Pro Val Glu Asp Val Thr Ala Leu Gly Gly His Val Trp Phe Gln115 120 125Leu Tyr Cys Leu Arg Glu His Ala Ala Thr Leu Gly Leu Ile Arg Arg130 135 140Ala Glu Asp Ala Gly Cys Arg Ala Leu Met Leu Thr Leu Asp Val Pro145 150 155 160Trp Met Gly Arg Arg Pro Arg Asp Ile Arg Asn Arg Phe Arg Leu Pro165 170 175Pro His Val Arg Pro Val His Leu Thr Ala Asn Ser Gly Thr Glu Ala180 185 190His Arg Gly Ala Ser Gly Gly Ser Ala Leu Ala Ala His Thr Ala Met195 200 205Glu Leu Ser Ala Ala Val Asp Trp Ser Tyr Leu Glu Thr Leu Arg Ala210 215 220Ala Ser Gly Leu Pro Leu Val Val Lys Gly Ile Leu His Pro Glu Asp225 230 235 240
Ala Arg Arg Ala Ala Asp Leu Gly Ile Asp Gly Ile Val Val Ser Asn245 250 255His Gly Gly Arg Gln Leu Asp Gly Ala Val Ala Ser Leu Asp Ala Leu260 265 270Pro Gly Val Ala Glu Ser Val Gly Gly Arg Cys Glu Ile Met Leu Asp275 280 285Gly Gly Val Arg Ser Gly Ala Asp Val Leu Lys Ala Leu Ala Leu Gly290 295 300Ala Ser Gly Val Leu Val Gly Arg Pro Val Ile Trp Gly Leu Ala Ala305 310 315 320Asp Gly Glu Arg Gly Val Arg Thr Val Leu Gly Leu Leu Gly Ala Glu325 330 335Ile Glu Asp Gly Leu Gly Leu Ala Gly Cys Gly Asp Val Ala Ala Ala340 345 350Gln Ala Leu Arg Thr Thr Arg Pro Gly Ala Gly Phe Val Ser355 360 365<210>3<211>356<212>PRT<213>野野村菌屬<400>3Met Glu Ser Leu Pro Pro Leu Ala Val Asp Tyr Val Glu Met Tyr Val1 5 10 15
Ala Asp Leu Lys Val Ala Thr Leu Pro Trp Thr Asp Glu Tyr Arg Phe20 25 30Ala Val Val Gly Thr Ala Asn Ala Ser Asp His Arg Ser Val Ala Leu35 40 45Arg Gln Gly Arg Ile Thr Leu Val Leu Thr Gln Ala Thr Ser Asp Gly50 55 60His Pro Ala Ser Ala Tyr Val Arg Thr His Gly Asp Gly Val Ala Asp65 70 75 80Ile Ala Leu Arg Thr Pro Asp Val Asp Val Val Phe Thr His Ala Val85 90 95Ala Ala Gly Ala Arg Pro Val Arg Ser Pro Ser Arg His Pro Gly Pro100 105 110Gly Pro Ala Cys Ser Ala Ala Ile Gly Gly Phe Gly Asp Val Val His115 120 125Thr Leu Val Gln Arg Asp Pro Gly Asp Asp Pro Gly Leu Pro Val Gly130 135 140Phe Ser Glu Ala Pro Ser Ala Ala Glu Ser Gly Ala Asp Ala Ala Glu145 150 155 160Leu Leu Asp Ile Asp His Phe Ala Val Cys Leu Pro Thr Gly Asp Leu165 170 175Asp Ile Ile Thr Asp Phe Tyr Val Ala Thr Leu Gly Phe Ser Glu Thr180 185 190
Phe Lys Glu Arg Ile Glu Val Gly Thr Gln Ala Met Glu Ser Lys Val195 200 205Val Gln Ser Ala Ser Gly Ala Val Thr Leu Thr Leu Ile Glu Pro Asp210 215 220Pro Met Ala Glu Ala Gly Gln Ile Asp Met Phe Leu Glu Arg His Ala225 230 235 240Gly Ala Gly Val Gln His Val Ala Phe Ser Ser Ser Asp Ala Val His245 250 255Ala Val Asn Thr Leu Ser Glu Arg Gly Val Arg Phe Leu Ser Thr Pro260 265 270Gly Ser Tyr Tyr Asp Leu Leu Glu Ser Arg Ile Gln Ile Arg Gly His275 280 285Thr Val Asp Gln Leu Arg Ala Thr Gly Leu Leu Ala Asp Glu Asp His290 295 300Gly Gly Gln Leu Phe Gln Ile Phe Thr Ala Ser Thr His Pro Arg Glu305 310 315 320Thr Leu Phe Phe Glu Val Ile Glu Arg Gln Gly Ala Arg Thr Phe Gly325 330 335Gly Ala Asn Ile Lys Ala Leu Tyr Glu Ala Val Glu Val Ala Arg Ser340 345 350Gln Gln Arg Ala355
<210>4<211>867<212>PRT<213>野野村菌屬<400>4Met Leu Phe Gly Arg Asp Arg Glu Leu Lys Ser Leu Thr Arg Leu Leu1 5 10 15Asp Ser Thr Ala Ala Gly Arg Gly Gly Val Ala Val Ile Thr Gly Pro20 25 30Val Val Gly Gly Lys Thr Ala Ile Leu His Glu Leu Gly Met Arg Ser35 40 45Ile Ala Ala Gly Ile Arg Leu Val Thr Ala Arg Cys Thr Pro Ala Glu50 55 60Gln Ser Leu Asp Trp Gly Val Ala Asp Gln Ile Leu Gly Arg Gly Ala65 70 75 80Ala Glu Arg Leu Thr Ala Arg Arg Gly Gly Asp Ala Val Glu Asp Val85 90 95Cys Val Ser Leu Phe Gln Met Ala Glu Ala Asn Pro Ile Leu Leu Thr100 105 110Ile Asp Asp Val Asp Leu Ala Asp Asp Pro Ser Leu Leu Ala Ile Leu115 120 125Ser Met Thr Pro Leu Leu Thr Asp Thr Arg Met Met Ile Ala Val Thr130 135 140Ile Cys Gln Asp Arg Pro Pro Ala Pro Leu Pro His Val Ala Glu Ser
145 150 155 160Leu Leu Arg Leu Pro Gly Ile Glu Leu Val Glu Leu Pro Leu Leu Pro165 170 175Arg Pro Ala Val Arg Gln Phe Ala Thr Glu His Leu Gly Ala Glu Thr180 185 190Ala Asp Gln Leu Ala Asp Asp Leu Tyr Arg Phe Ser Gly Gly Ser Pro195 200 205Leu Leu Val Arg Ala Leu Ile Glu Asp Gln Glu Ala Gly Ala Pro Gly210 215 220Leu Val Val Gly Asp Ser Phe Met Ser Ala Val Ala Ala Cys Val His225 230 235 240Gly Cys Glu Pro Glu Ala Val Arg Val Ala Glu Ala Val Ala Val Leu245 250 255Gly Glu His Ala Thr Pro Asp Ala Val Gly Glu Leu Val Gly Ile Ala260 265 270Pro Pro Ala Ala Thr Arg Ser Met Gly Met Leu Glu Arg Ala Gly Leu275 280 285Leu Ala Gly Gly Arg Phe Arg His Glu Ala Gly Arg Leu Ala Val Leu290 295 300Gly Arg Met Thr Ser Tyr Gly Arg Met Glu Ile Leu Arg Arg Ala Ala305 310 315 320Glu Ile Leu His Arg Arg Gly Gly Pro Pro Ser Ala Val Ala Thr Arg
325 330 335Leu Leu Glu Ala Gly Trp Ser Gly Glu Glu Trp Ala Phe Asp Val Leu340 345 350Val Glu Ala Gly Arg Gln Ala Phe Asp Glu Gly Asp Phe Val Ala Val355 360 365Met Lys Cys Leu Arg Leu Ala Leu Ala Ser Gly Trp Gly Thr Pro Arg370 375 380Arg Leu Asp Val Lys Val Met Leu Ala Ala Ala Glu Trp Arg Val Asp385 390 395 400Pro Ala Val Ala Ala Arg His Val Pro Asp Leu Leu Asp Ala Thr Arg405 410 415Ser Gly Ala Leu Arg Gly Ser His Gly Met Glu Leu Phe Arg Gln Leu420 425 430Leu Trp Tyr Gly Arg Phe Ala Asp Ala Ala Glu Leu Ile Asp Arg Leu435 440 445Arg Pro Ser Val Ala Asp Arg Asp Ala Asp Ala Ser Leu Ile Ala Met450 455 460Cys His Val His Pro Val Leu Leu Asp Arg Leu Pro Arg Ser Ala Arg465 470 475 480Gly Ser Met Gly Gln Thr Val Glu Asp Ala Arg Arg Ile Leu Arg Gln485 490 495Ala Glu Pro Thr Asp Glu Ala Met Asp Ser Ile Ile Ser Ala Leu Met
500 505 510Ala Leu Leu Leu Gly Gly Val Ser Glu Val Ala Ala Ser Cys Glu Thr515 520 525Leu Leu Lys Glu Pro Gly Val Thr Lys Ala Pro Thr Trp Lys Ala Ile530 535 540Ile Ser Ala Ile Arg Ala Glu Thr Ala Trp Arg Lys Gly Asp Leu Ala545 550 555 560Gly Ala Glu Ala His Ala Gln Glu Ala Leu Thr Ile Leu Gln Pro Ser565 570 575Gly Trp Gly Val Ala Ile Gly Ala Pro Leu Ser Thr Leu Leu His Ala580 585 590Gln Thr Ala Met Gly His Leu Asp Glu Ala Lys Ala Thr Val Ala Val595 600 605Pro Met Pro Arg Glu Thr Ala Glu Thr Ala Phe Gly Ile Gly Tyr Glu610 615 620Leu Ala Arg Ala His Tyr His Leu Val Thr Glu Gln Pro Arg Ala Ala625 630 635 640Phe Ala Gly Phe Leu Ala Cys Gly Gln Ala Val Gln Arg Trp Gly Ser645 650 655Ser Leu Ser Asp Val Val Pro Trp Arg Leu Gly Ala Ala Arg Ala Cys660 665 670Leu Gln Leu Gly Trp Arg Arg Arg Ala Ala Asp Leu Val Thr Ala Gln
675 680 685Ile Ala His Thr Ser Ser Gly Asp Leu Arg Thr Tyr Gly Val Ala Leu690 695 700Arg Leu His Ala Gln Leu Ser Lys Pro Ala Gln Arg Gln Arg Leu Leu705 710 715 720Met Gln Ser Val Asp Ala Leu Glu Ala Ala Gln Asp Arg Tyr Gln Leu725 730 735Ala Leu Ser Leu Cys Asp Leu Ala Gly Thr Pro Gln Leu Lys Gly Gly740 745 750Lys Asp Glu Ala Arg Ala Tyr Trp Val Arg Ala Gln Glu Leu Ala Arg755 760 765Glu Cys Asn Ala Lys Pro Leu Met Arg Arg Leu Ala Ala Gln His Asp770 775 780His Gly Glu Thr Ala Pro Leu Ser Gly Ala Glu Arg Arg Val Ala Val785 790 795 800Leu Ala Ala Arg Gly His Thr Asn Arg Glu Ile Ala Glu Ala Leu Tyr805 810 815Ile Thr Arg Ser Thr Val Glu Gln His Leu Thr Arg Ile Tyr Arg Lys820 825 830Leu His Val Gln Thr Arg Gly Asp Leu Gly Asn Leu Phe Ala Ala Asp835 840 845Ile Ala Asp Lys Ala Thr Ala Thr Ala Gly Arg Glu Pro Arg Glu Ala
850 855 860Val Arg Leu865<210>5<211>321<212>PRT<213>野野村菌屬<400>5Met Asp Pro Thr Gly Val Asp Ile Ala Thr Leu Pro Val Val Glu Ile1 5 10 15Glu Leu Ser Arg Leu Ser Ser Val Tyr Ser Pro Arg Thr Ser Gly Glu20 25 30Asp Pro Glu His Val Glu Thr Leu Leu Ser Ala Gln Gly Glu Leu Pro35 40 45Pro Ile Leu Val His Arg Pro Thr Met Arg Val Ile Asp Gly Leu His50 55 60Arg Leu Lys Val Ala Arg Val Arg Gly Glu Thr Thr Ile Ser Val Arg65 70 75 80Leu Ile Asp Gly Thr Glu Ser Asp Ala Phe Val Leu Ala Val Glu Ala85 90 95Asn Val Arg His Gly Leu Pro Leu Ser Leu Ala Asp Arg Lys Arg Ala100 105 110Ala Val Arg Ile Ile Gly Thr His Pro Gln Trp Ser Asp Arg Arg Val115 120 125
Ala Ser Ala Thr Gly Ile Ser Ala Gly Thr Val Ala Asp Leu Arg Arg130 135 140Arg Arg Gly Gln Gly Gly Asp Glu Ala Arg Ile Gly Arg Asp Gly Arg145 150 155 160Ile Arg Pro Val Asp Ser Ser Glu G1y Arg Arg Leu A1a Ala Glu Leu165 170 175Ile Arg Ser His Pro Asp Leu Ser Leu Arg Gln Val Ala Lys Gln Val180 185 190Gly Ile Ser Pro Glu Thr Val Arg Asp Val Arg Gly Arg Leu G1u His195 200 205Gly Glu Ser Pro Ile Pro Asp Gly Ser Arg Arg Leu Arg Thr Lys Pro210 215 220Glu Leu Leu Arg Arg Ala Glu Gln Asp Phe Gly His Val Asp Gly Arg225 230 235 240Asp Arg Gln Ala Val Leu Glu Arg Leu Lys Ala Asp Pro Ala Leu Arg245 250 255Leu Thr Glu Thr Gly Arg Ile Leu Leu Arg Met Leu Ser Leu His Ser260 265 270Ile Asp Gly Gln Glu Trp Glu Arg Ile Leu Arg Gly Val Pro Pro His275 280 285Trp Gly Thr Val Val Ala Arg Cys Ala Arg Asp His Ala Gln Ile Trp290 295 300
Ala Ala Phe Ala Asp Arg Leu Glu Gly Arg Ala Thr Asp Leu Ala Ala305 310 315 320Gly<210>6<211>369<212>PRT<213>野野村菌屬<400>6Met Thr Leu Glu Arg Thr Leu Ile Val Gly Thr Gly Leu Ile Gly Thr1 5 10 15Ser Ala Ala Leu Ala Leu Arg Glu Lys Gly Val Ala Val Tyr Leu Ser20 25 30Asp Val Asp Ala His Ala Val Arg Leu Ala Arg Ala Leu Gly Ala Gly35 40 45Gln Glu Trp Thr Gly Gln Arg Val Asp Leu Ala Leu Ile Ala Val Pro50 55 60Pro Pro Ser Val Gly Gln Arg Leu Ala Asp Leu Gln Gln Arg Arg Ala65 70 75 80Ala Arg Ala Tyr Thr Asp Val Thr Ser Val Lys Val Asp Pro Ile Ala85 90 95Asp Ala Glu Arg Leu Gly Cys Asp Leu Thr Ser Tyr Val Pro Gly His100 105 110
Pro Leu Ala Gly Arg Glu Arg Ser Gly Pro Ala Ala Ala Arg Ala Asp115 120 125Leu Phe Leu Gly Arg Pro Trp Ala Leu Cys Pro Arg Pro Glu Thr Gly130 135 140Ala Asp Ala Val Arg Leu Ala Arg Glu Leu Val Ser Met Cys Gly Ala145 150 155 160Glu Pro Tyr Thr Val Ser Ala Gly Glu His Asp Thr Ala Val Ala Leu165 170 175Val Ser His Ala Pro His Val Ala Ala Ser Ala Val Ala Ala Arg Leu180 185 190Arg Asp Gly Asp Asp Val Ala Leu Ala Leu Ala Gly Gln Gly Leu Arg195 200 205Asp Val Thr Arg Ile Ala Ala Gly Asp Pro Leu Leu Trp Arg Met Ile210 215 220Leu Ala Ala Asn Ala Leu Pro Val Ala Gly Val Leu Glu Arg Ile Ala225 230 235 240Ala Asp Leu Ala Ala Ala Ala Ser Ala Leu Arg Ser Gly Asp Leu Asp245 250 255Asp Val Thr Asp Leu Leu Arg Arg Gly Val Asp Gly His Gly Arg Ile260 265 270Pro Asp Lys His Gly Gly Pro Ala Arg Asp Tyr Thr Val Ile Gln Val275 280 285
Val Leu Gln Asp Arg Pro Gly Glu Leu Ala Arg Leu Phe Asn Ala Ala290 295 300Gly Leu Ala Asp Val Asn Ile Glu Asp Ile Arg Leu Glu His Ser Ala305 310 315 320Gly Leu Pro Val Gly Val Val Glu Val Ser Val Arg Pro Glu Asp Thr325 330 335Gly Arg Leu Thr Glu Ala Leu Arg Phe His Gly Trp His Val Pro Pro340 345 350Val Pro Asp Gly Asn Ser Arg Ile Asp Arg Thr Arg Ala Met Val Ser355 360 365Asp<210>7<211>217<212>PRT<213>野野村菌屬<400>7Met Arg Val Leu Val Val Glu Asp Gln Val Asp Leu Ala Asp Ser Val1 5 10 15Ala Arg Val Leu Arg Arg Glu Gly Met Ala Val Asp Val Ser His Asp20 25 30Gly Asp Asp Ala Gln Glu Arg Leu Ser Val Ile Asp Tyr Asp Val Val35 40 45
Val Leu Asp Arg Asp Ile Pro Gly Val His Gly Asp Glu Leu Cys Ala50 55 60Glu Ile Ala Val Asp Asp Arg Arg Thr Arg Val Leu Met Leu Thr Ala65 70 75 80Ser Gly Thr Thr Ala Asp Arg Val Ala Gly Leu Ser Leu Gly Ala Asp85 90 95Asp Tyr Leu Pro Lys Pro Phe Ala Phe Ala Glu Leu Val Ala Arg Ile100 105 110Arg Ala Leu Gly Arg Arg Ala His Pro Pro Ala Pro Pro Ile Leu Val115 120 125His Gly Asp Leu Arg Leu Asp Pro Ala Gln Arg Val Ala Ile Arg Gly130 135 140Gly Met Arg Leu Pro Leu Thr Thr Lys Glu Leu Ala Val Leu Glu His145 150 155 160Leu Leu Thr Ala Arg Gly Arg Val Val Ser Ala Glu Glu Leu Leu Glu165 170 175Arg Val Trp Asp Glu Gln Ala Asp Pro Phe Thr Thr Thr Val Lys Ala180 185 190Thr Ile Asn Arg Leu Arg Ser Lys Leu Gly Gln Pro Pro Val Ile Glu195 200 205Thr Val Pro Arg Glu Gly Tyr Arg Ile210 215
<210>8<211>196<212>PRT<213>野野村菌屬<400>8Met Arg Arg Ser Glu Gly Asp Asp Glu Pro Arg Thr Leu Pro Pro Arg1 5 10 15Ala Arg Asp Arg Val Tyr Thr Ala Val Thr Arg Val Leu Ala Val Leu20 25 30Leu Leu Pro Val Ala Phe Val Arg Gln Pro Gly Arg Ala Arg Glu Leu35 40 45Ala Cys Gly Trp Ala Leu Arg Met Arg Phe Pro Ala Glu Asp Leu Thr50 55 60Gly Leu Thr Asp Gly Ala Arg Ala Ala Phe Thr Ala Ala Arg Ala Glu65 70 75 80Ala Leu Trp Arg His Gly Gln Leu Val Gly Leu Thr Ser Gly Tyr Arg85 90 95Asp Pro Arg Val Gln Gln Arg Met Phe Glu Glu Glu Val Arg Arg Ser100 105 110Gly Ser Val Ala Ala Ala Arg Met Phe Val Ala Pro Pro Ala Glu Ser115 120 125Asn His Val Lys Gly Met Ala Leu Asp Val Arg Pro His Glu Gly Ala130 135 140Arg Trp Leu Glu Ala His Gly Ala Arg Tyr Asp Leu Tyr Arg Ile Tyr
145 150 155 160Asp Asn Glu Trp Trp His Phe Glu His Arg Pro Glu Cys Gly Gly Thr165 170 175Pro Pro Arg Arg Leu Pro His Pro Gly Ala Ala Trp Ala Ser Arg Asn180 185 190Gly Gly Arg Val195<210>9<211>319<212>PRT<213>野野村菌屬<400>9Met Asp Ala Glu Ser Val Arg Arg Gln Leu Arg Leu Gly Glu Asn Ala1 5 10 15Thr Ala Trp Leu Ser Arg Leu Glu Glu Leu Gly Pro Pro Pro Glu Pro20 25 30Val Arg Leu Pro Gln Gly Asp Glu Ala Arg Asp Leu Leu His Arg Leu35 40 45Glu Val Pro Ala Pro Asp Val Glu Glu Ile Val Ala Ala Thr Pro Gly50 55 60Pro Asp Arg Asp Pro Ala Leu Trp Trp Leu Leu Glu Arg Ala His His65 70 75 80Glu Leu Val Arg His Met Gly Asp Tyr Lys Val Lys Val Arg Gly Gly85 90 95
Pro Thr Leu Pro Tyr Glu Thr Gly Ala Ala Ala Arg Tyr Phe His Val100 105 110Tyr Val Phe Leu Ala Thr Leu Pro Ala Leu Arg Arg Phe His Ala Thr115 120 125Arg Asp Ile Pro Glu Ala Thr Thr Trp Glu Thr Leu Thr Gln Leu Gly130 135 140Glu Ser Val Ala Ile His Arg Arg Lys Tyr Gly Glu Gly Gly Thr Asn145 150 155 160Met Pro Trp Trp Leu Thr Leu Leu Val Arg Gly Leu Val Tyr Arg Leu165 170 175Gly Arg Leu Gln Tyr Asn Leu Ala Val Ala Lys Asp Gly Thr Pro Val180 185 190Leu Gly Leu His Ile Pro Glu Val Gly Gly Pro Leu Ile Pro Asp Ile195 200 205Tyr Tyr Asp Ser Leu Arg Arg Ala Arg Pro Phe Phe Glu Arg His Phe210 215 220Pro Glu His Gly Ala Arg Ala Ala Thr Gly Thr Ser Trp Leu Leu Asp225 230 235 240Pro Gln Leu Ala Glu Tyr Leu Ala Glu Asp Ser His Ile Leu Gln Leu245 250 255Arg Arg Gly Trp Thr Leu Leu Asp Ser Glu Pro Gln Asp Gly Asp Asp260 265 970
Ala Ile Leu Glu Phe Val Phe Arg Tyr Asn Gly Gln Pro Leu Glu Glu275 280 285Leu Pro Gln Arg Ser Thr Leu Glu Lys Ala Val Val Thr His Leu Leu290 295 300Ala Gly Arg His Trp Tyr Gln Arg Ser Gly Arg Ile Glu Leu Pro305 310 315<210>10<211>408<212>PRT<213>野野村菌屬<400>10Met Arg Val Leu Leu Ser Thr Ser Gly Ser Arg Gly Asp Val Glu Pro1 5 10 15Leu Leu Gly Leu Ala Val Gln Leu Arg Glu Leu Gly Ala Glu Thr Arg20 25 30Met Cys Ala Pro Pro Asp Cys Ala Glu Arg Leu Ala Glu Ala Gly Val35 40 45Pro Leu Val Pro Val Gly Thr Ser Met Arg Ala Lys Leu His Gly Lys50 55 60Arg Pro Pro Ser Leu Glu Asp Val Pro Arg Leu Asp Ala Glu Ala Ile65 70 75 80Ala Thr Gln Leu Asp Gln Val Leu Pro Ala Ala Glu Gly Cys Glu Val85 90 95
Met Val Val Ser Gly Val Leu Ser Ala Ala Val Ala Val Arg Ser Val100 105 110Ala Glu Lys Leu Gly Ile Pro Tyr Val Tyr Val Phe Tyr Cys Pro Ile115 120 125Tyr Val Pro Ser Pro Tyr Tyr Pro Pro Pro Pro Pro Leu Gly Glu Gln130 135 140Pro Ala Arg Asp Val Thr Asp Asn Arg Val Leu Trp Asp Arg Asn Asn145 150 155 160Gln Gly Ala Tyr Gln Arg Phe Gly Ala Ala Leu Asn Ser Arg Arg Ala165 170 175Ser Ile Gly Leu Pro Pro Val Asp Asp Ile Phe Ser Tyr Gly Tyr Thr180 185 190Asp Arg Pro Phe Leu Ala Ala Asp Pro Val Leu Ala Pro Leu Gln Arg195 200 205Thr Asp Leu Asp Val Val Gln Thr Gly Ala Trp Ile Met Pro Asp Glu210 215 220Arg Pro Leu Pro Ala Glu Val Glu Ala Phe Leu Glu Ala Gly Pro Pro225 230 235 240Pro Val His Val Glu Phe Gly Ser Gly Pro Ala Pro Thr Asp Ala Ala245 250 255Arg Val Ala Ile Glu Ala Ile Arg Ala His Gly His Arg Val Ile Val260 265 270
Ser Arg Gly Trp Ala Gly Leu Ala Pro Pro Asp Asp Arg Ser Asp Cys275 280 285Leu Thr Val Gly Glu Val Asn His Gln Val Leu Phe Gly Arg Val Ala290 295 300Ala Val Val His Ala Gly Ser Ala Gly Ile Thr Thr Ala Val Thr Arg305 310 315 320Ala Gly Ala Pro Gln Val Val Val Pro Gln Met Thr Asp Gln Pro Tyr325 330 335His Ala Gly Arg Val Ala Glu Leu Gly Ile Gly Val Ala His Asp Gly340 345 350Arg Val Pro Thr Val Glu Ser Leu Ser Ala Ala Leu Thr Thr Ala Leu355 360 365Ala Pro Glu Thr Arg Ala Arg Ala Ile Asp Val Ala Gly Lys Ile Arg370 375 380Ala Asp Gly Ala Ala Val Ala Ala Lys Leu Leu Leu Asp Thr Ala Ala385 390 395 400Gly Ala Gly Arg Asn Arg Thr Glu405<210>11<211>489<212>PRT<213>野野村菌屬<400>11
Met Glu Glu Phe Asp Val Val Val Ala Gly Gly Gly Pro Gly Gly Ser1 5 10 15Thr Val Ala Thr Leu Val Ala Met Gln Gly His Arg Val Leu Leu Val20 25 30Glu Lys Glu Val Phe Pro Arg Tyr Gln Ile Gly Glu Ser Leu Leu Pro35 40 45Ser Thr Val His Gly Val Cys Arg Met Leu Gly Val Thr Asp Glu Leu50 55 60Ala Ala Ala Gly Phe Pro Val Lys Arg Gly Gly Thr Phe Arg Trp Gly65 70 75 80Ala Arg Pro Glu Pro Trp Thr Phe Ser Phe Ser Val Ser Pro Arg Ile85 90 95Thr Gly Pro Thr Thr Phe Ala Tyr Gln Val Glu Arg Ala Arg Phe Asp100 105 110Glu Ile Leu Leu Gly Asn Ala Arg Arg Lys Gly Val Val Val Arg Glu115 120 125Gly Cys Ser Val Thr Glu Val Ile Glu Asp Gly Asp Arg Val Thr Gly130 135 140Leu Arg Tyr Val Asp Pro Asp Gly Gly Glu His Ala Val Ser Ala Arg145 150 155 160Phe Val Ile Asp Ala Ser Gly Asn Lys Ser Arg Leu Tyr Ser Ser Val165 170 175
Gly Gly Thr Arg Asn Tyr Ser Glu Phe Phe Arg Ser Leu Ala Leu Phe180 185 190Gly Tyr Phe Glu Gly Gly Lys Arg Leu Ala Glu Pro Tyr Ser Gly Asn195 200 205Ile Leu Ser Val Ala Phe Asp Ser Gly Trp Phe Trp Tyr Ile Pro Leu210 215 220Ser Asp Thr Leu Thr Ser Val Gly Ala Val Val Arg Arg Glu Met Ala225 230 235 240Glu Lys Ile Gln Gly Asp Arg Glu Lys Ala Leu Ala Ala Leu Ile Ala245 250 255Glu Cys Pro Leu Ile Ser Glu Tyr Leu Ala Pro Ala Arg Arg Val Thr260 265 270Thr Gly Lys Tyr Gly Gln Leu Arg Val Arg Lys Asp Tyr Ser Tyr His275 280 285Gln Thr Lys Phe Trp Arg Pro Gly Met Ile Leu Val Gly Asp Ala Ala290 295 300Cys Phe Val Asp Pro Val Phe Ser Ser Gly Val His Leu Ala Thr Tyr305 310 315 320Ser Gly Leu Leu Ala Ala Arg Ser Ile Asn Ser Val Leu Ala Gly Asp325 330 335Val Glu Glu Lys Ile Ala Leu His Glu Phe Glu Ala Arg Tyr Arg Arg340 345 350
Glu Tyr Ser Val Tyr Tyr Glu Phe Leu Leu Ala Phe Tyr Glu Met Asn355 360 365Val Asn Glu Glu Ser Tyr Phe Trp His Ala Lys Lys Val Thr Asn Asn370 375 380Lys Glu Tyr Thr Glu Leu Glu Ser Phe Val Asp Leu Val Gly Gly Leu385 390 395 400Ser Ser Gly Glu Thr Ala Leu Ala Thr Ser Gly Arg Ile Ala Glu Arg405 410 415Ser Ala Glu Phe Ala Ala Ala Val Asp Gln Met Ala Asp Gly Asp Asp420 425 430Ser Ser Met Val Pro Leu Phe Lys Ser Gln Val Val Lys Gln Val Met435 440 445Gln Glu Gly Gly Gln Glu Gln Met Arg Ala Val Leu Gly Ala Asp Ala450 455 460Glu Pro Glu Gln Pro Leu Phe Pro Gly Gly Leu Val Thr Ser Pro Asp465 470 475 480Gly Met Arg Trp Leu Thr His His Pro485<210>12<211>420<212>PRT<213>野野村菌屬<400>12Met Arg Ile Asp Ser Glu Trp Ser Phe Asp Pro Gly Met Asp Asp Asp
1 5 10 15Ile Asp Ala Gly Ala Pro Val Leu Gln Pro Thr Ala Asn Tyr Met Met20 25 30Arg Thr His Cys Asp Pro His Glu Asp Met Phe Ala Leu Arg Ala His35 40 45Gly Pro Leu Val Arg Ile Gly Gly Asp Ala Ala Thr Gln Leu Arg Val50 55 60Asp Tyr Val Trp Gln Ala Leu Gly Tyr Asp Val Val Arg Arg Ile Leu65 70 75 80Gly Asp His Glu Asn Phe Thr Thr Arg Pro Arg Trp Ser Ser Ala Pro85 90 95Ser Ile Ala Gly Glu Pro Ile Pro Pro Asn Leu Val Gly Gln Leu Ser100 105 110Val Tyr Asp Pro Pro Glu His Thr Arg Leu Arg Gly Met Leu Thr Pro115 120 125Glu Phe Thr Ala Arg Arg Ile Arg Arg Leu Glu Pro Ala Met Gln Asp130 135 140Leu Ile Asp Asp Arg Ile Asp Glu Leu Glu Ala Ala Gly Pro Pro Ala145 150 155 160Asp Val Gln Ala Leu Phe Ala Asp Pro Val Gly Gly Gly Val Leu Cys165 170 175Glu Leu Leu Gly Ile Pro Arg Asp Asp Arg Ile Glu Phe Ile Arg Arg
180 185 190Val Arg Gln Asn Val Asp Leu Ser Arg Gly Phe Lys Ala Arg Ala Ala195 200 205Asp Ser Ala Ala Phe Asn Arg Tyr Leu Asn Gly Leu Ile Ile Arg Gln210 215 220Arg Lys Asp Pro Asp Glu Gly Phe Ile Gly Met Leu Val Arg Glu His225 230 235 240Gly Asp Asp Val Thr Asp Glu Glu Leu Lys Gly Val Leu Thr Ala Leu245 250 255Ile Leu Gly Gly Val Glu Thr Val Ala Gly Ser Ile Gly Phe Gly Val260 265 270Leu Ala Leu Leu Asp His Pro Asp Gln Arg Gln Ser Leu Phe Ala Gly275 280 285Arg Glu Glu Ala Asp Arg Val Val Gly Glu Leu Leu Arg Phe Leu Ser290 295 300Pro Val Gln Gln Pro Asn Pro Arg Leu Ala Val Arg Asp Val Val Val305 310 315 320Asp Gly Gln Leu Ile Lys Ala Gly Asp Tyr Val Leu Cys Ser Ile Leu325 330 335Met Ala Asn Arg Asp Glu Ala Leu Thr Pro Asn Ala Asn Val Leu Asp340 345 350Val Arg Arg Asp Cys Gly Ser His Val Gly Phe Gly His Gly Ile His
355 360 365Tyr Cys Ile Gly Ala Ala Ile Ala Arg Thr Leu Leu Arg Met Ala Tyr370 375 380Gln Ser Leu Trp Arg Arg Phe Pro Gly Leu Arg Leu Ala Val Ser Ala385 390 395 400Glu Glu Val Lys Phe Arg Asn Ala Phe Ile Asp Cys Pro Asp Glu Leu405 410 415Pro Val Thr Trp420<210>13<211>398<212>PRT<213>野野村菌屬<400>13Met Ser Gly Asp Gly Ala Arg Pro Leu His Thr Arg Arg Gln Asp Leu1 5 10 15Asp Pro Ala Asp Glu Leu Arg Ala Ala Gly Thr Leu Thr Arg Ile Thr20 25 30Ile Gly Ser Gly Ala Asp Ala Glu Thr Thr Trp Leu Ala Thr Gly Tyr35 40 45Thr Val Val Arg Gln Val Leu Gly Asp His Arg Arg Phe Ser Thr Arg50 55 60Arg Arg Trp Asn Glu Arg Asp Glu Ile Gly Gly Arg Gly Asn Phe Arg65 70 75 80
Pro Arg Glu Leu Val Gly Asn Leu Met Asp Tyr Asp Pro Pro Glu His85 90 95Thr Arg Leu Arg Gln Lys Leu Thr Pro Gly Phe Thr Leu Arg Arg Ile100 105 110Arg Arg Leu Lys Pro Tyr Ile Glu Gln Ile Val Thr Glu Arg Leu Asp115 120 125Ala Leu Glu Arg Ala Gly Pro Pro Ala Asp Leu Val Glu Leu Val Ala130 135 140Asp Glu Val Pro Gly Ala Val Leu Cys Glu Leu Ile Gly Val Pro Arg145 150 155 160Asp Asp Arg Ala Met Phe Met Gln Leu Cys His Gly His Leu Asp Ala165 170 175Ser Arg Ser Gln Lys Arg Arg Ala Ala Ala Gly Ala Ala Phe Ser Arg180 185 190Tyr Leu Leu Ala Met Ile Ala Arg Glu Arg Lys Asp Pro Gly Glu Gly195 200 205Leu Leu Gly Ala Val Leu Ala Glu Tyr Gly Asp Thr Ala Thr Asp Glu210 215 220Glu Leu Arg Gly Phe Cys Val Gln Val Met Leu Ala Gly Asp Asp Asn225 230 235 240Ile Ser Gly Met Ile Gly Leu Gly Val Leu Ala Leu Leu Arg His Pro245 250 255
Glu Gln Ile Ala Ala Leu Gln Gly Asp Asp Gln Ser Ala Asp Arg Ala260 265 270Val Asp Glu Leu Ile Arg Tyr Leu Thr Val Pro Tyr Ala Pro Thr Pro275 280 285Arg Val Ala Met Glu Asp Val Thr Ile Gly Gly Gln Val Ile Lys Glu290 295 300Gly Glu Thr Val Ser Cys Ser Leu Pro Met Ala Asn Arg Asp Pro Ala305 310 315 320Leu Leu Pro Asp Ala Gly Arg Leu Asp Val Arg Arg Glu Pro Val Pro325 330 335His Val Ala Phe Gly His Gly Val His His Cys Leu Gly Ala Ala Leu340 345 350Ala Arg Leu Glu Leu Arg Thr Val Tyr Thr Ala Leu Trp Arg Arg Phe355 360 365Pro Thr Leu Arg Leu Ala Asp Pro Asp Arg Glu Pro Ser Phe Arg Leu370 375 380Thr Thr Pro Ala Tyr Gly Leu Thr Ser Leu Met Val Ala Trp385 390 395<210>14<211>384<212>PRT<213>野野村菌屬<400>14
Met Val Val Pro Leu Pro His Gln Arg Leu Arg Leu Asp Pro Val Pro1 5 10 15Ala Leu Phe Asp Leu Gln Glu Asp Gly Pro Leu His Glu Tyr Asp Thr20 25 30Glu Pro Gly Leu Asp Gly His Lys Gln Trp Leu Val Thr Gly Tyr Gly35 40 45Glu Ile Arg Glu Ile Leu Ala Asp Ala Asn Arg Phe Ser Ser Met Arg50 55 60Pro Val Glu Asp Glu Ala Glu Arg Ala Trp Leu Pro Gly Ile Leu Gln65 70 75 80Ser Tyr Asp Ala Pro Asp His Thr Arg Leu Arg Arg Thr Val Thr Arg85 90 95Ala Asn Thr Ala Arg Arg Ile Glu Ser Leu Arg Pro Val Val Glu Glu100 105 110Thr Val Glu Asp Cys Leu Ala Asp Leu Glu Ser Met Gly Ser Pro Val115 120 125Asp Phe Val Arg Asn Ala Ala Trp Pro Ile Pro Ala Leu Ile Ala Cys130 135 140Asp Phe Leu Gly Val Pro Arg Asp Asp Gln Ala Glu Leu Ser Arg Met145 150 155 160Phe Arg Asp Ser Arg Glu Ser Arg Val Pro Arg Gln Arg Asn Val Ser165 170 175
Gly Leu Gly Ile Val Asp Tyr Ala Arg Lys Leu Ala Ala Arg Glu Arg180 185 190Leu Asp Pro Gly Thr Gly Met Ile Gly Gly Ile Val Arg Glu His Gly195 200 205Gly Glu Val Thr Asp Glu Glu Leu Ala Gly Leu Val Glu Gly Ile Met210 215 220Ile Gly Ala Val Glu Gln Met Ala Ser Gln Leu Ala Ile Ala Val Leu225 230 235 240Leu Leu Val Thr His Pro Asp Gln Met Ala Leu Leu Arg Glu Arg Pro245 250 255Glu Leu Ala Asp Ser Ala Ala Glu Glu Val Phe Arg Tyr Ala Ser Ile260 265 270Val Glu Thr Pro Ser Pro Arg Thr Ala Leu Val Asp Thr Arg Leu Ala275 280 285Gly Arg Asp Ile His Ala Gly Asp Val Leu Thr Cys Ser Ile Leu Ala290 295 300Gly Asn Arg Ala Arg Glu Asp Arg Phe Asp Leu Thr Arg Gly Asn Pro305 310 315 320Glu His Leu Ala Phe Gly His Gly Val His Phe Cys Leu Gly Ala Pro325 330 335Leu Ala Arg Leu Gln Ala Gln Val Ala Leu Pro Ala Leu Val Arg Arg340 345 350
Phe Pro Ser Leu Arg Leu Ala Val Pro Ala Glu Asp Leu Arg Phe Lys355 360 365Pro Gly Lys Pro Ala Pro Phe Ala Val Glu Glu Leu Pro Val Glu Trp370 375 380<210>15<211>393<212>PRT<213>野野村菌屬<400>15Met Glu Val Phe Glu Glu Leu Asn Val Val Leu Pro Gly Glu Leu His1 5 10 15Trp Arg Asp Arg Phe Asp Pro Val Pro Gln Leu Arg Ser Phe Met Ala20 25 30Glu Gly Pro Met Thr Glu Leu Gly Ala Glu Glu Gly Pro Gly Gly Arg35 40 45Thr Ala Trp Leu Ala Thr Gly Phe Asp Glu Val Arg Gln Val Leu Gly50 55 60Ser Asp Lys Phe Ser Ser Arg Leu Leu Tyr Gly Gly Thr Ala Ala Gly65 70 75 80Ile Val Phe Pro Gly Phe Ile Thr Gln Tyr Asp Pro Pro Glu His Thr85 90 95Arg Leu Arg Arg Val Val Ser Pro Ala Phe Thr Val Arg Arg Met Glu100 105 110
Arg Phe Arg Pro Gln Val Asp Gln Val Val Glu Asp Cys Leu Asp Ala115 120 125Ile Glu Ser Ile Gly Gly Pro Leu Asp Phe Val Pro His Phe Gly Trp130 135 140Ser Ile Ala Thr Thr Ala Thr Cys Asp Phe Leu Gly Ile Pro Arg Asp145 150 155 160Asp Gln Ala Glu Leu Ser Arg Ser Leu His Ala Ser Arg Ser Gln Arg165 170 175Ala Ala Ser Arg Arg Gly Ala Ala Gly Asn Lys Phe Met Thr Tyr Met180 185 190Gly Gln Val Val Ala Arg Thr Arg Arg Asp Pro Gly Asp Asp Met Leu195 200 205Ser Val Val Val Arg Glu His Gly Asp Glu Ile Thr Asp Ala Glu Leu210 215 220Thr Gly Leu Ala Ala Phe Val Met Gly Ala Gly Gly Asp Gln Val Ala225 230 235 240Arg Phe Leu Ala Ala Gly Ala Trp Leu Met Ala Glu Val Pro Glu Gln245 250 255Phe Ala Leu Leu Arg Asp Lys Pro Asp Val Val Pro Asp Trp Leu Glu260 265 270Glu Met Val Arg Tyr Leu Thr Ile Asp Glu Lys Leu Thr Pro Arg Ile275 280 285
Ala Leu Glu Asp Val Arg Ile Gly Asp Arg Ile Val Lys Ala Gly Asp290 295 300Thr Val Thr Cys Ser Leu Leu Gly Ala Asn Arg Arg His Phe Pro Gly305 310 315 320Pro Asp Asp Gln Phe Asp Leu Thr Arg Asp Arg Ala Pro Asn Val Ala325 330 335Phe Gly His Gly Ile His His Cys Leu Gly Arg Pro Leu Ala Glu Leu340 345 350Ile Phe Arg Ser Ala Ile Pro Ala Leu Ala Arg Arg Phe Pro Ala Leu355 360 365Arg Leu Ala Glu Pro Glu Gln Glu Ile Arg Leu Gly Pro Pro Pro Phe370 375 380Asp Val Lys Ala Leu Leu Leu Asp Trp385 390<210>16<211>69<212>PRT<213>野野村菌屬<400>16Met Thr Asn Pro Phe Glu Asn Glu Asp Gly Ser Phe Leu Val Leu Val1 5 10 15Asn Asp Glu Gly Gln His Ser Leu Trp Pro Ser Phe Ala Glu Val Pro20 25 30Pro Gly Trp Thr Arg Val His Gly Val Ala Thr Arg Gln Glu Cys Leu
35 40 45Ala Tyr Val Glu Glu Asn Trp Thr Asp Ile Arg Pro Lys Ser Leu Ile50 55 60Ala Glu Ala Gly Ala65<210>17<211>1863<212>PRT<213>野野村菌屬<400>17Met Thr Ile Asp Asp Thr Arg Ala Lys Pro Arg Ser Ser Val Glu Asp1 5 10 15Val Trp Pro Leu Ser Pro Leu Gln Glu Gly Met Leu Tyr His Thr Ala20 25 30Leu Asp Asp Asp Gly Pro Asp Thr Tyr Thr Val Gln Thr Val Tyr Gly35 40 45Ile Asp Gly Pro Leu Asp Ala Gly Arg Leu Arg Ala Ser Trp Gln Ala50 55 60Leu Val Asp Arg His Ala Ala Leu Arg Ala Tyr Phe Arg Tyr Val Ser65 70 75 80Gly Ala Gln Met Val Gln Val Ile Ala Arg Glu Ala Glu Ile Pro Trp85 90 95Arg Glu Thr Asp Leu His Gly Leu Pro Asp Asp Leu Leu Asp Ser Glu100 105 110
Val Asp Arg Leu Ala Ala Asp Glu Leu Ala Glu Arg Leu Pro Leu Asp115 120 125Ala Ala Pro Leu Met Lys Leu His Leu Ile Arg Leu Gly Pro Ala Ser130 135 140His Arg Leu Val His Thr Leu His His Val Leu Leu Asp Gly Trp Ser145 150 155 160Met Pro Ile Leu His Arg Glu Leu Ala Ala Ile Tyr Ala Ala Gly Gly165 170 175Asp Ala Ser Gly Leu Pro Ala Ala Val Ser Tyr Arg Asp Tyr Leu Ala180 185 190Trp Leu Gly Arg Gln Asp Lys Glu Ala Ala Arg Ala Ala Trp Arg Gln195 200 205Glu Leu Ala Gly Leu Asp Thr Pro Thr Leu Val Ala Pro Ala Asp Pro210 215 220Ala Arg Val Pro Asp Met Gly Thr Ala Val Ile Glu Leu Ser Ala Glu225 230 235 240Leu Thr Asp Gly Leu Ala Arg Leu Ala Arg Gly His Gly Leu Thr Leu245 250 255Asn Thr Val Val Gln Gly Ala Trp Ala Met Val Leu Ala Gln Leu Ala260 265 270Gly Arg Thr Asp Val Val Phe Gly Ala Thr Ala Ser Gly Arg Pro Ala275 280 285
Glu Leu Ala Gly Val Glu Ser Met Val Gly Gln Leu Leu Gly Thr Leu290 295 300Pro Val Arg Val Arg Leu Glu Gly Gly Arg Arg Val Val Glu Leu Leu305 310 315 320Ala Glu Leu Gln Arg Ser Gln Ser Ala Leu Met Ala His Gln His Leu325 330 335Gly Leu Gln Glu Met Gln Ala Ala Val Gly Pro Gly Ala Val Phe Asp340 345 350Thr Leu Val Ile Tyr Glu Asn Phe Pro Arg Gln Gly Leu Gly Arg Ala355 360 365Glu Glu Asp Gly Gly Leu Asp Leu Arg Pro Val Arg Arg Gly Arg Asn370 375 380Ser Ser His Tyr Pro Phe Thr Leu Ile Thr Gly Pro Gly Ala Gln Met385 390 395 400Pro Leu Ile Leu Asp Tyr Asp Arg Gly Leu Phe Asp Glu Ala Ala Ala405 410 415Glu Ser Val Val Gly Ala Leu Ala Arg Val Leu Glu Arg Leu Val Ala420 425 430Glu Pro Asp Val Leu Val Gly Arg Leu Thr Leu Leu Ser Glu Ala Glu435 440 445Arg Ala Leu Val Val Glu Asp Trp Asn Ala Thr Ala Gly Pro Thr Pro450 455 460
Gly Gln Ser Val Leu Asp Leu Phe Gly Arg Arg Val Ala Thr Ala Pro465 470 475 480Asp Ala Val Ala Ile Thr Asp Ala Gly Gly Ala Asp Leu Thr Tyr Ala485 490 495Glu Val Asp Gln Ala Ala Asn Arg Leu Ala Arg His Leu Ala Ala Arg500 505 510Gly Ile Gly Arg Gly Asp Arg Val Gly Val Val Met Asp Arg Ser Pro515 520 525Asp Leu Leu Ile Ala Phe Leu Ala Ser Trp Lys Ala Gly Ala Ala Tyr530 535 540Val Pro Val Asp Val Glu His Pro Ala Glu Arg Ile Glu Phe Val Leu545 550 555 560Ala Asp Ser Gly Val Ser Ala Val Leu Cys Thr Arg Ala Thr Arg Glu565 570 575Val Ala Pro Ala Asp Ala Ile Val Ile Asp ALa Pro Glu Thr Arg Ala580 585 590Ala Ile Asp Ala Gly Ala Ala Thr Ala Pro Gln Ile Arg Leu Ser Ala595 600 605Asp Asp Leu Ala Tyr Val Met Tyr Thr Ser Gly Ser Thr Gly Leu Pro610 615 620Lys Gly Val Gly Val Pro His Gly Ala Val Ala Gly Leu Ala Gly Asp625 630 635 640
Glu Gly Trp Arg Ile Gly Pro Gly Asp Ala Val Leu Met His Ala Thr645 650 655His Val Phe Asp Pro Ser Leu Tyr Ala Met Trp Val Pro Leu Ala Met660 665 670Gly Gly Arg Val Val Leu Thr Glu Pro Gly Val Leu Asp Ala Leu Gly675 680 685Met Arg Gln Ala Val Glu Arg Gly Val Thr Phe Val His Leu Thr Ala690 695 700Gly Thr Phe Arg Ala Leu Ala Glu Ser Ser Pro Glu Cys Phe Ala Gly705 710 715 720Leu Val Glu Val Gly Thr Gly Gly Asp Val Val Pro Ala Gln Ser Val725 730 735Glu His Leu Arg Arg Ala Val Pro Gly Leu Arg Val Arg Asn Thr Tyr740 745 750Gly Pro Thr Glu Thr Thr Leu Cys Ala Thr Trp Lys Pro Ile Glu Pro755 760 765Gly Glu Glu Val Gly Arg Glu Leu Pro Ile Gly Arg Pro Met Thr Asn770 775 780Arg Arg Ile Tyr Ile Leu Asp Ala Phe Leu Arg Pro Val Ala Pro Gly785 790 795 800Val Ala Gly Glu Leu Tyr Ile Ala Gly Thr Gly Leu Ala Arg Gly Tyr805 810 815
Leu Gly Gly Pro Gly Leu Thr Ala Glu Arg Phe Val Ala Val Pro Ala820 825 830Ser Val Asp Pro Ser Pro Gly Glu Arg Met Tyr Arg Thr Gly Asp Leu835 840 845Ala Arg Trp Asn Arg Asp Gly Glu Val Val Phe Leu Gly Arg Thr Asp850 855 860Asp Gln Val Lys Ile Arg Gly Tyr Arg Val Glu Leu Gly Glu Val Glu865 870 875 880Ala Val Leu Ala Ala Gln Arg Gly Val Val Glu Ala Val Val Val Ala885 890 895Arg Glu Asp Gln Pro Gly Glu Lys Arg Leu Val Gly Tyr Phe Ile Ser900 905 910Asp Gly Thr Asp Ala Gly Pro Ala Glu Ile Arg Arg Glu Met Ala Leu915 920 925Val Leu Pro Ala Tyr Met Val Pro Leu Ala Val Val Ala Leu Pro Ala930 935 940Leu Pro Val Thr Pro Asn Gly Lys Val Asp Arg Leu Ala Leu Pro Ala945 950 955 960Pro Asp Leu Val Gly Arg Ala Pro Asp Arg Ala Gln Glu Ser Glu Thr965 970 975Glu Lys Val Leu Cys Ala Leu Phe Ala Glu Ile Leu Gly Val Asp Arg980 985 990
Val Gly Val Asp Asp Ala Phe His Asp Leu Gly Gly Ser Ser Ala Leu995 1000 1005Ala Met Arg Leu Ile Ala Arg Ile Arg Glu Glu Leu Gly Ala Asp1010 1015 1020Leu Pro Ile Arg Gln Leu Phe Ser Ala Ala Thr Pro Ala Gly Val1025 1030 1035Ala Arg Ala Leu Ala Ala Lys Ser Arg Pro Ala Leu Glu Pro Ala1040 1045 1050Glu Arg Pro Gly Arg Val Pro Leu Thr Ala Gln Gln Leu Ser Ala1055 1060 1065Trp Leu Leu Ala Ser Pro Gly Glu Ala Ala Gly Leu His Val Ser1070 1075 1080Val Ala Leu Arg Leu Arg Gly Arg Leu Asp Val Pro Ala Leu Glu1085 1090 1095Ala Ala Leu Gly Asp Val Ala Ala Arg His Glu Ile Leu Arg Thr1100 1105 1110Thr Phe Pro Gly His Ala Gln Ser Val His Gln His Val His Asp1115 1120 1125Ala Ser Pro Val Asp Leu Thr Pro Val Pro Ala Thr Glu Glu Ser1130 1135 1140Leu Pro Gly Leu Leu Thr Glu Leu Arg Glu Ser Val Phe Asp Leu1145 1150 1155
Thr Arg Glu Val Pro Trp Arg Gly Asp Leu Phe Arg Leu Ser Asp1160 1165 1170Gly Glu His Val Leu His Leu Met Val His Arg Ile Leu Ala Asp1175 1180 1185Asp Glu Ser Leu Asp Val Phe Leu Arg Asp Leu Ser Ala Ala Tyr1190 1195 1200Gly Ala Arg Arg Ala Gly Arg Ala Pro Glu Arg Ala Pro Leu Thr1205 1210 1215Leu Gln Phe Ala Asp Tyr Ala Ile Trp Glu Arg Arg Leu Leu Glu1220 1225 1230Gly Glu Arg Asp Ala Asp Gly Leu Ile Asn Glu Gln Leu Val Phe1235 1240 1245Trp Arg Asp Asn Leu Ala Gly Ile His Gly Glu Thr Val Leu Pro1250 1255 1260Phe Asp Arg Pro Arg Ser Ala Val Ala Ser Arg Arg Ala Gly Thr1265 1270 1275Val Ser Leu Arg Leu Asp Ala Gly Pro His Ala Arg Leu Val Glu1280 1285 1290Ala Val Asp Pro Ile Gly Ala His Pro Phe Gln Ile Val His Ala1295 1300 1305Ala Leu Ala Met Leu Leu Thr Arg Leu Gly Ala Gly His Asp Leu1310 1315 1320
Val Ile Gly Thr Lys Leu Pro Arg Asp Asp Asp Leu Ile Asp Leu1325 1330 1335Glu Pro Met Ile Gly Pro Phe Ala Arg Pro Leu Ala Leu Arg Thr1340 1345 1350Asp Leu Ser Gly Asp Pro Thr Phe Leu Glu Val Val Thr Arg Ala1355 1360 1365Gln Glu Ala Ile Arg Ser Ala Arg Gln His Leu Asp Val Pro Phe1370 1375 1380Ala Arg Ile Val Glu Leu Leu Asp Leu Pro Val Ser Leu Ser Arg1385 1390 1395His Pro Val Phe Gln Val Gly Leu Glu Val His Glu Glu Asp Leu1400 1405 1410Gly Ala Trp Asp Ala Thr Glu Leu Pro Ala Leu Arg Thr Ser Val1415 1420 1425Glu Pro Val Gly Pro Glu Ala Ile Glu Leu Asp Leu Ala Phe Arg1430 1435 1440Leu Thr Glu Arg Arg Asp Glu Asp Gly Ile Glu Gly Thr Leu His1445 1450 1455Tyr Ala Ala Asp Leu Phe Asp Gln Ala Thr Ala Glu Ser Leu Ala1460 1465 1470Arg Arg Leu Val Ser Phe Leu Glu Gln Val Ala Glu Asp Pro Gln1475 1480 1485
Arg Arg Val Ser Asp Leu Asp Val Leu Leu Asp Asp Ala Glu Arg1490 1495 1500Glu Arg Pro Ala Glu Ala Pro Ala Lys Trp Ser Glu Ala Val Pro1505 1510 1515Pro Val Ala Ala Asp Leu Ala Glu Gly Gly Pro Leu Gly Ala Leu1520 1525 1530Val Leu Asp Asp Arg Leu Arg Pro Ala Val Ala Val Gly Glu Leu1535 1540 1545Tyr Leu Thr Gly Ala Ala Val Asp Ala Glu Pro Gly Asp Arg Thr1550 1555 1560Leu Ala Cys Pro Phe Gly Ala Thr Gly Arg Arg Met Leu Pro Thr1565 1570 1575Gly Leu Leu Ala Arg Trp Thr Ala Gly Gly Thr Leu Val Val Val1580 1585 1590Gly Glu Arg Arg Gly Ser Ser Gly Ser Val Lys Thr Gly Thr Gly1595 1600 1605Asp Phe Glu Val Leu Leu Pro Leu Arg Ala Gly Gly Asn Arg Pro1610 1615 1620Pro Leu Tyr Cys Val His Ala Ser Gly Gly Leu Ser Trp Asn Tyr1625 1630 1635Ala Pro Leu Leu Arg Ser Leu Pro Pro Asn Gln Pro Val Tyr Gly1640 1645 1650
Val Gln Ala Arg Gly Leu Ala Arg Thr Glu Pro Leu Ala Ala Gly1655 1660 1665Val Glu G1u Met Ala Ala Asp Tyr Val Glu Gln Ile Arg Ala Val1670 1675 1680Gln Pro Thr Gly Pro Tyr His Leu Leu Gly Trp Ser Leu Gly Gly1685 1690 1695Arg Ile Ala Gln Glu Met Ala Arg Val Leu Glu Glu Gln Gly Glu1700 1705 1710Gln Val Gly Leu Leu Ala Leu Leu Asp Ala Tyr Pro Thr Asp Val1715 1720 1725Gly Arg Leu Arg Arg Pro Arg Gly Asp Ala Ala Asp Gln Glu Ala1730 1735 1740Ala Asp Phe Asp Arg Gln Gln Glu Gln Gln Ala Gln Leu Ala Ala1745 1750 1755Ala Val Ala Thr Glu Ala Gly Ala Arg Lys Arg Leu Asp Glu Val1760 1765 1770Met Glu His Leu Ala Arg Val Gly Pro Leu His Thr Ser Arg Ser1775 1780 1785Phe Gly Cys Asp Ile Leu Leu Phe Val Ala Thr Val Asn Arg Pro1790 1795 1800Ser His Leu Pro Val Ala Asp Ala Ile Ala Ser Trp Arg Pro Leu1805 1810 1815
Thr Thr Gly Thr Val Glu Pro His Glu Ile Glu Ile Asp His Met1820 1825 1830Gln Met Leu Gln Pro Ala Ala Leu Ala Arg Ile Gly Ala Val Val1835 1840 1845Ala Glu Lys Leu Arg Pro Arg Pro Asp Gly Glu Arg Thr Gln Arg1850 1855 1860<210>18<211>4083<212>PRT<213>野野村菌屬<400>18Met Ala Gln Ser Arg Ile Glu Asp Phe Trp Pro Leu Ser Pro Leu Gln1 5 10 15Gln Gly Leu Leu Phe His Thr Thr Tyr Asp Asp Asp Trp Pro Gly Leu20 25 30Tyr Val Gly His Trp Ile Leu Asn Leu Asn Gly Pro Val Glu Ala Asp35 40 45Arg Leu Arg Ala Ala Trp Glu Ala Leu Leu Ala Arg His Ala Ala Leu50 55 60Arg Ala Cys Phe Arg Gln Arg Lys Ser Gly Glu Thr Val Gln Leu Ile65 70 75 80Ala Arg Gln Val Glu Leu Pro Trp Arg Val Val Asp Leu Ser His Leu85 90 95
Ser Glu Pro Glu Glu Ala Val Arg Ala Val Ala Glu Glu Asp Arg Thr100 105 110Arg Arg Phe Asp Leu Ala Lys Ala Pro Leu Leu Arg Leu Thr Leu Ile115 120 125Arg Leu Ala Gly Asp Asp His Arg Leu Val Met Thr Cys His His Ala130 135 140Ile Met Asp Gly Trp Ser Met Pro Ile Met Leu Asp Glu Leu Ser Met145 150 155 160Leu Tyr Ala Ala Asp Gly Ser Pro Leu Asp Leu Pro Ala Val Pro Ser165 170 175Tyr Arg Asp Tyr Leu Val Trp Leu Asp Arg Gln Asp Lys Glu Arg Thr180 185 190Leu Ser Ala Trp Ala Ala Glu Leu Arg Gly Val Glu Glu Pro Thr Leu195 200 205Val Ala Pro Ala Asp Ala Asn Arg Ala Pro Ala Met Pro Glu Asn Ile210 215 220Thr Val Glu Leu Pro Glu Asp Leu Thr Arg Ala Leu Ser Glu Leu Ala225 230 235 240Arg Thr His Gly Leu Thr Leu Asn Thr Val Val Gln Gly Ala Trp Ala245 250 255Leu Leu Leu Ala Gln Leu Ala Gly Arg Thr Asp Val Val Phe Gly Ala260 265 270
Ala Val Ser Ala Arg Pro Pro Asp Leu Pro Gly Val Glu Gly Met Val275 280 285Gly Leu Phe Leu Asn Thr Val Pro Val Arg Val Arg Leu Ser Gly Ser290 295 300Thr Pro Val Ile Glu Phe Leu Ala Asp Leu Gln Lys Arg Gln Ser Ala305 310 315 320Leu Ile Pro His Gln Tyr Met Gly Leu Ala Asp Ile Gln Arg Thr Ala325 330 335Gly Ala Gly Ala Val Phe Asp Thr Leu Leu Val Phe Gln Asn Phe Pro340 345 350Arg Glu Leu Arg Pro Ser Asp Ala Ala Ala Ala Phe Asp Ile Arg Ile355 360 365Asp Gln Gly Arg Glu Ala Ala His Tyr Pro Leu Thr Leu Val Ala Val370 375 380Pro Gly Glu Ser Met Leu Leu Asn Leu Asp His Val Thr Asp Leu Phe385 390 395 400Asp Arg Glu Ala Ala Leu Ala Ile Leu Glu Arg Phe Thr Gly Ile Leu405 410 415Arg Gln Leu Ala Gly Ala Gly Asp Leu Thr Val Ala Glu Val Asp Val420 425 430Thr Ser Ala Ala Glu Arg Ala Leu Val Val Asn Ala Trp Ser Ala Ala435 440 445
Pro Arg Val Ala Pro Gly Glu Leu Ala Pro Asp Leu Phe Asp Arg Gln450 455 460Val Glu Arg Gly Arg Asp Arg Val Ala Val Val Glu Gly Lys Arg Ala465 470 475 480Val Ser Phe Gly Glu Leu Ala Glu His Ala Glu Arg Leu Ala Gly Tyr485 490 495Leu Ser Gly Arg Gly Val Arg Arg Gly Asp Arg Val Ala Val Val Met500 505 510Gly Arg Ser Pro Gly Leu Ile Ala Thr Leu Leu Ala Val Trp Lys Ala515 520 525Gly Ala Ala Phe Val Pro Val Asp Pro Ala Tyr Pro Ala Glu Arg Val530 535 540Gln Phe Met Leu Ala Asp Ala Glu Pro Ala Ala Val Val Thr Glu Arg545 550 555 560Ala Cys Gln Ala Ala Val Pro Ala Gly Gly Leu Asp Pro Ile Val Leu565 570 575Asp Asp Pro Asp Thr Leu Arg Ala Val Ala Glu His Ala Arg Leu Ser580 585 590Ala Gly Ala His Ala Asp Asp Leu Ala Tyr Val Met Tyr Thr Ser Gly595 600 605Ser Thr Gly Arg Pro Lys Gly Val Ala Val Ser His Gly Asn Val Ala610 615 620
Ala Leu Ala Gly Glu Pro Gly Trp Gly Leu Gly Pro Glu Asp Ala Val625 630 635 640Leu Met His Ala Ser His Ala Phe Asp Ile Ser Leu Phe Glu Leu Trp645 650 655Val Pro Leu Leu Ser Gly Ala Arg Val Val Leu Ala Glu Pro Gly Ala660 665 670Val Asp Gly Glu Ala Leu Ala Gly Tyr Val Ala Gly Gly Val Thr Cys675 680 685Ala His Leu Thr Ala Gly Thr Phe Arg Val Leu Ala Glu Glu Ser Pro690 695 700Glu Ser Val Ala Gly Leu Arg Glu Val Leu Thr Gly Gly Asp Ala Val705 710 715 720Pro Leu Ala Ala Val Glu Arg Val Arg Arg Ala Cys Pro Asp Val Arg725 730 735Val Arg His Leu Tyr Gly Pro Thr Glu Ala Thr Leu Cys Ala Thr Trp740 745 750Trp Leu Leu Gln Pro Gly Glu Pro Thr Gly Pro Val Leu Pro Ile Gly755 760 765Arg Pro Leu Ala Gly Arg Arg Val Tyr Val Leu Asp Ala Phe Leu Arg770 775 780Pro Val Pro Pro Gly Val Thr Gly Glu Leu Tyr Val Ala Gly Ala Gly785 790 795 800
Val Ala Gln Gly Tyr Leu Gly Arg Pro Ala Leu Thr Ala Glu Arg Phe805 810 815Val Ala Glu Pro Phe Val Pro Gly Gly Arg Met Tyr Arg Thr Gly Asp820 825 830Leu Ala Arg Trp Thr Asp Gln Gly Glu Leu Ala Phe Ala Gly Arg Ala835 840 845Asp Asp Gln Val Lys Ile Arg Gly Tyr Arg Val Glu Pro Gly Glu Ile850 855 860Glu Ala Val Leu Ala Gly Leu Pro Gly Val Gly Gln Ala Val Val Ser865 870 875 880Ala Arg Glu Glu Arg Leu Ile Gly Tyr Val Val Ala Glu Thr Gly Gly885 890 895Asp Leu Asp Pro Val Arg Ile Arg Glu Gln Leu Ala Ala Thr Leu Pro900 905 910Glu Phe Met Val Pro Ala Ala Val Leu Val Leu Asp Ala Leu Pro Leu915 920 925Thr Gly Asn Gly Lys Val Asp Arg Arg Ala Leu Pro Glu Pro Asp Phe930 935 940Ala Ala Gly Ala Val Asp Arg Glu Pro Ala Thr Asp Ala Glu Arg Ile945 950 955 960Leu Cys Gly Val Phe Ala Glu Val Leu Gly Ala Gly Arg Val Gly Val965 970 975
Ala Asp Ser Phe Phe Glu Leu Gly Gly Asp Ser Ile Ser Ser Met Gln980 985 990Val Ala Ala Arg Ala Arg Arg Gln Gly Ile Pro Leu Thr Pro Arg Gln995 1000 1005Val Phe Glu His Arg Thr Pro Glu Arg Leu Ala Ala Leu Ala Gln1010 1015 1020Gln Ala Pro Gly Arg Arg Ala Ser Ser Val Glu Pro Gly Val Gly1025 1030 1035Glu Ile Pro Arg Thr Pro Val Met Arg Ala Leu Gly Asp Asp Ala1040 1045 1050Val Arg Pro Gly Phe Ala Gln Ala Arg Val Val Val Thr Pro Ala1055 1060 1065Gly Phe Ala Pro Asp Ala Leu Val Thr Ala Leu Gln Ala Val Leu1070 1075 1080Asp Val His Asp Leu Leu Arg Thr Arg Val Glu Pro Asp Gly Arg1085 1090 1095Leu Met Val Ala Glu Pro Gly Ala Val Asp Ala Ala Gly Leu Val1100 1105 1110Thr Arg Val Ala Ala Gly Asn Gly Asn Leu Ala Glu Arg Ala Glu1115 1120 1125Arg Glu Ala Arg Thr Ala Ala Gly Thr Leu Asp Pro Ser Glu Gly1130 1135 1140
Ile Met Val Arg Ala Val Trp Val Asp Ala Gly Asp Ala Glu Pro1145 1150 1155Gly Arg Leu Ala Leu Val Val His His Leu Val Val Asp Ala Val1160 1165 1170Ser Trp Ala Ile Leu Leu Ser Asp Leu Arg Ala Ala Tyr Asp Glu1175 1180 1185Ala Val Ser Gly Gly Thr Pro Val Leu Glu Pro Ala Val Thr Ser1190 1195 1200Tyr Arg Gln Trp Ala Arg Arg Leu Ala Gly Gln Ala Leu Ser Glu1205 1210 1215Ser Thr Val Ala Glu Ala Gly His Trp Ala Gly Val Leu Glu Gly1220 1225 1230Gly Asp Leu Pro Leu Glu Arg His Pro Gly Gln Ser Ala Ser Trp1235 1240 1245Ser Arg Thr Leu Ser Asp Ala Gln Ala Arg Asn Leu Val Ala Arg1250 1255 1260Val Pro Ala Ala Phe His Cys Gly Val Gln Asp Val Leu Leu Ala1265 1270 1275Gly Leu Ala Gly Ala Val Ala Arg Trp Arg Gly Ala Asp Ala Gly1280 1285 1290Ile Leu Val Asp Val Glu Gly His Gly Arg His Ala Ala Asp Gly1295 1300 1305
Glu Asp Leu Leu Arg Thr Val Gly Trp Phe Thr Ser Val His Pro1310 1315 1320Val Arg Leu Asp Val Ser Gly Val Gly Pro Gly Ala Ala Ala Ala1325 1330 1335Gly Glu Leu Leu Lys Ala Val Lys Glu Gln Ala Arg Ala Val Pro1340 1345 1350Gly Asp Gly Leu Gly Tyr Gly Leu Leu Arg Tyr Leu Asn Pro Glu1355 1360 1365Thr Gly Ala Arg Leu Ala Glu Leu Pro Ser Ala Gln Ile Gly Phe1370 1375 1380Asn Tyr Leu Gly Arg Ser Gly Val Ala Ser Glu Asp Thr Ala Trp1385 1390 1395Gln Val Cys Glu Gly Ala Leu Gly Gly Gln Ala Ala Gly Pro Asp1400 1405 1410Leu Val Gln Ser His Ala Leu Glu Val Gly Ala Asp Val Gln Asp1415 1420 1425Thr Pro Ala Gly Pro Arg Leu Arg Leu Ala Ile Asp Gly Arg Asp1430 1435 1440Leu Asp Pro Ala Ala Val Glu Arg Leu Gly Glu Ala Trp Leu Asp1445 1450 1455Thr Leu Ala Gly Leu Ala Ala Leu Ala Asp Thr Pro Gly Ala Gly1460 1465 1470
Gly His Thr Pro Ser Asp Phe Glu Leu Val Glu Val Arg Gln Arg1475 1480 1485Asp Val Asp Glu Leu Glu Ala Val Ala Pro Gly Leu Thr Asp Val1490 1495 1500Trp Pro Leu Ser Pro Leu Gln Glu Gly Ile Leu Phe Glu Arg Ala1505 1510 1515Phe Asp Glu Asp Gly Val Asp Val Tyr Gln Thr Gln Arg Ile Leu1520 1525 1530Asp Leu Asp Gly Pro Leu Asp Ala Gln Arg Leu His Ala Ala Trp1535 1540 1545Gln Ser Val Ile Asp Arg His Glu Thr Leu Arg Thr Gly Phe His1550 1555 1560Gln Leu Gly Ser Gly Glu Thr Val Gln Val Val Val Gly Glu Ala1565 1570 1575Glu Val Leu Trp Arg Glu Ala Asp Leu Ser Arg Leu Asp Glu Pro1580 1585 1590Asp Ala Glu Val Glu Arg Leu Leu Ala Ala Asp Gln Ala Glu Arg1595 1600 1605Phe Asp Val Ser Arg Ala Pro Leu Leu Arg Leu Leu Leu Ile Arg1610 1615 1620Leu Gly Ala Ala Arg His Arg Leu Val Val Thr Ser His His Val1625 1630 1635
Leu Val Asp Gly Trp Ser Thr Pro Ile Leu Leu Gly Glu Met Leu1640 1645 1650Thr Ala Tyr Ala Asp Gly Arg Val Ser Pro Ala Pro Pro Ser Tyr1655 1660 1665Arg Asp Tyr Val Ala Trp Leu Ser Arg Gln Asp Glu Asp Ala Ala1670 1675 1680Arg Ser Ala Trp Arg Ala Glu Leu Ala Gly Leu Asp Glu Pro Thr1685 1690 1695Val Val Gly Leu Asp Ala Gly Lys Ala Pro Val Met Pro Asp Gly1700 1705 1710His Ala Glu Trp Leu Ser Glu Glu Ala Thr Arg Ala Leu Thr Gly1715 1720 1725Phe Ala Arg Gly His Gly Leu Thr Leu Ser Thr Val Val Gln Gly1730 1735 1740Ala Trp Ala Leu Val Leu Ala Arg Leu Ala Arg Arg Thr Asp Val1745 1750 1755Val Phe Gly Thr Val Val Ser Gly Arg Pro Ala Asp Ala Leu Pro1760 1765 1770Asp Val Glu Arg Met Val Gly Met Phe Ile Asn Thr Val Pro Val1775 1780 1785Arg Val Arg Leu Asp Gly Ala Val Pro Val Leu Asp Leu Leu Gln1790 1795 1800
Asp Leu Gln Arg Arg Gln Ser Ser Leu Thr Glu His Gln His Leu1805 1810 1815Gly Leu Pro Glu Ile Gln Lys Ala Ala Gly Pro Gly Ser Ile Phe1820 1825 1830Asp Thr Ile Leu Met Ile Val Asn Tyr Pro Leu Asp Ala Asp Gly1835 1840 1845Leu Asp Asp Gly Gly Val Ala Ile Ser Ser Ile Arg Thr Arg Thr1850 1855 1860Gly Thr Thr Tyr Pro Leu Ser Val Ser Val Ile Pro Gly Ala Arg1865 1870 1875Leu Gln IIe Gln Leu Asp Tyr Arg Pro Asp Trp Ile Gly Gly Asp1880 1885 1890Leu Ala Ala Glu Ile Thr Gly Gln Val Val Arg Val Leu Ala Arg1895 1900 1905Met Val Ala Glu Pro Ser Leu Pro Val Gly Arg Leu Ala Val Thr1910 1915 1920Ser Arg Ser Thr Arg Gly Ser Val Thr Glu Arg Trp Asn Ser Thr1925 1930 1935Gly Ala Ala Ala Gly Gly Ser Ser Val Pro Glu Leu Phe Arg Arg1940 1945 1950Gln Ala Asp Ala Ala Pro Asp Ala Thr Ala Val Ile Gly Asp Gly1955 1960 1965
Arg Thr Leu Ser Tyr Ala Gly Leu Asp Arg Glu Ser Asp Arg Leu1970 1975 1980Ala Gly His Leu Ala Arg Arg Gly Val Arg Arg Gly Asp Arg Val1985 1990 1995Gly Val Leu Met Glu Arg Gly Ala Asp Leu Ile Val Ala Leu Leu2000 2005 2010Ala Val Trp Lys Ala Gly Ala Ala Gln Val Pro Val Asn Val Asp2015 2020 2025Tyr Pro Ala Glu Arg Ile Glu Arg Met Leu Ala Asp Ala Gly Ala2030 2035 2040Ser Val Ala Val Cys Ala Gly Ala Thr Arg His Ala Val Pro Asp2045 2050 2055Gly Ile Glu Pro Val Val Met Asp Ala Pro Ala Thr Glu Ala Glu2060 2065 2070Arg His Glu Ala Pro Pro Leu Ala Val Gly Ala His Asp Val Ala2075 2080 2085Tyr Val Met Tyr Thr Ser Gly Ser Thr Gly Val Pro Lys Gly Val2090 2095 2100Ala Val Pro His Gly Ser Ala Ala Ala Leu Ala Gly Asp Pro Gly2105 2110 2115Trp Ser Gln Gly Ala Gly Asp Arg Val Leu Met His Ala Ser His2120 2125 2130
Ala Phe Asp Ala Ser Leu Leu Glu Ile Trp Val Pro Leu Val Ser2135 2140 2145Gly Ala Cys Val Met Val Ala Glu Pro Gly Ala Ile Asp Ala Gln2150 2155 2160Arg Leu Arg Asp Val Ile Ala Arg Gly A1a Thr Thr Val His Leu2165 2170 2175Thr Ala Gly Thr Phe Arg Val Leu Ala Glu Glu Ser Pro Asp Ser2180 2185 2190Phe Ser Gly Leu Arg Glu Val Leu Thr Gly Gly Asp Val Val Pro2195 2200 2205Leu Glu Ser Val Ala Arg Val Arg Arg Ala Cys Pro Glu Val Arg2210 2215 2220Val Arg Glu Leu Tyr Gly Pro Thr Glu Val Thr Leu Cys Ala Thr2225 2230 2235Trp His Leu Ile Glu Pro His Thr Glu Thr Gly Asp Thr Leu Pro2240 2245 2250Ile Gly Arg Pro Leu Ala Gly Arg Gln Val Tyr Val Leu Asp Ala2255 2260 2265Phe Leu Gln Pro Val Ala Pro Asn Val Thr Gly Glu Leu Tyr Leu2270 2275 2280Ala Gly Ala Gly Leu Ala His Gly Tyr Leu Gly Ala Pro Ala Ala2285 2290 2295
Thr Ser Glu Arg Phe Ile Ala Val Pro A1a Ser Val Asn Pro Ala2300 2305 2310Ala Ser Gly Glu Arg Met Tyr Arg Thr Gly Asp Leu Ala Arg Trp2315 2320 2325Thr Asp Arg Gly Glu Leu Leu Phe Ala Gly Arg Ala Asp Ser Gln2330 2335 2340Val Lys Ile Arg Gly Tyr Arg Val Glu Pro Gly Glu Ile Glu Ala2345 2350 2355Ala Leu Ala Glu Val Pro His Val Ala Gln Ala Val Val Val Ala2360 2365 2370Arg Glu Asp Arg Pro Gly Glu Lys Arg Leu Ile Ala Tyr Val Thr2375 2380 2385Ala Glu Glu Gly Ser Gly Leu Asp Pro Asp Ala Val Arg Glu His2390 2395 2400Leu Ala Gly Arg Leu Pro Glu Phe Met Val Pro Ala Ala Val Val2405 2410 2415Leu Leu Asp Gly Val Pro Leu Thr Pro Asn Gly Lys Ile Asp Arg2420 2425 2430Ala Ala Leu Pro Val Pro Glu Phe Thr Gly Lys Ala Ala Gly Arg2435 2440 2445Glu Pro Arg Thr Glu Ala Glu Arg Val Leu Cys Glu Leu Phe Ala2450 2455 2460
Glu Val Leu Gly Val Ala Arg Ala Gly Ala Glu Asp Ser Phe Phe2465 2470 2475Glu Leu Gly Gly Asp Ser Ile Leu Ser Met Arg Leu Ala Ala Arg2480 2485 2490Ala Arg Arg Glu Glu Leu Val Phe Gly Ala Lys Asp Val Phe Glu2495 2500 2505Arg Lys Thr Pro Ala Gly Ile Ala Met Val Ala Glu Arg Gly Gly2510 2515 2520Ala Thr Arg Ala Ser Leu Asp Asp Gly Val Gly Glu Val Met Ser2525 2530 2535Thr Pro Val Ile Arg Ala Leu Leu Glu Arg Asp Pro Asp Ala Met2540 2545 2550Thr Arg Gly Ala Leu Ser Gln Trp Val Thr Ala Gly Ala Pro Asp2555 2560 2565Asp Leu Ser Val Asp Val Leu Ala Ala Gly Leu Gly Ala Val Ile2570 2575 2580Asp Ala His Asp Met Leu Arg Ser Arg Ile Val Arg Thr Gly Ala2585 2590 2595Ala Gln Pro Arg Leu Val Val Ala Gly Arg Gly Ala Val Asp Ala2600 2605 2610Ala Thr Leu Val Glu Arg Val Glu Ala Gly Thr Gly Asp Val Asp2615 2620 2625
Glu Ile Ala Asp Arg Cys Ala Arg Asp Ala Ala Ala Arg Leu Asp2630 2635 2640Pro His Ala Gly Val Met Ile Arg Ala Val Trp Val Asp Ala Gly2645 2650 2655Pro Gly Arg Val Gly Arg Leu Val Val Ala Ala His His Leu Val2660 2665 2670Val Asp Val Val Ser Trp Arg Ile Leu Leu Pro Asp Leu Gln Val2675 2680 2685Ala Cys Glu Ala Val Ala Ala Gly Arg Arg Pro Val Leu Asp Pro2690 2695 2700Val Asp Val Ser Phe Arg Arg Trp Ala Arg Thr Leu Ala Asp Gln2705 2710 2715Ala Val Thr Arg Ala Thr Glu Leu Glu Thr Trp Thr Glu Ile Leu2720 2725 2730Asp Gly Ala Arg Ser Arg Leu Gly Glu Leu Asp Pro Ala Arg Asp2735 2740 2745Thr Val Ser Thr Ala Gly Arg Thr Ser Trp Thr Leu Pro His Asp2750 2755 2760Arg Ala Gly Val Leu Val Glu Gln Ala Thr Ser Ala Phe His Cys2765 2770 2775Gly Val His Glu Val Leu Leu Ala Thr Leu Ala Gly Ala Val Ala2780 2785 2790
His Trp Arg Gly Gly Thr Ala Val Val Val Asp Val Glu Gly His2795 2800 2805Gly Arg Arg Pro Ile Asp Glu Leu Asp Leu Ser Arg Thr Val Gly2810 2815 2820Trp Phe Thr Asp Val His Pro Leu Arg Leu Asp Val Thr Gly Ile2825 2830 2835Asp Pro Ala Glu Val Ile Ala Gly Gly Gly Ala Ala Gly His Leu2840 2845 2850Leu Lys Gln Val Lys Glu Asn Val Arg Ala Val Pro Asp Gly Gly2855 2860 2865Leu Gly Tyr Gly Ile Leu Arg Tyr Leu Asn Ala Gly Thr Gly Gln2870 2875 2880Ala Leu Ala Ala Ala Pro Lys Pro Glu Ile Gly Phe Asn Tyr Leu2885 2890 2895Gly Arg Phe Pro Ser Arg Ser Ala Gly Ala Pro Glu Pro Trp Gln2900 2905 2910Leu Leu Gly Thr Ile Gly Gly Thr Ala Glu Gln Asp Thr Ala Leu2915 2920 2925Arg His Ala Val Glu Ile Asp Ala Ala Val Leu Asp Gly Ala Ala2930 2935 2940Gly Pro Glu Leu Ser Leu Thr Val Thr Trp Ala Gly Arg Leu Leu2945 2950 2955
Gly Glu Ala Glu Ala Glu Ser Leu Ala Gln Ala Trp Leu Ala Met2960 2965 2970Leu Thr Gly Leu Ala Ala His Val Gly Gly Gly Gly Ala Gly Gly2975 2980 2985His Thr Pro Ser Asp Phe Pro Leu Ile Ser Leu Thr Gln Gln Asp2990 2995 3000Val Ala Glu Val Glu Ala Ala Val Pro Thr Leu Leu Asp Ile Trp3005 3010 3015Pro Leu Ser Pro Leu Gln Glu Gly Leu Leu Phe His Ala Ala Asp3020 3025 3030Glu Arg Gly Pro Asp Val Tyr Ala Gly Met Arg Lys Leu Ala Leu3035 3040 3045Asp Gly Pro Leu Asp Val Ala Arg Phe Arg Ala Ser Trp Gln Ala3050 3055 3060Leu Leu Asp Arg His Pro Ala Leu Arg Ala Ser Phe His Gln Leu3065 3070 3075Gly Ser Gly Ala Ala Val Gln Ala Ile Ala Arg Glu Val Pro Leu3080 3085 3090Asp Trp Gln Glu Thr Asp Leu Ser Arg Leu Pro Glu Asp Glu Ala3095 3100 3105Leu Ala Glu Phe Asp Arg Leu Ala Glu Gln Leu His Thr Glu Arg3110 3115 3120
Phe Asp Leu Thr Arg Ala Pro Gln Leu Arg Leu His Leu Val Arg3125 3130 3135Leu Gly Glu Arg Arg His Arg Leu Val Leu Thr Ser His His Ile3140 3145 3150Val Ala Asp Gly Trp Ser Leu Pro Leu Ile Thr Glu Asp Val Leu3155 3160 3165Thr Val Tyr Glu Ser Gly Gly Asp Gly Arg Ala Leu Pro Ala Ala3170 3175 3180Thr Ser Tyr Arg Asp Tyr Leu Ala Trp Ile Ala Arg Gln Asp Lys3185 3190 3195Ala Ala Ala Arg Glu Ala Trp Arg Ala Glu Leu Ala Gly Leu Asp3200 3205 3210Glu Ala Thr His Val Val Pro Pro Glu Thr Ile Thr Thr Pro Leu3215 3220 3225Glu Pro Glu Arg Val Gly Phe Glu Leu Asp Glu Ala Leu Ser Arg3230 3235 3240Arg Val Val Glu Phe Thr Gly Arg His Gly Val Thr Ala Asn Thr3245 3250 3255Leu Phe Gln Gly Ile Trp Ala Leu His Leu Ala Arg Leu Thr Gly3260 3265 3270Arg Asp Asp Val Val Phe Gly Ala Ala Val Ala Gly Arg Pro Pro3275 3280 3285
Glu Ile Pro Gly Val Glu Ser Ala Val Gly Leu Phe Met Asn Met3290 3295 3300Leu Pro Val Arg Ala Arg Leu Ala Gly Ala Glu Pro Phe Leu Asp3305 3310 3315Met Leu Thr Asp Leu Gln Glu Arg Gln Val Ala Cys Met Pro His3320 3325 3330Gln His Val Gly Leu Ser Glu Ile Asn Gln Leu Ala Gly Pro Gly3335 3340 3345Ala Ala Phe Asp Thr Ile Val Val Phe Glu Asn Tyr Pro Pro Pro3350 3355 3360Pro Pro Arg Pro Glu Gly Pro Asp Ala Leu Val Met Arg Pro Ala3365 3370 3375Gly Ile Pro Asn Asp Thr Gly His Tyr Pro Leu Ser Met Arg Ala3380 3385 3390Ser Val Ala Gly Arg Val His Gly Glu Phe Ile Tyr Arg Pro Asp3395 3400 3405Val Val Asp Arg Ala Glu Ala Glu Glu Met Leu Ala Ser Ile Leu3410 3415 3420Arg Ala Leu Glu Gln Val Val Ala Glu Pro Arg Val Pro Val Gly3425 3430 3435Arg Val Gly Leu Ile Gly Pro Glu Gln Arg Arg Leu Val Val Glu3440 3445 3450
Glu Trp Asn Arg Thr Gly Val Pro Pro Ala Ala Glu Pro Val Pro3455 3460 3465Met Leu Phe Arg Arg Gln Val Glu Arg Ser Pro Asp Ala Val Ala3470 3475 3480Val Val Asp Ala Ala Arg Ser Leu Ser Tyr Ser Gly Leu Leu Asp3485 3490 3495Glu Ala Glu Glu Leu Ala Arg Leu Leu Val Gly Leu Gly Val Arg3500 3505 3510Arg Glu Thr Arg Val Gly Val Leu Val Gly Arg Ser Ala Glu Leu3515 3520 3525Val Val Ala Leu Leu Gly Val Ser Ser Ala Gly Gly Val Phe Val3530 3535 3540Pro Met Asp Pro Asp Tyr Pro Arg Glu Arg Ile Ser Phe Ile Leu3545 3550 3555Ala Asp Ser Ala Pro Glu Val Leu Leu Cys Thr Ser Glu Thr Arg3560 3565 3570Gln Ala Val Pro Glu Glu Phe Ala Gly Ala Val Val Ala Leu Asp3575 3580 3585Ala Pro Leu Ala Ala Asp Pro Arg Thr Ala Leu Pro Arg Val Glu3590 3595 3600Ala Gly Asp Gly Ala Tyr Val Ile Tyr Thr Ser Gly Ser Thr Gly3605 3610 3615
Val Pro Lys Gly Val Leu Val Pro His Ala Gly Leu Gly Asn Leu3620 3625 3630Ala Ser Ala Gln Ile Glu Arg Phe Gly Val Thr Ser Ala Ser Arg3635 3640 3645Ile Leu Gln Phe Ala Ala Leu Gly Phe Asp Ala Ala Val Ser Glu3650 3655 3660Leu Cys Met Ala Leu Leu Ser Gly Gly Thr Val Val Leu Ala Asp3665 3670 3675Ala Glu Ser Met Pro Pro Arg Val Ser Leu Gly Asp Ala Val Arg3680 3685 3690Arg Trp Gly Ile Thr His Val Thr Val Pro Pro Ser Val Pro Ala3695 3700 3705Val Glu Asp Asp Leu Pro Asp Ser Leu Glu Thr Leu Val Val Ala3710 3715 3720Gly Glu Ala Cys Pro Pro Ala Leu Val Asp Arg Trp Ser Pro Gly3725 3730 3735Arg Arg Met Ile Asn Ala Tyr Gly Pro Thr Glu Thr Thr Val Cys3740 3745 3750Ala Thr Met Ser Ser Pro Leu Ser Pro Gly Arg Asp Val Val Pro3755 3760 3765Ile Gly Arg Pro Ile Thr Gly Leu Arg Ala Tyr Val Leu Asp Ala3770 3775 3780
Phe Leu Gln Pro Val Pro Pro Gly Val Thr Gly Glu Leu Tyr Val3785 3790 3795Ala Gly Ala Gly Leu Ala Arg Gly Tyr Leu Gly Arg Pro Gly Leu3800 3805 3810Thr Ala Glu Arg Phe Val Ala Val Pro Ala Ser Val Ser Pro Ala3815 3820 3825Arg Pro Gly Glu Arg Met Tyr Arg Thr Gly Asn Arg Ala Arg Trp3830 3835 3840Thr Arg Asp Gly Glu Leu Val Phe Thr Gly Arg Ala Asp Ala Gln3845 3850 3855Val Lys Val Arg Gly Tyr Arg Ile Glu Pro Gly Glu Ile Glu Ala3860 3865 3870Val Leu Ala Asp His Pro Gly Val Ala Gln Val Ala Val Val Ala3875 3880 3885Arg Glu Asp Gly Pro Gly Gln Lys Tyr Leu Val Ala Tyr Val Val3890 3895 3900Pro Ala Ala Glu Gln Val Ala Gly Ala Pro Ser Glu Ala Gly Gln3905 3910 3915Asp Gly Ala Leu Ile Ser Ala Leu Arg Glu Ser Ala Ala Gly Arg3920 3925 3930Leu Pro Glu His Met Arg Pro Ala Ala Phe Val Pro Leu Asp Thr3935 3940 3945
Met Pro Leu Thr Pro Asn Gly Lys Val Asp His Arg Ala Leu Arg3950 3955 3960Ala Pro Asp Phe Ala Arg Ser Ser Ser Gly Arg Asp Pro Arg Ser3965 3970 3975Ala Met Glu Ala Lys Leu Cys Glu Leu Phe Ala Glu Val Leu Gly3980 3985 3990Leu Glu Glu Val Gly Ala Gly Asp Ser Phe Phe Glu Leu Gly Gly3995 4000 4005Asp Ser Ile Thr Ser Met Gln Leu Ser Ala Leu Ala Arg Arg Lys4010 4015 4020Gly Leu Asp Leu Thr Pro Trp Gln Val Phe Asp Glu Lys Thr Ala4025 4030 4035Glu Arg Leu Ala Ala Val Val Lys Glu Leu Pro Ala Asp Gly Glu4040 4045 4050Gly Thr Gly Glu Pro Glu Pro Pro Ala Gly Thr Leu Val Asp Leu4055 4060 4065Ser Pro Asp Gln Leu Asp Gln Leu Glu Ala Gly Pro Ala Gly Gly4070 4075 4080<210>19<211>753<212>PRT<213>野野村菌屬<400>19
Met Ala Gly Phe Gly Ala Pro Phe Arg Asn Ser Asp His Val Val Ser1 5 10 15Lys Leu Thr Asn Glu Asp Ala Phe Glu Leu Val Glu Arg His Gly Ala20 25 30Asn Ala Ser Pro Leu Gly Arg Ala Met Leu Thr Val Arg Ala Gly Asp35 40 45Arg Ser Tyr Pro Glu Met Gly Val Gly Pro Val Ala Glu Ser Lys Asp50 55 60Leu Arg Trp Gln Gln Leu Thr Ser Gly Arg Phe Pro Glu Arg Lys Gly65 70 75 80Glu Ala Val Val Asp Leu Trp Asp Ala Gln Asn Trp Asp Val Ala Val85 90 95Gly Asp Arg Ile Arg Ile Gly Glu Arg Ala Thr Ala Ala Asp Phe Thr100 105 110Val Val Gly Ile Val Arg Ala Pro Ser Pro Val Ala Gln Ala Ser Val115 120 125Tyr Val Thr Trp Pro Gln Leu Met Arg Trp Ala Asp Asp Pro Ser Leu130 135 140Gly Ile Tyr Thr Val Thr Val Arg Gly Ala Val Gly Pro Val Pro Glu145 150 155 160Thr Ala Lys Val Gln Thr Pro Glu Gln Glu Ile Ala Ala Arg Thr Ala165 170 175
Gln Leu Gln Asn Gly Val Asp Thr Trp Ser Leu Leu Leu Leu Leu Phe180 185 190Ala Gly Ile Ala Val Phe Val Ser Ile Leu Val Ile Ala Asn Thr Phe195 200 205Ser Ile Leu Leu Ala Gln Arg Met Arg Asp Phe Ala Leu Leu Arg Cys210 215 220Val Gly Ala Thr Arg Arg Gln Val Val Ser Ser Val Arg Arg Glu Ala225 230 235 240Ala Val Val Gly Leu Leu Ser Ser Leu Ala Gly Val Leu Val Gly Ala245 250 255Gly Leu Gly Tyr Gly Leu Ile Ala Leu Ile Lys Thr Leu Ser Pro Ile260 265 270Thr Pro Ile Ala Ala Pro Ala Pro Pro Ala Pro Trp Leu Leu Gly Gly275 280 285Leu Ala lle Gly Leu Thr Ala Thr Leu Val Ala Ala Trp Leu Pro Ile290 295 300Arg Arg Val Val Arg Val Ser Pro Leu Ala Ala Leu Arg Pro Asp Thr305 310 315 320Ala Thr Asp Pro Arg Thr Ala Thr Gly Arg Ala Arg Leu Val Leu Gly325 330 335Val Phe Met Leu Ile Ala Gly Leu Val Leu Leu Ala Ser Ala Met Ala340 345 350
Trp His Ser Thr Val Leu Met Leu Ala Gly Gly Gly Ser Leu Phe Thr355 360 365Gly Val Leu Leu Phe Gly Pro Val Leu Ile Pro Arg Leu Leu Glu Ile370 375 380Thr Gly Thr Arg Leu Gly Thr Ile Gly Arg Leu Ala Thr Lys Asn Ala385 390 395 400Val Arg Asn Pro Arg Arg Thr Ala Thr Thr Ala Ala Ser Leu Leu Val405 410 415Gly Ile Thr Leu Ile Thr Ala Val Leu Thr Gly Val Ala Ile Thr Ser420 425 430Glu Ala Leu Asn Glu Arg Leu Asp Gly Gln His Pro Ile Asp Ala Ala435 440 445Leu Val Ser Thr Gly Lys Pro Phe Ser Ala Asp Phe Leu Asp Lys Val450 455 460Arg Gly Thr Ser Gly Val Asp Gln Ala Ile Ala Val Asp Gly Ala Val465 470 475 480Ala Thr Val Ser Gly Leu Asp Lys Pro Ile Pro Val Val Thr Ala Pro485 490 495Asp Ala Gln Arg Val Ala His Asp Gly Gly Ser Phe Ala Arg Val Glu500 505 510Pro Gly Val Leu Arg Leu Asp Glu Ser Ala Phe Arg Gln Leu Arg Leu515 520 525
Arg Ala Gly Asp Lys Val Arg Val Thr Val Gly Asp Arg Arg Ala Val530 535 540Leu Gln Val Ser Leu Ala Thr Gly Trp Gly Leu Gln Ala Val Val Ala545 550 555 560Pro Glu Thr Leu Ala Arg Leu Thr Asp Ser Ala Ala Pro Arg Ala Val565 570 575Trp Ile Arg Ala Ser Ala Asp Ala Asp Ser Thr Arg Leu Val Gly Glu580 585 590Leu Gly Asp Leu Ala Ala Ala Ala Gly Ala Asn Val Asn Asp Gln Leu595 600 605Glu Ala Arg Glu Thr Glu Asn Ala Pro Leu Met Ile Leu Thr Trp Ala610 615 620Ile Val Ala Leu Leu Gly Phe Ser Val Ala Ile Ala Leu Val Gly Ile625 630 635 640Ala Asn Thr Leu Gly Leu Ser Val Leu Glu Arg Val Arg Glu His Ala645 650 655Leu Leu Arg Ala Leu Gly Leu Thr Arg Arg Gln Leu Arg Arg Met Leu660 665 670Ala Ala Glu Ala Val Leu Leu Ser Leu Val Ala Ala Val Leu Gly Thr675 680 685Val Ile Gly Ile Gly Phe Ala Trp Val Gly Tyr Glu Thr Phe Val Lys690 695 700
Gln Ala Leu Asp Asn Ala Thr Met Gln Val Pro Trp Pro Leu Leu Ala705 710 715 720Val Val Val Leu Val Ala Ala Leu Ala Gly Leu Leu Ala Ser Val Leu725 730 735Pro Ala Arg Arg Ala Val Arg Val Thr Pro Ala Ala Gly Leu Ser Phe740 745 750Glu<210>20<211>232<212>PRT<213>野野村菌屬<400>20Met Thr Gly Gln Arg Ala Ala Leu Glu Thr Val Ala Ala Ser Ala Arg1 5 10 15Asn Leu Thr Lys Val Tyr Gly Gln Gly Glu Thr Arg Val His Ala Leu20 25 30Arg Gly Val Asp Leu Asp Leu Pro Arg Gly Lys Phe Thr Ala Ile Met35 40 45Gly Ser Ser Gly Ser Gly Lys Ser Thr Leu Met His Cys Leu Ala Gly50 55 60Leu Asp Gln Ala Ser Asp Gly Thr Val Thr Val Ala Gly Thr Asp Leu65 70 75 80Gly Ser Leu Asp Asp Asn Glu Leu Thr Val Phe Arg Arg Glu His Ile
85 90 95Gly Phe Val Phe Gln Ser Phe Asn Leu Leu Pro Met Leu Thr Ala Phe100 105 110Gln Asn Ile Thr Leu Pro Leu Glu Leu Gly Gly Arg Arg Ile Asp Asp115 120 125Ala Ala Thr Glu Arg Val His Val Leu Ala Glu Thr Leu Gly Met Ala130 135 140Asp Arg Leu Gly His Arg Pro Ser Glu Met Ser Gly Gly Gln Gln Gln145 150 155 160Arg Val Ala Ile Ala Arg Ala Leu Ile Thr Gly Pro Asp Leu Leu Phe165 170 175Ala Asp Glu Pro Thr Gly Asn Leu Asp Ser Thr Thr Ser Ala Glu Val180 185 190Leu Gly Tyr Leu His Lys Ser Thr Arg Glu Leu Gly Gln Thr Val Val195 200 205Met Val Thr His Glu Arg Glu Ala Ala Ala Tyr Ala Asp Gly Val Val210 215 220Thr Leu Glu Asp Gly Arg Ile Ala225 230<210>21<211>535<212>PRT<213>野野村菌屬
<400>21Met Ser His Ile Thr Met Thr Pro Pro Ser Ala Cys Arg Asp Pro Ala1 5 10 15Pro Ala Gly Arg Phe Pro Arg Trp Ala Val Trp Arg Ser Pro Pro Gly20 25 30Gln Pro Trp Trp Ala Arg Pro Ala Leu Leu Cys Ile Ala Ala Thr Ala35 40 45Ala Val Leu Tyr Ala Trp Asn Leu Pro Leu Val Asp Tyr Ala Pro Arg50 55 60Tyr Ser Asp Ala Val Lys Ser Met Ser Glu Asn Trp Lys Ala Phe Leu65 70 75 80Tyr Gly Thr Val Asp Val Gln Ala Thr Tyr Thr Leu Asp Lys Leu Ala85 90 95Gly Ala Phe Val Pro Gln Ala Ile Ser Val lys Ile Phe Gly Phe His100 105 110Ala Trp Ala Leu Ala Leu Pro Gln Val Ile Glu Gly Val Ile Ser Val115 120 125Leu Val Met Tyr Arg Ile Val Arg Arg Trp Ala Gly Val Val Pro Gly130 135 140Leu Leu Ala Ala Ala Val Phe Thr Ile Thr Pro Val Ala Ala Ser Met145 150 155 160Phe Gly His Ser Met Ala Asp Gly Ala Leu Val Met Cys Leu Val Leu165 170 175
Ala Val Asp Ser Tyr Gln Arg Ala Val Leu Glu Gly Arg Leu Arg Ser180 185 190Leu Val Trp Ala Gly Val Trp Val Gly Leu Gly Phe Gln Ala Lys Met195 200 205Leu Gln Ala Trp Met Ile Leu Pro Ala Leu Ala Ile Gly Tyr Leu Leu210 215 220Ser Ala Pro Ile Gly Leu Arg Arg Arg Leu Gln His Leu Gly Ile Ala225 230 235 240Gly Val Val Thr Leu Val Val Ser Leu Ser Trp lle Thr Leu Tyr His245 250 255Val Thr Pro Ala Ala Asp Arg Pro Tyr Ile Ser Gly Thr Thr Asn Ser260 265 270Ser Ala Ala Ala Met Val Phe Gly Tyr Asn Gly Leu Gly Arg Leu Gly275 280 285Ile Asn Leu Pro Gly Ala Leu Pro Pro Asn Tyr Met Gly Ser Val Ile290 295 300Gly Pro Ala Pro Pro Lys Arg Ser Thr Gln Leu Pro Arg Pro Arg Pro305 310 315 320Gly Met Val Ile Pro Glu Ile Gly Ile Glu His Gly Gly Gly Trp Gly325 330 335Lys Leu Phe Gly Gly Arg Leu Gly Val Ala Ser Gly Trp Leu Tyr Pro340 345 350
Leu Ala Leu Met Ala Leu Leu Cys Gly Leu Trp Trp Trp Arg Arg Ala355 360 365Glu Arg Thr Asp Pro Ala Arg Gly Gly Met Val Met Trp Gly Val Trp370 375 380Leu Leu Thr Phe Ala Leu Pro Tyr Ser Ala Val Phe Val Ile Pro His385 390 395 400Ser Ala Tyr Val Ala Val Leu Ala Pro Pro Val Ala Ala Leu Ser Gly405 410 415Ile Gly Ile Val Met Phe Trp Arg Ala Tyr Arg Ser Gly Gly Arg Met420 425 430Ala Trp Ile Phe Pro Leu Ala Ile Val Ala Glu Leu Ala Trp Ala Val435 440 445Trp Leu Trp Ser Phe Tyr Pro Thr Phe Leu Pro Trp Ala Met Trp Gly450 455 460Ala Val Ala Leu Gly Val Val Ala Val Val Ala Leu Ala Leu Ala Arg465 470 475 480Leu Val Arg Pro Arg Arg Ser Ser Leu Val Ser Ala Gly Leu Thr Ile485 490 495Gly Val Ala Ala Met Leu Ala Ala Pro Ala Thr Trp Ser Ala Ser Val500 505 510Leu Asp Pro Arg Tyr Gly Gly Ser Ser Phe Asp Ala Asn Ala Gly Pro515 520 525
Ala Ala Arg Thr Pro Gly Gly530 535<210>22<211>270<212>PRT<213>野野村菌屬<400>22Met Leu Gln Asp Ala Asp Arg Thr Arg Ile Leu Ala Ile Ser Pro His1 5 10 15Leu Asp Asp Ala Val Leu Ser Val Gly Ala Ser Leu Ala Gln Ala Glu20 25 30Gln Asp Gly Gly Lys Val Thr Val Phe Thr Val Phe Ala Gly Ser Ala35 40 45Ala Pro Pro Tyr Ser Pro Ala Ala Glu Arg Phe His Ala Arg Trp Gly50 55 60Leu Ser Pro Thr Glu Asp Ala Pro Leu Arg Arg Arg Asn Glu Asp Ile65 70 75 80Ala Ala Leu Asp Gln Leu Gly Ala Gly His Arg His Gly Arg Phe Leu85 90 95Asp Ala Ile Tyr Arg Arg Ser Pro Asp Gly Gln Trp Leu Leu His His100 105 110Asn Glu Gly Ser Met Val Arg Gln Gln Ser Pro Ala Asn Asn His Asp115 120 125
Leu Val Ala Ala Ile Arg Glu Asp Ile Glu Ser Met Ile Ala Glu Cys130 135 140Asp Pro Thr Leu Val Leu Thr Cys Val Ala Ile Gly Lys His Pro Asp145 150 155 160His Lys Ala Thr Arg Asp Ala Thr Leu Leu Ala Ala Arg Glu Arg Gly165 170 175Ile Pro Leu Arg Leu Trp Gln Asp Leu Pro Tyr Ala Ala Tyr Ser Gln180 185 190Asp Leu Ala Glu Leu Pro Asp Gly Leu Arg Leu Gly Ser Pro Glu Leu195 200 205Ser Phe Val Asp Glu Glu Ala Arg Thr Arg Lys Phe Gln Ala Met Lys210 215 220His Tyr Ala Thr Gln Leu Ser Val Leu Asp Gly Pro Asn Lys Asn Leu225 230 235 240Phe Ala Lys Leu Asp Glu His Ala Arg Asn Ala Ala Pro Asp Gly Gly245 250 255Tyr Asn Glu Thr Thr Trp Pro Val Ile Arg Tyr Ala Ala Glu260 265 270<210>23<211>420<212>PRT<213>野野村菌屬<400>23
Met Ala His Arg Leu Arg Arg Leu Thr Thr Ala Phe Arg Ser Val Arg1 5 10 15Leu Arg Leu Thr Leu Val Tyr Gly Ala Leu Phe Ala Ala Ser Gly Val20 25 30Val Leu Leu Ala Ile Thr Tyr Leu Leu Phe Arg Gly Ser Arg Pro Phe35 40 45Val Leu Val Asp Gly Asp Pro Gly Gly Arg Phe Arg Ala Phe Ala Arg50 55 60Gln Gln Gln Ala Ala Ile Leu Glu Asn Leu Leu Phe Gln Ser Leu Ile65 70 75 80Ala Leu Ala Leu Met Thr Val Ile Ser Phe Leu Leu Gly Trp Leu Val85 90 95Ala Gly Arg Met Leu Arg Pro Leu Arg Thr Met Asn Thr Thr Leu Lys100 105 110Arg Ile Ser Ala Arg Asn Val His Glu Arg Leu Ala Leu Pro Gly Pro115 120 125Arg Asp Glu Leu Arg Asn Leu Ala Asp Thr Val Asp Glu Leu Leu Glu130 135 140Arg Leu His Ser Ala Leu Asp Ala Gln Lys Arg Phe Val Ala Asn Ala145 150 155 160Ala His Glu Leu Arg Thr Pro Leu Thr Leu Glu His Ala Leu Leu Glu165 170 175
Glu Ser Leu Leu His Arg Asp Ala Asp Thr Pro Ser Met Arg Ser Ile180 185 190Met Glu Arg Leu Leu Asp Leu Ser Arg Gln Gln Gly Arg Leu Leu Glu195 200 205Ser Leu Leu Thr Leu Ala Lys Ser Glu Gly Gly Leu Asp His Arg Glu210 215 220Pro Leu Asp Leu Ala Glu Ile Ala Glu His Thr Ile Arg Thr Met Glu225 230 235 240Gly Thr Gly Pro Gly Ala Asp Gly Asn Asn Pro Arg Ala Gly Val Ser245 250 255Ala Asp Arg Arg Ala Asp Gly Asn Ser Pro Thr Ala Gly Ala Ala Thr260 265 270Asp Ser Trp Ala Asp Gly Lys Ser Leu Arg Ala Gly Cys Pro His Pro275 280 285Arg Leu Val Thr Gly Ile Ala His Ala Pro Thr Thr Gly Asp Pro Ala290 295 300Leu Val Glu Arg Leu Ile Thr Asn Leu Leu Asp Asn Ala Met Arg Tyr305 310 315 320Asn Val Pro Gly Gly Gln Val Glu Leu Ser Thr Arg Ala Glu Ala Gly325 330 335Lys Ala Val Val Ser Ile Ala Asn Thr Gly Pro Val Val Pro Pro Glu340 345 350
Gln Val His Arg Leu Phe Glu Pro Phe Gln Arg Leu Asp Arg Thr Arg355 360 365Ala Asp Asp His His Gly Leu Gly Leu Ser Ile Val Arg Ala Ile Ala370 375 380Val Ala His Asp Ala Thr Leu Thr Ala His Ala Arg Pro Gln Gly Gly385 390 395 400Leu Ser Val Glu Ile His Phe Pro Leu Met Arg Arg Ala Leu Arg Arg405 410 415Leu Ala Pro Ser420<210>24<211>709<212>PRT<213>野野村菌屬<400>24Met Ser Leu Pro Thr Cys Ala Cys Gly Leu Thr Pro His Ala Pro Ser1 5 10 15Cys Ala Pro Arg Ser Glu His Ala Gly Gly Arg Ser Ser Glu Ser Arg20 25 30Thr Asp Ile Gln Gly Leu Arg Ala Ile Ala Val Ala Ala Val Val Ala35 40 45Phe His Leu Trp Pro Gly Gly Pro Thr Gly Gly Tyr Val Gly Val Asp50 55 60Val Phe Phe Val Ile Ser Gly Tyr Leu Ile Thr Ser His Leu Leu Arg
65 70 75 80Gln Pro Gly His Gly Gly Gly Arg Leu Leu Asp Phe Trp Ala Arg Arg85 90 95Val Arg Arg Leu Ile Pro Ala Ala Ser Leu Ala Leu Leu Val Thr Leu100 105 110Ala Ala Ser Val Val Trp Leu Pro Leu Thr Val Leu Gly Thr Ala Ala115 120 125Arg Glu Val Ile Ala Ala Thr Val Tyr Val Glu Asn Leu Arg Leu Ala130 135 140Leu Thr Gln Ala Asn Tyr Leu Asp Val Asp Gln Pro Asp Trp Pro Ala145 150 155 160Gln His Tyr Trp Ser Leu Ser Ile Glu Glu Gln Phe Tyr Leu Gly Trp165 170 175Pro Leu Leu Leu Gly Ser Ala Ala Trp Leu Ala Ala Arg Val Ala Arg180 185 190Gly Arg Arg Pro Pro Glu Asn Phe Thr Arg Trp Ser Ala Val Val Val195 200 205Thr Gly Ala Val Val Ala Ala Ser Leu Ala Trp Ser Val Gln Lys Thr210 215 220Ala Thr Asp Pro Ala Ala Ala Tyr Phe Val Ser Thr Thr Arg Phe Trp225 230 235 240Glu Leu Ala Leu Gly Gly Leu Leu Ala Ala Val Leu Thr Val Arg Ala
245 250 255Met Pro Arg Ala Arg Ala Val Arg Ala Gly Leu Ala Trp Ala Gly Leu260 265 270Gly Met Ile Gly Trp Ala Val Val Arg Phe Asp Ala Glu Thr Ala Phe275 280 285Pro Gly Ala Ala Ala Leu Val Pro Thr Val Gly Ala Cys Leu Val Ile290 295 300Ala Ala Ala Ala Asp Gly Leu Arg Gly Gly Pro Gly Arg Ala Leu Ala305 310 315 320Trp Arg Pro Val Gln Trp Leu Gly Asn Ala Ser Tyr Ala Val Tyr Leu325 330 335Trp His Trp Pro Pro Ile Met Ile Leu Pro Tyr Ala Leu Gly Arg Ser340 345 350Leu Thr Val Ile Glu Ser Val Gly Val Ile Ala Leu Thr Leu Val Leu355 360 365Ala Ala Leu Ser Gln Tyr Leu Val Glu Asp Arg Leu Arg Trp His Pro370 375 380Val Leu Val Arg Ser Arg Arg Leu Thr Phe Ala Met Leu Ala Ser Cys385 390 395 400Val Val Val Val Ala Gly Ala Gly Ala Gly Val Val Ala Tyr Ala Asp405 410 415Ala Ala Glu Arg Thr Glu Ser Ala Ala Phe Glu Ala Ala Ala Ser Arg
420 425 430Ala Gly Ser Cys Leu Gly Ala Gly Val Val Arg Asp Pro Ala Cys Gln435 440 445Asp Leu Gly Leu Leu Met Pro Pro Gln Val Ala Leu Lys Asp Lys Pro450 455 460Ala Val Tyr Ala Asp Gly Cys Val Asn Lys Glu Pro Phe Ile Ala Arg465 470 475 480Asn Thr Cys Thr Tyr Gly Pro Asp Ala Ala Gly Arg Arg Ile Ala Leu485 490 495Val Gly Asn Ser His Ala Gly His Trp Val Pro Ala Leu Glu Lys Ala500 505 510Leu Trp Ser Glu Arg Trp Gln Leu Thr Thr Tyr Val Gln Leu Ala Cys515 520 525Tyr Thr Val Asp Gln Pro Leu Val Leu Glu Gly Ala Gly Val Ser Glu530 535 540Asn Cys Gln Lys Ile Asn Lys Trp Ala Val Gly Ser Ile Val Asn Gly545 550 555 560Gly Tyr Asp Leu Val Ile Met Ser Asn Arg Thr His Val Pro Leu Ala565 570 575Gly Val Ser Pro Ala Gly Gln Gln Ala Ala Ala Glu Arg Ala Tyr Arg580 585 590Asp Thr Leu Arg Ala Phe Thr Gly Ala GlV Leu Pro Val Leu Val Leu
595 600 605Arg Asp Thr Pro Ala Met Pro Asp Ser Val Pro His Cys Ile Ala Lys610 615 620His Pro Asp Asp Leu Asp Ser Cys Gly Gly Pro Ala Gly Val Val Leu625 630 635 640Arg Pro Asp Pro Leu Ala Ala Ala Ala Arg Ala Asp Asp Thr Gly Leu645 650 655Val Ser Val Ala Ser Val Asp His Leu Val Cys Gly Glu Arg Cys Gly660 665 670Pro Val Ile Gly Gly Leu Ile Ala Tyr Ser Asp Arg Ser His Leu Thr675 680 685Thr Thr Phe Ala Arg Thr Leu Ala Pro Glu Val Thr Ala Ala Val Arg690 695 700Gly Ala Leu Thr Arg705<210>25<211>648<212>PRT<213>野野村菌屬<400>25Met Ala Ile Val Ser Pro Phe Gly Gly Leu Leu Lys Gly Asp Gly Glu1 5 10 15Asp Asp Pro Ala Pro Ser Arg Ile Arg Pro Gly Thr Leu Arg Arg Val20 25 30
Leu Gly Tyr Phe Arg Pro His Val Gly Lys Val Ala Leu Phe Val Leu35 40 45Val Thr Ala Leu Asp Ser Ile Phe Val Val Ala Ser Pro Leu Met Leu50 55 60Lys Asp Leu Val Asp Lys Gly Val Leu Gly Asn Asp Leu Glu Leu Val65 70 75 80Ile Leu Leu Ala Cys Leu Ala Ala Gly Phe Ala Val Met Ser Thr Leu85 90 95Leu Gln Leu Val Ser Ala Tyr Ile Ser Gly Arg Ile Gly Gln Gly Val100 105 110Ser Tyr Asp Leu Arg Val Gln Ala Leu Asp His Val Gln Arg Leu Pro115 120 125Ile Ala Phe Phe Thr Arg Thr Gln Thr Gly Val Leu Val Gly Arg Leu130 135 140His Thr Glu Leu Val Met Thr Gln Met Ala Phe Thr Gln Met Leu Thr145 150 155 160Ala Ala Ala Ser Ala Val Thr Val Leu Leu Val Leu Ala Glu Leu Phe165 170 175Tyr Leu Ser Trp Ile Val Ala Leu Leu Thr Leu Val Leu Ile Pro Val180 185 190Phe Leu Val Pro Trp Ser Tyr Val Gly Arg Arg Met Gln Arg Tyr Thr195 200 205
Arg Gly Leu Met Glu Glu Asn Ala Gly Leu Ala Gly Leu Leu Gln Glu210 215 220Arg Phe Asn Val Gln Gly Ala Met Leu Ser Lys Leu Phe Gly Arg Pro225 230 235 240Ala Glu Glu Met Ala Glu Tyr Glu Ser Arg Ala Gly Arg Ile Arg Gly245 250 255Leu Ala Val Ser Val Thr Leu Tyr Gly Arg Met Ala Pro Ala Ile Phe260 265 270Ala Leu Met Ala Ala Leu Ala Thr Ala Leu Val Tyr Gly Val Gly Gly275 280 285Gly Leu Val Leu Ser Gln Ala Phe Gln Leu Gly Thr Leu Val Ala Leu290 295 300Ala Thr Leu Leu Gly Arg Leu Phe Gly Pro lle Thr Gln Leu Ala Ser305 310 315 320Ile Gln Glu Asn Ala Leu Thr Val Leu Val Ser Phe Glu Arg Ile Phe325 330 335Glu Leu Leu Asp Leu Lys Pro Leu Ile Glu Glu Arg Pro Asp Ala Val340 345 350Ala Leu Lys Ala Gly Lys Ala Ser Asp Val Gln Phe Glu Asn Val Ser355 360 365Phe Arg Tyr Pro Ser Ala Asp Glu Val Ser Leu Pro Ser Leu Glu Gln370 375 380
Asn Val Arg Thr Gly Gln Glu Arg Gly Glu Ala Thr Pro Glu Val Leu385 390 395 400Arg Asp Val Ser Leu His Val Pro Ala Gly Thr Leu Thr Ala Leu Val405 410 415Gly Pro Ser Gly Ala Gly Lys Ser Thr Leu Thr His Leu Val Ser Arg420 425 430Leu Tyr Asp Pro Thr Ser Gly Thr Val Arg Val Gly Gly His Asp Leu435 440 445Arg Asp Leu Thr Phe Asp Ser Leu Arg Glu Thr Val Gly Val Val Ser450 455 460Gln Asp Thr Tyr Leu Phe His Asp Thr Ile Arg Ala Asn Leu Leu Tyr465 470 475 480Ala Arg Pro Asp Ala Thr Glu Asp Glu Leu Val Glu Ala Cys Arg Gly485 490 495Ala Gln Ile Trp Asp Leu Ile Ala Ser Leu Pro Arg Gly Leu Asp Thr500 505 510Val Val Gly Asp Arg Gly Tyr Arg Leu Ser Gly Gly Glu Lys Gln Arg515 520 525Leu Ala Ile Ala Arg Leu Leu Leu Lys Ala Pro Ser Val Val Val Leu530 535 540Asp Glu Ala Thr Ala His Leu Asp Ser Glu Ser Glu Ala Ala Val Gln545 550 555 560
Arg Ala Leu Thr Thr Ala Leu Arg Ser Arg Thr Ser Leu Val Ile Ala565 570 575His Arg Leu Ser Thr Ile Arg Glu Ala Asp His Ile Leu Val Ile Asp580 585 590Asp Gly Arg Val Arg Glu Arg Gly Thr His Glu Glu Leu Leu Ala Glu595 600 605Gly Gly Leu Tyr AlaAsp Leu Tyr His Thr Gln Phe Ala Lys Ser Gly610 615 620Val Asn Gly Thr Arg Pro Gly Gln Gly Asp Gly Ala Glu Pro Val Gln625 630 635 640Glu Val Val Gly Gly Gly Glu Arg645<210>26<211>2097<212>PRT<213>野野村菌屬<400>26Met Ser Ala Gly Thr Arg Ala Thr Pro Thr Thr Val Leu Asp Leu Phe1 5 10 15Ala Arg Gln Val Gly Arg Ala Pro Asp Ala Val Ala Leu Val Asp Gly20 25 30Asp Arg Val Leu Thr Tyr Arg Arg Leu Asp Glu Leu Ala Gly Ala Leu35 40 45
Ser Gly Arg Leu Ile Gly Arg Gly Val Gly Arg Gly Asp Arg Val Ala50 55 60Val Met Met Asp Arg Ser Ala Asp Leu Val Val Thr Leu Leu Ala Val65 70 75 80Trp Gln Ala Gly Ala Ala Tyr Val Pro Val Asp Ala Ala Leu Pro Ala85 90 95Arg Arg Val Ala Phe Met Val Ala Asp Ser Gly Ala Cys Leu Met Val100 105 110Cys Ser Glu Ala Thr Arg Asp Ala Val Pro Gln Gly Val Glu Ser Ile115 120 125Ala Leu Thr Gly Glu Gly Gly Cys Gly Thr Ser Ala Val Thr Val Asp130 135 140Pro Gly Asp Leu Ala Tyr Val Met Tyr Thr Ser Gly Ser Thr Gly Thr145 150 155 160Pro Lys Gly Val Ala Val Pro His Arg Ser Val Ala Glu Leu Thr Gly165 170 175Asn Pro Gly Trp Gly Val Glu Pro Gly Glu Ala Val Leu Met His Ala180 185 190Pro Tyr Thr Phe Asp Ala Ser Leu Phe Glu Ile Trp Val Pro Leu Val195 200 205Ser Gly Ala Arg Val Val Ile Ala Ala Pro Gly Ala Val Asp Ala Arg210 215 220
Arg Leu Arg Glu Ala Val Ala Ala Gly Val Thr Arg Val His Leu Thr225 230 235 240Ala Gly Ser Phe Arg Ala Val Ala Glu Glu Ser Pro Glu Ser Phe Ala245 250 255His Phe Arg Glu Val Leu Thr Gly Gly Asp Val Val Pro Ala Tyr Ala260 265 270Val Gln Lys Val Arg Ala Ala Cys Pro His Val Arg Ile Arg His Leu275 280 285Tyr Gly Pro Thr Glu Thr Thr Leu Cys Ala Thr Trp Gln Leu Leu Glu290 295 300Pro Gly Asp Val Val Gly Pro Val Leu Pro Ile Gly Arg Pro Leu Pro305 310 315 320Gly Arg Arg Ala Trp Val Leu Asp Ala Ser Leu Arg Pro Val Glu Pro325 330 335Gly Val Val Gly Asp Leu Tyr Leu Ser Gly Ala Gly Leu Ala Asp Gly340 345 350Tyr Leu Asp Arg Ala Gly Leu Thr Ala Glu Arg Phe Val Ala Asp Pro355 360 365Ser Ala Ala Gly Arg Arg Met Tyr Arg Thr Gly Asp Leu Ala Gln Trp370 375 380Thr Ala Asp Gly Glu Leu Leu Phe Ala Gly Arg Ala Asp Asp Gln Val385 390 395 400
Lys Val Arg Gly Phe Arg Ile Glu Pro Gly Glu Val Glu Ala Ala Leu405 410 415Thr Ala Gln Pro His Val Arg Glu Ala Val Val Val Ala Ile Asp Gly420 425 430Arg Leu Ile Gly Tyr Val Val Ala Asp Gly Asp Val Asp Pro Val Leu435 440 445Met Arg Arg Arg Leu Ala Ala Ser Leu Pro Glu Tyr Met Ile Pro Ala450 455 460Ala Leu Val Thr Leu Asp Ala Leu Pro Leu Thr Gly Ser Gly Lys Val465 470 475 480Asp Arg Arg Ala Leu Pro Glu Pro Asp Phe Ala Ser Ala Ala Pro Arg485 490 495Arg Glu Pro Gly Thr Glu Pro Glu Arg Val Leu Cys Asp Leu Phe Ala500 505 510Glu Leu Leu Gln Pro Glu Gly Arg Gly Val Gly Val Asp Asp Gly Phe515 520 525Val Glu Leu Gly Gly Asp Ser Ile Val Ala Ile Arg Leu Ala Ala Arg530 535 540Ala Ser Arg Val Gly Leu Leu Val Thr Pro Ala Gln Ile Phe Lys Glu545 550 555 560Lys Thr Pro Ala Arg Leu Ala Ala Val Ala Gly Ala Val Pro Ala Gly565 570 575
Arg Pro Ala Asp Gly Pro Leu Ile Thr Leu Thr Ala Glu Glu Glu Ala580 585 590Glu Leu Ala Thr Ala Val Pro Gly Ala Glu Glu Val Trp Pro Leu Ala595 600 605Pro Leu Gln Glu Gly Leu Tyr Phe Gln Ala Thr Leu Asp Asp Glu Gly610 615 620His Asp Ile Tyr Gln Ala Gln Trp Ile Leu Glu Leu Ala Gly Pro Leu625 630 635 640Asp Ala Ala Arg Leu Arg Ala Ser Trp Glu Ala Val Phe Ala Arg His645 650 655Pro Glu Leu Arg Val Ser Phe His Arg Arg Ala Ser Gly Thr Met Leu660 665 670Gln Val Val Ala Gly His Val Val Leu Pro Trp Arg Glu Val Asp Leu675 680 685Ala Asp Ala Gly Asp Ile Asp Ala Ala Val Ala Ala Leu Ile Ser Glu690 695 700Glu Gln Glu Gln Arg Phe Asp Leu Ala Lys Ala Pro Leu Phe Arg Leu705 710 715 720Val Leu Val Arg His Gly Glu Asp Arg His Arg Leu Leu Val Val His725 730 735His His Ile Leu Thr Asp Gly Trp Ser Val Ala Val Ile Leu Asn Glu740 745 750
Val Ala Glu Ala Tyr Thr Asn Gly Gly Arg Leu Pro Asp Arg Thr Gly755 760 765Ala Ala Ser Tyr Arg Asp Tyr Leu Ala Trp Leu Asp Arg Gln Asp Lys770 775 780Asp Ala Ala Arg Ala Ala Trp Gln Ala Glu Leu Ser Gly Leu Glu Gly785 790 795 800Pro Ala Pro Ile Ala Lys Ala Ala Thr Thr Thr Gly Ala Gly Thr Gly805 810 815Tyr Glu Tyr Arg Ile Ala Phe Leu Thr Pro Asp Leu His Thr Arg Leu820 825 830Thr Glu Leu Ala Arg Asp His Gly Leu Thr Leu Asn Thr Leu Ala Gln835 840 845Gly Ala Trp Ala Met Val Leu Ala Arg Leu Ala Arg Arg Thr Asp Val850 855 860Val Phe Gly Thr Thr Val Ala Cys Arg Pro Ala Glu Leu Pro Glu Val865 870 875 880Glu Ser Val Pro Gly Leu Met Met Asn Thr Val Pro Val Arg Val Pro885 890 895Leu Gln Gly Ala Gln Ser Val Val Asp Leu Leu Thr Gly Leu Gln Glu900 905 910Arg Gln Ala Ala Leu Leu Pro His Gln His Leu Gly Leu Thr Glu Ile915 920 925
Gln Arg Ala Ala Gly Pro Gly Ala Thr Phe Asp Thr Leu Leu Val Phe930 935 940Glu Asn Tyr Pro Arg Asp Phe Ala Gly Gln Phe Thr Tyr Leu Gly Thr945 950 955 960Ile Glu Gly Thr His Tyr Pro Leu Thr Leu Gly Ile Ile Pro Gly Asp965 970 975His Phe Arg Ile Gln Leu Val Tyr Arg Arg Gly Gln Val Gly Glu Ser980 985 990Val Ala Glu Ser Ile Leu Gly Trp Phe Thr Gly Ala Leu Met Thr Mer995 1000 1005Ala Ala Asp Pro His Gly Pro Val Gly Arg Ile Gly Val Gly Glu1010 1015 1020Ala Arg Ala Gly Gly Ser Asp Arg Ala Met Ala Ala Gly Glu Pro1025 1030 1035Leu Pro Val Leu Leu Arg Arg Val Val Lys Asp Arg Pro Asp Glu1040 1045 1050Val Ala Val Val Asp Gly Asp Gly Glu Leu Ser Phe Gly Glu Leu1055 1060 1065Trp Glu Arg Ala Thr Ala Leu Ala Ala Glu Leu Arg Ala His Gly1070 1075 1080Ile Gly Pro Glu Ser Arg Val Ala Val Met Val Gly Arg Ser Ala1085 1090 1095
Trp Trp Ala Val Gly Val Leu Gly Val Cys Leu Ala Gly Gly Ala1100 1105 1110Phe Met Pro Val Asp Pro Ala Tyr Pro Ala Glu Arg Val Arg Trp1115 1120 1125Ile Leu Ala Asp Ser Asp Pro Arg Leu Val Leu Cys Ala Gly Thr1130 1135 1140Thr Arg Glu Ala Val Pro Glu Glu Phe Ala Asp Arg Leu Val Val1145 1150 1155Val Asp Glu Leu Asp Leu Ala Gly Ser Asp Asp Ala Gly Leu Pro1160 1165 1170Arg Val Ser Pro Asp Asp Ala Ala Tyr Val Ile Tyr Thr Ser Gly1175 1180 1185Ser Thr Gly Thr Pro Lys Gly Val Val Val Ser His Ala Gly Leu1190 1195 1200Gly Asn Leu Ala Met Ala Gln Ile Asp Arg Phe Ala Val Ser Pro1205 1210 1215Ser Ser Arg Val Leu Gln Phe Ala Ala Leu Gly Phe Asp Ala Met1220 1225 1230Val Ser Glu Met Leu Met Ala Leu Leu Ser Gly Ala Arg Leu Val1235 1240 1245Met Ala Pro Glu Pro Ala Leu Pro Pro Arg Val Ser Leu Ala Glu1250 1255 1260
Ala Leu Arg Arg Trp Glu Val Thr His Val Thr Val Pro Pro Ser1265 1270 1275Val Leu Ala Thr Ala Asp Ala Leu Pro Ala Gly Leu Glu Thr Val1280 1285 1290Val Val Ala Gly Glu Ala Cys Pro Pro Gly Leu Ala Glu Arg Trp1295 1300 1305Ser Ala Gly Arg Arg Leu Val Asn Ala Tyr Gly Pro Thr Glu Ala1310 1315 1320Thr Val Cys Ala Ala Met Ser Arg Pro Leu Thr Gly Ser Arg Glu1325 1330 1335Val Val Pro Ile Gly Thr Pro Ile Ala Gly Gly Arg Cys Tyr Val1340 1345 1350Leu Asp Ala Phe Leu Arg Pro Leu Pro Pro Gly Ile Thr Gly Glu1355 1360 1365Leu Tyr Val Ala Gly Ile Gly Leu Ala Arg Gly Tyr Leu Gly Arg1370 1375 1380Ala Ser Leu Thr Ala Glu Arg Phe Val Ala Asp Pro Phe Val Ala1385 1390 1395Gly Glu Arg Met Tyr Arg Thr Gly Asp Leu Ala Tyr Trp Thr Gly1400 1405 1410Glu Gly Glu Leu Val Phe Ala Gly Arg Asp Asp Asp Gln Val Lys1415 1420 1425
Ile Arg Gly Tyr Arg Val Glu Pro Gly Glu Val Glu Ala Val Leu1430 1435 1440Ala Gly Gln Pro Gly Val Asp Gln Ala Val Val Val Ala Arg Glu1445 1450 1455Gly Arg Leu Leu Gly Tyr Val Val Ser Gly Gly Gly Val Asp Pro1460 1465 1470Val Arg Leu Arg Glu Gly Val Ala Arg Val Leu Pro Glu Tyr Met1475 1480 1485Val Pro Ala Ala Val Val Val Leu Gly Ala Val Pro Val Thr Ala1490 1495 1500Asn Gly Lys Val Asp Arg Glu Ala Leu Pro Asp Pro Gly Phe Gly1505 1510 1515Gly Arg Val Ser Gly Arg Glu Pro Arg Thr Glu Val Glu Arg Ala1520 1525 1530Leu Cys Gly Leu Phe Ala Glu Val Leu Gly Leu Pro Gly Val Thr1535 1540 1545Ala Val Gly Pro Asp Asp Ser Phe Phe Glu Leu Gly Gly Asp Ser1550 1555 1560Ile Thr Ser Met Gln Leu Ala Ser Arg Ala Arg Arg Glu Gly Met1565 1570 1575Leu Phe Gly Ala Arg Glu Val Phe Glu Arg Lys Thr Pro Ala Gly1580 1585 1590
Leu Ala Ala Ile Val Asp Val Gly Gly Glu Leu Ala Ala Gly Pro1595 1600 1605Ala Asp Gly Val Gly Glu Ile Ala Trp Thr Pro Ile Met Arg Ala1610 1615 1620Leu Gly Asp Gly Ile Val Gly Ser Arg Phe Ala Gln Trp Val Val1625 1630 1635Leu Gly Ala Pro Pro Asp Leu Arg Ala Asp Val Val Ala Ala Gly1640 1645 1650Leu Ala Ala Val Val Asp Thr His Asp Val Leu Arg Leu Arg Val1655 1660 1665Val Asp Asp Arg Ala Gly Arg Arg Leu Ala Val Gly Glu Arg Gly1670 1675 1680Ser Val Asp Thr Ala Gly Leu Val Thr Arg Leu Glu Cys Gly Gly1685 1690 1695Arg Pro Pro Asp Glu Val Val Glu Arg Ala Val Arg Glu Ala Val1700 1705 1710Gly Arg Leu Asp Pro Val Ala Gly Val Met Ala Gln Ala Val Trp1715 1720 1725Val Asp Ala Gly Pro Ala Arg Thr Gly Arg Leu Val Val Val Val1730 1735 1740His His Leu Ala Val Asp Gly Met Ser Trp Arg Ile Leu Val Pro1745 1750 1755
Asp Leu Arg Leu Ala Cys Glu Ala Val Ala Glu Gly Arg Asp Pro1760 1765 1770Val Leu Glu Pro Val Trp Gly Ser Phe Arg Arg Trp Ala Ala Leu1775 1780 1785Leu Glu Glu Ser Ala Leu Ser Arg Glu Arg Val Gly Glu Leu His1790 1795 1800Thr Trp Arg Thr Ile Val Asp Gln Glu Asp Arg Pro Val Gly Arg1805 1810 1815Arg Arg Leu Ser Ala Gly Asp Ala Ala Gly Gly Val Arg Ser Arg1820 1825 1830Ser Trp Val Met Ser Gly Asp Glu Ala Ser Leu Leu Val Gly Lys1835 1840 1845Val Pro Val Ala Phe His Cys Gly Val His Glu Val Leu Leu Ala1850 1855 1860Gly Leu Ala Gly Ala Val Ala Arg Trp His Gly Asp Asp Gly Val1865 1870 1875Leu Val Asp Val Glu Gly His Gly Arg His Pro Ala Glu Gly Met1880 1885 1890Asp Leu Ser Arg Thr Val Gly Trp Phe Thr Ser Met His Pro Val1895 1900 1905Arg Leu Asp Val Ala Gly Ile Glu Leu Ala Ala Val Pro Ala Gly1910 1915 1920
Gly Arg Ala Ala Gly Gln Leu Leu Lys Ala Val Lys Glu Gln Ser1925 1930 1935Arg Ala Ala Pro Gly Asp Gly Leu Gly Tyr Gly Leu Leu Arg His1940 1945 1950Leu Asn Pro Glu Thr Gly Pro Val Leu Ala Ala Leu Pro Ser Pro1955 1960 1965Gln Ile Gly Phe Asn Tyr Met Gly Arg Phe Val Thr Val Asp Gln1970 1975 1980Gly Gly Ala Arg Pro Trp Gln Pro Val Gly Gly Ile Gly Gly Ser1985 1990 1995Leu Asp Pro Gly Met Gly Leu Pro His Ala Leu Glu Val Asn Ala2000 2005 2010Ile Val His Asp Arg Leu Ala Gly Pro Glu Leu Val Leu Thr Val2015 2020 2025Asp Trp Arg Asp Asp Leu Leu Glu Glu Thr Asp Ile Glu Arg Leu2030 2035 2040Cys Gln Val Trp Leu Asp Met Leu Ser Gly Leu Ser Arg Gln Ala2045 2050 2055Glu Asp Pro Ser Ala Gly Gly His Thr Ala Ser Asp Phe Ala Leu2060 2065 2070Leu Asp Leu Asp Gln Asp Glu Ile Glu Gly Phe Glu Ala Ile Ala2075 2080 2085
Ala Glu Leu Ser Gly Gly Gln Thr Ser2090 2095<210>27<211>1063<212>PRT<213>野野村菌屬<400>27Met Asn Thr Pro Ser Thr Pro Ala Gly Ser Ala Leu Glu Glu Val Trp1 5 10 15Pro Leu Ser Pro Met Gln Glu Gly Ile Leu Tyr His Ala Ala Leu Asp20 25 30Glu Ala Pro Asp Leu Tyr Leu Ile Gln Gln Ser Gln Ile Ile Glu Gly35 40 45Pro Leu Asp Thr Glu Arg Phe Arg Leu Ala Trp Glu Ser Leu Leu Asn50 55 60Arg His Ala Ala Leu Arg Ala Cys Phe His Arg Arg Lys Ser Gly Glu65 70 75 80Ser Val Gln Leu Ile Pro Arg Lys Val Pro Leu Pro Trp Ser Glu Arg85 90 95Asp Leu Ser Gly Leu Ser Glu Glu Asp Ala Leu Ala Glu Ala Ser Val100 105 110Ile Ala Glu Lys Glu Arg Ala Thr Arg Phe Asp Pro Ala Lys Pro Pro115 120 125
Leu Leu Arg Gln Val Leu Ile Arg Phe Gly Pro Asp Lys His Cys Leu130 135 140Val Thr Thr Ser His His Leu Val Met Asp Gly Trp Ser Arg Ala Ile145 150 155 160Leu Glu Ser Glu Leu Leu Glu Leu Tyr Ala Ala Gly Gly Ala Glu Pro165 170 175Gly Leu Arg Pro Ala Gly Ser Tyr Arg Asp Tyr Leu Ala Trp Leu Glu180 185 190Arg Gln Asp Lys Glu Ala Ala Arg Ala Ala Trp Arg Ala Glu Leu Ala195 200 205Gly Ala Asp Arg Ser Thr Leu Gly Ile Pro Glu Ala Ser Arg Lys Thr210 215 220Gln Gly Gln Arg Val Arg Glu Val Leu Gly Tyr Ala Pro Asp Phe Thr225 230 235 240Ser Ala Leu Val Asp Phe Ala Arg Arg His Gly Leu Thr Leu Asn Thr245 250 255Leu Val Gln Gly Ala Trp Ala Leu Val Leu Ala Arg Leu Thr Arg Arg260 265 270Arg Asp Val Val Phe Gly Ala Val Val Ser Gly Arg Pro Ala Glu Val275 280 285Pro Gly Val Glu Gln Ala Val Gly Leu Phe Ile Asn Thr Val Pro Val290 295 300
Arg Val Arg Leu Asp Gly Gly Gln Pro Val Ile Gln Leu Leu Thr Glu305 310 315 320Leu Gln Glu Arg Gln Ser Thr Leu Ile Ser His Gln His Leu Gly Leu325 330 335Gln Glu Ile Gln Lys Leu Ser Gly Val Ser Phe Asp Thr Val Val Ser340 345 350Phe Glu Asn Tyr Val Asp Pro Gly Ala Gly Pro Gly Ser Asp Arg Glu355 360 365Leu Arg Leu Arg Leu Lys Glu Phe His Gln Ser Ala Pro Tyr Ala Leu370 375 380Leu Leu Gly Ile Met Pro Gly Glu Ser Leu Gln Thr Asp Val Glu Tyr385 390 395 400Arg Pro Glu Leu Leu Asp Ala Arg Val Ala Lys Glu Ala Leu His Gly405 410 415Leu Ala Arg Val Leu Glu Arg Met Ile Ala Glu Pro Glu Thr Ala Val420 425 430Gly Arg Leu Asp Val Val Gly Asp Ala Gly Arg Glu Leu Val Val Glu435 440 445Arg Trp Asn Glu Thr Gly Asp Ala Ile Gly Ala Pro Ser Ala Val Asp450 455 460Leu Phe Arg Arg Gln Val Ala Arg Ala Pro Ala Ala Thr Ala Val Thr465 470 475 480
Ala Gly Asp Leu Ala Trp Ser Tyr Ala Glu Leu Asp Glu Arg Ser Gly485 490 495Arg Leu Ala Arg Ala Leu Thr Glu Arg Gly Val Arg Arg Gly Asp Arg500 505 510Val Gly Val Val Leu Gly Arg Ser Ala Glu Val Leu Ala Ala Trp Leu515 520 525Gly Val Trp Lys Ala Gly Ala Ala Phe Val Pro Val Asp Pro Asp Tyr530 535 540Pro Ala Asp Arg Val Ala Phe Met Leu Ala Asp Ser Ala Val Ala Met545 550 555 560Val Val Cys Gln Glu Ala Thr Ser Gly Val Val Pro Pro Gly Tyr Gln565 570 575Gln Leu Leu Val Asn Asp Ala Asp Asp Gly Glu Ala Ala Leu Val Pro580 585 590Ile Gly Ala Asp Asp Leu Ala Tyr Val Met Tyr Thr Ser Gly Ser Thr595 600 605Gly Thr Pro Lys Gly Val Ala Ile Pro His Gly Gly Val Ala Ala Leu610 615 620Ala Gly Asp Pro Gly Trp Gly Val Gly Pro Gly Asp Ala Val Leu Met625 630 635 640His Ala Pro His Thr Phe Asp Ala Ser Leu Tyr Asp Val Trp Val Pro645 650 655
Leu Val Ser Gly Ala Arg Val Met lle Thr Glu Pro Gly Val Val Asp660 665 670Ala Glu Arg Leu Ala Gly His Val Ala Asp Gly Leu Thr Ala Val Asn675 680 685Phe Thr Ala Gly His Phe Arg Ala Leu Ala Gln Glu Ser Pro Glu Ser690 695 700Phe Ser Gly Leu Arg Glu Val Ala Ala Gly Gly Asp Val Val Pro Leu705 710 715 720Asp Val Val Glu Arg Val Arg Arg Ala Cys Pro Arg Leu Arg Val Trp725 730 735His Thr Tyr Gly Pro Thr Glu Thr Thr Leu Cys Ala Thr Trp Lys Ala740 745 750Ile Glu Pro Gly Asp Glu Val Gly Pro Val Leu Pro Ile Gly Arg Ala755 760 765Leu Pro Gly Arg Arg Leu Tyr Val Leu Asp Ala Phe Leu Arg Pro Leu770 775 780Pro Pro Gly Ile Ala Gly Asp Leu Tyr Leu Ala Gly Ala Gly Val Ala785 790 795 800His Gly Tyr Leu Gly Arg Ala Ser Leu Thr Ala Glu Arg Phe Val Ala805 810 815Asp Pro Phe Val Ala Gly Glu Arg Met Tyr Arg Thr Gly Asp Leu Ala820 825 830
Tyr Trp Thr Gly Glu Gly Glu Leu Val Phe Ala Gly Arg Asp Asp Asp835 840 845Gln Val Lys Ile Arg Gly Tyr Arg Val Glu Pro Gly Glu Val Glu Ala850 855 860Val Leu Ala Gly Gln Pro Gly Val Asp Gln Ala Val Val Val Ala Arg865 870 875 880Glu Gly Arg Leu Leu Gly Tyr Val Val Ser Gly Gly Gly Val Asp Pro885 890 895Val Arg Leu Arg Glu Gly Val Ala Arg Val Leu Pro Glu Tyr Met Val900 905 910Pro Ala Ala Val Val Val Leu Gly Ala Val Pro Val Thr Ala Asn Gly915 920 925Lys Val Asp Arg Glu Ala Leu Pro Asp Pro Gly Phe Gly Gly Arg Val930 935 940Ser Gly Arg Glu Pro Arg Thr Glu Val Glu Arg Ala Leu Cys Gly Leu945 950 955 960Phe Ala Glu Val Leu Gly Leu Pro Gly Val Thr Ala Val Gly Pro Asp965 970 975Asp Ser Phe Phe Glu Leu Gly Gly Asp Ser Ile His Ser Val Lys Leu980 985 990Ala Ala Arg Ala Thr Arg Ala Gly Met Pro Phe Thr Val Val Glu Val995 1000 1005
Phe Glu His Lys Thr Pro Ala Gly Leu Ala Thr Ile Val Asp Val1010 1015 1020Gly Gly Glu Pro Ala Ala Gly Pro Ala Asp Pro Pro Ser Asp Ser1025 1030 1035Asp Leu Leu Gly Leu Ala Gln Asp Glu Ile Ala Glu Phe Glu Ala1040 1045 1050Glu Phe Asp Asp Glu Arg His Ser Leu Arg1055 1060<210>28<211>277<212>PRT<213>野野村菌屬<400>28Met Ile Ser Lys Ala Met His Gly Pro Ile Arg Pro Ala Arg Ala Asp1 5 10 15Thr Leu Leu Ala Ser Val Gly Glu Arg Gly Ile Leu Cys Asp Phe Tyr20 25 30Asp Glu Asn Ala Ser Glu Ile Phe Arg Asp Leu Glu Ala Asp Ala Gly35 40 45Gly Thr Glu Glu Ala His Gly Phe Ala Ala Leu Val Arg Pro Glu Ser50 55 60Gly Ala Ile Leu Glu Leu Gly Ala Gly Thr Gly Arg Leu Thr Ile Pro65 70 75 80Leu Leu Glu Leu Gly Trp Glu Val Thr Ala Leu Glu Leu Ser Thr Ala
85 90 95Met Leu Thr Thr Leu Arg Thr Arg Leu Ala Asp Ala Pro Ala Asp Leu100 105 110Arg Asp Arg Cys Thr Leu Val His Ala Asp Met Thr Ala Phe Lys Leu115 120 125Gly Glu Arg Phe Gly Thr Ala Ile Leu Ser Pro Ser Thr Ile Asp Leu130 135 140Leu Asp Asp Ala Asp Arg Pro Gly Leu Tyr Ser Ser Val Arg Glu His145 150 155 160Leu Arg Pro Gly Gly Arg Phe Leu Leu Gly Met Ala Asn Pro Asp Ala165 170 175Ser Gly Arg Gln Glu Pro Leu Glu Arg Thr Gln Glu Phe Thr Gly Arg180 185 190Ser Gly Arg Arg Tyr Val Leu His Ala Lys Val Tyr Pro Ser Glu Glu195 200 205Ile Arg Asp Val Thr Ile His Pro Ala Asp Glu Ser Ala Asp Pro Phe210 215 220Val Ile Cys Val Asn Arg Phe Arg Val Ile Thr Pro Asp Gln Ile Ala225 230 235 240Arg Glu Leu Glu Gln Ala Gly Phe Asp Val Val Ala Arg Thr Pro Leu245 250 255Pro Gly Val Arg Asn His Glu Leu Val Leu Glu Ala Gln Trp Gly Ser
260 265 270Val Glu Asp Ala His275<210>29<211>531<212>PRT<213>野野村菌屬<400>29Met Ser Glu Glu Leu Leu Phe Leu Arg Pro Asp Thr Ile Ile Glu Pro1 5 10 15Leu Ala Asn Arg Phe Tyr Ala Ser Met Tyr Ala Thr Ala Pro Val Thr20 25 30Ala Ala Met Asn Leu Ala Phe Arg Asn Leu Pro Met Leu Glu Ser Tyr35 40 45Leu Ala Ser Pro Glu Trp His Phe Ala Ala Ala Arg Asp Pro Lys Phe50 55 60Arg Gly Gly Phe Phe Val Asn Ile Glu Glu Gln Arg Lys Asn Glu Val65 70 75 80Glu Ala Leu Leu Ala Ala Ile Arg Arg Asp Ser Ala Asp Val Leu Arg85 90 95Phe Ala Glu Ala Ile Ala Glu Ala Glu Lys Ile Ile Arg Glu Glu Ala100 105 110Thr Gly Tyr Asp Leu Arg Pro Leu Tyr Pro Lys Leu Pro Pro Glu Leu115 120 125
Ser Gly Leu Val Glu Ile Ala Tyr Asp Thr Gly Asn Ala Ala Ser Leu130 135 140His Phe Leu Glu Pro Leu Ile Tyr Lys Ser Lys Ala Tyr Ala Glu Asp145 150 155 160Cys Gln Ser Val Gln Leu Ser Val Glu Thr Gly Ile Glu Arg Pro Phe165 170 175Val Met Ser Thr Pro Arg Leu Pro Ser Pro Asp Val Leu Glu Leu Asn180 185 190Ile Pro Phe Arg His Pro Gly Leu Glu Glu Leu Phe Leu Ser Arg Ile195 200 205Arg Pro Thr Thr Leu Ala Ala Leu Arg Glu Ala Leu Glu Leu Gly Asp210 215 220Ala Glu Ala Ala Arg Leu Ala Asp Leu Leu Val Pro Glu Pro Ser Leu225 230 235 240Ala Ser Asp Arg His Val Ala Ala Gly Ala Arg Ile Arg Tyr Trp Gly245 250 255His Ala Cys Leu Leu Met Gln Thr Pro Asp Val Ala Ile Met Thr Asp260 265 270Pro Phe Ile Ser Ala Asp Thr Asp Ala Thr Gly Arg Tyr Thr Tyr Asn275 280 285Asp Leu Pro Asp Arg Leu Asp Tyr Val Leu Ile Thr His Gly His Ser290 295 300
Asp His Leu Val Pro Glu Thr Leu Leu Gln Leu Arg Gly Arg Val Gly305 310 315 320Thr Phe Val Val Pro Arg Thr Ser Arg Gly Asn Leu Cys Asp Pro Ser325 330 335Leu Ala Leu Tyr Leu Arg Ser Phe Gly Leu Pro Ala Ile Glu Val Asp340 345 350Asp Phe Asp Glu Ile Glu Phe Pro Gly Gly Lys Ile Val Ser Thr Pro355 360 365Phe Phe Gly Glu His Ala Asp Leu Asp Ile Arg Ala Lys Ser Thr Tyr370 375 380Trp Ile Asn Leu Gly Gly Lys Ser Ile Trp Val Gly Ala Asp Ser Ser385 390 395 400Gly Leu Asp Pro Val Leu Tyr Arg His Ile Arg Arg His Leu Gly Ala405 410 415Val Asn Ile Ala Phe Leu Gly Met Glu Cys Asp Gly Ala Pro Leu Asn420 425 430Trp Gln Tyr Gln Pro Phe Ile Thr Lys Ala Leu Pro Lys Lys Met Ser435 440 445Asp Ser Arg Lys Met Ser Gly Ser Asn Ala Glu Gln Ala Gly Ala Ile450 455 460Val Thr Glu Leu Gly Ala Glu Glu Ala Tyr Ile Tyr Ala Met Gly Glu465 470 475 480
Glu Ser Trp Leu Gly His Val Met Ala Thr Ser Tyr Asn Glu Asp Ser485 490 495Tyr Gln Leu Gln Gln Ile Ala Glu Phe Glu Ala Trp Cys Ser Arg Lys500 505 510Gly Val Lys Ala Ala His Leu Leu Asp Gln His Glu Trp His Trp Ser515 520 525Ser Ser Arg530<210>30<211>523<212>PRT<213>野野村菌屬<400>30Met Thr Gly Gly Thr Gly Ala Asp Ala Ala Ser Ala Gly Ala Ser Ser1 5 10 15Thr Arg Pro Glu Leu Arg Gly Glu Arg Cys Leu Pro Pro Ala Gly Pro20 25 30Val Lys Val Thr Pro Asp Asp Pro Arg Tyr Leu Asn Leu Lys Leu Arg35 40 45Gly Ala Asn Ser Arg Phe Asn Gly Glu Pro Asp Tyr Ile His Leu Val50 55 60Gly Ser Thr Gln Gln Val Ala Asp Ala Val Glu Glu Thr Val Arg Thr65 70 75 80
Gly Lys Arg Val Ala Val Arg Ser Gly Gly His Cys Phe Glu Asp Phe85 90 95Val Asp Asn Pro Asp Val Lys Val Ile Ile Asp Met Ser Leu Leu Thr100 105 110Glu Ile Ala Tyr Asp Pro Ser Met Asn Ala Phe Leu Ile Glu Pro Gly115 120 125Asn Thr Leu Ser Glu Val Tyr Glu Lys Leu Tyr Leu Gly Trp Asn Val130 135 140Thr Ile Pro Gly Gly Val Cys Gly Gly Val Gly Val Gly Gly His Ile145 150 155 160Cys Gly Gly Gly Tyr Gly Pro Leu Ser Arg Gln Phe Gly Ser Val Val165 170 175Asp Tyr Leu Tyr Ala Val Glu Val Val Val Val Asn Lys Gln Gly Lys180 185 190Ala Arg Val Ile Val Ala Thr Arg Glu Arg Asp Asp Pro His His Asp195 200 205Leu Trp Trp Ala His Thr Gly Gly Gly Gly Gly Asn Phe Gly Val Val210 215 220Thr Lys Tyr Trp Met Arg Val Pro Glu Asp Val Gly Arg Asn Pro Glu225 230 235 240Arg Leu Leu Pro Lys Pro Pro Ala Thr Leu Leu Thr Ser Thr Val Thr245 250 255
Phe Asp Trp Ala Gly Met Thr Glu Ala Ala Phe Ser Arg Leu Leu Arg260 265 270Asn His Gly Glu Trp Tyr Glu Arg Asn Ser Gly Pro Asp Ser Pro Tyr275 280 285Thr Gly Leu Trp Ser Gln Leu Met Ile Gly Asn Glu Val Pro Gly Met290 295 300Gly Glu Ser Gly Phe Met Met Pro Ile Gln Val Asp Ala Thr Arg Pro305 310 315 320Asp Ala Arg Arg Leu Leu Asp Ala His Ile Glu Ala Val Ile Asp Gly325 330 335Val Pro Pro Ala Glu Val Pro Glu Pro Ile Glu Glu Arg Trp Leu Ala340 345 350Ser Thr Pro Gly Arg Gly Gly Arg Gly Pro Ala Ser Lys Thr Lys Ala355 360 365Gly Tyr Leu Arg Lys Arg Leu Thr Asp Arg Gln Ile Gln Ala Val Tyr370 375 380Glu Asn Met Thr His Met Asp Gly Ile Asp Tyr Gly Ala Val Trp Leu385 390 395 400Ile Gly Tyr Gly Gly Lys Val Asn Thr Val Asp Pro Ala Ala Thr Ala405 410 415Leu Pro Gln Arg Asp Ala Ile Leu Lys Val Asn Tyr Ile Thr Gly Trp420 425 430
Ala Asn Pro Gly Asn Glu Ala Lys His Leu Thr Trp Val Arg Lys Leu435 440 445Tyr Ala Asp Val Tyr Ala Glu Thr Gly Gly Val Pro Val Pro Asn Asp450 455 460Val Ser Asp Gly Ala Tyr Ilo Asn Tyr Pro Asp Ser Asp Leu Ala Asp465 470 475 480Pro Gly Leu Asn Thr Ser Gly Val Pro Trp His Asp Leu Tyr Tyr Lys485 490 495Gly Asn His Pro Arg Leu Arg Lys Val Lys Ala Ala Tyr Asp Pro Arg500 505 510Asn His Phe His His Ala Leu Ser Ile Arg Pro515 520<210>31<211>141<212>PRT<213>野野村菌屬<400>31Met Thr Ser Thr Ser Gly Arg His Leu Tyr His Arg Gln Val Arg Phe1 5 10 15Ser Asp Ile Asp Ala His Gly His Val Asn Asn Val Arg Phe Leu Glu20 25 30Tyr Leu Glu Asp Ala Trp Ile Ala Leu Tyr Leu Asp Asn Ala Gly Pro35 40 45
Pro Gln Glu Asp Arg Asp Gly Leu Pro Ala Val Gly Phe Ala Val Val50 55 60Arg His Glu Ile Phe Tyr Arg Arg Pro Leu Arg Phe Arg His Gly Ser65 70 75 80Val Arg Val Glu Ser Trp Val Thr Lys Val Asn Arg Val Thr Cys Glu85 90 95Met Ala Ala Gln Ile Cys Ser Asp Gly Glu Val Phe Val Glu Ala Arg100 105 110Ser Met Ile Met Gly Phe Asp Thr His Thr Ala Lys Pro Arg Arg Leu115 120 125Thr Leu His Glu Arg Thr Phe Leu Lys Arg Tyr Leu Arg130 135 140<210>32<211>372<212>PRT<213>野野村菌屬<400>32Met Gly Val Asp Val Ser Met Thr Thr Ser Ile Ala Ser Ala Glu Asp1 5 10 15Leu Ser Val Leu Thr Gly Leu Ser Glu Ile Thr Thr Phe Ala Gly Val20 25 30Gly Thr Ala Val Ser Ala Thr Ser Tyr Ser Gln Ala Glu Leu Leu Glu35 40 45Ile Leu Asp Ile Arg Asp Pro Arg Ile Arg Ser Leu Phe Leu Asn Ser
50 55 60Ala Ile Glu Arg Arg Phe Leu Ala Leu Pro Pro Gln Gly Arg Asp Gly65 70 75 80Glu Arg Val Ala Glu Pro Gln Gly Asp Leu Leu Asp Lys His Lys Lys85 90 95Leu Ala Val Asp Met Gly Cys Arg Ala Leu Glu Ser Cys Leu Lys Ser100 105 110Ala Gly Ala Thr Leu Ser Asp Val Arg His Leu Cys Cys Val Thr Ser115 120 125Thr Gly Phe Leu Thr Pro Gly Leu Ser Ala Leu Ile Ile Arg Glu Leu130 135 140Gly Leu Asp Pro His Cys Ser Arg Ala Asp Ile Val Gly Met Gly Cys145 150 155 160Asn Ala Gly Leu Asn Ala Leu Asn Leu Val Ala Gly Trp Ser Ala Ala165 170 175His Pro Gly Glu Leu Ala Val Val Leu Cys Ser Glu Ala Cys Ser Ala180 185 190Ala Tyr Ala Leu Asp Gly Thr Met Arg Thr Ala Val Val Asn Ser Leu195 200 205Phe Gly Asp Gly Ser Ala Ala Leu Ala Val Val Ser Gly Asp Gly Arg210 215 220Ala Ala Gly Pro Arg Val Leu Lys Phe Ala Ser Tyr Val Ile Thr Asp
225 230 235 240Ala Ile Glu Ala Met Arg Tyr Asp Trp Asp Arg Asp Gln Asp Arg Phe245 250 255Ser Phe Phe Leu Asp Pro Gln Ile Pro Tyr Val Val Gly Ala His Ala260 265 270Glu Ile Val Val Asp Lys Leu Leu Ser Gly Thr Gly Leu Arg Arg Ser275 280 285Asp Ile Gly His Trp Leu Val His Ser Gly Gly Lys Lys Val Ile Asp290 295 300Ala Ile Val Val Asn Leu Gly Leu Ser Arg His Asp Val Arg His Thr305 310 315 320Thr Ala Val Leu Arg Asp Tyr Gly Asn Leu Ser Ser Gly Ser Phe Leu325 330 335Phe Ser Tyr Glu Arg Leu Ala Gly Glu Gly Val Thr Arg Pro Gly Asp340 345 350Tyr Gly Val Leu Met Thr Met Gly Pro Gly Ser Thr Ile Glu Thr Ala355 360 365Leu Ile Gln Trp370<210>33<211>213<212>PRT<213>野野村菌屬
<400>33Met Asn Gly Glu Leu Glu Leu Ser Leu Asp Gly Thr Gln Ala Leu Thr1 5 10 15Ala Ser Val Glu Glu Leu Asn Gly Leu Cys Asp Arg Ala Glu Asp His20 25 30Arg Ala Pro Gly Pro Val Ile Val His Val Thr Gly Val Pro Arg Leu35 40 45Gly Trp Ser Lys Gly Leu Thr Val Gly Leu Val Ser Lys Trp Glu Arg50 55 60Val Val Arg Arg Phe Glu Arg Leu Gly Arg Leu Thr Val Ala Val Ala65 70 75 80Ser Gly Asp Cys Ala Gly Pro Ser Leu Asp Leu Leu Leu Ala Ala Asp85 90 95Val Arg Ile Ala Ala Pro Ala Thr Arg Leu Leu Pro Ser Trp Ala Gly100 105 110Gly Ala Ala Trp Pro Gly Met Ala Val Tyr Arg Leu Thr Gln Gln Ala115 120 125Gly Thr Gly Gly Ile Arg Arg Ala Val Leu Leu Gly Ala Pro Ile Asp130 135 140Ala Asp Arg Ala Leu Ala Leu Asn Leu Ile Asp Glu Val Ser Ala Asp145 150 155 160Pro Ala Ala Ser Leu Ala Gly Leu Ala Gly Ala Gly Asp Gly Ala Glu165 170 175
Leu Ala Ile Arg Arg Gln Leu Met Phe Glu Ala Ser Ser Thr Thr Phe180 185 190Glu Asp Ala Leu Gly Ala His Leu Ala Ala Val Asp Arg Ala Leu Arg195 200 205Arg Glu Thr Leu Ser210<210>34<211>434<212>PRT<213>野野村菌屬<400>34Met Thr Thr Asp Trp Pro Ala Leu Pro Pro Arg Ala Pro Leu Ala Leu1 5 10 15Trp Thr Leu Thr Ala Glu Ala Gln Arg Val Asp Asp Leu Leu Ala Gly20 25 30Leu Pro Glu Pro Pro Ala Arg Thr Ser Ala Gln Arg Asp Ala Ala Ala35 40 45Ser Ala Leu Asp Lys Val Arg Arg Met Arg Ala Asp Tyr Met Glu Ala50 55 60His Ala Glu Glu Ile Tyr Gly Glu Leu Thr Ser Gly Arg Thr Arg His65 70 75 80Leu Arg Ile Asp Glu Leu Val Arg Ala Ala Ala Arg Ala Tyr Pro Gly85 90 95
Leu Val Pro Thr Asp Glu Gln Met Ala Ala Glu Arg Ala Arg Pro Gln100 105 110Ala Glu Lys Glu Gly Arg Glu Ile Asp Gln Gly Ile Phe Leu Arg Gly115 120 125Val Leu Arg Ala Pro Lys Ala Gly Pro His Leu Leu Asp Ala Met Leu130 135 140Arg Pro Thr Pro Arg Ala Leu Glu Leu Leu Pro Glu Phe Ile Glu Ser145 150 155 160Gly Glu Val Arg Met Glu Ala Val Leu Leu Arg Arg Arg Asp Gly Val165 170 175Ala Tyr Leu Thr Leu Cys Arg Asp Asp Cys Leu Asn Ala Glu Asp Ala180 185 190Gln Gln Val Asp Asp Met Glu Thr Ala Val Asp Leu Ala Leu Leu Asp195 200 205Pro Gln Val Arg Val Gly Leu Leu Arg Gly Gly Glu Met Ser His Pro210 215 220Arg Tyr Arg Gly Arg Arg Val Phe Cys Ala Gly Val Asn Leu Lys Lys225 230 235 240Leu Ser Ser Gly Asp Ile Ser Leu Val Asp Phe Leu Leu Arg Arg Glu245 250 255Leu Gly Tyr Ile His Lys Ile Val Arg Gly Val Tyr Thr Asp Gly Ser260 265 270
Trp His Ser Lys Leu Thr Asp Lys Pro Trp Met Ala Val Val Asp Ser275 280 285Phe Ala Ile Gly Gly Gly Ala Gln Leu Leu Leu Val Phe Asp Gln Val290 295 300Leu Ala Ala Ser Asp Ser Tyr Ile Ser Leu Pro Ala Ala Thr Glu Gly305 310 315 320Ile Ile Pro Gly Val Ala Asn Tyr Arg Leu Thr Arg Phe Thr Gly Pro325 330 335Arg Ala Ala Arg Gln Met Ile Leu Gly Gly Arg Arg Ile Arg Ala Asp340 345 350Glu Pro Asp Ala Arg Leu Met Ile Asp Glu Val Val Pro Pro Glu Glu355 360 365Met Asp Ala Ala Ile Asp Arg Ala Leu Ala Arg Leu Asp Gly Asp Ala370 375 380Val Pro Ala Asn Arg Arg Met Leu Asn Leu Ala Glu Glu Pro Pro Glu385 390 395 400Ala Phe Gly Arg Tyr Leu Ala Glu Phe Ala Leu Gln Gln Ala Leu Arg405 410 415Ile Tyr Gly Arg Asp Val Ile Gly Lys Val Gly Arg Phe Ala Ala Gly420 425 430Ser Ala
<210>35<211>265<212>PRT<213>野野村菌屬<400>35Met Ser Glu Pro Arg Val Arg Tyr Glu Lys Lys Glu His Val Ala His1 5 10 15Val Thr Met Asn Arg Pro His Val Leu Asn Ala Met Asp Arg Arg Met20 25 30His Glu Glu Leu Ala Glu Ile Trp Asp Asp Val Glu Ala Asp Asp Asp35 40 45Val Arg Thr Val Val Leu Thr Gly Ala Gly Thr Arg Ala Phe Ser Val50 55 60Gly Gln Asp Leu Lys Glu Arg Ala Leu Leu Asp Glu Ala Gly Thr Gln65 70 75 80Ala Ser Thr Phe Gly Ser Arg Gly Gln Ala Gly His Pro Arg Leu Thr85 90 95Asp Arg Phe Thr Leu Ser Lys Pro Val Val Ala Arg Val His Gly Tyr100 105 110Ala Leu Gly Gly Gly Phe Glu Leu Val Leu Ala Cys Asp Leu Val Ile115 120 125Ala Ser Glu Glu Ala Val Phe Gly Leu Pro Glu Val Arg Leu Gly Leu130 135 140
Ile Pro Gly Ala Gly Gly Val Phe Arg Leu Pro Arg Gln Leu Pro Gln145 150 155 160Lys Val Ala Met Gly His Leu Leu Thr Gly Arg Arg Met Asp Ala Ala165 170 175Thr Ala Phe Arg Tyr Gly Leu Val Asn Glu Val Val Pro Leu Asp Glu180 185 190Leu Asp Arg Cys Val Ala Gly Trp Thr Asp Asp Leu Val Arg Ala Ala195 200 205Pro Leu Ser Val Arg Ala Ile Lys Glu Ala Ala Met Arg Ser Leu Asp210 215 220Ilo Pro Leu Glu Glu Ala Phe Thr Thr Ser Tyr Pro Trp Glu Glu Arg225 230 235 240Arg Arg Arg Ser Gly Asp Ala Ile Glu Gly Val Arg Ala Phe Val Glu245 250 255Lys Arg Asp Pro Val Trp Thr Ser Arg260 265<210>36<211>428<212>PRT<213>野野村菌屬<400>36Met Ile Pro Pro His Thr Leu Leu Val Phe Phe Val Gln Ala Ala Ala1 5 10 15Leu Leu Leu Leu Ala Leu Leu Leu Gly Arg Leu Ala Val Arg Leu Gly
20 25 30Leu Ala Ala Val Val Gly Glu Leu Cys Ala Gly Val Ile Leu Gly Pro35 40 45Ser Val Leu Gly Gln Val Ala Pro Gly Ala Glu Gln Trp Leu Phe Pro50 55 60Ser Pro Ser Ser His Met Leu Asp Ala Val Gly Gln Leu Gly Val Leu65 70 75 80Leu Leu Ile Gly Leu Thr Gly Ala His Leu Asp Leu Arg Leu Ile Arg85 90 95Arg Gln Gly Ala Thr Ala Val Arg Val Ser Ala Phe Gly Leu Val Val100 105 110Pro Met Ala Leu Gly Ile Gly Ala Gly Leu Leu Leu Pro Ala Glu Phe115 120 125Arg Gly Thr Gly Gly Ser Ala Val Phe Ala Leu Phe Leu Gly Val Thr130 135 140Met Cys Val Ser Ser Ile Pro Val Ile Ala Lys Thr Leu Met Asp Met145 150 155 160Asn Leu Leu His Arg Asn Val Gly Gln Leu Thr Leu Thr Ala Gly Met165 170 175Ile Asp Asp Ala Phe Gly Trp Val Leu Leu Ser Val Val Thr Ala Met180 185 190Ala Thr Ala Gly Ala Gly Ala Gly Thr Val Val Leu Ser Ile Ala Ser
195 200 205Leu Leu Gly Val Ile Val Phe Ser Val Val Ile Gly Arg Pro Ala Val210 215 220Arg Val Ala Leu Arg Thr Thr Glu Asp Gln Gly Val Ile Ala Gly Gln225 230 235 240Val Val Val Leu Val Leu Ala Ala Ala Ala Gly Thr His Ala Leu Gly245 250 255Leu Glu Pro Ile Phe Gly Ala Phe Val Ala Gly Leu Leu Val Ser Thr260 265 270Ala Met Pro Asn Pro Val Arg Leu Ala Pro Leu Arg Thr Val Thr Leu275 280 285Gly Val Leu Ala Pro Leu Tyr Phe Ala Thr Met Gly Leu Arg Val Asp290 295 300Leu Thr Ala Leu Ala Arg Pro Glu Val Leu Ala Val Gly Leu Leu Val305 310 315 320Leu Ala Leu Ala Ile Ile Gly Lys Phe Leu Gly Ala Phe Leu Gly Ala325 330 335Trp Thr Ser Arg Leu Ser Arg Trp Glu Ala Leu Ala Leu Gly Ala Gly340 345 350Met Asn Ala Arg Gly Val Ile Gln Met Ile Val Ala Thr Val Gly Leu355 360 365Arg Leu Gly Val Ile Thr Asp Glu Ile Phe Thr Ile Ile Ile Val Val
370 375 380Ala Val Ile Thr Ser Leu Leu Ala Pro Pro Leu Leu Arg Leu Ala Met385 390 395 400Thr Arg Ile Glu Ala Thr Ala Glu Glu Glu Ala Arg Leu Leu Ala Tyr405 410 415Gly Leu Arg Pro Gly Glu Ala Arg Glu Asp Val Arg420 425<210>37<211>251<212>PRT<213>野野村菌屬<400>37Met Ser Thr Trp Phe Arg Cys Phe Asp Arg Arg Pro Leu Ala Thr Met1 5 10 15Arg Leu Ile Cys Phe Pro His Ala Gly Gly Ser Ala Val Phe Tyr Arg20 25 30Asn Trp His Arg Leu Ala Ala Pro Glu Ile Glu Val His Ala Val Gln35 40 45Tyr Pro Gly Arg Ala Asp Arg Leu His Glu Pro Leu Val Gly Asp Ala50 55 60His Arg Leu Ala Glu Ser Val Gly Arg Glu Leu Arg Pro Leu Leu Asp65 70 75 80Arg Pro Val Ala Leu Phe Gly His Ser Met Gly Ser Leu Ile Ala Tyr85 90 95
Glu Thr Ala Arg Leu Leu Thr Gly Ser Gly Ile Pro Pro Ala His Leu100 105 110Phe Val Ser Gly Gly Val Ala Ala His Asp Arg Gly Arg Leu Ala His115 120 125Arg Val Ala Pro Ala Ser Glu Glu Ala Leu Ile Asp Arg Leu Arg Leu130 135 140Leu Gly Gly Thr Asp Ala Glu Ala Leu Ala Ser Ala Glu Phe Arg Ala145 150 155 160Phe Ala Leu Pro Tyr Val Arg Asn Asp Phe Gln Leu Val Gln Ser Tyr165 170 175Arg His Thr Pro Gly Pro Pro Leu Thr Val Pro Ile Thr Ala Phe Thr180 185 190Gly Ala Asp Asp Pro Val Val Arg Leu Asp Ala Val Ala Arg Trp Ala195 200 205Glu Leu Thr Ala Arg Glu Phe Ser Cys His Val Leu Pro Gly Gly His210 215 220Phe Phe Leu Gly His Glu Gln Ala Ala Leu Trp Ala His Leu His Ala225 230 235 240Arg Leu Gly Ile Ala Thr Pro Ala His Cys Gly245 250<210>38<211>428
<212>PRT<213>野野村菌屬<400>38Met Asp Ser His Val Leu Ala His Gln Leu Ser Lys Glu Thr Leu His1 5 10 15Gly Ser Leu Met Asp Pro Ala Ile Glu Ser Met Asn Leu Leu Asn Glu20 25 30Ile Ala Gly Asn Tyr Pro Asp Ala lle Ser Met Ala Ala Gly Arg Pro35 40 45Tyr Glu Glu Phe Phe Asp Val Gly Leu Ile His Asp Tyr Leu Glu Ala50 55 60Tyr Arg Asp His Leu Arg Asn Asp Arg Arg Met Asp Asp Ala Gly Ile65 70 75 80Ser Arg Met Leu Phe Gln Tyr Gly Thr Thr Lys Gly Ile Ile Ser Asp85 90 95Leu Val Ala Arg His Leu Ala Glu Asp Glu Asn Ile Glu Ala Asp Pro100 105 110Ala Ser Val Val Ile Thr Val Gly Phe Gln Glu Ala Met Phe Leu Val115 120 125Leu Arg Ala Leu Arg Ala Asn Glu Arg Asp Val Leu Leu Ala Pro Thr130 135 140Pro Thr Tyr Val Gly Leu Thr Gly Ala Ala Leu Leu Thr Asp Thr Pro145 150 155 160
Val Trp Pro Val Gln Ser Thr Asp Asn Gly Ile Asp Leu Asp His Leu165 170 175Glu His Gln Leu Lys Arg Ala Gln Asp Gln Gly Ala Arg Val Arg Ala180 185 190Cys Tyr Val Thr Pro Asn Phe Ala Asn Pro Thr Gly Thr Ser Met Asp195 200 205Leu Pro Ala Arg His Arg Leu Leu Glu Val Ala Ala Ala His Gly Ile210 215 220Leu Ile Leu Glu Asp Asn Ala Tyr Gly Leu Leu Gly Gln Asp Arg Leu225 230 235 240Pro Thr Leu Lys Ser Leu Asp His Ala Ala Thr Val Val Tyr Leu Gly245 250 255Ser Phe Ala Lys Thr Gly Met Pro Gly Ala Arg Val Gly Tyr Val Val260 265 270Ala Asp Gln His Val Ala Gly Gly Gly Ser Leu Ala Asp Glu Leu Ala275 280 285Lys Leu Lys Gly Met Leu Thr Val Asn Thr Ser Pro Ile Ala Gln Ala290 295 300Val Ile Ala Gly Lys Leu Leu Arg His Asp Phe Ser Leu Ala Arg Ala305 310 315 320Asn Ala Arg Glu Thr Ala Ile Tyr Gln Arg Asn Leu His Leu Thr Leu325 330 335
Asp Glu Leu Thr Arg Arg Leu Gly Ala Val Pro Gly Val Thr Trp Asn340 345 350Ala Pro Thr Gly Gly Phe Phe Ile Thr Val Thr Val Pro Phe Val Val355 360 365Asp Asp Glu Leu Leu Glu His Ala Ala Arg Asp His Gly Val Leu Phe370 375 380Thr Pro Met His His Phe Tyr Gly Gly Lys Asp Gly Phe Asn Gln Leu385 390 395 400Arg Leu Ser Ile Ser Leu Leu Asn Pro Gln Leu Ile Glu Glu Gly Val405 410 415Ser Arg Leu Ala Gly Leu Val Thr Ala Cys Leu Pro420 425<210>39<211>18<212>DNA<213>合成的<400>39atgcgcgtgt tgatctcg 18<210>40<211>18<212>DNA<213>合成的<400>40cggctgaccg cggcgaac 18
<210>41<211>20<212>DNA<213>合成的<400>41cgtgggggtg gatgtatcga20<210>42<211>17<212>DNA<213>合成的<400>42tcaccattgg atcagcg 17<210>43<211>18<212>DNA<400>43tcaggagacg aaccccgc 18<210>44<211>18<212>DNA<213>合成的<400>44gtgcacgaaa gtcccgtc 18<210>45<211>18<212>DNA<213>合成的<400>45atggactccc acgttctc 18
<210>46<211>18<212>DNA<213>合成的<400>46tcaggggaga catgcggt 18<210>47<211>29<212>DNA<213>合成的<400>47ttttgaattc tcaggcgatc cgtccgtct 29<210>48<211>31<212>DNA<213>合成的<400>48tttttctaga gcccggacac ccgggggctg a31<210>49<211>31<212>DNA<213>合成的<400>49tttttctaga agtcatggtg atgtgcgaca t31<210>50<211>30<212>DNA<213>合成的<400>50
ttttaagctt atgttgcagg acgccgaccg 30
權(quán)利要求
1.分離的核酸，該核酸包括選自下列的核苷酸序列a)dbv基因簇(SEQ ID NO1)，該基因簇編碼合成A40926所需的多肽；b)核苷酸序列，該核苷酸序列與dbv基因簇(SEQ ID NO1)編碼相同的多肽，而不同于dbv基因簇的核苷酸序列；c)dbv ORF 1至37中的任何核苷酸序列，該核苷酸序列編碼多肽SEQ ID NO2至38；d)核苷酸序列，該核苷酸序列與dbv ORF 1至37中任何一個(gè)ORF編碼相同的多肽(SEQ ID NO2至38)，而不同于所述ORF的核苷酸序列。
2.權(quán)利要求1的分離的核酸，該核酸包括選自下列的核苷酸序列e)dbv ORF 3至4、6至10、18至20、22至23、29至30、以及36(SEQ ID NO4至5、7至11、19至21、23至24、30至31、以及37)中任何一個(gè)核苷酸序列；f)核苷酸序列，該核苷酸序列與dbv ORF 3至4、6至10、18至20、22至23、29至30、以及36中任何一個(gè)編碼相同的多肽(SEQ IDNO4至5、7至11、19至21、23至24、30至31、以及37)，而不同于所述ORF的核苷酸序列；g)核苷酸序列，該核苷酸序列編碼的多肽與dbv ORF 3、6至9、18至20、22至23、29至30、以及36中的任何一個(gè)編碼的多肽(SEQID NO4、7至10、19至21、23至24、30至31、以及37)在氨基酸序列中具有至少80％、優(yōu)選86％、更優(yōu)選90％、最優(yōu)選95％或以上的同一性；h)核苷酸序列，該核苷酸序列編碼的多肽與dbv ORF 4和10中的任何一個(gè)編碼的多肽(SEQ ID NO5和11)在氨基酸序列中具有至少87％、優(yōu)選90％、更優(yōu)選95％或以上的同一性。
3.權(quán)利要求2的分離的核酸，包括核苷酸序列的組合，所述核苷酸序列編碼合成A40926的4-羥苯甘氨酸殘基所需的多肽，由dbv ORF1、2、5和37(SEQ ID NO2、3、6和38)組成；或編碼相同多肽的核苷酸序列，而不同于所述ORF核苷酸序列。
4.權(quán)利要求2的分離的核酸，包括核苷酸序列的組合，所述核苷酸序列編碼合成A40926的3，5-二羥苯甘氨酸殘基所需的多肽，由dbvORF 30至34、以及37(SEQ ID NO31至35、以及38)組成；或編碼相同多肽的核苷酸序列，而不同于所述ORF核苷酸序列。
5.權(quán)利要求2的分離的核酸，包括核苷酸序列的組合，所述核苷酸序列編碼合成A40926的七肽骨架所需的多肽，由dbv ORF 16、17、25、26和36(SEQ ID NO17至18、26至27、以及37)組成；或編碼相同多肽的核苷酸序列，而不同于所述ORF核苷酸序列。
6.權(quán)利要求2的分離的核酸，包括核苷酸序列，所述核苷酸序列編碼氯化A40926的氨基酸3和6的芳族殘基所需的多肽，由dbv ORF10(SEQ ID NO11)組成；或編碼相同多肽的核苷酸序列，而不同于所述ORF核苷酸序列。
7.權(quán)利要求2的分離的核酸，包括核苷酸序列，所述核苷酸序列編碼A40926的氨基酸6酪氨酸殘基的β-羥基化作用所需的多肽，由dbv ORF 28(SEQ ID NO29)組成；或編碼相同多肽的核苷酸序列，而不同于所述ORF核苷酸序列。
8.權(quán)利要求2的分離的核酸，包括核苷酸序列的組合，所述核苷酸序列編碼在A40926位置2和4、4和6、1和3、以及5和7處的氨基酸芳族殘基交聯(lián)所需的多肽，由dbv ORF 11至14(SEQ ID NO12至15)組成；或編碼相同多肽的核苷酸序列，而不同于所述ORF核苷酸序列。
9.權(quán)利要求2的分離的核酸，包括核苷酸序列的組合，所述核苷酸序列編碼A40926N-?；咸侨┧岚窔埢募映杉靶纬伤璧亩嚯?，由ORF 9、23和29(SEQ ID NO10、24和30)組成；或編碼相同多肽的核苷酸序列，而不同于所述ORF核苷酸序列。
10.權(quán)利要求2的分離的核酸，包括核苷酸序列，所述核苷酸序列編碼A40926甘露糖殘基的附著所需的多肽，由ORF 20(SEQ ID NO21)組成；或編碼相同多肽的核苷酸序列，而不同于所述ORF核苷酸序列。
11.權(quán)利要求2的分離的核酸，包括核苷酸序列，所述核苷酸序列編碼A40926的N-甲基化所需的多肽，由ORF 27(SEQ ID NO28)組成；或編碼相同多肽的核苷酸序列，而不同于所述ORF核苷酸序列。
12.權(quán)利要求2的分離的核酸，包括核苷酸序列的組合，所述核苷酸序列編碼A40926或一些其部分前體向細(xì)胞質(zhì)外的輸出、以及賦予生產(chǎn)性菌株對A40926的抗性所需的多肽，由ORF 7、18、19、24和35(SEQ ID NO8、19至20、25和36)組成；或編碼相同多肽的核苷酸序列，而不同于所述ORF核苷酸序列。
13.權(quán)利要求2的分離的核酸，包括核苷酸序列的組合，所述核苷酸序列編碼調(diào)節(jié)dbv基因簇的一個(gè)或多個(gè)基因表達(dá)所需的多肽，由ORF 3、4、6和22(SEQ ID NO4、5、7和23)組成；或編碼相同多肽的核苷酸序列，而不同于所述ORF核苷酸序列。
14.權(quán)利要求1的分離的核酸，包括由dbv基因簇組成的核苷酸序列，所述dbv基因簇編碼A40926的合成所需的多肽，其中，在編碼附著甘露糖殘基所需多肽的核苷酸序列中引入框內(nèi)缺失。
15.權(quán)利要求1的分離的核酸，包括攜帶dbv ORF 1至37(SEQ IDNO2至38)中至少一個(gè)的至少一個(gè)額外拷貝的核苷酸序列，或包括與所述dbvORF編碼的相同多肽的核苷酸序列，而不同于所述dbv ORF的核苷酸序列。
16.權(quán)利要求1至15中任何一項(xiàng)的分離的核酸，其核苷酸序列為DNA序列。
17.重組DNA載體，該載體包括如權(quán)利要求1至15中任何一項(xiàng)所定義的DNA序列。
18.權(quán)利要求17的重組載體，該載體為ESAC載體。
19.以權(quán)利要求17或18中任何一項(xiàng)的載體轉(zhuǎn)化的宿主細(xì)胞。
20.權(quán)利要求19的轉(zhuǎn)化的宿主細(xì)胞，該細(xì)胞屬于放線菌目，優(yōu)選屬于鏈孢囊菌科、小單孢菌科、假諾卡氏菌科或鏈霉菌科，更優(yōu)選屬于野野村菌屬、游動放線菌屬、擬無枝酸菌屬、鏈霉菌屬等。
21.通過能夠經(jīng)生物合成途徑產(chǎn)生A40926或其前體的微生物增加A40926生產(chǎn)的方法，所述方法包括a)以權(quán)利要求17的重組DNA載體轉(zhuǎn)化經(jīng)生物合成途徑產(chǎn)生A40926或A40926前體的微生物，其中，所述DNA載體編碼所述途徑中限速的活性的表達(dá)；b)在適于細(xì)胞生長、所述基因表達(dá)以及所述抗生素或抗生素前體產(chǎn)生的條件下，培養(yǎng)以所述載體轉(zhuǎn)化的微生物。
22.產(chǎn)生A40926或其前體或衍生物的轉(zhuǎn)化的微生物，其基因組中的A40926生物合成基因經(jīng)過權(quán)利要求15的核苷酸序列的插入而修飾。
23.產(chǎn)生A40926或其前體或衍生物的方法，該方法包括培養(yǎng)權(quán)利要求22的轉(zhuǎn)化的A40926生產(chǎn)性微生物。
24.轉(zhuǎn)化的A40926生產(chǎn)性微生物，其基因組中具有A40926生物合成基因，其中，至少一個(gè)選自dbv ORF 1至37(SEQ ID NO2至38)的A40926生物合成基因被破壞。
25.權(quán)利要求24的轉(zhuǎn)化的微生物，其中被破壞的生物合成基因是參與甘露糖殘基附著的基因。
26.產(chǎn)生A40926前體或衍生物的方法，該方法包括權(quán)利要求24的轉(zhuǎn)化的A40926生產(chǎn)性微生物。
27.產(chǎn)生不同于A40926或其前體的糖肽的方法，該方法在于a)(i)以重組DNA載體轉(zhuǎn)化微生物，該微生物通過生物合成途徑產(chǎn)生有別于A40926或其前體的糖肽或糖肽前體，所述載體或其部分包括權(quán)利要求1至13中任何一項(xiàng)的一個(gè)或多個(gè)核苷酸序列，編碼一個(gè)或多個(gè)修飾所述糖肽或糖肽前體的多肽的表達(dá)；以及(ii)在適于細(xì)胞生長、所述基因表達(dá)以及所述抗生素或抗生素前體產(chǎn)生的條件下，培養(yǎng)以所述載體轉(zhuǎn)化的微生物；或b)(i)以重組DNA載體轉(zhuǎn)化微生物，所述的載體包括權(quán)利要求1至13中任何一項(xiàng)的一個(gè)或多個(gè)核苷酸序列，編碼一個(gè)或多個(gè)修飾所述糖肽或糖肽前體的多肽(活性多肽)，所述微生物選自不產(chǎn)生糖肽或糖肽前體、并且可以有效表達(dá)引入的核苷酸序列的微生物；(ii)在適于活性多肽存在的條件下，制備所述微生物的細(xì)胞提取物或細(xì)胞級分，所述細(xì)胞提取物或細(xì)胞級分至少含有所述的活性多肽；以及(iii)將糖肽或糖肽前體添加到所述細(xì)胞提取物或細(xì)胞級分中，并在所述的活性多肽可以修飾該糖肽或糖肽前體的條件下溫育所述混合物。
28.分離的多肽，包括參與A40926生物合成途徑的多肽序列，該多肽序列選自a)由dbv ORF 1至37(SEQ ID NO2至38)中任何一項(xiàng)編碼的ORF多肽，或者與由dbv ORF 1至37(SEQ ID NO2至38)中任何一項(xiàng)編碼、優(yōu)選由dbv ORF 3至4、6至10、18至20、22至23、29至30(SEQ ID NO4至5、7至11、19至21、23至24、30至31、以及37)中任何一項(xiàng)編碼的ORF多肽氨基酸序列相同的多肽；b)多肽，該多肽與由dbv ORF 3、6至9、18至20、22至23、29至30、以及36(SEQ ID NO4、7至10、19至21、23至24、30至31、以及37)中任何一項(xiàng)編碼的多肽氨基酸序列具有至少80％、優(yōu)選86％、更優(yōu)選90％、最優(yōu)選95％或以上的同一性；以及c)多肽，該多肽與由ORF 4和10(SEQ ID NO5和11)中任何一項(xiàng)編碼的多肽氨基酸序列具有至少87％、優(yōu)選90％、更優(yōu)選95％或以上的同一性。
29.分離的多肽，包括參與A40926生物合成途徑的多肽，選自由權(quán)利要求3至16中任何一項(xiàng)核酸編碼的多肽。
全文摘要
本發(fā)明涉及抗生素領(lǐng)域，更特別涉及編碼糖肽類抗生素A40926生物合成途徑的核酸分子的分離。公開內(nèi)容為參與A40926生產(chǎn)的基因產(chǎn)物的功能。本發(fā)明提供編碼A40926生產(chǎn)的全新生物合成基因、編碼的多肽、含有編碼所述多肽的核酸序列的重組載體、使用上述載體轉(zhuǎn)化的宿主細(xì)胞以及使用該轉(zhuǎn)化的宿主細(xì)胞產(chǎn)生糖肽類抗生素的方法，這些方法包括產(chǎn)生A40926、其前體、其衍生物或不同于A40926或其前體的被修飾糖肽的方法。
文檔編號C07K14/36GK1732263SQ200380107411
公開日2006年2月8日 申請日期2003年10月15日 優(yōu)先權(quán)日2002年10月23日
發(fā)明者S·董納迪奧, M·索斯奧, F·貝爾特梅提 申請人:維柯龍藥品公司