CN107868789A - 可利霉素生物合成基因簇 - Google Patents

可利霉素生物合成基因簇 Download PDF

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CN107868789A
CN107868789A CN201711008720.2A CN201711008720A CN107868789A CN 107868789 A CN107868789 A CN 107868789A CN 201711008720 A CN201711008720 A CN 201711008720A CN 107868789 A CN107868789 A CN 107868789A
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王以光
姜洋
赵小峰
赫卫清
戴剑漉
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Shenyang Fu Yang Pharmaceutical Technology Co Ltd
Shenyang Fuyang Pharmaceutical Technology Co Ltd
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Abstract

本发明提供了可利霉素生物合成基因簇，含有的基因至少包括聚酮合酶基因5个(orf10‑14)，与糖基合成相关的orf有16个(9、16‑22、24、26、28、29、33‑35、41)，与糖基转移相关的6个orf(7、8、30‑32、40)中的至少5个，此外，还含有外源引入的碳霉糖4”‑O‑异戊酰转移酶基因orf44。通过基因簇序列信息和结构分析，可以进一步对其产生菌进行遗传操作，获得新型、更有效的抗生素，如通过基因操作来改变其PKS合成模块式结构、进行内酯环后修饰的改变、糖基因的置换或修饰，创造新的大环内酯类抗生素，也可以通过对抗性基因或调节基因的遗传操作，提高抗生素的产量。所提供的基因及其蛋白质、抗体，也可用以筛选和发展可用于医药、工业、农业的化合物或蛋白。

Description

可利霉素生物合成基因簇
本申请是中国专利申请201511028754.9的分案申请。
原申请日：2015.12.31
原申请号：201511028754.9
原申请发明创造名称：可利霉素生物合成基因簇
技术领域：
本发明属于微生物基因资源和基因工程领域，具体涉及基因工程抗生素生物合成基因簇的克隆、分析、功能研究及其应用。
技术背景：
可利霉素曾用名生技霉素、必特螺旋霉素，是利用合成生物学技术研制的16元环大环内酯类抗生素[专利号：ZL971044406、ZL 021487715]，是以4”-O-异戊酰螺旋霉素Ⅲ、Ⅱ、Ⅰ为主组分的在4”-位羟基多种酰基化的螺旋霉素，其中Ⅲ组分约占30％以上、Ⅱ组分25％左右，Ⅰ组分不超过10％。
可利霉素结构式
异戊酰螺旋霉素Ⅲ：R＝COCH2CH3 R′＝COCH2CH(CH3)2
异戊酰螺旋霉素Ⅱ：R＝COCH3 R′＝COCH2CH(CH3)2
异戊酰螺旋霉素Ⅰ：R＝H R′＝COCH2CH(CH3)2
可利霉素对革兰氏阳性菌有较强的活性，对红霉素和β-内酰胺类抗生素耐药菌、流感杆菌、淋球菌、军团菌、脆弱拟杆菌、产气荚膜梭菌有抗菌活性。尤其对肺炎支原体、沙眼衣原体和肺炎衣原体具有较强的活性[余兰香等，四川生理科学杂志；1998,20(3),专利号：2003101224209]，有较好的抗生素后效应和抗生素亚抑菌浓度效应。其与同类药没有完全交叉耐药性。药代动力学研究表明，可利霉素有较高的亲脂性，在胞内抗菌活性强，口服吸收快，绝对生物利用度高，组织渗透性强，其组织浓度高于血浆浓度，组织分布广，消除半衰期长，在体内维持时间长[孙丽文等，中国药理学通报2000，16(6)：694-8；钟大放等，Jchromatography B.2003，791：45；史向国等，Asian Journal of Drug Metabolism andPharmacokinetics.2003，3(2)：134；史向国等，Chinese Chemical letter 2004,15:431；史向国等，Acta Pharmacologica Sinica,2004,25:1396]。药理、毒理及已完成的临床三期研究结果表明，可利霉素用于治疗呼吸道感染其疗效确切，不良反应率低，尤其对肝脏损害小，安全性好[林赴田等，第八次全国抗生素学术会议论文汇编1997,p.167；赵春燕等，中国抗生素杂志1998,23(4)：306；孙涛等，中国抗生素杂志2001，26(1)：49-51]。可利霉素是利用基因重组技术获得的基因工程菌发酵直接产物，制备工艺简便、可以有效地避免化学污染及节省能源。其口服制剂服用方便，每日只需服用一次，有利于提高患者的用药依从性，也便于进入基本医保药物系列。
可利霉素是利用基因重组技术，将碳霉素产生菌4”-O-异戊酰基转移酶基因在螺旋霉素产生菌(Streptomyces spiramyceticus F21)中进行克隆表达，获得基因工程菌(Streptomyces spiramyceticus WSJ-1)的发酵产物。所述螺旋霉素产生菌(Streptomycesspiramyceticus F21)，是本实验室于1982年从中国甘肃永昌县土壤中分离得到的，该菌的形态培养特征、生理生化特征、细胞壁化学组成以及16S rRNA基因序列和5个看家基因蛋白水平在系统发育树分析中的地位，与国外报道的螺旋霉素产生菌Streptomycesambofaciens ATCC23877和已报道的链霉菌均无共同之处，故极可能为一株链霉菌新种[戴剑漉等，微生物学通报2012，39(4)：503-514]。
螺旋霉素产生菌Streptomyces ambofaciens ATCC23877中与螺旋霉素生物合成相关基因簇测序已经完成[Karray F.Microbiology 2007,153:4111-4122]，其他大环内酯类抗生素如阿维菌素、刀豆霉素、红霉素、查耳霉素、泰洛菌素和麦迪霉素生物合成基因簇序列也已有报道[Ikeda H.et al Nat.Biotechnol.2003,21(5):526-531、Haydock et alMicrobiology 2005,151,3161-3169；Oliynyk M.et al Nat.Biotechnol.2007,25(4):447-453；Wards L.et al Antimicrob.Agents&Chemotherapy 2004,48(12):4703-4712；Cundiffe E.et al Antonie Van Leeuwenhoek 2001,79(3-4):229-234；Midoh Naoki etal US patent 7070980]。大环内酯类抗生素生物合成基因簇全长约50-80kb，其共同特征是，由编码16元大环内酯环生物合成模块式结构的聚酮合酶(PKS)、聚酮合成延长单位相关酶、负责内酯环不同基团修饰的酶、糖基合成和转移相关酶的基因以及与抗性和调控功能相关基因等组成。大环内酯是由模块结构形式组成的PKS催化，以类似脂肪酸生物合成的方式，通过连续缩合反应将一些简单的羧酸分子催化形成的。每一个模块在聚酮链形成过程中只负责一步缩合反应，它至少包含一个β-酮酯酰合成酶(KS)结构域，一个酰基转移酶(AT)结构域和一个酰基载体蛋白(ACP)结构域。此外，它还可能包含一个β-酮酯酰还原酶(KR)结构域，一个脱水酶(DH)结构域和一个酯酰还原酶(ER)结构域，它们决定了加入延伸单位的还原步骤。同时，还需要硫酯酶(TE)结构域的作用，以催化聚酮链的环化与释放。最后，还要经过羟基化、甲基化、甲氧基化和酰基化等修饰步骤，形成多种多样的大环内酯类抗生素的结构。通常大环内酯均与不同数量的糖基(或糖胺基)相连，如可利霉素含有三个糖基，分别是福洛糖胺、碳霉糖胺和碳霉糖。它们是由糖基合成和转移相关酶负责。抗性基因赋予产生菌拮抗自身产生抗生素的能力，通常与ABC转运蛋白相关。调控功能相关的基因参与自身生物合成抗生素的调控。
通过基因簇序列信息和结构分析，可以进一步对其产生菌进行遗传操作，获得新型、更有效的抗生素，如通过基因操作来改变其PKS合成模块式结构、进行内酯环后修饰的改变、糖基因的置换或修饰，创造新的大环内酯类抗生素；也可以通过对抗性基因或调节基因的遗传操作，提高抗生素的产量。[Wilkinson B.et al Chem Biol 2000,7(2):111-117；Kalz L.et al Med Res Rev 1999,19(6):543-58；Goodman CD et al AntimicrobialAgents and
Chemotherapy,2013,57(2):907–913；Wang W et al Proc Natl Acad Sci U S A2014,111(15)：
5688-93；Stratigopoulos G et al Mol Microbiol.2004,54(5)：1326-34；Novakova R et al Folia Microbiol.2011,56(3):276-82]。
发明内容：
本发明提供了可利霉素生物合成连锁基因簇，共有44个基因开放阅读框(orf)，核苷酸序列全长89315bp(Seq.1)，其中含有5个编码聚酮合酶(orf10-14)，包括8个模块，37个结构域，以及与聚酮合成延长单位及修饰相关的orf有9个(1、4-6、15、36-39)，与糖基合成相关的orf有16个(9、16-22、24、26、28、29、33-35、41)，与糖基转移相关的orf有6个(7、8、30-32、40)。此外，还有与抗性相关的orf有2个(3和25)，与调控可能相关的orf有4个(2、23、27、42)。这些核苷酸序列分别选自Seq.1中的orf1(1-645)、orf2(1810-1208)、orf3(3133-2285)、orf4(3614-4840)、orf5(4846-5511)、orf6(7150-5801)、orf7(8444-7179)、orf8(9729-8482)、orf9(10543-9830)、orf10(16215-10543)、orf11(21076-16328)、orf12(32511-21124)、orf13(38599-32585)、orf14(52259-38643)、orf15(53099-54310)、orf16(54495-54845)、orf17(54842-56041)、orf18(56038-56946)、orf19(56930-57967)、orf20(57937-60174)、orf21(60836-61984)、orf22(62796-62077)、orf23(63633-65645)、orf24(67379-66318)、orf25(69004-67352)、orf26(69349-70650)、orf27(72156-70708)、orf28(72422-73462)、orf29(74601-73561)、orf30(74913-76160)、orf31(76218-77486)、orf32(77606-78781)、orf33(78783-79775)、orf34(79772-80779)、orf35(82055-80823)、orf36(83164-82052)、orf37(84400-83279)、orf38(84713-84393)、orf39(85576-84710)、orf40(85825-87042)、orf41(87094-87702)、orf42(89315-88143)。此外，还含有与Seq1.不连锁的外源基因Seq.2全长2337bp中的orf43(866-60)和orf44(2337-1174)。
本发明还提供了一个4’磷酸泛酰巯基乙胺基转移酶(PPT)的氨基酸序列，由Seq.3序列中的214个氨基酸组成，命名为IA-W1，编码基因的核苷酸序列选自Seq.1中的1-645碱基。
本发明还提供了一个TetR家族转录调控因子的氨基酸序列，由Seq.4序列中的200个氨基酸组成，命名为IA-W2，编码基因的核苷酸序列选自Seq.1中的1810-1208碱基。
本发明还提供了一个23S rRNA甲基转移酶的氨基酸序列，由Seq.5序列中的282个氨基酸组成，命名为IA-W3，编码基因的核苷酸序列选自Seq.1中的3133-2285碱基。
本发明还提供了一个3-O-酰基转移酶的氨基酸序列，由Seq.6序列中的408个氨基酸组成，命名为IA-W4，编码基因的核苷酸序列选自Seq.1中的3614-4840碱基。
本发明还提供了一个O-甲基转移酶的氨基酸序列，由Seq.7序列中的221个氨基酸组成，命名为IA-W5，编码基因的核苷酸序列选自Seq.1中的4846-5511碱基。
本发明还提供了一个巴豆酰基辅酶A还原酶的氨基酸序列，由Seq.8序列中449个氨基酸组成，命名为IA-W6，编码基因的核苷酸序列选自Seq.1中的7150-5801碱基。
本发明还提供了一个糖苷转移酶的氨基酸序列，由Seq.9序列中的421个氨基酸组成，命名为IA-W7，编码基因的核苷酸序列选自Seq.1中的8444-7179碱基。
本发明还提供了一个糖苷转移酶辅助蛋白的氨基酸序列，由Seq.10序列中的415个氨基酸组成，命名为IA-W8，编码基因的核苷酸序列选自Seq.1中的9729-8482碱基。
本发明还提供了一个NDP-氨基己糖N-二甲基转移酶的氨基酸序列，由Seq.11序列中的237个氨基酸组成，命名为IA-W9，编码基因的核苷酸序列选自Seq.1中的10543-9830碱基。
本发明还提供了一个包括酮基合成酶(KS)8-酰基转移酶(AT)8-酮基还原酶(KR)8-酰基载体蛋白结构域(ACP)8-链释放硫酯酶(TE)的聚酮合酶结构域氨基酸序列，由Seq.12序列中1890个氨基酸组成，命名为IA-W10，编码基因的核苷酸序列选自Seq.1中的16215-10543碱基。
本发明还提供了一个包括KS7-AT7-KR7-ACP7的聚酮合酶结构域氨基酸序列，由Seq.13序列中的1582个氨基酸组成，命名为IA-W11，编码基因的核苷酸序列选自Seq.1中的21076-16328碱基。
本发明还提供了一个包括KS5-AT5-KR5-ACP5-KS6-AT6-DH6(脱水酶)-ER6(烯酰基还原酶)-KR6-ACP6的聚酮合酶结构域氨基酸序列，由Seq.14序列中的3795个氨基酸组成，命名为IA-W12，编码基因的核苷酸序列选自Seq.1中的32511-21124碱基。
本发明还提供了一个包括KS4-AT4-DH4-KR4-ACP4的聚酮合酶结构域氨基酸序列，由Seq.15序列中的2004个氨基酸组成，命名为IA-W13，编码基因的核苷酸序列选自Seq.1中的38599-32585碱基。
本发明还提供了一个包KS1-AT1-ACP1-KS2-AT2-KR2-ACP2-KS3-AT3-DH3-KR3-ACP3的聚酮合酶结构域氨基酸序列，由Seq.16序列中的4538个氨基酸组成，命名为IA-W14，编码基因的核苷酸序列选自Seq.1中的52259-38643碱基。
本发明还提供了一个细胞色素P-450氧化酶的氨基酸序列，由Seq.17序列中的403个氨基酸组成，命名为IA-W15，编码基因的核苷酸序列选自Seq.1中的53099-54310碱基。
本发明还提供了一个NDP-己糖异构酶的氨基酸序列，由Seq.18序列中的116个氨基酸组成，命名为IA-W16，编码基因的核苷酸序列选自Seq.1中的54495-54845碱基。
本发明还提供了一个NDP-己糖氨基转移酶的氨基酸序列，由Seq.19序列中的399个氨基酸组成，命名为IA-W17，编码基因的核苷酸序列选自Seq.1中的54842-56041碱基。
本发明还提供了一个NDP-葡萄糖合酶的氨基酸序列，由Seq.20序列中的302个氨基酸组成，命名为IA-W18，编码基因的核苷酸序列选自Seq.1中的56038-56946碱基。
本发明还提供了一个NDP-葡萄糖-4,6脱水酶的氨基酸序列，由Seq.21序列中的345个氨基酸组成，命名为IA-W19，编码基因的核苷酸序列选自Seq.1中的56930-57967碱基。
本发明还提供了一个NDP-己糖2,3脱水酶/硫酯酶的氨基酸序列，由Seq.22序列中的745个氨基酸组成，命名为IA-W20，编码基因的核苷酸序列选自Seq.1中的57937-60174碱基。
本发明还提供了一个NDP-己糖氨基转移酶的氨基酸序列，由Seq.23序列中的382个氨基酸组成，命名为IA-W21，编码基因的核苷酸序列选自Seq.1中的60836-61984碱基。
本发明还提供了一个NDP-氨基己糖N二甲基转移酶的氨基酸序列，由Seq.24序列中的239个氨基酸组成，命名为IA-W22，编码基因的核苷酸序列选自Seq.1中的62796-62077碱基。
本发明还提供了一个转录调控因子的氨基酸序列，由Seq.25序列中的670个氨基酸组成，命名为IA-W23，编码基因的核苷酸序列选自Seq.1中的63633-65645碱基。
本发明还提供了一个NDP-氨基己糖异构酶的氨基酸序列，由Seq.26序列中的354个氨基酸组成，命名为IA-W24，编码基因的核苷酸序列选自Seq.1中的67379-66318碱基。
本发明还提供了一个ABC转运蛋白的氨基酸序列，由Seq.27序列中的550个氨基酸组成，命名为IA-W25，编码基因的核苷酸序列选自Seq.1中的69004-67352碱基。
本发明还提供了一个NDP-己糖脱水酶的氨基酸序列，由Seq.28序列中的433个氨基酸组成，命名为IA-W26，编码基因的核苷酸序列选自Seq.1中的69349-70650碱基。
本发明还提供了一个类似于GTP酶的氨基酸序列，由Seq.29序列中的482个氨基酸组成，命名为IA-W27，编码基因的核苷酸序列选自Seq.1中的72156-70708碱基。
本发明还提供了一个NDP-糖异构酶的氨基酸序列，由Seq.30序列中的346个氨基酸组成，命名为IA-W28，编码基因的核苷酸序列选自Seq.1中的72422-73462碱基。
本发明还提供了一个NDP-己糖酮基还原酶的氨基酸序列，由Seq.31序列中的346个氨基酸组成，命名为IA-W29，编码基因的核苷酸序列选自Seq.1中的74601-73561碱基。
本发明还提供了一个糖基转移酶辅助蛋白的氨基酸序列，由Seq.32序列中415个氨基酸组成，命名为IA-W30，编码基因的核苷酸序列选自Seq.1中的74913-76160碱基。
本发明还提供了一个糖基转移酶的氨基酸序列，由Seq.33序列中的422个氨基酸组成，命名为IA-W31，编码基因的核苷酸序列选自Seq.1中的76218-77486碱基。
本发明还提供了一个糖基转移酶的氨基酸序列，由Seq.34序列中的391个氨基酸组成，命名为IA-W32，编码基因的核苷酸序列选自Seq.1中的77606-78781碱基。
本发明还提供了一个NDP-己糖酮基还原酶的氨基酸序列，由Seq.35序列中的330个氨基酸组成，命名为IA-W33，编码基因的核苷酸序列选自Seq.1中的78783-79775碱基。
本发明还提供了一个NDP-己糖还原酶的氨基酸序列，Seq.36由序列中的335个氨基酸组成，命名为IA-W34，编码基因的核苷酸序列选自Seq.1中的79772-80779碱基。
本发明还提供了一个NDP-己糖甲基转移酶的氨基酸序列，由Seq.37序列中的410个氨基酸组成，命名为IA-W35，编码基因的核苷酸序列选自Seq.1中的82055-80823碱基。
本发明还提供了一个甲氧基丙二酰合成酶的氨基酸序列，由Seq.38序列中的370个氨基酸组成，命名为IA-W36，编码基因的核苷酸序列选自Seq.1中的83164-82052碱基。
本发明还提供了一个脱氢酶的氨基酸序列，由Seq.39序列中的373个氨基酸组成，命名为IA-W37，编码基因的核苷酸序列选自Seq.1中的84400-83279碱基。
本发明还提供了一个酰基携带蛋白的氨基酸序列，由Seq.40序列中的106个氨基酸组成，命名为IA-W38，编码基因的核苷酸序列选自Seq.1中的84713-84393碱基。
本发明还提供了一个甲氧基丙二酰脱氢酶的氨基酸序列，由Seq.41序列中的288个氨基酸组成，命名为IA-W39，编码基因的核苷酸序列选自Seq.1中的85576-84710碱基。
本发明还提供了一个糖基转移酶的氨基酸序列，由Seq.42序列中的405个氨基酸组成，命名为IA-W40，编码基因的核苷酸序列选自Seq.1中的85825-87042碱基。
本发明还提供了一个NDP-己糖异构酶的氨基酸序列，由Seq.43序列中的202个氨基酸组成，命名为IA-W41，编码基因的核苷酸序列选自Seq.1中的87094-87702碱基。
本发明还提供了一个转录调控因子蛋白的氨基酸序列，由Seq.44序列中的390个氨基酸组成，命名为IA-W42，编码基因的核苷酸序列选自Seq.1中的89315-88143碱基。
本发明还提供了外源插入的23S rRNA甲基化酶(硫链丝菌素thiostrepton、tsr抗性标记相关)氨基酸序列，由Seq.45序列中的269个氨基酸组成，命名为IA-W43，编码基因的核苷酸序列选自Seq.2中的866-57碱基。
本发明还提供了外源插入的4”碳霉糖苷异戊酰转移酶氨基酸序列，由Seq.46序列中的388个氨基酸组成，命名为IA-W44，编码基因的核苷酸序列选自Seq.2中的2337-1171碱基。
在获得可利霉素生物合成基因簇信息、通过基因阻断及同源性比较分析各基因编码蛋白可能功能基础上，进一步描述本发明整个可利霉素生物合成基因簇共44个基因，其基因簇结构如图1所示，具体为：
(1)聚酮合酶基因orf10-14，共5个基因；
(2)与聚酮合成延长单位及修饰相关的基因orf1、orf4-6、15、36-39，共9个基因；
(3)与糖基合成相关基因orf9、16-22、24、26、28、29、33-35、41，共16个基因；
(4)与糖基转移相关基因orf7、8、30-32、40，共6个基因；
(5)与抗性相关基因orf3和25，共2个基因；
(6)与生物合成调控相关基因orf2、23、27、42，共4个基因；
(7)外源引入的基因工程菌标记基因orf43(硫链丝菌素-thiostrepton、tsr抗性基因)和与之连锁的碳霉糖4”-O-异戊酰转移酶基因orf44，共2个基因。
Seq.1中有5个聚酮合酶基因(orf10-14)，核苷酸互补序列及其氨基酸序列，是可利霉素内酯环合成所必须的，其中，包含8个模块，37个结构域如图2所示。Orf14包含3个模块：加载结构域1以及模块2和3；加载模块域中，KS1、AT1和ACP1负责内酯环的起始合成，催化一个乙酸作为起始单位，模块2含有KS2、AT2、KR2和ACP2结构域；模块3含有KS3、AT3、DH3、KR3和ACP3结构域，负责引入另2个乙酸延伸单位，最终形成可利霉素C11-15碳链骨架。Orf13包括模块4，含有KS4、AT4、DH4、KR4、ACP4，负责第3个乙酸单位的延伸，最终形成可利霉素C9-10碳链骨架；Orf12包括模块5和6，模块5含有KS5-AT5-KR5-ACP5结构域，负责引入丙酸延伸单位；模块6含有KS6-AT6-DH6-KR6-ER6-KR6-ACP6结构域，负责引入丁酸延伸单位，最终形成可利霉素C5-C8碳链骨架。Orf11包括模块7，含有KS7-AT7-KR7-ACP7结构域，负责引入乙醇酸延伸单位，最终形成可利霉素C3-C4碳链骨架。Orf10包括模块8，含有KS8-AT8-KR8-ACP8-TE结构域，负责引入一个乙酸延伸单位，并在硫酯酶(TE)参与下完成碳链的环化及释放。可利霉素聚酮合酶基因结构示意图见图2。聚酮合酶基因各结构域及其氨基酸的位置如表1所示。
可利霉素聚酮合成延长单位及修饰相关基因orf1、orf4-6、15、36-39的核苷酸序列或互补序列及其相应的氨基酸序列：即IA-W1，编码PPT修饰聚酮体合成的酰基载体蛋白(ACP)，使之成为有活性的蛋白；IA-W4编码3-O-酰基转移酶,负责可利霉素3位羟基酰基化；IA-W5和IA-W6分别编码O-甲基化酶和巴豆酰辅酶A还原酶，负责聚酮体延长单位的供应；IA-W15编码P450细胞色素单氧化酶，负责聚酮体碳链的氧化；IA-W36-39分别编码甲氧基丙二酰合成酶、脱氢酶、酰基携带蛋白和甲氧基丙二酰脱氢酶，它们均参与聚酮体延长单位的合成与修饰。
表1聚酮合酶基因各结构域及其氨基酸的位置：
表1.1聚酮合酶基因IA-W14各结构域及其氨基酸的位置
表1.2聚酮合酶基因IA-W13各结构域及其氨基酸的位置
表1.3聚酮合酶基因IA-W12各结构域及其氨基酸的位置
表1.4聚酮合酶基因IA-W11各结构域及其氨基酸的位置
表1.5聚酮合酶基因IA-W10各结构域及其氨基酸的位置
与可利霉素糖基合成相关基因orf9、16-22、24、26、28、29、33-35和41，共12个基因，其中：orf18,19和28编码参与可利霉素基本糖基单元合成、脱水和异构化酶；orf9、20、21、24、26和29编码参与福洛糖胺合成中NDP-氨基己糖N-二甲基化、2,3脱水、氨基化、异构化、脱水和酮基还原酶；orf16、17、22编码参与碳霉糖胺NDP-氨基己糖异构化、氨基化和N-二甲基化酶；orf33、34、35和41编码碳霉糖NDP-氨基己糖酮基还原、甲基化和异构化酶。
与可利霉素糖基转移相关基因orf7、8、30-32、40，共6个基因，其中：orf7编码碳霉糖胺糖基化酶；orf8编码其糖基化辅助蛋白；orf31和32编码福洛糖胺糖基化酶；orf30编码其糖基化辅助蛋白；orf40编码碳霉糖糖基化酶。
与可利霉素抗性相关基因orf3和25，共2个基因，其中：orf3编码23S rRNA甲基化酶；orf25编码ABC转运蛋白，它们通过对核糖体RNA甲基化以及泵出机制，赋予可利霉素产生菌对自身产生抗生素的抗性。
与可利霉素生物合成调控相关基因orf 2、23、27、42，共4个基因，其中：orf2编码TetR家族转录调控抑制因子，可能参与可利霉素生物合成负调控；Orf23、42分别编码两个正调控转录因子，后者为途径特异正调控因子，对可利霉素的生物合成直接进行调控；orf27编码GTP酶，可能通过调控细胞的功能对可利霉素的生物合成进行调控。
与可利霉素生物合成相关，外源引入orf43和orf44，其中orf43编码与硫链丝菌素抗性相关的23S rRNA甲基化酶基因，该基因与碳霉糖4”-O-异戊酰转移酶基因orf44连锁，其抗性表达可以为可利霉素基因工程菌提供鉴别性标记。
本发明Seq.1、2的互补序列可依据DNA碱基互补原则随时得到。Seq.1、2的核苷酸序列或部分核苷酸序列，可以通过聚合酶链式反应(PCR)或用合适的限制性内切酶，酶切相应的DNA或使用其它合适的技术得到。通过本发明所提供的核苷酸序列或部分核苷酸序列，可利用聚合酶链式反应(PCR)的方法或包含本发明序列的DNA作为探针进行Southern杂交的方法，从其它生物体得到与可利霉素生物合成基因相似的基因。
本发明还提供了至少获得部分Seq.1、2中DNA序列构建重组DNA载体的途径。
本发明还提供了阻断可利霉素生物合成基因的途径，至少其中之一的基因包含有Seq.1中的核苷酸序列。
本发明所提供核苷酸序列或至少部分序列的克隆基因或DNA片段，可以通过阻断可利霉素生物合成的一个或几个步骤而得到新的可利霉素衍生物。包含DNA片段或基因，可以用来提高可利霉素或其衍生物的产量。
本发明所提供核苷酸序列或至少部分序列的克隆DNA，可用来从基因组文库中定位更多的文库质粒。这些文库质粒至少包含有本发明中的部分序列，也包含有可利霉素产生菌基因组中与之邻近区域的DNA。
本发明所提供的核苷酸序列可以被修饰或突变。其途径包括插入或置换、聚合酶链式反应、错误介导聚合酶链式反应、位点特异性突变、不同序列的重新连接或通过紫外线或化学试剂的突变。
本发明所提供的核苷酸序列，可以通过序列的不同部分或其它来源的同源序列进行直接进化(DNA shuffling)。
本发明的核苷酸序列或至少部分序列的片段或结构域或模块或基因，可以用来构建聚酮合酶库或聚酮合酶衍生库或组合库。通过缺失或失活来自相同或不同聚酮合酶系统的一个或多个聚酮合酶结构域、模块或基因，或增加一个或多个聚酮合酶结构域、模块或基因，产生新的聚酮化合物。
本发明的生物合成修饰基因、糖基合成及糖基转移酶基因的核苷酸序列，提供了通过缺失、置换或改造这些糖基合成、转移和修饰基因而得到可利霉素衍生物的途径。
本发明提供的核苷酸序列或至少部分序列的片段或结构域或模块或基因，可以通过加倍量来提高可利霉素或其衍生物的产量。
本发明的核苷酸序列或至少部分序列的克隆基因，可以通过合适的表达系统在外源宿主中表达，以得到修饰的或更高生物活性或更高产量的可利霉素。这些外源宿主包括链霉菌、大肠杆菌、芽孢杆菌、酵母、植物和动物等。
本发明的核苷酸序列或至少部分序列的基因或基因簇，可以在异源宿主中表达并通过DNA芯片技术，了解它们在宿主代谢链中的功能。
本发明的氨基酸序列或至少部分序列的多肽，可能在去除或替代某个或某些氨基酸之后仍有生物活性甚至有新的生物学活性，或者提高了产量或优化蛋白动力学特征或其它致力于得到的性质。通过合适的技术缺失，连接本发明中的氨基酸序列，可以得到新的蛋白或酶，进而产生新的或相关联的产物。
本发明所提供的氨基酸序列，可以用来分离需要的蛋白质并可用于抗体制备。
本发明所所述的氨基酸序列，提供了预测聚酮合酶三维结构的可能。
本发明所提供的基因及其蛋白质、抗体，也可用以筛选和发展用于医药、工业、农业的化合物或蛋白。
附图说明：
图1-可利霉素生物合成基因簇结构
图2-可利霉素聚酮合酶基因结构
图3-IA-W4 3-O-酰基转移酶基因阻断重组质粒的构建及双交换示意图
图4-IA-W42转录调控等基因阻断重组质粒的构建示意图
图5A-IA-W4 3-O-酰基转移酶基因阻断PCR验证
其中：1-原株；2、3、4-基因阻断变株；5-DNA markerIII
图5B-其他基因阻断的PCR验证
其中：III-DNA markerIII；C-原株；M-基因阻断变株
图6-IA-W4 3-O-酰基转移酶基因阻断变株发酵产物HPLC分析
其中：a-可利霉素对照品b-基因阻断变株发酵提取物
Ⅰ、Ⅱ、Ⅲ-分别为可利霉素主组分异戊酰螺旋霉素Ⅰ、Ⅱ、Ⅲ三个组分吸收峰
本发明通过基因阻断实验获得了突变菌株，并通过实验证明，基因阻断导致突变菌株产生可利霉素组分变化，或者不再产生可利霉素，从而提示，所获基因簇信息是与可利霉素生物合成相关。本发明外源引入的硫链丝菌素抗性标记基因(orf43)和与之连锁的碳霉糖4”-O-异戊酰转移酶基因(orf44)，是通过基因同源重组整合在染色体上的，本实验室已经研究证明其为可利霉素生物合成所必须的(1999年生物工程学报15卷2期171-176)。
实施方案：
以下所提供实施例，仅为帮助本领域技术人员更好地理解本发明，但不以任何方式限制本发明。
《实施例1》可利霉素产生菌(S.spiramyceticus)总DNA提取
R2YE培养基配方(g/100ml)：
加入微量元素溶液0.2ml，定容至100ml蒸馏水，pH6.5
微量元素溶液(g/100ml)：
15磅灭菌，121℃，20min
S.spiramyceticus菌种接种于25ml R2YE培养基，28℃摇床培养48h，转种于100mlR2YE培养基，28℃摇床培养24h，离心5000rpm 10-15min，收集菌体(约10g菌体)，主要按UPTECHTMlife science公司产品说明书操作。加入50ml的25mM的EDTA溶液震荡洗涤，离心，弃上清；用25ml溶菌酶溶液(10mg/ml，用10mM的pH8.0的Tris-HCl、2mM EDTA、1.2％TritonX-100配制，加入0.5ml 100mg/ml RNase)悬浮菌丝体，37℃培养约1-2h，培养细胞至半透明状；加入2.5ml蛋白酶K溶液，55℃30min；加入20ml 10％SDS溶液70℃10min；加入等体积无水乙醇，充分震荡；将溶液转移到DNA纯化柱，12000rpm离心1min；加入50ml含蛋白酶溶液洗柱，室温离心12000rpm 1min；再用50ml漂洗液洗柱二次，每次离心12000rpm 1min；加入5-10ml TE洗脱液，室温放置2-5min，12000rpm离心1min；收集溶液，-20℃保存总DNA。
《实施例2》通过基因阻断验证Seq.1基因信息的功能
选取基因簇两端IA-W1和IA-W42以及IA-W4、17、21、23和27等基因进行阻断，获得突变菌株，并通过实验证明，这些阻断菌株产生可利霉素能力发生变化，或者不再产生可利霉素。从而提示，所获得的基因簇信息是产生可利霉素所必须的。根据上述编码基因及其上下游序列设计引物，并插入合适的酶切位点，引物序列见表2。
表2基因阻断实验所设计使用的引物序列
经PCR扩增分别获得相应的同源基因片段，采用相应的酶切位点，并插入筛选标记抗性基因(阿普霉素-Am)连接到温敏型载体pKC1139[Bierman M.et al Gene1992；116(1):43-9]或大肠杆菌/链霉菌载体pGH112[优宝生物公司]，获得含有同源基因的重组质粒，经原生质体转化，转入可利霉素产生菌中，经培养后，进行单菌落分离，获得同源片段双交换基因阻断株。IA-W4 3-O-酰基转移酶基因阻断重组质粒构建及基因同源片段双交换示意见图3。IA-W42转录调控基因等阻断重组质粒构建示意见图4。
分别采用相应引物对阻断株及原株的总DNA进行PCR验证，如图5A和B所示。图5A结果表明，IA-W4基因阻断变株的编码基因orf4中缺失613bp。图5B中举例显示PCR验证结果，表明与原株相比，阻断变株相关编码基因由于插入筛选标记抗性基因，PCR产物长度呈现增加。
发酵实验及对产物的HPLC检测证明，IA-W4阻断变株不再产生4”-异戊酰螺旋霉素Ⅲ和Ⅱ，而是以4”-异戊酰螺旋霉素Ⅰ为主组分(图6)。证明本发明所提供Seq.1基因信息中的IA-W4 3-O-酰基转移酶基因，参与了可利霉素的生物合成，该基因的阻断，使变株丧失了可利霉素内酯环3位羟基被酰基化的功能。
其他基因阻断株经发酵实验及对产物抗菌活性和HPLC检测，证明阻断株已不再产生有活性的可利霉素。说明本发明所提供Seq.1基因簇参与可利霉素的生物合成。
《实施例3》可利霉素产生菌的基因转移及阻断株的筛选
3.1原生质体的制备：取新鲜的可利霉素产生菌斜面孢子接种于R2YE液体培养基中，28℃,220rpm摇瓶振荡培养48h，培养液以10％的转种量，转种于新鲜的补加了0.5％甘氨酸的R2YE液体培养基中，28℃振荡培养20h。取10ml菌液于离心管中，3000rpm离心收集菌丝体，沉淀用P-buffer
洗涤2次后用适量P-buffer悬浮，加入溶菌酶的P-buffer溶液(终浓度为2mg/ml)，混合均匀，于37℃水浴中保温30-45min，每隔10-15min振荡一次。用10×40的相差显微镜观察原生质体的形成情况，当镜检显示绝大部分菌丝已形成原生质体时，停止酶解。经脱脂棉过滤，滤液用P-buffer离心洗涤2次。最后用1ml P-buffer悬浮原生质体，分装EP管、100μl/管，-70℃保存备用。
3.2质粒DNA转化原生质体：取100μl原生质体，加入10μl质粒DNA溶液，轻弹管壁混匀，迅速加入400μl含25％PEG-1000(英国Koch-light公司产品)的P-buffer，吹吸混匀，室温放置5min，取200μl涂布于失水的R2YE平板上，28℃培养20h，以50μg/ml tsr的无菌水覆盖，28℃培养5～7天，挑取转化子。
3.3基因阻断变株的筛选
将转化子挑取在加有Tsr 50μg/ml培养基
去离子水配制，自然pH值，15磅灭菌，121℃，30min。
28℃培养5～7天，在不加药的培养基传四-五代，分离单孢子，将单孢子分别对应地在加阿普霉素(Am 50μg/ml)的培养基上进行筛选，筛选出在Am生长和不在Tsr生长的基因阻断株。挑取抗性标记表达稳定的阻断株，提取基因组DNA，采用实施例2中相应引物PCR扩增，根据产物大小及DNA测序判断基因阻断的正确性。
《实施例4》可利霉素产生菌及基因阻断株发酵、产物活性检测及鉴定
4.1发酵
菌株在斜面培养基(g/L)：
去离子水配制，自然pH值，15磅灭菌，121℃，30min。
28℃培养10-12d，菌株长好后挖块接种到装量30ml发酵培养基的100mL三角瓶，28℃振荡培养96-120h。
发酵培养基(g/L)：
去离子水配制，15磅灭菌，121℃，30min。
4.2发酵产物活性检测：
发酵液经离心取上清液稀释后，以枯草芽孢杆菌为检定菌，参考《中华人民共和国药典》2005年版(二部)乙酰螺旋霉素微生物检定法。采用杯碟法，用标准曲线法进行测定。
4.3发酵产物提取及鉴定：
发酵液室温3000rpm离心15min，上清液用1M NaOH调至pH 8.5后，用1/2体积乙酸乙酯萃取，取出乙酸乙酯相于平皿中吹干，挥干后溶于色谱纯甲醇，过滤后进样10-20μl。色谱议：岛津LC-10ATvp液相色谱议，二级管阵列检测器，色谱柱：Kromasil C18(4.5mm×150mm，5μm)，流动相：CH3OH/1％NaH2PO4(55:45)，检测波长：231nm，流速：1ml/min柱温：25℃。以可利霉素标准品作为对照(购自中国药品生物制品检定所)，对变株发酵产物进行鉴定。
本发明所述基因和蛋白见序列表。
序列表
<110> 沈阳福洋医药科技有限公司
<120> 可利霉素生物合成基因簇
<130> 2017
<160> 46
<170> SIPOSequenceListing 1.0
<210> 1
<211> 89315
<212> DNA
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 1
gtggagagcc gagggggcga cgaggccgac tatgccgcgc tccatcccga ggaagaggcg 60
gtggtggcac aggcggtgga caaacggcgc cgcgagttca ccgcggtgcg cgcctgcgcc 120
cgccgggcca tggagaagct cggcttcccg ccgcagccca tcctgccgag tgagcgcggc 180
gccccgcgtt ggccggaggg cctgctcggc agcatgaccc actgcgacgg ttaccgcgcc 240
gccgccctcg tccgcgccac cgacctggcc tccctcggca tcgatgccga accgcacggt 300
tcgctcccgg acggcgccct gcattccgtg gcgctccccg ccgagcggga gcgcctggcc 360
ctcctcgccg ccgggcagcc cggcgtccac tgggaccggc tgctgttcag cgcgaaggag 420
tccgtctaca aggcgtggtt cccgctgacc gggaagtggc tgggcttcga ggaggcgtac 480
atcgatctcc accaggattc cggaacggcg cagcacggcc gcttccgcgc cgaactgctc 540
gtccccggac cgctggtggg gggacgaagg atcaagcatt tcgaggggcg gtggatcgtc 600
cgcgagggcc tggtcaccac cgcattgacg gtcccccacc cctgatcccc ctcgcgcgcc 660
cgaaagccgg ctccgggtgg ggccagcccc gccgcccgcg gggcgtagcg ggattccggc 720
acggaccgtg cgaccgtacg ttcttccata gtggtcgggt acatccattc ccggctggca 780
gaacgacgtc gcccgcaccc agatctggca gtggctgcgc cacgggtcac cgaccgcgcg 840
acggtcctgg accttctgga cgcggaggtc gcggcgctgg gcgcggagta cccctggggc 900
ccggtggacg aggcccgcga cctcttggaa cgtaccgctc tggcacggga cttgccggac 960
ttcttcgcct cggtcggcta cgccctcacc tggtggagca cccctaccac cggggctgag 1020
gggccccggt ggcgccgccg gggccgaggg gcgcggcggc tgtggtcgag cagggcgcgg 1080
tacgggttgg tggatccgta ccgcgcctgc ttcgccttcc ccgtacgagc cgtcaccacg 1140
agcaccaccg acgaccgcgg gcaccgtcgg cgtcggcatc ggcatcggct caaccgcgtc 1200
tccggcctca gcgcggcgcc aggccgcgga gcgcgaggtc gacgagggcg tcggtgtatt 1260
cgtgcgtgag gggcccgtcg cccatcagcc agtgctgggc gacgggcccg gccagcatca 1320
gcacagcgat ccgcggatcg acgtcctgcg cgatctgacc ggccccccgg gcagagccca 1380
agcgctccag gcagagccgt aacgggggct ccaccaggcg cgccgtcagc tccttgccga 1440
gcgcagggtc ggctatgccc gcggcgacga gggcgcgggc gggcacgtcg taccccgggt 1500
cggtcatggt gtcgacagcg gaccggagaa cggccttgag atcggcctcc agatcgccgg 1560
tgtcgcggac agcgcccccg gcccgcgcga tgtcctcggt cagggagacg accgcgtccc 1620
ggaggatggc cgccttggag ggccaccggc ggtagatggt ctgtttgccg acgcctgccc 1680
tggcagcgac cccttcgatg gtcactctgg gatatccgac ctcgtgaacg agttccagcg 1740
tggcgcccag gatcgcacgg tgtgcgcggc gactgcggtg ggcggtttca ggtgcgcggt 1800
gggaggacat ggtccacagc atagacctcg acgaaccgat acgtatcgtc ttgacaagac 1860
gatacgtatc gtcgaagctc atggatgtac cgagacgcaa cgcctcggct caccgacgac 1920
aggagaagcc catggccaag ggagcaaaga agatgctggg cctcggcggc acccgctcga 1980
acctctcccg cagcgcgatg cgcggcggga actcgggcgg aattcccggc ggcggcatca 2040
gcccgcagga gcagaagcgg gagctgctgc gcaaactcaa ggaagcgcgg tccaccaagc 2100
agaccccctc gtcgtgaagg cctccacctg aggggaccgg ctgcgtatgg gctttcgtac 2160
gcagccggtt ccccctcccc gaggtccaca ggtccgagcg tccacaggtc cgggctgcgg 2220
gaacgccggc ccccggaata cgggctccga agtgccggaa ctcggagagc gggcccacga 2280
agcatcagca gtcggccgtc cgttggtgtg cgcggaacag cgcggtccac tccgggaccg 2340
tgaggtcctt gacccgatcg gcgggccgca cccccgcgcc gcgcacgaac tgggcgtgtc 2400
cgcggcgcag cacctttcgc gcggcctcgc ctatcgtcat ctggccggtg tcgaagacct 2460
gctgggtgaa ccgctgatag gcggtgcgct cacgccaggg cacgggcggc ttgcgatggg 2520
gggtcaccat caatgtctgg gtatcggcgc gcggcacggg gttgaactcc tgtcgcgaga 2580
aggccagccc tttctcaaac gcgtaccacg gctcccactg ggcgttgaag agatttccgc 2640
cccaggctcc ggtccgcttt cccacatact cgcgctgaag caggaacacg ccctggcgca 2700
tccggtccgg acccaactcc aggcaacgtc tcagtatctt ggtgccggag acaaagggca 2760
gattgccaat caaccggacc ggctgccctg gcaattgcag tgtcagaaag tcctcgttca 2820
ccaccgtgac atcgggcagc gattcggcgg ccagccgacg ggcccattgg gtgtcgattt 2880
ccaccgcgag taagggactt ccggtcgatg cgagcgcttt ggtcacccgg ccggatcccg 2940
cgcctatctc gacggtcaga aggtcattcg gcgaaccggg cgcgatggca tccgagctgt 3000
ccagctgagc ggagaacctg caggctgcag cggctgcccg gaagaaattc tgaccccatt 3060
ccctccgcgc gacgcagcgc gacgcagcgg gagcggaggc ggatcgcggc ggccgtgggg 3120
atttcgattt cacccgggcg acattaccaa cccctcaccc aatgatccat caacaaccgg 3180
tatgcccaac ggaattcggc catcctcgga cccgatcacg acatcggccg acgagccctt 3240
cgggaccgac tggtgactgc cgtgcgaacc ggcattgtcg gcgaatcatc cggacgatcc 3300
acgaattccg gggcattcga gcccggcccg gcgcgttacg gcccggcgcc tgtccgggcc 3360
gtaacggtgt tcccacgggc tcatggtgat tcaccacagt ctcgactgcg acggccaacg 3420
ccgtgagccg aacgggaatg aatcctggcc gacttcgtca ggttcaacgg gcgccgggcc 3480
ggcgcggccg gtggccgctg actgtgtcat ctccatgttg tcggccgaac gcaccgcgcc 3540
ccaggatgac ccagcccatt ccctgcggtc accccggcca cagtccccat cccgaaagag 3600
gagcgagaat ccagtgctcc atcgcgtcga tctgtcgtcg ctcaccggcc tccgctggta 3660
cgcggcgttg acagtattcg cctgccacat cgcccagcag ggcttcttcg ccgaccagca 3720
ggtcggcagc gcactgctgc acatcaccac gctcggctcg atggcggtct cggtcttctt 3780
catactgagt ggcttcgttc tggcgtggtc ggcccgcgac gaggactcca ccccgacttt 3840
ctggcggcgc cgcatcgcga agatctatcc gctgcacatc gtcacgttcg gcattgcggc 3900
cctgatcatc ttctccctct cggaaccggt ccttcccggt ggctccgtgt gggacggcct 3960
ggtgcccaat atcctgctgg tgcagtcctg gcttcccgac gcgtcccttg cggccagttt 4020
caacacgccg agctggtcgc tctcctgtga actcgccttc tatctgtcgt tcccgctgtg 4080
gtatcggctg gtgcggaaga ttccggtggg gcgactgtgg tggtgcgccg ccgggatcgc 4140
cacggccgtg atgtgtgtgc cgttcgtgac gggcctgctc ccggcgagcg aggaggcggc 4200
ccccgggatg ccgctcaacg aggtgtggtt cgcgtactgg ctgccgccgg tgcggatgct 4260
ggaattcgtc ctcggcatcg tgatggcgct gatcctgcgc gcaggcgtgt ggcggggccc 4320
acgggcgggg acctgcacgc tgctgctcgc cgcgagttac ggcctcaccc aggtggtgcc 4380
cccgatgttc actctcgccg cgtgctccat cgtgcccgcc gccctgctga tcaccgccct 4440
ggccgacgcc gatgtgcacg gtcggcgcac ggggctgcgc tccgcgatgc tggtgcggct 4500
gggccagtgg tccttcgcct tctatctggt ccatttcatg gtcatccgct acggacaccg 4560
actgatgggc ggcgagtcgg gatacgagcg ccagtggagc accccggccg cgatcgctct 4620
gtccctggcg atgctgatgg tcgcgatcct ggtcggcggg ctgctgcaca ccgtcgtcga 4680
gcagccctgc atgcgactgt tcggcagccg cacgccctcc gccgtcccga agcccggcac 4740
cgcccctgcg ccccgaagtt cgcccggccc cgacgtcacg ggcgtaccag tcgtcacgca 4800
cacgcccgac gtgacgaacg agctctcccc gaaaggatga tgagcgtggc agaccagacc 4860
gctctcagcc cagcgctgct ggaatacgcc cggagcgtcg cgctgcggga cgacggcctg 4920
ctgcgtgaac tgcacggggt aaccgcgggg cttcccgggg gccgggccat gcagatcatg 4980
cccgaggagg cacagttcct cgccctgctg atccggctcg tcggcgcccg gcgcgtgctg 5040
gagatcggca cgttcaccgg ctacagcacg ctgtgcatgg cgcgagcact gcccgccgac 5100
ggcagaatcg tcacctgtga catcagcgac aagtggcccg gcgtgggcgc cccgttctgg 5160
cggcgggccg gggtggactc cctgatcgac ctgcgcgtcg gcgacgccgc ccgaaccctc 5220
gccgagctgc gcgagcacga gggggacggc gtgttcgacc tggtcttcgt cgacgccgac 5280
aagaccgggt acccgcacta ctacgagcag gcgctggcgc tggtccgccc cggcgggctg 5340
gtggcgatcg acaacacgct gttcttcggc cgggtggccg atcccgccgt cgacgacgcc 5400
gacaccgtcg ccgtgcgcag gctcaacgac ctgctgcgcg acgacgaacg cgtggacatc 5460
gcgttgctga cgatcgccga cgggatcacg ctggcccgcc gacgggagtg agatcgcacg 5520
gcgtggggcg cagacgcaac gtcgtgaacg acggcggatt cgcgccaacg cccgcctgtg 5580
caaagcgact tcgcgacgtc tccgggacgc tgctggaatc ggctgccgcc gccggcctgc 5640
tacgacaggc cggcggcggc agcgtgtgcg gacctcgtgc ggtggccccg taccgcgacg 5700
aggggcccct gcaccggaag cagcacggca agcgtccgca cgccctcgga cgcatccgag 5760
ggcgtgcacc gggaacgccc cggagggccc gcccgaccgg tcagcggaac cggttgatgg 5820
cgtcgatgtg cttcgcgcgc ttctcctcgt cgcgcacgcc cagcccctcc gtcggggcca 5880
ggcacagcac gccgaccttg ccctgatgga ggttgctgtg cacgtcgtgc acggcgagcg 5940
cggtgtcggc cagcgggtag gtgcaggaga gcgtggggtg gatcttcccc ttggcgacga 6000
gtcggttcgc ctcccacgcc tcgcggtagt tggcgaagtg ggttccgacg atgcgcttga 6060
ggtgcatcca caggtagcgg ttgtcgaact cgtggcggaa gcccgaggtg gaggcgcacg 6120
tgacgatcgt gccgcccctg cgggtgacgt agacggacgc cccgaaggtc tcccggccgg 6180
ggtgttcgaa gacgatgtcg acgtcctcgc cgccggtcag ctccctgatg cggccgccga 6240
accgcttcca ctcccgcggg ttctgggtgt cctcgtcggt ccagaagcgg tagtcctcgg 6300
cggagcggtc gatgatggcc tcagcgccca tggcccggca cacctgagcc ttgcgctcgc 6360
tggagaccac gcagacggga ttggccccgc cggcgagggc gagctgggtg gcgtacgagc 6420
ccagaccacc gctggcgccc cagatcagca cgttgtcgcc ctgcttcatg ccggcgccgt 6480
tgcgggagac cagctgacgg tacgcggtgg agttgaccag accgggcgcg gccgcctcct 6540
cccaggtgag gtgggctgcc ttgggcatca gctggttgga cttgacgagg gccacctcgg 6600
ccaggccccc gaagttggtc tcgaagcccc agatccgctg ggccgggtcg agcatggtgt 6660
cgtcgtgccc gtcggcgctc tccaactcca ccgacagaca gtgcgccacg acctcgtcgc 6720
cgggcttcca gacgttcacc ccggggcccg tgcgcagcac cacgccggcc aggtcggagc 6780
cgaggatgtg gtagggcagg tcgtggcggg cggccgacgg cgatgtgcgg ccgtagcgct 6840
ccaggaagcc gaaggtcggc agcggctcga agatggacga ccagaccgtg ttgtagttga 6900
cggagctggc catcaccgcg atcagtgcct cgccgggccc cagttcgggc agcggcacct 6960
cgtcgacgcg cagcgacttg cgcgggtcct tgtccgtgct cgtcatgccg cggaacatgt 7020
cggtgtcctc tttgcggacg gtcacggccc ggaaggactc gggcaggcgc agcgccgcga 7080
tgtcctcggg ggtgcggtcc ggcgcggtga tcgcggcgag cagcgcgctc tgggcatggc 7140
tttcgggcat gggggacgga ctccgttcga tcgtttcgtc aggtcgcccg gtgcagggcg 7200
gtgaggcgct ccagggtggg gacgatcccg gcaggcgtgg ggtcggcgag catctcctcg 7260
ctgagccgcc gcgcgcctgc tttgatcgcg gggtcgtgca cggccgtgtg caccgcgtcg 7320
gccaggccgc gtgccgtgag ggtcgcggcg ggcaggtcga acccggcgga gaggcgctgg 7380
agttgctggg ccttgagcgg cgcgtcccac agcgagggca gcaggatctg cggcactccg 7440
tggagcaggg cggtggacca ggtgcccgct ccgccgtgat ggatgatcgc ggcgcagctc 7500
ggcagcagcg cgtcgagcgg cacgaagtcc accggtacga cgttgtcggg aaggacgccg 7560
aggcgctcgc gctgggaggc gtcgagggtg gccaccacct cgatgtccag ccgtcccagc 7620
gcctccagca gttcggagta ggagaccgcg tcgcggccgt aggtctcgcg ggcagacacc 7680
ccgagggtga ggcagacgcg ggggcgatcg ggcttcttgg cgagccaggg ttcgatcacg 7740
gagcgcccgt tgtagggcac atagcacatg ggcaccatgg tctgccccag gtcgagccgg 7800
gtgctgcggg gccccgggtc gatcacccag tggccgagca cgtcgcgttc gtcgaaggcg 7860
tacccgtatc ggtcgagcgt ccagccgagc cattcggcga tggggtcctc gcgcagttcc 7920
tccggtacct gctcgagcgc tgcgaggaag cgccggcggg agcgtccgat ggcatcgggg 7980
ccccagagga tgcgggcgtg ggcggcgccg caggcgcggg ccgcgaccgg ccccgcgtag 8040
gtccagggtt cccagacgac caggtcgggg cgccagccac gggcgaaatc gacgatctcg 8100
tccatcgtgg cggcgccgtt gaacggggcg aagcacaggg cggccatcat gctctgctgg 8160
ccgagcagat actcccaggt ggtctcctcc tcgctctcca cctcgccgaa ctcgaagccc 8220
cgctggtagg ggacgaggtc gctgcccatc tcggcgagca gctccgcggc gggtcggtcg 8280
tcgccgacgg ggacggcggt caggccggtg gaggtgatga cgtcggtgag cgagggcggg 8340
ctcgccaccc gtacctcgtg cccggctgcg cgcagcgccc aggccagggg caccaggctg 8400
tagtagtggg tgttgtgggc gagggaggtc agcaggacgc gcacggtgac tccggtctgg 8460
gacgggggtg tacgggcggg gtcatcccgg gtggacccgg aggcgggcgc aggcgcctac 8520
gaccggggaa cgcggccggg tcagcggcgc gccctcggcc cgcagtccgg gcaggcggcc 8580
ggccatgacc tggaccgcgg tggtggtggc caggcggatg agcgggaggg cgagcgccag 8640
gtgcggcccg tccgggccgc cgagcggctc cggccccggg gtctcccgtc cggcggcggc 8700
cagcaccaca atgtgctcgt cggcggcgat ccggcggccg ccgagttcga ggtcggtgtg 8760
cgcgaccctg ctctccagcc gggccggggg gcggtggcgc agcgtctgct cgacggccct 8820
cgcggcggcc ggggtccggc gggccctttc ccactccccc ggccggccca gcagccggtg 8880
caccgtgtgc gcgacggcgg tggcggccgg ctcgggggcg ccgatggcga ggaccagcgc 8940
gatgcgctcg acgtcgcggg gtgcgacgcc atcgcgcagg aggagggcga ggacgtcgtc 9000
gggccggggc ccgccgctct cgacggcccg cagcttctcc gcgacgagct ccgggaccag 9060
gtcggccagg gtccgcacgg cgtcggcgga ctcccgggcg acggccagga tctgcggggc 9120
cagccgggcg tcgagctggg gggcgcaggc ggcgagcgcc cgcgcggcgg cgtcgcggtc 9180
gcggtccggc actccgagga acccgagcac cagctcgacg gcgtacggcc gggcgacctc 9240
ggtgacgagg tcgaacccgg cgccaccggt tggcaggaga cggcggagca ctcggcgggc 9300
ggtggtgcgc gccgcgcagg gcgcctcggc cggggcgcaa cggttgagta cggggtcggc 9360
cagcgcccgc aggcgtacga gctccgcgcg ttcgtggcgg gggaacgcct cggcgagggg 9420
cagcagttcc tcgtccggac ggcggccggc ccggtccagc gtgccgaaac gtgggtcggc 9480
caggacagcc gccgccacct ctgggtccgc ggtcacccag gcgcccagca gttcgctgtg 9540
gaaccacggt ccggcggcgc agatttcccg ttcgagcggc tcggggtcgg agacggcgcg 9600
cagaatcagc gcgtacgggt cgccctgatt gcccgcgcac cagtgcgcgg cacgggtcag 9660
ctgaagccga cggccgagct cccgggtgcc cgcgctcgcg ggagccggct ccatggcaag 9720
gatgggcatg gcttcctctc gtcatctcgg atggcacgaa gtcggacggt acgaaggggg 9780
tggcgaaggc gtgtcgccac ggggaggtcc gcctcggcgg cgggcagctt cagcggcggg 9840
tgccgatgaa cagtccgcgg ccggaggggc cgccctcctg gtagaccacg tcgcagccgg 9900
cgcgctcgaa ggcggcttcg tagtcggcgc gcgggaacag ggtgatggcg tggtcctcgg 9960
tgaggtgacg gatgccgccg ccgggctcgg cgacgaggta gtgcacctcg atgcgggtgg 10020
cgttcccctc ccgcacagaa tgcgagaccc ggcagatggt gcgctcgccc gcctcggtga 10080
cgctggcgcc gacgtagccg ggggtgaagg agctggggaa ccaccagggt tcgacgacga 10140
tgacgccgcc cggttcgagg tggtcggtga aggaccgcag cgtgctgtcg agttcgtccg 10200
tggtccgcag gtggcctatg gagctgaaca tgcagatcac cgcgtcgaac cggcggccca 10260
gggcgaacga gcgcatgtct ccttcgtgga aggtgacgcc ggggttgcgg tcggtcgcga 10320
gggccagcat gtcgtgggag agctccaggc cctcgacgtg gtcgaagagg ccgtcgaggt 10380
ggcgcaggtg ctggccggtg ccgcaggcga cgtcgagcag tgaccgggtg tccgggcggt 10440
ggacgcgcac cagtgcggcg atctcctcgg cctcctgccg gtagtccttg cccttcccct 10500
cgtggaccag gtcgtagacg gccgcgatgt cgttggcgta catcagtgtt ctcctccggt 10560
gagcagggcg ggcggcccgg ccgggtgcgg gacggcctcc agccagtcgt gcaccacgga 10620
cgcggtgtgc cgcgcgtgtt cggtgagcat ggtgaagtgg ttgccgggca cgtcggcgac 10680
ggtccgggcg aacgggaccc gggagcgcca gtcgccctgt gcctcgccga cgggccactc 10740
gcgcaggggt tcggacgccc ggacgagcag gacgggggcg ttcagggcgg tgagccgggc 10800
gccgagcagc agccggtggt agccggccat ggcggtgagc cggtggtcct ccagggggac 10860
ggtgctgcgt tcgagggccc ggctgagcag gtcgtcgcgc cacacgccca tcgcgccggg 10920
gtcctcggga cggtagacgt ccatcagcac gacggccgtg gggccggtgc cgcgctcctc 10980
caggcgggcg gccagggcat gggcgacgtt cgcgccggcg gagtgaccgg cgagcgcgaa 11040
cggcttgccc gcggcgtgct ccaggaggac gtcggcctgg acgtcgagca gggcgtcgag 11100
ggatgcgggc agcggctccg cggggccgcc gaaaccggac agggggagaa cgaccgtctc 11160
ccggctgtcg cgcagccctt cggcgaaggg gacgtactcg ccggggccgg agccgaccgc 11220
ggtgccggcg cagcagtaca gcgtggggtg cgtcgtcggg ccggtcgcga ggagcaccgg 11280
cgcggggcgg gcggagccgg gctgttcccg ggagtaggcg ggccggaacg cggccaggga 11340
ggccatcagc tccacggcct cgcccgacct gctctgttcg acggcggcgc ggaaggaggc 11400
gagcagcccg ctctcggccg gtacggcgct ctcgtgacgg ccggtggccc cggcgtcagc 11460
gaggccggcc aggtggtgtg ccagtgcggt gggatcctcg tggtcgaaga cgagggtgct 11520
gggcaggtcg agcccggtgt cctcggccag tcggccgcgc agccgcaccg cggccagcga 11580
gtcgaagccg atgtcccgga agggggcctg tgcgtcgccc cggttctcct cggtgtggcc 11640
gaggaccgct gcgatgtggc ggagcaccag ttccagggcg agccgcggcc ggtcctcggg 11700
ccgcgcccgt acgaggtcgg gtgcggtggg ggtgtcgtcg gcgggctgcc cggcggcggc 11760
gagcgccgta cgggcgacgg ggatgccgga gatcaggggg ctggggcgga aggcggtgaa 11820
gccgggggcg aaccgttccc agtcgaggtc ggccacggtc accgtggcgt cgccgctgtc 11880
gacggcctgg tgcagggcgg tgagcgccgt ctccgggcgg aggggaacaa ggccatggcg 11940
ggcgaggtat ccctcggggg ccatctcgcc catgccgccg ccgtcccaga cgccccaggc 12000
gacggaggtg gcgggacggc cctgcgcacg acgccgctcc gccaacgcgt ccaaatgcgc 12060
attggccgcc gcatacaccg actgcccccc actcccccac accgccgcac ccgacgagaa 12120
caacacgaac acatccagat ccacacccgc cgtcaactcg tccagcaact cagcccccac 12180
cgccttaccc gccaacaccc ccgcagcctc cgccaacgac acctcaccca acgccgacac 12240
ctgagccaca cccgccgcat gaaacacccc acacaacggc acccccaacc cctccaccac 12300
acccaacaac cccaccaccg acgcacgatc cgccacatca cacgcaacga acgtcacctt 12360
cgcccccaac cccaccaact cccgctccaa ctccaccgcc cccggcgccc caccaccacg 12420
ccgacccgcc agcaccacat gctccgcacc cccacgcgcc aaccaccgcg ccacatgacc 12480
acccacacca cccaacccac ccgtcaccaa cacacacccc cgcggccgcc acgacctcga 12540
ggccgagggc acagcggcag gcagcaggcg gcggccgaac aaccccgacc cgcgaatcgc 12600
cacctggtcc tcaccgccgc ggccggagac gacagcggcc agacgccgcc agtcacgccc 12660
gcccggctcg gccggcagat ccaccagacc gccccactgc acaggcgcct ccaacgccgc 12720
cacccgccca agcccccaca cacgcgcacc catcgcacac ggcacctcac ccggcccgac 12780
cgccaccgca ccccgagtgg ccacccacag cggtgtctcc accgcggcat ccgccatcgc 12840
ctgcaccatc agcagcaccg ccgtcgtccc ctcgtccagc cccgggtgcc cggcgagcgt 12900
ggctccgccc gtgtcgggga gcagcagcac gccggccaag ctctccgggc tccgcgcgag 12960
ttcggccagc cgagcagcca gggcgtcccg gtccagtgcg tccgtccgcg gcgctccggc 13020
ggcctgcccg agcggccgca ccaggcggat cacttccgcg ccggccgcgc gcagcgcccg 13080
ctccgcggcg tccgcggagt ccgtgcactg cccatgctcg accatcagcc agcgatccga 13140
ggggctgaac ctgacagcgt ctggggcgat cgcctgccag gcgacgcggt agcgcagccc 13200
tgcggtctgc gcggtcgtgc ggcgccggtc gtgccaggcg gctaagtgcg gtaggacggc 13260
ctgcagttgg ctttcgattc ccgcaccgtc ggcgcccagt cgcgccgcgg ccgaggcagc 13320
gtcgcccgcg tgcaccgcgg cccacagggc gtcgtcctgc tctgcttccg cgacgggccc 13380
tgcggagggg gcggaggtcg cgggggcgac cgtgggcgag gcggcggtgg gggcgagcca 13440
gtagcggctg tgctggaagg cgtaggtggg caggtcggtc cggcgtgcgc ccgtaccgct 13500
gtagagcgcg gaccagtcga ggtccgcgcc gcgaacgaac gccctcgcag cggcccggag 13560
cgcggtgtcg ccctccggtc gcccgcggcg cagcgcgggg gcgaacacgg tgtcggcctc 13620
gtcggccagt gactcctccg ccatgccgga gaggactgcg tcggggccga gctcgatgaa 13680
ggtcgtggcg tcacgggccc gcgcggtgcg cactgcgtcg gcgaaacgca ccggctcccg 13740
cacctggcgg gtccagtagc cagggtccct cagctgggcg gcggtggcga gttcgccggt 13800
cacttcggag acgaccggca gccggggagc gtggtagtcg accgtttcgg cgatcacgcg 13860
gaagtcggcg agcatggcgt ccatgcgcgg cgagtggaag gcgtggctca cccgcaggcg 13920
cttggtacgg cggccccggg cggccagttc accggccgcc gccagtacgg ccgcttcgtc 13980
cccggaaagc acgagggcct gcggtccgtt gaccgcagcg atgaccgcgc caccggcgac 14040
gacgggctcc agcgcggcga cctcccgctc ggtggcctgc acggcggcca tcgcgccgcc 14100
ctcgggcagg gcccgcatca gccggccgcg tgccgcgacc agccgggcgg cgtcggccgc 14160
cgagaacact cccgccgcgt gagccgccac caggccgccg atcgagtgcc ccacgaggac 14220
gtccggcacc aggccccagc tctcgaagag ccggaacagt gcggtctcga ccgcgaacag 14280
ggcgggctgg gtgtagtcgg tacggtcgag cagtgtggcg tccggcgcgg agggttcggc 14340
gaacatcacc gacagcaaag ggcgttcgag gtgggcgtcg aactccgccg cgatctcgtc 14400
gagggcgtcg gcgaagacgg ggaacctcct gcggagctcc tgaccggcgc cgagccgctg 14460
ggcgccctga ccggaacaga ggaaggcgat cccgcggccg cgccgcgcga cgcctgtgac 14520
catgttctcc ggcgtccggc cggcggccag cgcggcgagg tcctcccggg ccgcccgggc 14580
gtcgtgcacc agcgcaaccg cccggtgttc cagggcttcc ctggtggtgg ccagggagta 14640
tccgaggtcg acggcagtgg tgagatcggc gtcggtgtcc tccgtgggcc cccggcgggc 14700
gagggcggcg agccggtcgg cctggccacg cagtgcctcc tccgagcggg cggagatcac 14760
ccagggaagg ggggtcgcgg ccgtgatgcg ggggtcaggg gcgggcccgt cgctgccgtc 14820
ggcctcactc ggaggttcct cgatgacgac atgggcgttc gtcccactga cgccgaaggc 14880
agagacagcc gcccgacgca cccggcccgc ccgccggggc caggaccggg cctcggtcag 14940
caactccacc gaccccgaac cccactcgac cttcgacgac ggagcatcca catgaagagt 15000
gcgaggcaac gacgaatgcc gcatcgcctc caccatcttg atcacaccac ccacacccgc 15060
agcggcctga gcatgcccga tgttcgactt caacgacccc aaccacaacg gatcacccac 15120
ccgctcacgc ccatacgtcg ccagcaacgc acccgcctcg atcggatccc ccaacgccgt 15180
acccgtgcca tgcgcctcca ccgcatccac atcccccggc gccagcccgg catcagccaa 15240
cgcctcacgg atcaccctcc gctgggccgg accactgggc gccgtcagac cgttactcgc 15300
accatcctga ttgaccgcac tcccccgcac caccgccagc acccgatgcc cataccgacg 15360
agcatccgac aaccgctcca ccaacaacac accaacaccc tcggcccaca cagtgccgtc 15420
cgcaccctcc gcaaacgcct tgcaccgccc gtccgacgcc agcccacgct gccgggagaa 15480
ctccacgaac accgtcgggt cgggcatgac cgctacgccc ccggccagcg cgagatcgca 15540
ctcgccccgc cgcagcgact gcaccgccag atgcaatgcc accaacgacg acgagcaggc 15600
cgtctcgatc gtcagcgccg ggccctccag gcccagggtg taggcgatac ggcccgacat 15660
caccgcgtcg gcgttgcccg tcagcagata gccctcggtg ccctcgggcg cccgcgcggt 15720
gtcggcgacg tatccggtgt gtgcggctcc gacgaacaca ccggtacggc tgccgcgcag 15780
cgacgcgggg acgaccccgg cccgctccag cgcctcccag gacgtctcca acagcagtcg 15840
ctgctgcggg tccatcacca gcgcctcgtt cggcgagacg ccgaagaagg cggcgtcgaa 15900
gtcgccgacg ccggtgagga agccgccctc gcggcagtag gtagtgccgg gcgtgtcggg 15960
gtcgggcgag tagacggcgg cttcgtccca gccgcggtcg gcggggaagc gggtgatcgc 16020
gtcgacgccg tccgcggcga gctcccacag gtcgtcgggg gtggtcacgc cgccggggta 16080
gcggcatgcc atgcccacga tcgcgacggg ctcgtgcgcg gcggccagga gctctcggtt 16140
gtgtcgacgc agccgctcgg tctccttgac cgaggtgcgc agcgcaccca gcacttcgtc 16200
catggacggt gacatcttcg gcttcctcgt ctgctcgctg tggggggcgt cggtggtacg 16260
gcgcactgcc ggtccgcacg cacccggtac gggccgctac cggccggcac acaccggtac 16320
gggggggtta ctgctctggt gctccgccgc gggtggtccc cgcttcggtg gacccgtcgt 16380
tcgccggcgc gccgtcggcc ggtccggtgc cgcccgtcgc cagccggacg agggcatccg 16440
cgtcgagctc gtcgatctcg gcgtcgtggg cagccggctc cggtgcgggt ggcgacgcgt 16500
cgttcccgcc tgtgccggcc gggcccggcg cgccgccccg ttcggggtcg ctcgcgccgg 16560
tcagctcctc cagcagcgcg ttgccgagcc ggtcaacggt ggggtggtcg aagatgatcg 16620
tcgcgggcag cacgagcccg gtcgcctcgg ccagccggcc gcgcacccgc accgcggcca 16680
gcgagtcgaa gccgagttcc ttgaaggcga cgtcgtggcc gatacggccg atcccgtcgt 16740
ggcccaggac ctctgccgcc accgtgcgga ccaggtcgac cagcaccttc gtgcgctcgc 16800
gcggggtgag tgcggcgtcg atgcggcggc gcagatcgtc cgacgcgccg acggtgggct 16860
gggccgcccg cagcgcgcgg acctggggga tgccggagat cagggggctg ggccggaagg 16920
cggtgaaccc ggtgacgaag tgctcccagt cgatgtcggc gaccgtgaca caggtgtcgt 16980
cctggttcag cgccgtgtgc agggcctcaa tgcccgactc cggtcgcatc ggggcgagtc 17040
cgcgctcggt gtagaagtcc ctgacgccgt cgcccgcgcc catgccgccg ccgtcccaca 17100
ggccccaggc gacggaggtg gcgggacggc cctgcgcacg acgccgctcc gccaacgcgt 17160
ccaaatgcgc attggccgcc gcatacaccg actgcccccc actcccccac accgccgcac 17220
ccgacgagaa caacacgaac acatccagat ccacacccgc cgtcaactcg tccagcaact 17280
cagcccccac cgccttaccc gccaacaccc ccgcagcctc cgccaacgac acctcaccca 17340
acgccgacac ctgagccaca cccgccgcat gaaacacccc acacaacggc acccccaacc 17400
cctccaccac acccaacaac cccaccaccg acgcacgatc cgccacatca cacgcaacga 17460
acgtcacctt cgcccccaaa cccaccaact cccgctccaa ctccaccgcc cccggcgccc 17520
caccaccacg ccgccccgcc agcaccacat gctccgcacc cccacgcgcc aaccaccgcg 17580
ccacatgacc acccacacca cccaacccac ccgtcaccaa cacacacccc cgcggccgcc 17640
acgaacgccg cctcacacca ggcgcagccg gcagcatgcg gcggccgaac agcccggatc 17700
cgcgaatcgc cacctggtcc tcaccgccgc ggccggagac gacagcggcc agacgccgcc 17760
agtcacgccc gcccggctcg gccggcagat ccaccagacc gccccactgc acaggcgcct 17820
ccaacgccgc cacccgccca agcccccaca cacgcgcacc catcgcacac ggcacctcac 17880
ccggcccgac cgccaccgca ccccgagtgg ccacccagac ccgggctttc ggtgcgccgt 17940
ccgtcacggc ctgggtcacg agcagcacgg cggccgtgcc cgggtcgagc gggaaggcat 18000
cggccggtgc ggcgtccgct gcccggccgg gtagcaccag tacgcccgcc aacccctgcg 18060
ggcccgcggc gagttcggcc agccgctcgg tgagggcgac gcgcgcgacc tcggccggat 18120
ccagcggaca acgctccacc accgcgccgg ccgtgccgag tgccgttgcc gcggcgtcgg 18180
cctcgtccgg cgcagcgccg gggagctcca ccagcagcca gcgcccggac ggcgcaccgg 18240
aaccgccggt ctccagggcg gtccaggtga cccggtagcg ccaggcggcg gactcgtcgg 18300
cgggggcctt ggcggtgcgc cggccgacgg cggtcggcag ccagaaccgg tcacgccgga 18360
aggcgtacgt gggcaggggt acacggcggg cgccggcgcc ttcgaagagg gggctccagt 18420
cgacccgtac tccatgggcg aacgcggcgc ccaccgaggc gcggaaccgg tccaggccgc 18480
cggagccgcg gtggagggtg gacagcgcgg tggcgtgcac gccctcggcc tcggcgatct 18540
cgtcgatcga ggagcccagc agggggtgcg ggcccatctc gacgaaggtg cggtggccct 18600
ggcgcagcag cgcccgcagg gtggactcga actccaccgg ttcgcgcgtg ttccggtacc 18660
agtacgcggc gtccagaccc tcagggtcgt gtgctccggc ggtcacggtg gagaagaacg 18720
gcagccgggc ggcggtcggc cggacgtcgg cgagcgtgcc gaggagctcg gtgcggaact 18780
gctccacctg cggcgagtgg ccggcgaagt cgacgccggc gaggggccag cgcagtaccc 18840
cgtcggcgga caaccggacg ccgaactcct ccagcgcctg cgcgtcaccg gccacggtga 18900
ccgaggcggg gccgttgacc gcggcgacag agatccgctc cgcccagggc tccagcagct 18960
cgcggacccg gtcggccggg gccatcacgg agaccatgcc gccgtttccg gccagtcgcc 19020
cccacaacct gctgcgctcg gcgatcaccc gggccgcgtc gtcgagggac agggcgcctg 19080
ccgcgtaggc ggcggcgacc tctccctggg agtggccgac gacggcggcg ggccgtacgc 19140
catgggcctc ccacagcgcc gcgagggaga ccatcatggt gaacagcgtc ggctggacca 19200
cgtccgcgcg gtcgatcggc ggggcgtcgg ggccgccgcg cagtacgtcg agcaccgacc 19260
agtcgagatg tgctgcgagc gcccgcgcgc actcctcggc cttgacgcgg aaggccgggg 19320
ccgactccag cagttcggcg cccatgccgg tccactggga gccctgcccc gggaagacga 19380
agacgggggg ccggccgctg cccgcctcgc cgacggcgac gtcgacgtcc ctcctgccct 19440
ccgccagcgc ggtcagccgg gcgatcagcg actcccggtc gtcggcgagg accgaggccc 19500
ggttcgagag tgcggcacga gtggtggcgg cggagtaggc ggcgtcggcg gcggtgatct 19560
cctcgtggtc ggccaggtgt gcggcgagcc tgcgggcctg ctcgcgcagg ggttgcgcac 19620
cggcggccga cagcgggagg acggtggtgg gggagacggg cggctcctcg ggttcctcgg 19680
gttcggcccg ggcggtcggc gcctcctcga caacgatgtg ggcgttggtg ccgctgatgc 19740
cgaacgagga gatcgcggcc cggcgcgggc cgtcggcccg ctgcggccag ggcctggcct 19800
ccgcgagcag ctccacggct cccgcacccc attcgatctt ggacgaggcg gtggtggcgt 19860
gcagggtgcg gggcagcgtg ccgtgccgca tcgcctccac catcttgatg acaccagcca 19920
caccggcggc ggcctgcgtg tgcccgatgt tggacttcag cgaccccaac cacagcgggt 19980
cgcccgcccg ttcgcgcccg taggtggcca tcagcgcact ggcttcgatc ggatcgccca 20040
gcggtgtgcc cgtgccgtgc gcctcgaccg cgtccacgtc ggcgggagtc agcccggcat 20100
cggccaacgc gtcgcggatc accttctgct gggccggacc gctgggcgcg gtcaggccgt 20160
tgctggcgcc gtcctggttg acggcgctgc cccgcaccac cgccagtacc gggtggccct 20220
tcttctgagc ctccgacagc cgctccacca gcagcattcc ggctccctcg gcggggccga 20280
agccgtcggc cgcctccgcg aaggccttgc agcggccgtc gggggcgagc ccgcgctgcc 20340
gggagaactg agtgaagagg gcgaagtcgg cgatgaccgt ggcgccgccg gccagtgcga 20400
ggtcgcactc gccccggcgc agcgactgca ctgccaggtg cagtgccacc agcgacgagg 20460
agcaggccgt gtcgatcgtc agcgccgggc cctccaggcc cagggcgtag gcgacccggc 20520
ccgcggtgaa gctgacgatt ccggccagga gctgggcctc cagctcggct tcgagcccct 20580
cgacgccctt ctggtagccg ctctcccacg ccccggcgaa cacgccggtg cggctgccgg 20640
ccagggactg ggggtcgagg ccggcccgct ccagtgcctc ccaggacgtc tccagcagca 20700
gccgctgctg gggatccatg gtgagcgcct cgttggggga gatcccgaag aggccggggt 20760
cgaaccggtc ggccccctgc acgaagcccc cctcgcggca gtacgtggtg ccgggcgtgt 20820
cggggtcggg cgagtacatc gcctccacgt cccagccgcg gtcggccggg gccaggctga 20880
cggcgtcggt cccggcgagc agcaggtccc acagttcgtc cgggctgcgg acgccgccgg 20940
gcagccggca ggccgccccg acgatcgcga tcggctcgtg ggcccgctcg tccagggtgc 21000
gcagctgctc ggtggcccgg tgcagctcgc ccgtcacgcg cttgaggtag gcgcgcagct 21060
tctcttcgtt cgccatggtg gtacttccct tcgaggactg gcgacggggc gccgaaccag 21120
tggtcacgac gcgccgtacc gctcgtcgat gaacgcgaag atctcgtcgt cgtcggcggt 21180
gctcaggacg tcggcgatgt cgtcgtcgac gccggccgcg ccgtcgtgca gggcgcgcca 21240
gcggtcggcg agtgcgtcca ggcgcagggc gacctcggcg cgggcgtcgg gggcgggtgc 21300
gaccgccgcg agaccttcgg gggtgagggc ggccagggcc tcctcgatcc ggtcgagttc 21360
ggacagcagc ggtgcggtgg tgggcggccg ctggggcgcc agcaggccgt cgaggtgcgc 21420
ggccagcgca gccggggtgg ggtggtcgaa caccagggtg gcggggagcc tgaccccggt 21480
gaccgcgccc atccggttgc gcagttccac ggccgtgagc gagtcgaatc cgacctcgcg 21540
gaacggccgg tcggagcgga cctccgcggc ggagccgtgg cccagcaccg cggccacgtg 21600
ttcgcttacc aagctgagca gctggtcgtg gcgttcttcg gcggagagcc tggccagccg 21660
ttcggcgagc ggctcgccgg tgtgccccgc gtccggtgtc gggtacgggc cggcggccgg 21720
ggttgcggac ccggcggccg gggcgggtcc gacgaggtcc gacagcagag cggggactgt 21780
tccggtggcg cgcagcgcgg ccgggtcgaa ccgcatgggg atctgcacgg cctcgtccac 21840
tcgcagggct gcgtcgaaca gtgcggcgcc cagggtcgct gacaggggag ggaagccgtt 21900
gcgggcgaag cgccgctgga ggctctcctg gtccagtccg ccggccatcc ggctggtgtc 21960
ggaccacagt ccccaggcca gcgacaccgc ggggaggccg agggcccgcc gccggacggc 22020
gagggcatcg agcgtggcgt tggccgctgc gtaattgccc tgcgccgggc tgcccagcag 22080
accggcgctg gaggagaaga ggacgaatgc cgacaggtcg aggtcgcggg tgagttcgtc 22140
caggtggacg gcggcctcca ccttgggacg cagcacgcgc cgcatccgct cgggggtgag 22200
cgtgggcagc acgccgtcgt cgaggacgcc ggcgctgtgc accaccgccg tcagcgggtg 22260
ctcggccggt acgccggcga gcagccggcg gaccgcgtcc gcgtcggaga cgtcgcaggc 22320
gacgacggtg gccgaggcgc ccagggcggt gaggtcggca accagttccg cggcgccctc 22380
gccgtccggg ccgcggcgtg cggcgatcag cagctggcgt acgccgtgat gggtcgccag 22440
gtggcgggcg atgcggccgc cgagggcccc ggtgccgccg gtgatgagca ccgtgccgta 22500
cgggtgccag gcgggcggca tggtcaggac gagctttccg gtgtgcctgg cctggctgat 22560
ggtgcgcagg gcgtccgcgg cccggcgcac gtcgtgggtg acgacgggca gtgggtgcag 22620
cactccggcg gcgaacagtt ccatcagttt ccgcagcagt cggccgagtt cgtcgggtcc 22680
ggcctcgttg aggtcgaacg cccggtagcg gactccgggg tggtcggcgc cgacctgctc 22740
ggggtcccgt acgtcggtct tccccagctc caggaaccgg ccgcccgggc ggagcagccc 22800
gagggaggcg tccacgaact ccttggtgag cgagttcaga acgacgtcgg cgcgggacgt 22860
gccgtccgta ccggcgaagg cggtggcgaa gtcgagggtg cgggaggagg cgaggtgttc 22920
gtcggtgatt cccatggcgc gcaggacgtc ccacttgccg gtgctcgcgg tggccagcac 22980
ctcggcgccg aggtggcggg cgatctgcac cgcggccatg ccgacgcctc cggcggcggc 23040
gtgcacgagc accttctccc ccggtcgcag gtccgccagg gtgaccagcc cgtagtaggc 23100
gctgaggaac accgcgggga ccgaggcggc ccgggcgtag gaccagccgt ccgggatcgg 23160
gacgagcagc cggtggtcgg ccacgcacac cgggcccagg ccgccgttcc acaggccgag 23220
cacccggtcg ccgggggcga cgccggtgac gccggggccg acctcgacga cggtgccggc 23280
gccctcggtg cccatttccg cctcgcacgg atacatgccg agggcgatga gggcatcgcg 23340
gaagttcacg cctgcggcgc gtacggcgac gcgcacttgg ccgtgctcca gcggggcctc 23400
cgcgtccggg gcgggcacca gcgcgaggcc gtcgagggtg aggtcggcgc ctcggccgag 23460
ccgccaggcg cccttctccg gcggggtgag cggcccgtcc gtgctgtcgg cggcccgctc 23520
cagccggggt acgtacaccc tcccggcacg caccgcggtc tgcggttcgc cggaggcgag 23580
ggcggtgggc agcgccctcg cggacgccgg gtcgtcgtcc aggtccacca gcaggaaccg 23640
gtcgggctcc tcggcctgcg cggagcgcag caggccccat gcggcggccg cggccgggtc 23700
gctcacctcg gcgtcgccgc gtacggcgac cgcgccgcgg gtggccacga ccaggcgggc 23760
gccttccggg gcgtccgggg ctgcgagccg gcgctggaca aggtccagca cctggcaggc 23820
gacggcgtgg gcgtcggcgg cgacatcgcc ggttccggtc ggcactccga acacgaaggc 23880
gtccggcgcc gcttcgccgg ccgcggtcgg cagcgggccg tccgggccga gtgcgtcggg 23940
caggtgtgcg tcggcggcct cggccaggcc cagcacgtcg ggccccgcga ccacccagcg 24000
caccgaggaa gcggcgccgg cgccgttgcc ggtacggagg ccggtgcccg agccgctggt 24060
gagctcccgc caggcgatgc ggaagagcgc gtcggcgccg accgggcggc cgcccaggag 24120
ctgctcgggg tcgaccggcc gcatgaggaa cgagtcgatc tcggcgaccg cccgtccctc 24180
ggtgtcggcg caccggatgc ggacggcgtc ctgggagacg ggcgagatgc gcacgtgcag 24240
ccgctcggct ccggtgcggt acagccggac gccgcgcagc gcgaagggca tccggatgcg 24300
gccgtcctca gggaagaagc cgcccaggct catggtctgc agcgccgcgt ccaacagcgc 24360
ggggtggatt ccgaaccgtg ccgcgtcgcc ctgggcctgg acgggcagcg cgacctccgc 24420
gtggatgtcg gagccggagc ggtgcgcgct caccagtccg cggaagaacg gcccgtagcc 24480
gtagccgagt tcggcgaaac gctcgtagaa gtcgccggtg tccagttgtt cggcgccggg 24540
cggcggggct gtcgccgagg cgtccggcac gtcggcggcg tcctccgcgg tgagcagccc 24600
ctcggcgtgc agggtccagt ctgcggcgcc ctcggcgcgg gcgtgcacgg cgaagcggcg 24660
ggcgtcgtct gcgcccgggg cgccgacgtt cagccgcagc cggacaccgc cggactcggg 24720
cagcgccagg ggtgcggcca gggtgagttc ctcgatccgg ccggtgccgg cctggcggcc 24780
ggcccagagg gccaggtcgg cgaacgcggc gcccggcagc agcgccgccc ccatcagtgc 24840
gtggtcggcc agccacgggg tggcgtcggt gcccaggcgc gcggtgtaca tctgagcgcc 24900
ggagtcgggc agttccacgc cgccgccgag cagcgggtgg tcggcggcgt ccaggccgag 24960
ggaggcgggg tcgtcgccac ggctggtggg gctgtaccag tagcgctcgc gctggaaggg 25020
gtaggtgggc agttccacat gacgcgagtc ggggccgaag atggcctccg cgtcgatctc 25080
cacgccgtgg gtgtaggcgc ggcagacggc gacggccagg cagcgggggc cgccctgacc 25140
gcgacgcagg gtgccgagaa ccgccgcgga ggcgccggcg tcgctgatcg tctcctggag 25200
ggagacggcc agcatggggt gcgggctcga ctccaggaac acgtcgtggc cgtcggcgat 25260
cagggcgcgg gtggccttct cgaactccac cggctcgcgc atgttgcggt accagtagtc 25320
ggcgttcagc tcggcggtgt cgagcagccc accggtgacc gtcgagtaga acgggatgtc 25380
ggaggatcgc ggcgcgaccg gggcgagcac ctcccgcaga tgctcctcca gcatgtcgac 25440
ctgcggcgag tgcccggcgg tgtcgacgcc ggggatcggg cgggcgtgca ccccctccgc 25500
gctgagttcg gcgaccagct ctgccagggc gtccgggtct ccggagacgg cgcaggtctc 25560
ggggccgttg acggcggcga cggcgagccg gtcgctccag ggctccagcc ggggacgcag 25620
gtcgcgctcg gacatggtca ccgcgaccat gccgcccttg ccggccagcc gcagccatgc 25680
ctggctgcgc agggcgacga tgcgcgccgc gtcgtccagc gagagggcgc cggcgacgtg 25740
ggcggcggcg atctctccct gggaatgccc gacgaccgcg gccggttcga cgcccagcga 25800
acgccaggtc tcggcgagcg agaccatcat ggtgaacaac acgggctgca ccacgtcgac 25860
ccggtcgagc gagggcgcgc cgggttcccg gcacagcacg tccagtacgg accagccgag 25920
gtggggccgg agcgcggcgt cgcaggcgcg tgcggtctcc aggaaggagc tggagtcgct 25980
ggagcggtcg aacagcccgt cggccatctc gggccattgc gagccctggc cggggaagac 26040
gaacaccacc tggtcggcgg tgccggcggt gccccgcagc acgagcgggt gcggccggcc 26100
ttcgacgagg tcgtcgaggg ccgcgatcag ctccgtgaag ttctcgccga ccacggcggc 26160
ccgctgctcg aagcgggtgc gggtggtgat gagggtgtag ccgacgtcgg ccgggtgcag 26220
ctcggggtgg gcgagcaggt ccgcgcgcag ccggcgcgcc tggtcgcgca gggcggcgtc 26280
gttgtgcgcg gacatcatca acggcacggt cacctcgtgc caccactcct cggaccagac 26340
gtcgccgtcg gcggccggtt cgggcgcgag cagctcgggc gcggtgggct ccggcggctc 26400
ctcgacgacg acgtgggcgt tggtgccgct gatgccgaag gaggagattc cggcccggcg 26460
cagtccgtcg gcccgctggg gccagggcct ggcctcgtcg agcagttcca cggctcccgc 26520
atcccattcg atcttggacg aggcggtggt ggcgtgcagg gtgcggggca gcgtgccgtg 26580
ccgcagggcc agcaccatct tgatgacacc ggccacaccg gcggcggcct gggtgtgtcc 26640
gatgttggac ttcagcgagc ccagccagag cgggtcgtcg cgccggtccc ggccgtaggt 26700
ggcgagcagt gcgcctgctt cgatcgggtc gcccagcggt gtgccggtgc cgtgcgcctc 26760
gaccgcgtcg acgtcggcgg gggtgagccc ggcatcggcg agcgcctcgc ggatcacctt 26820
ctgctgggcc ggaccgctgg gcgccgtcag gccgttgctg gcgccgtcct ggttgacggc 26880
gctgccccgc accaccgcca gtaccgggtg gcccttcttc tgagcctccg acagccgctc 26940
caccagcagc attccggctc cctcggcgag gccgacgccg tcggccgtct cggcgaacgc 27000
cttgctgcgg ccgtccggcg agaccgctcg ctggcgggcg aactccacca gcatctcggg 27060
ggtggacatc accgtggcgc cgccggccag ggcgtagtcg cactcgcccc ggcgcagtga 27120
ctgcaccgcc aggtgcaggg cggcgaggga ggccgagcag gcggtgtcga cggtgacggc 27180
ggggccctcc aggccgaaga cgtaggagag ccggccggac atcacgctgg cggaattgcc 27240
ggttgcgatg taaccgtcga agctctcgtc gccgtcctgg agcagcggca cgtagtgctg 27300
cccgttggtg ccgacgaaga ctccggtgcg gctgccgcgc agctccaccg ggtcgatgcc 27360
ggcccgttcg aaggattccc aggaggtttc caggatcagc cgctgctgcg ggtccatggc 27420
cagggcctcg cgggggctga tgccgaagaa gccggggtcg aactcggccg cgtcgtgcag 27480
gaatccgcct tcgcgcacgt aggtgtggtg tccgggtgag ccggggtcgg ggtcgtagag 27540
ggcttcgttg ttccatcccc ggtcggtcgg gaacggggtg atggcgtcga cctcgccggt 27600
cagcaggtcc cacaggtcct cgggggactg gaccccgccg ggcagccggc aggccatgcc 27660
gatgatggcg atgggctcgt ccgtctgtgt cggggtctcg gggccggtcc ggtcggcggt 27720
gtcgccccgg ccgaggagtt cctcgccgag gtggcgggcg agcgcggccg ggttggagtg 27780
gtcgaagacc agggaggtgg gcagcttgag gccggtggcg gtgctgagcc ggtcgcgcag 27840
ctccagggcg gtcagcgagt cgaagccgag gtcgcggaag gcgcgggcgc tgttcaccgc 27900
gtcgccggag gactgcccga ggacggcggc ggcgtgggcg cggaccagcc gcagcagggt 27960
gacgtgccgc ttgtggccgg actgcgcggt cagttcgcgg acgagttcgg aggtggtcga 28020
gtcgccgttg ctcggggcga gttcgaccgc gcgcagccgc tgcacgtccg ggatgtcgtc 28080
gaacagtacg gcggggcgca cccaggtgta ggaggcggcg aatcggttcc actcgacgtc 28140
ggcgaccgca ccgcaggcgc tgccgcgctc cagcatgcgg cgcagggtcc gcactgcctc 28200
gtccgggtcg aggggggcca ggccacgccg gttgaggaac tccgcttcgg cgccgtcggc 28260
gggcgtgccg ccggcccagg ggctccaggc cacggagagt gcgggcactc cggcggcgcg 28320
ggcgcgttcg gccagcgcgt cgaggtgcgc ggtggcggcc gcgtagcagc cctgggccgc 28380
gccgccccac acgccggaga ccgaggagaa cagcaccagc gcatcgaggc cggcggcggg 28440
cgccaggtcg accaggtggc cggcggccgt ggtcttggcg gcgagggcgg tggcgatgtc 28500
gccgggcgcc gtctcgttca gcggggccag cggtacgagc ggcggggcgt gcacgacgac 28560
ggagggcgcg tgctcgccga gcaggccggc cagggtggtg cggtcggtga cgtcgcagcg 28620
tacggggacg acggaggctc cggtgagtcc ggcggcggcg gcctgtgcgg gggcgtcggg 28680
cccggccagc accacgcggt ccgcgccgtc ctccaggagg gagcggatca gccgaccggg 28740
caccgtcgtg atgtcgccgg cgatgaggac ggtgccccgg gcgcgccagg ccggggagcc 28800
ggcgtcggcc gggttccgca ggacgcggcg gccgaagacg cccgccatcc ggatggcgat 28860
ctggtcctcg ccgccgggtt cggcgaggac gccggcgagg cggtcgagga cccgggcgtc 28920
gggctgcgcg ggcaggtcga tgaggccgcc ccacacctcg ggcagctcca gcgcggccac 28980
ccgtcccagg ccccacagtt gggctccggc ggtgcacggc agttcgtcgg gggcggtggc 29040
gaccgcgccg caggtgacgg tccacagcgg tgcggtgctg ccgaggtcgg ccagggcctg 29100
gaccagggcg agtgtggcgg tgactgcggt gggcacggcg gggtggtcgg gccggccgtc 29160
ggtgcacagt ccgagcagcg aaacggcgcc ggtgacggcg gtgtcgccgt tgattgccga 29220
ttcgagcagg ccgagcagtt cggcgcgtcc ggtgcgggcc gggtcgacgg cgatgcggcg 29280
gaccgttccg ccgaaggagg cgatcgcctg ttccacggtg tcggcgaggg cggcgtgctg 29340
ttccccggtg ggcacgatca gcaggcgcag gcccgggcgc cagccgccgg tggcggagcg 29400
cagccccttc cactcgacgt ggtagccgag ccggtcgccg gactccgggg cgccttcgcc 29460
ggtttcggcg gtcttcgccc ggtcgggccg ggcggagccg acccagtagc gttcgcgctg 29520
gaaggcgtag gtcggcaggt tcacccggcc ggccccgggg tggagcgtgg cccagtccac 29580
cggtacgccg acgacctggg cctccgccgc ggaggtgagg aagcgccgca gaccgccctc 29640
gtcgcgccgc agcgagccga cggccggtac cgcggtgccg acgctttcca cggtctggcg 29700
tacgccgacg gtgaggacgg ggtgcgcgga gcactccacg aacgcgtcga tgccgtcggc 29760
gagcatggcg cgcacggtcg gctcgaagcg caccgggagc cgcaggttgc ggtaccagta 29820
gtcggcgtcg agggcggccg tgtcgaggag cgccgcctcg acggtggagt agaagggcac 29880
gtcgcctctg tacggccgga ccggggcgag gacggtggcg agctcctccc ggatgctctc 29940
gacgtagtgg gagtgggagg cgtagtcgac gtcgatgcgg cggactcggg agccctcggc 30000
ctccagggcg accagcagcg cctccagggc gccgggctct ccgcagacga cggtcgaccc 30060
ggggccgttg acggcggcga tctccacgcc gccggcgagc cgtgcctcga catcggtcgc 30120
gggcagggcc accgaggcca tgccgcctcg cccggccagt tcgcgggcga tgacctggga 30180
gcgcagggcc acgatccggg cggcgtcgtc cagggagagc gcgcccgcca cgcaggccgc 30240
ggcgatctcg ccctgggagt ggccgatgac ggcggcgggt tcgacaccga gggatcgcca 30300
cagcgccgcg agtcccacca tgacggcgaa ggtggccggc tggacgacgt cgacgcggtc 30360
gaggccgggc gccccgggcg cgccgcgcag tacgtcgctg agggtccagt ccacgtacgg 30420
ggagagcgcg ctctggcaga gctccagttc ggcggcgaag gccggggccg tgtccagcag 30480
ttcggcgccc atcccggccc actgggagcc ctggccgggg aagacgaagg cgacccggcg 30540
gatgtccgcc gcggtgccgt gtacggcgtc cggggtggtc tcgccggcgg cgagggcggc 30600
gagggcgtcg accggggcgc cgttgtctcc gagcagcacg gcgcgttggg tgagggcggc 30660
gcggtcggcg gccagcgcat ggccgatgtc ggtcggcgag gtgtcgggga ggcgctcaag 30720
gtgcgcgcgc aggcgtgcgg cctgggcgcg cagggcggga gcggtctcgg cggacagcgg 30780
ccagaccacg gtggaggggg tcgcgggcgt gtcgccggtc atggacgctt cgtccggtgc 30840
ggacgcgggg cgaggagcgg acgcgtcgcg tggtgcggac gcgtggcctg gcgcggacgc 30900
gacgcgtggt gcggacgcat ggcccggcac ggacgcgacg cgtggtgcgg acgcatggcc 30960
cggcacggac gcatggcccg gcacggacga gacactggtt ccagccgccg cgcctgccgc 31020
gggtacctca cctgtcacag gcgcgtcgcc ggtcacgggc tcctcgcctg ccacaggtgc 31080
gtcaccggct gcggctgcgc cgcctgttgc ggtctcggcg ggcggttcct cgatgatgac 31140
gtgggcgttg gtgccgctga cgccgaaggc ggagatcgca gcccgccggg gacggtgctc 31200
gcgctgcggc cagggccggg cgtcggtgag caactccacg gcgctcgggt cccattcgac 31260
cttggccgag ggtgcgtcga cgtggagggt gcggggcagc gtggagtgcc gtatcgcctc 31320
caccatcttg atgacgccgg cggctccggc ggcggcctgg gtgtgcccga tgttggactt 31380
cagcgagccc agccacagcg ggtcccggcc ctggcgctca cttccgtagg tggccatcag 31440
cgcaccggcc tcgatggggt cgcccagagg ggtgccggtg ccatgcgcct ccaccgcgtc 31500
cacgtccccc ggggccagtc cggcatcagc caacgcctcg cggatcacct tccgctgggc 31560
cggaccactg ggcgcggtca ggccgttgct cgcgccatcc tgattgaccg cactcccccg 31620
caccaccgcc agcacccgat gcccataccg acgagcatcc gacaaccgct ccaccaacaa 31680
cacaccaaca ccctcggccc acacagtgcc gtccgcaccc tccgcaaacg ccttgcaccg 31740
cccgtccgac gccagcccac gctgccgcga gaactccacg aacaccgtcg gcgtcgccat 31800
caccgtcacc ccaccggcca acgccatgtc acactcaccc cgccgcaacg actgcaccgc 31860
cagatgcaac gccaccaacg acgacgaaca cgccgtgtcc atggtcacag cggggccctg 31920
caggccgagc gtgtaggcca cccggccgga tgcgacgctg cccgcggtgc cgaggccgag 31980
ctgtccgctg ggatcggcgg cggtgccgac ctggtggctg ccgtagtcgt ggtacatcac 32040
gccggtgaag actccggtac gggtgccgcg cagcgagtcc ggcacgatcc cggcccgctc 32100
caacgcctcc cacgacgtct ccagcaacaa ccgctgctgc ggatccatcg ccgccgcctc 32160
acgcggcgaa ataccgaaga actccgcatc gaactcggcc gcctcgtgca ggaagccgcc 32220
ctcccgcacg taactcttgc ccggcacgcc cggctccggg tcgtacagcc cctcggcgtc 32280
ccagccgcgg tccgcgggga acggggagat cgcgtccgta ccggcggcca cgaggtccca 32340
gaggtcctcc ggcgacgcca caccgcccgg gtagcggcac gccatgccca caatcgcgat 32400
cggctcacga ctcgccgact cgacttcgcg cagccgctcg cgcgcgctgt gcaggtcggc 32460
catcgcgcgc cgcaggtact cccgcaactt ctcctcgttc gttgcagaca cggttctcct 32520
catgcgtcat gtcatgggtc agggtgcgga gcggttcagc agccggcgcg cggcgcggtc 32580
cggctcactg gaaatcgctg tcgagcaggt cgaacaagtc gtcgtcggag gccgacctga 32640
gccggtcgat caccacatcg ccggggccgt gggggctttc tccggcgccc ggtccggatt 32700
gctcgccgga gccgacggtg agcgcggcca gcaggccgcg cagccgctgt gcggcgcgga 32760
cacgggcatc gccgtcgtcg gtcgcggcga ggctgcgctc cagccggtcg aatgcgctgg 32820
acaggtcttc ggcaccggcc ggttcgtccg ggaccgggcc ggccggttcc gctcggcctg 32880
ccgccgtcaa ctcgccgagc aggagttcgg cgagggacag cggtgtgggg tggtcgaaca 32940
cgagggtcgc gggcaaccgc agcccggtgc gcgcgttcag ccggttgcgg agatcgacag 33000
ccgtgaggga gtcgaatccg gcgtccttga aggaacgggc ggcgcccacc gcggcggtgt 33060
cgccgtgtcc cagcaccgcc gcgacctcgg tccgcaccag gtcgagcagg agggccgtcc 33120
gctcgggcgc ggagcgcccc gcgagccggg tcgccagtgc cgcggcggcg tcggccgggg 33180
cgggaggccg gtggccggta ccggcctcgc ccccggcgcc cgccacggct ccgggcgcgc 33240
tcccgccgtc tgccgggacg ccgaccaggt cacgcagtac ctccggcaga acggtggcac 33300
gggccgcggc gcgcaggtcg aggcgcacgg gcagcagtgc gggctcgggc ctgaccaggg 33360
cccggtcgaa cagctccagc gcggcccggg ggtcgagcgg ggcgacgccg gagcgccgga 33420
tacgcgcggc gtccgctctc tccagcccgg tggccaggcc caggccggac caccagcccc 33480
agccgagcga cagcgcgggg tgcccggcgg cgcgccgccg ggcggccagg gcgtccagga 33540
acgcgttggc cgcggcgtac ccggcctggc ccgcactgcc cagggcggcc gagaccgagg 33600
agtacaacac cagtggaacc ggcccgagtt cacgggtcag ctcgtccagg tggacggcgg 33660
cgtccgcctt gggccgcagt accgcgtcga tccgctcggc agtctggacg gagagcacac 33720
cgtcgtcgag caccccggcg gtgtgcacga cgcaggtcag cggatgttcg gcggggagct 33780
cgccgagcag gcggcggagg gcgtcgcggt cggcgacgtc acaggcccgg acggtgacct 33840
cggcgcccag attcgtgagt tccgcggcca gttcggcggc gccgggtgcg tcggggccgc 33900
gcctgctgac gagcaggagg tggcgcgcct tgtgccgttc cacaaggtgc cgggcggttt 33960
ctgcggccag tgctccggtg ccaccggtga tcagcacggt gccgttgggg tccagcgtct 34020
cggccggctc cccggcaccg gtctcgtcgg ccgctgtgtc gctgccggtg tccaggtcgg 34080
ccacgtcggc cacgtcggcc acccgtacga ggcgcgggac ggcggcgcgt ccatcgcgca 34140
cggccaactg agcggtgtcc gtggccagca ggccgggcaa ggcccgcagc gacgcctgcg 34200
cgccgtcgac gtccaccaga gtgaagcggc cgggctgttc ggcctgggcg acccggacga 34260
gcccccagac agcggcaccc gcgggatcgg ccgcgcctcc ctcgggaccg gccgcacccc 34320
gggtcaggac cacgagccgc gggcggccgc cgggacgggt ggctgtacgg gcgtccgtac 34380
ggacgccgga gtctgcaccg gcatccgcgt tggtgtcggt gtcggtgtcg gtgtcggcga 34440
gtcgggcctg tacggcttcg agagtccggc gcaccgtcgc acgcagctcg tcgaggaggc 34500
cgaggagcct gccgtggggc gccgtacgac tggcggtggc ggtggcggtg gcggtggcgg 34560
tggtcaagtc gaggaggatc acttcggcgt ccgcgccgac ctgcggcggc agcggctcgt 34620
cgaaggggag cacgtgggta cgggcgtcga tgccgacggc acgcagcccg gccgcggtgg 34680
cttcggcctc cggtccgacg accgcccagc gcgtgactgc ggcgacggac actcgcccgg 34740
gaagcggcac ccagtccacg cggtagagag gggcggcggg tgcggcggga agccggtccg 34800
cgggtatgcg acgcagtgcc agggagcggg cggaaagcac tggggagccc tcgcggtcga 34860
ccgcggcgat cgacaccgcg ccgccgtcga cggccgccac ccgtacccgg agcgcatgtc 34920
cggcggcatc gtggcgccgt acgtcggtcc aggagaacgg cagcaagccg tgtccgccgt 34980
cgcccaacgg gtcgagcagc gcgatcgggt ggagagccgc gtcgagcagg gcggggtgca 35040
ccccgtaacg ggcggcatcg gcggcgtgcg cgtcgggcag ccgcacttcg gcgaagatct 35100
cgtcgccgcg acgccatgcc gcgcgcagcc ctcggaaggc cccttcgtag cgcactccgg 35160
cggctgcgaa gagcgggtac tgaccggcga tgtcgagcgg ctcggcgccg gcagggggcc 35220
aggcgccggt gagttcggcg aaggcgtcgg caccggttcg gtcggcaccg tgggggtggc 35280
cgctctcgtg ggggtgggga gccccgtggg ggtggccggc ctcgtgcgtg tggtcggcat 35340
ggtcggcagc cggggcgagc agcccggagg cgtgccgggt ccagccgttg tcacgatcct 35400
gcgccgcgag gtgcggggaa cgggtggaat gcgaggggtc ggcgacgggt tcgggccgtg 35460
agtggagact cacctcacgg gcacccccgg ggccggaggc aggagcggcc acgacgaccc 35520
ggatctggac cgggttgtcc gcagcccagg tcagcgcggt ctcgaaggcc agttcggcga 35580
cgcgcggcag accgatccgg cttcctacct ggagcagcat ctccagcagt gcggatcccg 35640
gcaccacgcc gcggtcccac accaagtggt cggcgagcca cgggaggtcc gcagcggaga 35700
tccggccggt ccacacctcg gtttcggcgc cgggcagttc cacggcggcg gcaagcagcg 35760
ggtgttccac cccatgcagg cctgccgccg acaccccgcc ggtcgtgagc cggggcagag 35820
ccgccagcca gtagcggtcc cgatggaagg cgtacgtggg caggtcgacc cgccggccgg 35880
caggctcgga gggagccggc ggcaccggaa ggccccgggc gtagagggtg gcgagtgcgg 35940
tggtgaaggt ctccagctcc ggccggtcac gccgcagtac cggcacgaaa gcaagatcac 36000
cctcgtcccc gtcgagacac tgccccgcca tcaccgtcag aacagcatgc ggacccacct 36060
ccacaaacgt atccacaccc acatcacgag cagcccccac accatccgcg aaccgcaccg 36120
cctcccgaac atgccgcacc cagtactccg gatcccccaa ctcatccaaa cccgcaaccg 36180
cacccgtcac actcgacacc accgccacac cagaacgagg ccggtgaaac tccaccgaag 36240
cagcaacccg acgaaactcc tccaacatcg gatccatcaa caccgaatga aacgcatgcg 36300
aaacctccaa ccacctgcac tccacaccac gacccaccaa acccgccacc acaccatcca 36360
gcacccccgc ctcacccgac agcaccaccg acgccggacc attcaccgcc gcaaccgaca 36420
cccgaccacc caacccagcc accaaacccg ccagctcggc ctcagacgcc cccaccgaca 36480
ccatcgcccc acccacaggc aacgcaccca tcaaccgacc acgcgccacc accaaccgca 36540
ccgcatcagc caacgaaaac acacccgcca catacgccgc agccacctcc cccaccgaat 36600
gacccaacac caccgacaca cccacacccc gagcctccaa cgcccggaac aacgccacct 36660
ccaacgcaaa caacgccggc tgagcaaact ccgtacaccc caacaacccc gcatccacac 36720
tccccgcctc cgcaaacatc acctcacgca gagaccgacc ccccacctcc cccacaaccc 36780
ccaacacctc atccaacaca cccgcaaaca ccccacccgc cccatacaac tcacgcccca 36840
taccaaccca ctgcgcaccc tgacccgtaa acaacacccc cacccgacgc ccccgcaccg 36900
ccgaaccccg caccacaccc gacgcggcac cccccgcagc aaccacaccc gccgccacag 36960
catccagacc ggccagcagc tccccacgct cccgaccgac aaccaccgca cgctcaccga 37020
acgacgcacg cgacaccaca agcgaatgcg caacatccac cggatcagca cccacacgct 37080
ccacgtgctc ccgcaaccgc accgcctgcc cccgcaacgc ctcctccgaa cgggccgaca 37140
ccggccacgc cagaaccgaa gaggactcag ccgcagcagt gacaacagcc tcggcttcgg 37200
ccgactcctc gaccgacggt tcctcgatga cgacatgggc gttcgtcccg ctcacgccga 37260
aggcagaaac agccgcccga cgcacccggc ccgcccgccg gggccaggac ctggcctcgg 37320
tcagcaactc caccgccccc gaaccccact cgaccctcga cgacggagca tccacatgaa 37380
gagtgcgagg caacgacgaa tgccgcatcg cctccaccat cttgatcaca ccacccacac 37440
ccgcagcagc ctgagcatgc ccgatgttcg acttcaacga ccccaaccac aacggatcac 37500
ccacccgctc acgcccatac gtcgccagca acgcacccgc ctcgatcgga tcccccaacg 37560
ccgtacccgt accatgcgcc tccaccgcat ccacatcccc cggagccagc ccggcatcag 37620
ccaacgcctc acggatcacc ctccgctggg ccgcaccact gggcgccgtc agaccgttac 37680
tcgcaccatc ctgattgacc gcactccccc gcaccaccgc cagcacccga tgcccatacc 37740
gacgagcatc cgacaaccgc tccaccaaca acacaccaac accctcggcc cacacagtgc 37800
cgtccgcacc ctccgcaaac gccttgcacc gcccgtccga cgccagccca cgctgccgcg 37860
agaactccac gaacaccgtc ggcgtcgcca tcaccgtcac cccaccggcc aacgccatgt 37920
cacactcacc ccgccgcaac gactgcaccg ccagatgcaa cgccaccaac gacgacgaac 37980
acgccgtgtc caccgtcaac gccggcccct ccaaccccaa cacataagca acccggccgg 38040
atgcgatgct gccggcgctg ccgttcacga ggtagccctc gtactccggc ggggccgagt 38100
cgaactgcga tccgtagtcg tcgtacatca cgccggtgaa gactccggta cgggtgccgc 38160
gcagcgagtc cggcacgatc ccggcccgct ccaacgcctc ccacgacgtc tccagcaaca 38220
accgctgctg cggatccatc gccgccgcct cacgcggcga aataccgaag aactccgcat 38280
cgaactcggc cgccccgtgc agaaacccgc cctcccgcac ataactacga cccaccgcct 38340
ccggatcggg gtcgtacaac ccctcgacgt cccagccacg gtcgacaggg aacggagaga 38400
tcgcgtccgc accggcggcc gccaggtccc acaggtcctc cggcgacgcc acaccgcccg 38460
ggtagcggca cgccatgccc acaatcgcga tcggctcacg actcgccgac tcgacttcgg 38520
ccaggcggga cttggtcttg tggagttcgg cggtggcacg cttcaggtag ctgcggatct 38580
tgtcgttctc ggcggtcatt gctgccacca actcctcggc atgcggtcgg tccacggtgc 38640
ggtcacagct gctcgtccag gaaggcaaag atctcgtcgt cggtcgcctc gtcgagccgg 38700
tccgttacgg tcgccccggc gccgtcggca gcggcgggcg cggcgggcgc ggtgcggccc 38760
tggggtccga cgacgccgcg cccaggggtg tcgagcgcgg tcagaagccc gacgagccgc 38820
tgtcgtacct cgactcgacg ggcgtcgtcc gagcccagca gggcgaccgc ccgcgcaagt 38880
tcgccgatcc cctccagcgc ggcgtccacg accggggctc cggcggggcg gggcagctcc 38940
ccgtcgatcc actcggccat gtccttgggc gtggggtggt cgaaggccag cgtggtcggc 39000
agccgcaggc cgaccaggcg gctgagccgg ttgcgcagct ccaccgccgc cagggagtcg 39060
acgccgatct cccggaaggg gcgttcgggc tcgatctcgg cggccgacgc gtgcccgagg 39120
acctcggcga cctgttcggt gaccaggtcc agcacggccg tggaccgctc cgctgcgtcg 39180
agcgccacga tccgggcgat gcgtccggtg ccggactccg cccccttgcc gtgccggtcg 39240
gcagccgcag gggtgccggt actgctatgg cgcagggctg cgggaagcag gccgcgcagc 39300
aacggaggca ccgcggccgc gccgcgctcc ttggccgtgc gccgcagagc ggcgccgtcg 39360
aggaggagcg ggacgaggac ggcgggcccg tcccggtgcg cggtcagagc ctggtcgagc 39420
agcccgagcc cttgctcggg cggcatcgcc gcgatgccct cgcggcgcag ccgatggagc 39480
gccacgtcgt ccagaccccc ggccatgccc gccctctcgt cccacaggcc ccaggccagg 39540
gacaccgcgg gcagcccggc tgcgcgacgg gctcccgcga gcgcgtcgag gaccgcgttg 39600
gcggccgcgt aggagccctg ccccggacgg ccgaggagtc cggcggcagc ggagaacagg 39660
acgaacgcgc gcagcggtcg gtcgagggtg gcctcgtgca ggttccgtac ggcgtcggcc 39720
ttcgaccgca ggacggtgtc gagccgttcc tgagtcaggc cggtcagggc gccgtcgtcc 39780
agcacgccgg cggtgtgcac cacaccggtc agcgggtgtt ccggcgacac tgcgacaacg 39840
gccttccgca cggccgcggg gtcggcgaga tcgcatgcca ggaaggtggc ggtgacgccg 39900
aggccgacga gctcccgttc caggagggcg gcttcgggag catccggccc gcgcctgctg 39960
accaggagca tgtggcgcac gccgtgccga cgcgccaggt gcggggcgac gcgccgcccc 40020
agggcgccgg tgcagccggt gatcagtacc gtgcccgcag ggtcgaacac ggcgtccacg 40080
gcggaaccat cgggatcgaa cgcgccgtct gaggcggggc cgccggtcgc cgcgccgccc 40140
ctctcggccg gcccggccgc ttccggcgcg acgctctgtg ccgcgaccgc tgccgctgcg 40200
gagtccactg ccgtcgccgg ggttgctgcc gtcgccgggg tggtgatcgg aacgagggcc 40260
ggtgcgagca acgccccggc gcgcagggcg agttgcggct cgcccgattc cagagcccgc 40320
ggtagggccg cacgggattc cggggagtcg tccacatcga cgagggtgaa gcggtcgggg 40380
tactccgact gggcggagcg gagtagcccc cacagtgccg cacccgccag gtccggcact 40440
tcgccggaac cggcctcgac cgcgccccgg gtgaggacga cgagccggga atccgccaga 40500
cgttcgtcct cggtccactc ccgcaccaag gccaggccac ggccgagggc gacgcgtacg 40560
gggtcgtcgc cccagtccgt acccgtacgg gcatgagccg tagccgtacg gacatgggcc 40620
ttacccctac ggacacgagc atccgcaccc gcgtccacgc ccgcacccgc acccgccgac 40680
gactcggcgg gccgaatgtc ggtggccggc acaaccacca gtccgggtac gggcgttccc 40740
gcagtcaggg cagtgcgcag ggcggcgagg tcggcatggg cggcgggctc cgcgccgggc 40800
agggcgcgca aggtcgcgca ctcctccgtc gcagcctgtt ccgcagctgt ttcgcccgcg 40860
gcgggtccga gcaccgtcca gccatgggcg ccgggggtgt cggacctctg cggtactggc 40920
tgccagtcga cgcggtacag cggttccggc gcgccggccg tgcccagggc caccgggcgc 40980
agcagcagtg cgtccagggt gaggacgggg gcgcctgccg gatcggcggc ccgcaccgag 41040
aaggctgatt cggcgccgct gcccgccggt gccagcctga cgcggagcgt ctcggctcct 41100
gtggcgtgga gcgcgatgcc ctgccaggag aacggtgcca acgtggtgcc gcccgtgtcg 41160
ggcagcaacc caccggcccg ccatgggtgg agggccgcgt cgaagagtgc gggatggata 41220
ccgaaaccgt caccggccgt gcccgtcgcg gacagccgca cctcggcgaa gagctcgttg 41280
ccgaggcgcc atgccccgga cagtccgctg aaggccgggc cgtagtcgta gccgtccgcg 41340
gcgaacccct catacaactc cccgacgtct accggttcgg cccccggcgg cggccaggcc 41400
ccggcggccc aggccgtgtc cggaacggcc ggctccgcgg gcgcgagcac gccttccgcg 41460
tgtttggtcc actccggttc ctcgccgtcc caccccggtg tctcggggcg tgcggcaagt 41520
gcgacagcgc gccggccctg cccgtcggct gcctcgacca gcacctggag tcgcagtccg 41580
ccctgttcgg ggaggagcag gggcgcatgg agcgtcagct cctcgacgcc tcccgcgccc 41640
acctcttcgg cggcccgcag caacaggtcg gcgatcgccg tcccggggag cagcaccgtg 41700
ccggagatgg cgtggtcggc cagccacggg tgggtggaga gcgccaccct gccggtgagg 41760
agcaacgcgc cggagccgac tatcggcgtg gcgccgctga ggaacgggtg gtccttccat 41820
tccagcccga agcgggcagc ggccgaggag ccggtggagc cggacaccga gcccgtcgcc 41880
cagtagccac ggcgttggaa ggggtaggtg ggcaggtcga cccgccggcc gccgaaaccc 41940
gaatggaggg cagcgacgtc gagttcggca tcccgcgtat acagcgtggc gagtgcggtg 42000
gtgaaggtct ccagctccgg ccggtcacgc cgcagtaccg gcacgaaagc aagatcaccc 42060
tcgtccccgt cgagacactg ccccgccatc accgtcagaa cagcatgcgg acccacctcc 42120
acaaacgtat ccacacccac atcacgagca gcccccacac catccgcgaa ccgcaccgcc 42180
tcccgaacat gccgcaccca gtactccgga tcccccaact catccaaacc cgcaaccgca 42240
cccgtcacac tcgacaccac cgccacacca gaacgaggcc ggtgaaactc caccgaagca 42300
gcaacccgac gaaactcctc caacatcgga tccatcaaca ccgaatgaaa cgcatgcgaa 42360
acctccaacc acctgcactc cacaccacga cccaccaaac ccgccaccac accatccagc 42420
acccccgcct cacccgacag caccaccgac gccggaccat tcaccgccgc aaccgacacc 42480
cgaccaccca acccagccac caaacccgcc agctcggcct cagacgcccc caccgacacc 42540
atcgccccac ccacaggcaa cgcacccatc aaccgaccac gcgccaccac caaccgcacc 42600
gcatcagcca acgaaaacac acccgccaca tacgccgcag ccacctcccc caccgaatga 42660
cccaacacca ccgacacacc cacaccccga gcctccaacg cccggaacaa cgccacctcc 42720
aacgcaaaca acgccggctg agcaaactcc gtacacccca acaaccccgc atccacactc 42780
cccgcctccg caaacatcac ctcacgcaga gaccgacccc ccacctcccc cacaaccccc 42840
aacacctcat ccaacacacc cgcaaacacc ccacccgccc catacaactc acgccccata 42900
ccaacccact gcgcaccctg acccgtaaac aacaccccca cccgacgccc ccgcaccgcc 42960
gaaccccgca ccacacccga cgcggcaccc cccgcagcaa ccacacccgc cgccacagca 43020
tccagaccgg ccagcagctc cccacgctcc cgaccgacaa ccaccgcacg ctcaccgaac 43080
gacgcacgcg acaccacaag cgaatgcgca acatccaccg gatcagcacc cacacgctcc 43140
acgtgctccc gcaaccgcac cgcctgcccc cgcaacgcct cctccgaacg ggccgacacc 43200
ggccacgcca gaaccgaaga ggactcagcc gcagcagtga caacagcctc ggcttcggcc 43260
gactcctcga ccgacggttc ctcgatgacg acatgggcgt tcgtcccgct cacgccgaag 43320
gcagaaacag ccgcccgacg cacccggccc gcccgccggg gccaggacct ggcctcggtc 43380
agcaactcca ccgcccccga accccactcg accctcgacg acggagcatc cacatgaaga 43440
gtgcgaggca acgacgaatg ccgcatcgcc tccaccatct tgatcacacc acccacaccc 43500
gcagcagcct gagcatgccc gatgttcgac ttcaacgacc ccaaccacaa cggatcaccc 43560
acccgctcac gcccatacgt cgccagcaac gcacccgcct cgatcggatc ccccaacgcc 43620
gtacccgtac catgcgcctc caccgcatcc acatcccccg gagccagccc ggcatcagcc 43680
aacgcctcac ggatcaccct ccgctgggcc gcaccactgg gcgccgtcag accgttactc 43740
gcaccatcct gattgaccgc actcccccgc accaccgcca gcacccgatg cccataccga 43800
cgagcatccg acaaccgctc caccaacaac acaccaacac cctcggccca cacagtgccg 43860
tccgcaccct ccgcaaacgc cttgcaccgc ccgtccgacg ccagcccacg ctgccgcgag 43920
aactccacga acaccgtcgg cgtcgccatc accgtcaccc caccggccaa cgccatgtca 43980
cactcacccc gccgcaacga ctgcaccgcc agatgcaacg ccaccaacga cgacgaacac 44040
gccgtgtcca ccgtcaacgc cggcccctcc aaccccaaca cataagcaac ccggccggag 44100
atcacgcttc cgagcgtccc cgtgagcaca tgcccgccgt aggtttcggc ggcgtccccc 44160
aactggcttg cgtagtcctg ctgggagatg ccggtgaaga ctccggtacg ggtgccgcgc 44220
agcgcgtccg gcacgatccc ggcccgttcc aacgcctccc acgacgtctc cagcaacaac 44280
cgctgctgcg gatccatcgc cgccgcctca cgcggcgaaa taccgaagaa ctccgcatcg 44340
aactcggccg ccccgtgcag aaacccgccc tcccgcacat aactacgacc caccgcctcc 44400
ggatcggggt cgtacaaccc ctcgacgtcc cagccacggt cgacagggaa cggagagagg 44460
gtgtgcccgt cttcggccac caggcgccac aggtcctccg gcgacgacac gccgcccggg 44520
tagcggcacg ccatgcccac gatcgcgatc ggctcgcgct cgtcggccgt ggcccgggcg 44580
cgggtgtccg cgacaggctc cgcttcgctg tcggtaccga acagttcgtc gtgcagatgg 44640
gcggccaggg aggtcgggtt ggggtggtcg aagagcaggg tgctcggcag gttcagcccg 44700
gtggcagcgg tcaggcggtt gcgcagttcg agaacggtga gcgagtcgaa cccggcggac 44760
cggaacgcga tctccgggtc gaccgcgtcg gccgaggcgt ggcgcaggat ctcggcggcc 44820
tcggagcaca ccaggtcgag cagggcccgt cgccgttccg tcgacgaggg gccgacggag 44880
agccagggtc ggccttcgtc cgctccggct ccgcttccgc ccggcccacc gtggcccggc 44940
cgcgtccccc gggggagagt ggcacggcct tgcgcggcac gggcggaacg cgctgagcgg 45000
gcggcgggaa caccgtcgaa aagtgcccag gtgcggcggg tgacggaacg cccgacgaag 45060
gtttcccagt ccacatcggc gacgatcagc gaggtcgcga cggccgcaga ggccccggcg 45120
gcagcggagg tcccaccggc gccgaccgcg tcgtccagta cgtcgagcgc gtgctcggga 45180
tccagggccg cgacgccgtc ccgctcgaag gacttcgtcg ccgttccgga cgccatcccg 45240
gctccggccc acgggcccca ggcgatcgag gtggcacgcc ctccccgggc ccggcgccgg 45300
tgcgccaggg cgtcgagcgc ggcattggcc gccgcgtagg cggcctgccc cccgttgccc 45360
cacactccga cgatggagga gaagagaacg aaggcgtcca gcgggaggtc ggcggtgagc 45420
tcgtccaggt ggcgggccgc agtgaccttg gcacgcagta cggcgtctat ccggtcggag 45480
gtgagcgagt cgagcacacc gtcgtcgagc acgcctgccg cgtgcagtac ggcggcgagg 45540
ggccggtctt cgggaatgcc cgcgagcagc gcggcaagcg cgtcccggtc ggcgacgtcg 45600
caggctgcga cggtcacttc ggtaccgagg gctgtcagct cctcgacaag ttcgcccgct 45660
ccggggccgg ccgccccgcg ccggccgacc aggagcagat gcggggcgcc cgcccgggcg 45720
agcctgcggg cgacctgcgc gcccagggcg ccggtgcccc cggtgatcag tacggtgcct 45780
gaggaccgcc ggtttcccgg cacgactccg tcgggcgtgt cgccctgcgc gtcccgggcg 45840
gcggcggtgg tggcggcgcg gacggggacg gggaccacgc ggcggacatg gactccggag 45900
ggccgtaccg cgaactggtt gtcctcgccc tcggcgagca gcgtcccgac gaacgcacgg 45960
agcgcggcag gcgacggctc cccgggcagg tccgccaaac cgccccagcg ctgggcaagt 46020
tcgagtgcgg cgacctgccc cagcccccag agctgagcgc ctgcgacgga aggggcctcg 46080
cccggctgag cagccaccgc gtcgcgcgta gtgatccaga gcggggcgtc gggtcccgcc 46140
tcgcccaggg cctggatcag cgcgacggcg tcggccgtgt ccggctcggc cggggcgagc 46200
cacaggacgt gcgtgctgcg tgcggcaccg tcaccggcgg cccgcagcag gtctgcggcc 46260
gcctcccgac cggtaccgac cggcacgaca gcggtgtgga cctcggtgcc gcgcacggcg 46320
agttcacgcg cgatcgcggt ggcgagcccg gagtccgtcg tgtcgtcgtc cgaggccagc 46380
agcagcatac gacccgccgg ccgggggact ccgcagccga cggcggcggg ctgccaggtg 46440
acgcggtagc ggagcccggc cgtcgccgaa gtcacccctt gagcagcggt cggaacgtcc 46500
tcggacgaac cggcggccat ggcggtgggc actgcggcgg gggcggggtc cagccagaaa 46560
cgggcgcgct ggaaagggta tgtgggcaga tcgatgcgtc gtgcgtccct cttccgattc 46620
ggcgcgtccc agtcgatctg ggcgccccgg gcgtagaggg tggcgagtgc ggtggtgaag 46680
gtctccagct ccggccggtc acgccgcagt accggcacga aagcaagatc accctcgtcc 46740
ccgtcgagac actgccccgc catcaccgtc agaacagcat gcggacccac ctccacaaac 46800
gtatccacac ccacatcacg agcagccccc acaccatccg cgaaccgcac cgcctcccga 46860
acatgccgca cccagtactc cggatccccc aactcatcca aacccgcaac cgcacccgtc 46920
acactcgaca ccaccgccac accagaacga ggccggtgaa actccaccga agcagcaacc 46980
cgacgaaact cctccaacat cggatccatc aacaccgaat gaaacgcatg cgaaacctcc 47040
aaccacctgc actccacacc acgacccacc aaacccgcca ccacaccatc cagcaccccc 47100
gcctcacccg acagcaccac cgacgccgga ccattcaccg ccgcaaccga cacccgacca 47160
cccaacccag ccaccaaacc cgccagctcg gcctcagacg cccccaccga caccatcgcc 47220
ccacccacag gcaacgcacc catcaaccga ccacgcgcca ccaccaaccg caccgcatca 47280
gccaacgaaa acacacccgc cacatacgcc gcagccacct cccccaccga atgacccaac 47340
accaccgaca cacccacacc ccgagcctcc aacgcccgga acaacgccac ctccaacgca 47400
aacaacgccg gctgagcaaa ctccgtacac cccaacaacc ccgcatccac actccccgcc 47460
tccgcaaaca tcacctcacg cagagaccga ccccccacct cccccacaac ccccaacacc 47520
tcatccaaca cacccgcaaa caccccaccc gccccataca actcacgccc cataccaacc 47580
cactgcgcac cctgacccgt aaacaacacc gccgtcccac ccgaaacagc cgtgccccgg 47640
acggtcttcg gcctcgtgtg tcccgcggcg agcgcgtcca ggcctgccat cagctccgca 47700
cggtcgccac cgacgaccac cgcacgctca ccgaacgact cacgcgtcac cgcaagcgaa 47760
tgcgcgacgt ccaccggatc ggcgcccaca cgctccacgt gctcccgcaa ccgcgccgcc 47820
tgcgcccgca acgcctcctc cgagcgggcc gacaccggcc atgccagagt cggtgcgagt 47880
tcggctgtgg gagcggtgac agtcggcggc tcggtgggcg tctctgccgg cgcctcctca 47940
atgaccaggt gggcgttggt gccgctgatc ccgaaggagg acaccgcggc ccgccgcggg 48000
cggcccgcgc gctccggcca ccggcgcgcc tcggccagca gttccaccgt gcccgacgac 48060
cagtcgacat gtgtgctggg ccggtccgcg tgaagcgtcc gcggcagcgt gccgtgtcgc 48120
atggccagca gcatcttgat gacgcctgcg gccccggcgg cggcctgggt gtgcccgacg 48180
tttgacttca gcgaccccag ccacagcggt tctcccaccc gctcacgccc gtacgtggcc 48240
agcagcgcgc ccgcctctat cgggtcgccc agcgccgtac ccgtgccgtg cgcctcgacg 48300
gcgtccacat cgcccggggc gagtccggcg tcggccaggg ccgcccggat gacgccttcc 48360
tgcgcggaac cattgggcgc ggtgaggccg ttgctggcgc cgtcctgatt gaccgcactg 48420
ccccggacga ccgccagcac ccggtgacct gcgcgccggg cgtcggagag ccgctccagt 48480
gccagtacgg caacgccctc ggaccaggcc gtaccgtcgg catcggcgga gaacggcatg 48540
cagcggccgt cgggggccag cccgcgctgc cgggagaact ccacgaacat gccgggcccg 48600
gacatcaccg tggcgccgcc cgccagagcc agtccgcact cgccccggcg cagcgcctgc 48660
acggccaggt gcagcgccac cagagacgag gaacatgcgg tgtcgacggt gagcgccggt 48720
ccgcgcgtgc cgagggtgta ggcgatccgg ccggaggcca cgctcgccgt ggtgccggtg 48780
agcagatacc cctcgtatcc gtccgctcct tcgtgaagcc tcggcccgta ctccggtgcg 48840
acggcgccga tgaacacgcc ggtgtcgccg ccgcgcagcg actcggggag cactccggcg 48900
tcttcgagcg cctcccacga ggtttccagc agcagccgct gctgcgggtc catggcggtc 48960
gcctcacgcg gcgagatgcc gaagaactct gcgtcgaact cggccgcctg gtgcaggaag 49020
ccgccctgtc gcacgtaggt cttgccgggg acgcccggtt cggcgtcgta cagcccgtcg 49080
aggtcccagc cgcggtcggc ggggaaggac gagatcgcgt cggtgccgga cgccagcagg 49140
tcccagaggg cggcccgcga gtcgacgccg ccggggaggc ggcaaccgac gccgacgatg 49200
gcgatcgggt cgtcgtcccg tgtgccgccc cgggcggccg ccgccccgac cgcctcgtgc 49260
tcgccggggt gcgcgctctt tgtcccgtgc agtgcggcca ccaggtgttc ggcgacggca 49320
cgcggggtgg gcaggtcgta gacgagcgtg gcggcgaggg tgagccccgt ggcccggttc 49380
agcaggtcat ggagctcgac cgcggtggct gattccaggc cctgggaggt gaaggtgcgg 49440
tcgagcgcga tctcgtcggg gtcgtcgtgg cccaggacgg tcgcggtggt ctcgcgtacc 49500
agacggacga gctgctcggg agacatcggc tccggggacg ccgtgagcgg ttcgtcgtcc 49560
gggtccctga ggggcgcctc ggtgctctcc gggggcgcgg tgttccccgc ggcgtcggtg 49620
gtggtcaggc ccggcccggc gtcggccgcg attccacggc tcagcgccgg cgaccagtga 49680
gtacggcgtt ggaaggggta ggtgggcagg tcgacccgcc ggccgccgaa acccgaatgg 49740
agggcagcga cgtcgagttc ggcatcccgc gtatacagcg tggcgagtgc ggtggtgaag 49800
gtctccagct ccggccggtc acgccgcagt accggcacga aagcaagatc accctcgtcc 49860
ccgtcgagac actgccccgc catcaccgtc agaacagcat gcggacccac ctccacaaac 49920
gtatccacac ccacatcacg agcagccccc acaccatccg cgaaccgcac cgcctcccga 49980
acatgccgca cccagtactc cggatccccc aactcatcca aacccgcaac cgcacccgtc 50040
acactcgaca ccaccgccac accagaacga ggccggtgaa actccaccga agcagcaacc 50100
cgacgaaact cctccaacat cggatccatc aacaccgaat gaaacgcatg cgaaacctcc 50160
aaccacctgc actccacacc acgacccacc aaacccgcca ccacaccatc cagcaccccc 50220
gcctcacccg acagcaccac cgacgccgga ccattcaccg ccgcaaccga cacccgacca 50280
cccaacccag ccaccaaacc cgccagctcg gcctcagacg cccccaccga caccatcgcc 50340
ccacccacag gcaacgcacc catcaaccga ccacgcgcca ccaccaaccg caccgcatca 50400
gccaacgaaa acacacccgc cacatacgcc gcagccacct cccccaccga atgacccaac 50460
accaccgaca cacccacacc ccgagcctcc aacgcccgga acaacgccac ctccaacgca 50520
aacaacgccg gctgagcaaa ctccgtacac cccaacaacc ccgcacccac actccccgcc 50580
tccgcaaaca tcacctcacg cagagaccga ccccccacct cccccacaac ccccaacacc 50640
tcatccaaca cacccgcaaa caccccaccc gccccataca actcacgccc cataccaacc 50700
cactgcgcac cctgacccgt aaacaacacc gccgtcccac ccgaaacagc cgtgccggtc 50760
cgcactcccg cagaggtctt accgcgagcg aacgcgtcga gggaggcggc gagttcctct 50820
cggtcgccgc agcgcagtgc ggcgcggtgc tcgaagagag tgcgcgtggt ggccagggag 50880
taagcgatgt cccgcgggtc cgcgccggtc cggcccaggt ggtcgtgaag ccgcgcggcc 50940
tgcgcccgca gcgccgcgcg ggagcgggcc gacagcagca ggggcggggc cgggtgcggg 51000
gcggcggctt cggaggccga cgacgggatg gcgtccggtc cggccggggc cggctggggc 51060
aggtgctcca gcaccacatg gcagttggtg ccgccgatac cgaacgagct gacgcccgcc 51120
agcaggggtg cgccgctcgg gccggggtgc agttcggtcg gggccgtctg caccttcagc 51180
cggagccggt ccaaggggat ggcgggattg ggggtgtcga agttgagcga gccgggcagg 51240
gtgcgttccc gcaggcagag cacggccttg accagtcccg cgatgcccgc ggcgccctcc 51300
aggtggccga tgttggtctt caccgacccc accaacaagg gagtgtccgc cgaccgtccg 51360
gagccgtgga ccgcgccgag ggcgtgcgcc tcgaccgggt cgcccacggg ggtgcccgta 51420
ccgtgcagtt cgacgaagtg cacctcagcg gggtcgaccc cagcctgggc gcaggcggac 51480
cggagcaccg cttcctggcc ctcacggtca ggggcggtca gcccggggcc gccgccgtcg 51540
ttgccgatgg cgacgccgcg caccacgcag tacacggggt cgccgtcggc cagggcgtcg 51600
gcgaggggtt tgagtacgac ggcggcgccg ccctcaccgc gcacatagcc gttggcgcgg 51660
gcgtcgaagg tgtggcagcg gccgtcggga gacagcgcgc cgagccgttc catggcggcc 51720
gaaccctcgt cggcgaggat caggttgacg cccccggcga cggcgatgcg ggaggtgccg 51780
gctcgcaggc tctcgacggc gagggccacg gcgaccagtg acgacgactg cgcggtgtcg 51840
accgcaaggc tggggccgcg cgttcccagg acgtaggaga gccggttggc gagcatggcc 51900
cgctggaggc cggtggcggt gtgggcgcca atcggcgcgc cggcccggtg gagcagcgtg 51960
gcgtagtcgt cgttcatggc ccccacgaag acgcccaccg cctcgcctcg cagcgaaccc 52020
gggacgattc cggcgtcctc cagtgcttcc cagccgagtt cgagcatcag gcgctgttgc 52080
gggtcggtct cggcggcctc gcgcggtgac atgccgaaga acgcggcgtc gaagtcgccg 52140
accgcctcga tcatgccgcg ccgacgaccg tctgcggcac ggcctatcgc ttccgttccg 52200
tcggtcagca gtttccagaa ttcctggatt cccggtgcgc tgggaaatcg gcacgacatt 52260
ccaacaacgg caacggcatt ggaccggtcg tcacttcggg aaatcacgag atcttcagac 52320
acctgcatcc ctcatatgct cgccatgcca tgtcgcggaa tgttctgccg tttctggatc 52380
ttcacgagcg tacagcggac gaacagttgg gcgacaggaa cgaccaacga acggcaatca 52440
attgtgtcaa gttccgcgga ttcgccgcgg attctcatga cacgggtcgc cgacgactgt 52500
ggactgggat cttccggaag gctttccggc gaaaagggag cggcattgtg tcaggtctgt 52560
attgccgagc tgcggcgact gcgcgcaagc accccgcccg ccggggccgg agtcggcgcc 52620
ggcgcccggt cgggtgcagt gactcacggc ctgcgcccca agggccgacg gcccgctcac 52680
gcggtcaccc ggcatttccc cgacctggcc cctgccttgc cccagccccc tgcccctggc 52740
tgggcctcgg tgcggaattc cgcgaactcc ttcgcgaatc ctctgacaca tgaactcgca 52800
catgaacgtg cacgcgaact cctgggtgaa cgcgcacgtg atctcccagg tgaaccgcga 52860
agctttcagc accgggtcgg ctcggcacaa ccgccccgcg gtgaatatgt caggttcccc 52920
gcgccgctcc gtccgctccc gagcggcatc tcgacaaggt tccccggacg gggagtcatt 52980
gtgtcaggtc cgccttgctg gcgttcttca ccgattcata agctctgccg ggatcgaggg 53040
accgatactg ccgtgtcgcg cgttcggtcc gcacaccgat tttcaaggag ttcgactgat 53100
gggtgaggct gtgtcgggac cgatggagtt gagcaaggat gcggatgccc gggggctgct 53160
ggactggttc gctttcaaca ggacacgtca tccggtgttc tgggacgagg gccggcaggc 53220
gtggcaggtc ttcggttacg acgactacgt gacggtgtcg aacaacccgc agttcttctc 53280
gtcggacttc aacatggtga tgccgacgcc gcccgagctg gaaatgatca tcgggccggg 53340
cacgatcggc gcgctggacc cgcccgcgca cggaccgatg cgcaagctcg tgagccaggc 53400
cttcactccc cggcggatcg cccggctgga acccagggtg cgcgcgatca ccgaggaact 53460
cctggacaag gtacgggaac agaacgtcat cgatgccgtc ggcgacctct cctacgcact 53520
gccggtcatc gtgatcgccg aactgctggg cgtacccacc ggcgaccggg acctgttccg 53580
ggagtgggtc gacaccctgc tgacgaacga gggcctggag tacccgaacc tcccggacaa 53640
cttcaccgag acgatcgcgc ccgcgctcaa ggagatgacc gactacctcc tggaacagat 53700
ccacgccaag cgggaagccc cggccgacga cttgatcagc ggtctggtcc aggccgagca 53760
ggacggccgc cggctgaccg atgtcgagat cgtcaacatc gtcgcgctgc tgctgaccgc 53820
cgggcacgtc tcctccagca ccctgctcag caacctcttc ctcgtcctgg aggagaaccc 53880
gcaggcactg gaagacctgc gggccgatcg cacgctggtg cccggcgcga tcgaggagac 53940
actgcgctac cgcagcccct tcaacaacat cttccgcttc gtcaagcagg acaccaccat 54000
cctcggcccg ctcatggaga agggccagat ggtgatcgcg tggagccagt ccgccaaccg 54060
ggacccccgg cacttccccg acccggacac cttcgacatc cgccgctcgg acggcacccg 54120
gcacatggcc ttcggccacg gcatccacca ctgcctgggc gccgccctgg cccgcctaga 54180
gggcaaggtc atgctcgaac tcctcctgga gcgggtcgac ggcttccgca tcgaccacga 54240
aaacacgctg ttctacgagg ccgaccagct cactccgaag tacctgcccg tccgcgtcga 54300
ctggaactga acccgagggt tccgtccccg ggccagggcc gtcccgagcc ggccgtggac 54360
ctcacgaccg cccgataagg agcgccgcca tcgccgagaa cacagccgag cctcccgccc 54420
ggcgggtcgg caggatcaag ccgtgccggc tgatcaggct cgagcagcac atcgacccgc 54480
gcggcagcct gtccgtggtc gagtccggcg tgaccgtgga cttccccgtc caacgcgtct 54540
actacatgca cggccagacc cagtcctcac ccccacgcgg cctgcacgca caccgcaccc 54600
tggaacaact cgtcatcgcc gtccacggcg ccttctccat caccctcgac gacggcttcc 54660
agcacgccac ctaccgcctc gacgaacccg gagccggact ctgcatcggc cccatggtct 54720
ggcgcgtcct caaagacttc gcccccgaca ccgtcgccct cgtcctcgcc tcacagcact 54780
acgaagaatc cgactactac cgcgactacg acaccttcct gcacgacgca cggagcctca 54840
catgacaatc cccttcctcg acgcaggcgc cggctaccgg gagttgcggg ccgacatcga 54900
cgcggccctc cagcgggtgt ccgcctccgg ccgctatctg ctcggcgctg aactggaggg 54960
tttcgaggag gagttcgccg cgtactgcga caacggccac tgcgtggcgg tcggcagtgg 55020
ctgcgacgcg ctggagctgt ccctgcgcgc gctggacatc ggtcccgggg acgaggtggt 55080
ggtgcccgca cacaccttca tcgggacctg gctggccgtg tccgccaccg gggcgcagcc 55140
ggtggccgtc gatccgacgc cggacgggct ttccctggac ccggcgctgg tggaggcggc 55200
cgtcacccct cgcaccaagg ccctgatgcc cgtacatctg cacggacacc cggccgatct 55260
ggacccgctg ctggcggtcg ccgaacggca cggcctggcc gtggtcgagg acgccgcgca 55320
ggcgcacggc gcccgttacc ggggccgccg gatcggctcg ggccacgtgg tcgcgttcag 55380
cttctacccc ggcaagaacc tcggcgccat gggcgacggc ggcgcggtgg tcacccggga 55440
cgccggagtg gccgatcgga tccggctgct gcgcaactgc ggctcccggg agaagtaccg 55500
gcacgaggtg cgggcgacca actcccggct cgacgagctc caggccgccg tgctgcgcgc 55560
caagctgccg cggctcgacg cgtggaacgc ccgccgggcg cgcacggccg aacgctacac 55620
ccgggccctg ggttcccttc cgcagatcgc cgtccccgtc accgctcgct gggccgaccc 55680
ggcgtggcac ctgtacgtga tccgctgcgc ggaacgcgac gagctgcgcc gccggctcga 55740
gcgggccggg gttcagaccc tgatccacta ccccgtaccg ccgcaccggt ccccggccta 55800
cgccgacgcc ccggccgggg ctccggccgg ggcccacccg cgcagtgaac gcctggcggc 55860
gcagagcctc agccttcccc tgggaccgca cctcggggac gacgagtccc gtgccgtcgt 55920
ggcggcggtc cgggcggcgg ccgcggggct ggcggcgtac ccgacgccgg acggcacgcc 55980
gcgcacgccg cgcacgacgc cggacggcca gcgttttcct ctagcgacgg agaaacgatg 56040
accgaggtca tgtcagggcg ttccggaatg aaagggatca tcctcgcggg cggcggaggc 56100
acccgcctgc gccccttgac cggcacgctg tccaagcaac tgctgcccgt ctacgacaag 56160
ccgatgatct actacccgct gtccgtcctg atgctgggcg gcatccgcga gatcctcgtc 56220
atctcctcca cccagcacat cgaactcttc cagcaactgc tgggcgacgg ctcccggctc 56280
ggcctggaca tcacctacgc cgaacagccc gagccccagg gcatagccca ggccctcacc 56340
atcggcaccg accacatcgg tgactccccg gtcgcgctca tcctgggcga caacatcttc 56400
cacggccccg gcttctcctc cgtactccgg ggcagcatcc gccacctcga cggctgtgta 56460
ctgttcggct acccggtcag cgacccgcag cgctacggcg tcggcgagat cgacgaccag 56520
ggcatgctgc tgtccctgga ggagaaaccc gcccggcccc gctccaacct cgccgtcacc 56580
ggcctctacc tctacgacaa cgacgtcgtc gacatcgcca agaacatccg gccctccgca 56640
cgcggcgaac tcgaaatcac cgacgtcaac caggtctacc tggagcagaa acgcgcccgg 56700
ctgatcgaac tgggccacgg cttcgcctgg ctcgacatgg gcacccacga ctccctcctc 56760
cagggcggcc agtacgtcca actcctcgaa caacgccagg gagtacggat cgcctgcatc 56820
gaggagatcg ccctgcgcat gggcttcatc gacgccgaca ccctctactg gctcggccgc 56880
gagctgggca cctccggata cggcgcctac ctgatggagg tggccaccca tgcaggcgcc 56940
gcatgagtcc ccgcaccggc ccacccgctt cgccgacggt cggcagccgg cccgtatcct 57000
cgtcaccgga ggcgccggct tcatcggctc gcgcttcgtg aacgccctgc tggacggctc 57060
gctgccggag ttcggcaagc ccgaggtgag ggtgctcgac gcgctcacct acgcgggcaa 57120
cctggccaat ctggccccgg tgggcgactg tccccggctg cggatcttcc agggggacat 57180
ctgcgaccgc agcgcagtcg cccaggccat ggcgggggtc gatctggtgg tgcacttcgc 57240
ggccgagtcg cacgtggacc ggtcgatcga cgacgccgac gccttcgtgc gcaccaatgt 57300
gctgggcacc caggtcctcc tccaggaggc gctggccata cgccccggcc tgttcgtgca 57360
cgtttccacg gacgaggtct acggctcgat cccggtgggg tcgtggcccg aggaccaccc 57420
gctgagcccc aactccccct atgcggcctc caaggcgtcc tccgacctgc tggcactggc 57480
ctaccaccgc acgcacgggc tgccggtgtg cgtcacccgt tgttccaaca actacgggcc 57540
gtaccagtac ccggaaaaga tcatcccgct gttcaccagc aacctgctcg acggcaggac 57600
cgtcccgctg tacggggacg gcggcaaccg gcgcgactgg ctgcacgtga acgaccactg 57660
ccggggcatc gccctggtgg cccggggcgg tcgccccggc gaggtctaca acatcggcgg 57720
cggcgccgag ctgaccaacg tcgagctcac cgaacgtctg ctgaagctgt gcggagccga 57780
ctggtcggcg gtgcggcagg tgccggaccg caagggccac gaccagcgct actccgtcga 57840
ctacaccaag atcgccaccg agttgggata cgcgccgcgg atcaccatcg acgagggact 57900
ggagcagacc gtgcgctggt accgggagaa ccacgcgtgg tggacgcctg tgaagagggg 57960
acgatgacgt tgatgtccgc atccgtggac ccgcgtgacc tttggctccg ccggtaccag 58020
ccttccgcgt cgcccgccgt gcggctggtg tgcttcccac acgcgggcgg ctcggcgagt 58080
tccttcctgc cgttcacccg gcaactgccc gacagaatcg aggtgtctgc cgtccagtac 58140
cccggacgcc aggaccgcag gagcgagcct ctgatcgaca ccatcgaggg cctggccaag 58200
cccctggccg acatgctgga gacacgggcc gggccccctg tggtgctgtt cgggcacagc 58260
atgggcgcgc tggtcgcgta cgaggtcgcc cgcgtgctcc agcagcgggg agcggccccg 58320
gtgcgcctgg tggtctccgg acgccgggcc cccgcctcgg accgaccgat gaccgtgcac 58380
ctctacgacg acgaccggct ggtcgaggaa ctccgcacgc tcgacggcac cgacagccaa 58440
gtgttcgccg atccggagct gctccagctg gtgctgcccg cgatccgcaa cgactaccgg 58500
gccgtgggga cctacaccca ccgtccgggg gcgcccctgg actgccccct caccgtgttc 58560
accggtgccg acgaccccac tgtgaccgcg gccgaggcgg cggcctggca cgaggtggcg 58620
gcggccggcg ccgagatgcg gaccttcccc ggcggccact tcttcccgta ccagcggacc 58680
gcggaggtgt gcggagccct ggtggacacg ctcgcgccgc tgctctcgac cgggacgcgc 58740
ggcgtccggc gggtccgccc cggggacgtc ggcacggtcg aatacgccgg ccaccggcgc 58800
accgcggaac gggtgctgct ctccgccgac acgctcgaca gtccggtcac ctcgctggcg 58860
gacgtgcccc gctggctgga ggcgtaccgc cgggcgcacc gcttccacgt cgagccgatc 58920
ccgttcgacc ggctccggcg gtggtccttc gagccgggca ccggcgacct gcggcacgag 58980
acgggtcgct tcttctccgt ggaagggctg cgcaccagct cggacgccga cccggtcgcc 59040
cgcgtccagc cgatcatcgt gcagcccgag gtggggctgc tcggcatcct ggcgcgggag 59100
ttcgacgggg tcctgcactt tctgatgcag gccaaaccgg agcccggcaa cgtcaacggg 59160
ctgcagctct cccccacggt gcaggccacc cgcagcaact tcgacgaggt gcaccacggc 59220
cggtccaccc cgttcctcga ccacttcatc caccgtcccg gccgacgggt cctgatcgac 59280
accatccagt ccgaacaggg cgactggttc ctgcacaagc gcaaccgcaa catggtcgtc 59340
gagatcgaca cggacatcga ggccgatgcc accttccgct ggctgaccct gggtcagatc 59400
cgcaggctga tgctccagga cgacctcgtc aacatggaca cccgcagcgt gctggcctgt 59460
ctgccgaccg cgcacggcgc gcccgacgac gacgaggact tcccggcggc gctccggcgc 59520
tccttctacg gggaggccgc accgctgcac gacctgcacg ccatcaccag ctgcctcacc 59580
gacgtccggg cactgcgggt gctgcgccag cagagcgtgc cgctcgacga cgcccgtcgg 59640
gacggctggg agcggaccga gagcacgatc cggcaccgca gcggtaagca cttcgagatc 59700
atggcggtgg aggtgacggc ggagcggcgc gaggtggcgt cgtggaccca gccgctgctc 59760
cgcccgtgct cccaggggct cgtggctctg atcacccggc ggatcaacgg ggtgctgcac 59820
gccctggtgg aggcgcggtc ggacgtaggc accctgaacg tcgccgagtt cgggccgacc 59880
gtccagtgcc ggccagccga atcggacggc atgtcgcccc cgtacctgga ccaggtcctg 59940
acggccggag ccgaccgcat ccgctacgac gtggtgcagt ccgaggaggg cgggcgcttc 60000
taccacgcgc gcaatcgcta catggtggtc gaggcggggc cggagctcga cacgggctgc 60060
ccgcccggct tctgctgggc gaccttcggc cagctcaccg aactgctcgc gcacggcaac 60120
tacctcaacg tcgaactccg caccctcgtc gcgtgcgcac acgcctccta ctgaatgcct 60180
acgaaaacta caccgcgggg gaatcggcac cacgcccgcc ggtcaaccat cggcaaagaa 60240
ggcagaggac cgttctcgca catcagcgac gtgcgggaag cgacggaacg cccggcacgg 60300
accgcgcaca attacgggag agaacctccg ggtatccgcg gataaccgct tcctcccaag 60360
ccttcctcac cccccgaagg accgtgcaag aaatcccgat ggccgacgac attcctttcg 60420
atcctccccg gatatggaga tcccgtgggc gagcgtgcga atatcgtgca cgggcacgta 60480
catcgccctg ctcgattcca gccaattcct gccatcggtc ccgcattccc actcctgcgg 60540
cgcgctcggt gccgtaggtc ccgcgccggt ggacacgcgg cttccgagac cgggcacatg 60600
ccggtggatg cgcgacttcc accaccggcc acacccggcg gatgcgcgat ttccacgagg 60660
tgaccgacag cgacttcacc ggaatggcgg cccgccgggc atcgccgcgc caccgctttc 60720
cggccgctcg ccccgccgcc gcccgggaca ccgcacggga cgggaagcga ccgcggcccg 60780
gcgtcgagcg aacctgccca agcccggacg agacagcgcg acgcgagagg tgaccatgat 60840
caatctcttt caaccccaga tgggtgccga ggaactggcg gcgatcgccg gggtcttcga 60900
cgaccaatgg ctcggtcacg gaccacggac caaagcattc gagtccgcgt tcgccgacca 60960
cctcggggtc ggccccgagc acgtcgtctt cctcaactcg ggtacggcgg gcctcttcct 61020
ggccctggaa tcgctcggac tgcagcccga cgacgaggtc gtgctccctt cgcccagctt 61080
cctcgccgca gcgaacgccg ttcagctgac gggagcgcgc ccggtcttct gcgacgtcga 61140
cccccggacg ctgaacccgg ccctggagca catcgagcag gccgtcaccg cgcgcaccag 61200
ggccgtcatc gcactccact acggcggata ccccggcgac atcgtccgca tcgccgagca 61260
ctgccggaac cagggcatca ccctgatcga ggacgccgcg tgttcggtgg cctcccgcat 61320
cgacggccga gtggtcggca ccttcgggga cctcgccatg tggagcttcg acgcgatgaa 61380
ggtcctcgtc accggcgacg gcgggatgat ctacgtcaag gatcccgggg cggccgcccg 61440
catccggcgc ctcgcctatc acggcctcac ccagtccagc ggcctgggat acgccagggt 61500
ctcggcgcgc tggtgggaga tggacgtccc cgagccgggc cgacgcgtca tcggaaacga 61560
cctcaccgcg gccatcggcg cggtgcagtt gcggcggctc cccgatttcg tggcccgccg 61620
caaggagatc gtcgccctct acgaaagcga actgcgcaca atggagggcg tgtcgacgcc 61680
gcccgcgctc ccggaaggac acgagtccac gcactacttc tactggatcc agctgccccc 61740
cggcgtccgg gaccgggtgg cgcgcgacct gctcaccgac ggcatctaca ccaccttccg 61800
ctacgccccc ctgcacaagg tgcccgccta cggtcacgcc ggacgcgaac tgcccggcgt 61860
ggagtgggcg tccgagcgga ccctgtgcct gcccctgcac ccgggcctgt cggacgccga 61920
cgtcctcacc gtcgtgtcct ccttgcgcaa agctctgaac gccggggcgc aggctcccgc 61980
ataacaggcg catacggtac ggcccctgcc cggcggttct ccgccgggca ggggccgttt 62040
cgcgtccggg acggtctccg tcgtcccgtc ggctcgctag gcgcgcgtgc cgaggaaaaa 62100
gccgggggag ccgttgcccg tctcgacgta ctcgacgtgc aggccggcct tgcggtacgc 62160
ggtctcgtac tccgcacggg agaacagcgt gaggtagtcc acctcgctgc ggtgccggat 62220
gccgtcggtg gtgtgcgcga tcaggtagtg gatttccatc cgggtcttct tgccctccct 62280
ggtcgagtgg gcgacgcggg cgacgccctg gtctcccgac tccgtcctga gggcgtgggt 62340
ggagacgtag ccgtccagga aggtgtcggg gaagtaccac ggttcgacgg ccaggacgcc 62400
gtccgcggag aggtgccggg acatggcggc gatcgcgtcc tccaggtcgg ccgcggtctc 62460
cagatacccg atcgaactga acatgcagac cacggcgtcg aacgtctcgc cgaggttgaa 62520
cgagcgcatg tcgccgcggt ggagggtcac atcggagagc cgctcctcgg cgcgggccgc 62580
catccattcg gagagctcca ggccgctcac acggtcgtag agcttggcga aggcctccag 62640
gtgcgtgccg gtgccgcagg cgatgtcgag caggctggag gcgttcggcg tgcgttcccg 62700
gatcaggccg gtgacccggg cggcctcgcc ggcgtagtcc ttgcggtcct ggtacagcag 62760
gtcgtagacc tcggccgcac tgtcgttctc gtacatggga atcctccggg ccgtgttggg 62820
gggggaaccg ttggtgtgtc gaagaggagt gcgccgtgcg gtcgggggca cgggcggcat 62880
tccgctgcgg aggccgtcgt tcggacgcgt cgtgcgcacg ccgaacccgc tatgcgcgta 62940
cgggagttcc atcgaccgaa gccgtgcggg tatccgaccc gcaccggtcc ttcgcggtga 63000
tctccgtacg gacacccaac agttcacgcc gagtcgaggt caaggaacgg cagcctggtc 63060
agtcaagtcc ggcggtccgc acttggggca gtgggcgccg acgcgccccg ggccccgggg 63120
cgggcgccgg tcgggccgtc ccgcggagcc ccattcccgt cctcccgcag aagggatgca 63180
gaatcggaca gccgacggct tgtttcaccg gaaaacgcgt ggtgcgcccc gagtcgccgg 63240
tagcttatcc accgttcgcc gaggcggttc aagtggcagc gttcaaccgc gatccggtct 63300
ttatggaatt catatctgcc cgctggcttg atgagtcggg cctcatgtcc ggaagtcgat 63360
cccggccggg agtgcgcggc gatccgcccg gacgccgaat gccgtggccg gcacccgtcc 63420
ggtaacgtcc tgcggggtac ggacggcggt ccggccgtcc atcagaatcg gacgaacggg 63480
atgaaatgtt atggcgaggg agcgaaagga agcgggtgcg gaggatttac cgcagcccgt 63540
tccaggaccc tcggcgatct agatcgggta ccctgatagc gtaataacct gtcattgtat 63600
tcgtaaagca cagggatggg ggcgcctgcg gcatgagtta cctggattat ggtgaagaag 63660
cgtctgaaga agacgagtcg gacgacgcac tcaccttcct cgaatttgtt gcccggtcgg 63720
ccccgcggag cgaatacgac cggctcatgg cgcgcgcgga acgcgcgggc gccgacgagg 63780
aacggatgcg tcggctggag cgcttcaacc ggctcgccct caccgcgcag tcgatgatcg 63840
agtaccgccg cgaccgggag gcggagctcg cggcgctggt cgacgccgcg cacgagttcg 63900
tcgccgccca gcagtacaag gacctgctcg aatccgtcgc ccgcagagca cggctgctgc 63960
tcaagctgga tgtcgcctac gtcagtctgc accaggagga cctgcaccac gaggaccggc 64020
ccggcacggt ggtgctgagc gccgacggca acgcggtcaa ggtcgccgac agctaccggc 64080
tgccggccga cggcgggctg ggcggcatgg tgcgcacctg ccacgctccc ttctggaccc 64140
ccgactacct cggggacagc agcttcgtgc acgtcgagac cgtcgacgac atcgtccgcg 64200
cggaagggct gcgcgcggtc ctggccgttc cgctgtgcgt cggcgacgac tcggtggggg 64260
tgctctacgt cgccgatcgc caggtccggc acctgacccc caacgaggtc accctgctgt 64320
gttcgctcgc cgatctggcc gccgtcgcga tcgagcgtat ccggctggtc gaggagctcc 64380
gcgacaccat cgggcggctg cgcgaggacg tcggtgaggc ccgcgccgcc ctcgcgggca 64440
cccgcaggtc cgccgacctc cagtcgcacc tgatcactca ggtcctcgaa aggcgcgggg 64500
ccgacgcctt actcgccgcc gccgccgaat ccctgggcgg cggcaccagc ctctgcagcc 64560
cgctcggccg gccgctcgcc gagtacggga acctgcgccc cgtcgccccc gccgacctgc 64620
gcgccgcctg ccgcagggcc gccgaaaccg gccgacccac ccccgtcgca ccggggtact 64680
ggacggtccc cctgtacccc ggggagtaca acgccggctt cctgctgacc gacgtcggac 64740
ccgaggcgga ccacacggtc gtaccgctgc ttcccatggt cgcccgtacg ctcgcgctgc 64800
atctgcgcat ccagcgcaac gactccacca aggcccagag ccaccaggac ttcttcgacg 64860
atctggtcgg ggcgccgcgc tcgcccgccc tcctcaggga gcgcgccctg ctgttctccc 64920
tcagcttccg ccgcccgcat gtcgtgctgg tggcgagcgg accccacgga gcctcggcgc 64980
ggctggagtc ctccggcgcc gactacgcga aggaactcgg cgggctgtgc agcgtacggg 65040
acggcgccgt cgtcctgctg ctgcccggcg acgaccccgt ggccgtggcg cagaccgccg 65100
ccccggaact caccgatcgg gtggggcacc cggtcaccgt gggggccgcg ggccccgcct 65160
cgaccgtcga cggcatcagc gacgcccacc gcgaggccgc gcagtgcctg gagacccttc 65220
gcgcgctcgg cggtgacggt ggcaccgcct gcgcctccga cctggggttt ctcggaatgc 65280
tcctggccga ggaaaacgat gtccccggct acatcaagac gaccatcggc cccgtgatcg 65340
actacgacac ccaccgcttc acggatctca tccccacgct gagggtgtat ctggagtcgg 65400
gcaggagccc cacccgcgcc gcggagacgc tgcgcgtgca ccccaacacc gtctcgcggc 65460
ggctggagcg catcggccaa ctgctgggag aggactggca ggggccggag cgggtgctgg 65520
acatccaact ggccctgcgg ctgtaccagg tgcgttcggc gctctcctcg cgctccgcgt 65580
ccgcctcgct ccccccgcgc ccggcgcccg cctcccggac cgtgctcgga tcgcagcgcg 65640
agtgagcgcg ggcggccagg cgatgcgcgg ccggacggcg cccggtggcc gcgccaccgc 65700
cgtggtcacc cggtgacgga ctcctggtgg ccgcgccacc gcccgtcctg cgacagccgc 65760
agcgcatggg cgatcgaggc cggcgtcacg tgccggtgcc ggccctggaa cgagcgcccc 65820
tcgaagtcac ggatgccgac gtccacgccg acccgggcga agtcggcgtc cacccggtcg 65880
gtcagcgccg ccagcggcag cagcgcccgg tgccccaacg ggccgaggtc ggtcagccac 65940
aggcttcggg tccggcttcg ggccccgatc gggtttcggc ttcggcgtcc gtttcgggtc 66000
ccggtgggga ttcggcttcg ggtcaagcgg agtagtgatc atcacgccct tcgcagggcg 66060
ctcgaattcc ggtgactgcg tgcgccacag ccttacggaa ttctccgggc cctcgcagac 66120
acaccgggca caccctttca gcgccgcccc ggctcccgcg attcactccg ggcccacggc 66180
ccgtctcgcc ctgaaaaccg gtggtcaact caccgtggcg accctctcga cggtggcggg 66240
acattccacc gaatggcacc gagaaacgac gccactgcac ccgtgctgcg gcattccctt 66300
ttccgtcgct ttggtcatgt gaggctccgt gcgtcgtgca ggaaggtgtc gtagtcgcgg 66360
tagtagtcgg attcttcgta gtgctgtgag gcgaggacga gggcgacggt gtcgggggcg 66420
aagtctttga ggacgcgcca gaccatgggg ccgatgcaga gtccggctcc gggttcgtcg 66480
aggcggtagg tggcgtgctg gaagccgtcg tcgagggtga tggagaaggc gccgtggacg 66540
gcgatgacga gttgttccag ggtgcggtgt gcgtgcaggc cgcgtggggg tgaggactgg 66600
gtctggccgt gcatgtagta gacgcgttgg acggggaagt ccacggtcac gccggactcg 66660
accacggaca ggctgccgcg cgggtcgatg tgctgctcga gcctgatcag ccggcacggc 66720
ttgatcctgc cgacccgccg ggcgggaggc tcggctgtgt tctcggcgat ggcggcgctc 66780
cttatcgggc ggtcgtgagg tccacggccg gctcgggacg gccctggccc ggggacggaa 66840
ccctcgggtt cagttccagt cgacgcggac gggcaggtac ttcggagtga gctggtcgcc 66900
ctcgtagaac ggtgaactcg atccggcgtt cggcttccgg catccgagcc cgtcgacgtc 66960
agcggaacat acgaagcacc gaggcagtcg gcaagacgga cgtgacacag tgggcgcctc 67020
tgtcggaagc ggcgcccgga cccggcgcac cgcaccggtg gacacgaatt tccgtaccgt 67080
cggcggaagt tgacggacgc ctcgcctttt ccgcacgaag gcgcgcgaag gcgcgcgaag 67140
ttccttggcc ggacgacagc gccgaccgcg acctgacatc cgttcatcgg caagtcctgc 67200
cgcttccgca ggcgcccggg ctcagggaac agcggtgcag ccagagcacc ggcccccgcc 67260
cgtcggcgcg gatcgccgtc gggcgggcgg gttttgagcc ttgaccgcgg ccccttcgga 67320
acgaggtccc gggcccgcgt gagggcgtgg ctcagcctgc gctgaactcg gcgatgcacc 67380
cgtggtccat ggcaagccgg gccccggtga accgggaccg catccggcgg tcgtgggtga 67440
cgacgaccac ggcgccccgg tagtccacga gtgcctgctc cagttcctcg accagcaccg 67500
gggtgaggtg gttggtgggt tcgtccagta gcagcaggtc catcgggtcg ctcaccagcc 67560
gggcgatctc gatccggcgg cgctgcccgt acgacaggtc cttcacccgt cgccgcaggt 67620
cggacgggct gaacaggccc aacgagagca gtttctccgc gtggtcctcc aggtagccct 67680
cccggccgtg ggcgaaggcc cgcagcaccg tgagctcggg cgaccagggc gtctcgtcct 67740
gccgcaggtg cccgactcgg cagccgacgc gcaccgagcc gctgtccggc gccagttccc 67800
cggagagcac ccgcagcaag gtggacttgc ccgcaccgtt gggtccggtg atcagcagcc 67860
gctcgccggg ccggatcttc agggagtcga cgtcgagccg gtccgcgacc cgcacgtcgg 67920
tgagttcggc caccgcctcc tccgcctccg ggcccgcggt gtcgatgcgg gcggcgaagg 67980
acagcgggtc cgcgggggcc agggccgggt tctcggtcag ctgcgccacg cgttgcttgg 68040
cgttgcggat ccgcaccatc gcgccgtggt cgcgtccgcg cctgcggtag gcgccgtggc 68100
cgaacacgga gagggacatc ttgcgcggga tgttgtccat ccgcgccacg ttggaggtga 68160
tcagcccctg gttgcgctca agttcggcac gccattcctc gtactcccgc agccgccgct 68220
cgcgttccac ggccttggcc gtcagataac cctcgtaacc gttgccgtag cgggtgacgc 68280
ggccggagtc gacctccagg atcgtggtgg tgagccggtc caggaacacc cggtcgtggg 68340
tgaccgcgat caccgtgccg cggtggccct gcaggtggtt ctccagccat tccatcgccc 68400
ggtcgtcgag gtcgttggtc ggctcgtcca gcagcaacag ttcgggcgcc gaggccaggg 68460
tcgccgcgag ggcgaggcgg gagcgctcgc cgccggagag ggttccgagc ttccggtcgc 68520
ggtccaggct cggcagtccg aggccgtgca gcgcgacctc cacgcgtacg tcggcctcgt 68580
aaccgccacg ggcctggtac tgctcgacca gaccggcgta gcgctggagg agggcggaca 68640
gctcccgttc ggaaccgtcc tcgtcgcgct cggtcagttc cgcctcgacc tcgtgcatcg 68700
acgcttcgag ctcgcgcagg tcggacaggg ccagatcgac ggcgtcttgg acggtggcgt 68760
cgagcggcag ttccaacgtc tgtgccagat agccgatgcc gccgggggcg accacggtga 68820
gcatgccgtt gtcgggctgc tcgcgcccgg cgaggacctt gagcagtgtg gacttgccgg 68880
aaccgttgtc gccgatcacg ccgaccttct cgcccggctt gatgctgaag ccgacccggt 68940
cgagtacgac acagtcgtgg tagcgcttga tgacgtcatg cagggcgaat tgcgcaatcg 69000
acacgtgtgt gtctcctgtt tcacgatgag gatgagtgaa tgcgtgagcg cgctcggcga 69060
aacggccgga agaaagcgac acaaacgcca ccacagcgga ctgaccgatg cagtggtgtg 69120
tcagcagcac gctgctggat gcggcaacgg agtccagctc aacgccgcgc atcctcatct 69180
atcacagaga tcccatgcga tgaactataa acgggccacc cgatgccggg caaggggatt 69240
cgggttcccc ggcccgacgt gatgcagtcg gaacgggatg atcgcccgtc cggcggtcgg 69300
gtgcctagcc tcgggaacaa ccacagcggt ctttcaggag ggctggccat gggcgagacc 69360
aagaaccgga tcaccgaact ggtccgcgcg taccaccggg aacaggcgac cgggaatttc 69420
gttcccggga cgacgcacgt accggtctcg ggcgcggtac tgagcgagga cgaccggttg 69480
gcgctggtgg agacggcact ggagatgcgg atcgcggccg gcccggcctc ccggagcttc 69540
gagcggcagt tcgcccggta cctcgggcta cggaaggcgc atctgaccaa ctccggctcc 69600
tccgccaacc tcctcgccct cagcgcgctc acctcaccgc agctggagga caggcggctg 69660
aaaccgggtg acgaggtcgt cacggtcgcc gccgggttcc cgacgacggt caacccgatc 69720
ttccacaacg agctggtgcc ggtcttcgtg gacgtcgaac tcggcacgta caacaccacg 69780
cccgagcgca tcgagcgggc catcggcccc cggaccaggg cgatcatgat cgcgcacgcc 69840
ctcggcaacc ccttcgaggc cgaagaggtg gcccgactcg ccgacgagcg cggcctgttc 69900
ctcgtcgagg acaactgcga cgcggtgggc tcccgctacc ggggcagact cacgggctcc 69960
ttcggcgacc tgtcgaccgt cagcttctac cccgcgcacc acatcgcgat gggcgaggga 70020
ggctgcgtgc tcaccgacaa cctggccctc gcgcggatcg tggagtcact gcgcgactgg 70080
gggcgcgact gctggtgcga acccggcgag gacaaccgtt gcctcaagcg gttcgaccag 70140
aaaatggggg acctgccgcc cggctacgac cacaagtaca tcttctcgca tgtcggttac 70200
aacctgaagt ccaccgatct gcaggcggca ctcgggctgt cccagctgac gcggatcgag 70260
gagttcaccg acgcccggcg cgccaactgg cgccggatgc gggagacgtt ggacgggttg 70320
cccggcctgc tgctgccgga ggcgacaccg ggcagcgacc cgagctggtt cgggttcctc 70380
atcaccgtgg acccggacgc cacgtacagc cgggcggccc tggtcgacca cctggagtca 70440
cgccggatca gcacccgccg cctgttcggc ggcaatctcg tccgccaccc cgcctacacc 70500
ggccgtcagt accgggtgtc gggcgccctg gagaacagcg acctgatcac cgatcagacc 70560
ttctggatcg gggtcttccc cggcatcacc acggagatgg tcgactacgt caccgacacc 70620
gtccgggagt tcgtgctcaa gcactcctga cacgtccgcg gaacgtcggg gtggggaggg 70680
ccctgtcggc cctccccacc ccgacgttca cggccgcggg tgcgcctgca actccgaggc 70740
gaggtcgggg tggaccagcg ccgtgagcag ggtgccctcc ggcgtgtgct cggcactgag 70800
cacctcgccc tcgtcgtgcg cccgcgccac caggcccccc tcgtcgtagg ggatcacgac 70860
ctcgacctcc acggcggggt gcggcagcag gcggtcgatc agctcctgca actcgtcgat 70920
gccctgcccc gacctggcgg agacaacgat cgcgtccggc tcctgctcca gcaggcgggc 70980
gagtacgtcc gggtccgcga cgtcggcctt gttgacgacc acgatctcgg tggactcggc 71040
ggcgcccacg tcccgcagca cctcgcgtac ggaggccagc tgcgcgccgg ggtccgggtg 71100
cgacccgtcg accacgtgca gcaccaggtg cgcgtccgcg acctcttcga tcgtggagcg 71160
gaacgcctcc accaggtgat gcgggagatg ccgtacgaag cccacggtgt cggcgatggt 71220
gtacgtgcgc ccgctgggcg tggtcgcccg ccgcacggtc gtgtccaggg tggcgaacaa 71280
ggcgttctcc accaggacac cggcgccggt gaggcggttg agcagtgagg acttcccggc 71340
gttggtgtag ccggcgagag cgaccgacag caccttgttg cgccgtcgtt cctcccgctt 71400
cacgtcccgg cccgtcttta actgctccag ttcccggcgc agtcgggcca tcttgtcgtt 71460
gatccgccgc cggtccgtct cgatcttcgt ctcaccgggg ccgcgcgtgg ccatgccgcc 71520
gccaccgccg ccgcccatct gccgggacag cgactggccc cagccgcgca gccgcggcag 71580
catgtactgc atctgcgcca gcgccacttg cgccttgccc tcccgggact gggcgtgctg 71640
cgcgaagatg tccaggatca gcgccgtgcg gtccacgacc ttgacgccca cgacctcctc 71700
gaggtgcatc agctggctgg ggctcagctc tccgtcgcac accacggtgt cggcgccggt 71760
ctcctcgacg atgtcgcgca gctgcgacgc cttgcccgag ccgatgtacg tcgccgggtc 71820
gggcttctgc cggcgctgca cgaccccgtc cagcacgagg gcgcccgcgg tctcggccag 71880
cgccgccagc tcggcgagcg agctctcggc ctcggcggcc gttcccgagg tccagatgcc 71940
gacgagcacc acccgctcca gtcgcagctt gcggtactcg acctcggaga cgtcggtcaa 72000
ttcggtggac agccccgcga cgcggcggag ggaggcccgg tcctcgcggt cgaactgctc 72060
gccgtcccac ccttcggcgt cggccgcggc caatgtgtcg ttcatcagtg cgtcggctcg 72120
ctgggaggtg ccggcggagt cttcgggatg tgtcaaagta cgtcccttct gggggctcag 72180
gagcgttccg gggtggtgtg cggtcggctc ggcgggatgc gcacgggtcg ggaaatgggc 72240
cgacgtgccc gcaccgcgcc ccacaggccg gtgccgctga agtcgctgcc ggaactcacg 72300
tgttgaccac cctagccatc ccgccgaggt gcgcaaacaa gtatcggtga tcacgtctcc 72360
agctgacaga gtctgcaccg ggtactgcgc acgcgggcgt ggagcgggca agtgtgatgt 72420
catgcgagta ctcattatcg gaggttcaca gttcgtgggc cgggcctacg ccgccgaggc 72480
gctggccgcc gggcacgagg tcaccacgtt caaccggggc gtcagcggca cggacctgcc 72540
cggcgtcgag gcggtcaggg gtgatcgcga ggcggccggc gacctggagc ggctggtgtc 72600
cggaaggcgc tgggacgcgg tcgtggacac ctgcggctac gtgccccgta cggtgggcgc 72660
ctcggccgcg gcgctgtccg ggcacgcgga cgcctacctc tacgtctcca gcatcgcctg 72720
cctgcccgac tggacgcagg cggtccgccc ggtcgacgac gactcaccgg cctacgactg 72780
cccgccggac gcaggcccgg accacgccga cggcgactac ggcaccctga aggccggctg 72840
cgagcgcgcc gtggaccagc acttcgtggg ccgcaccctg cacctgcggg ccggcgtcat 72900
cctcgggccg cacgacaaca tgcgcatgct cgacgcctgg ctgtggcgca tgcgcgccgc 72960
cgagggggag caccgccggg ttctggcccc gggcggcccc gaggtcggca tgcgcctgat 73020
cgacgtgcgc gatgtcgccg ccttcggcct cgactgcctc gccgagggcc gcaccggcgc 73080
gtacatcgtc aacccgccgg agaagaacac cacgttcggg aatctgctca cggagtgcgt 73140
caaggccacc gggtccgccg ccgagccggt atgggtcgac gaccggtttt tcgccgacca 73200
cggcgtgagc ccgtggacgg acctgccgct gtgggttccc gacaccgcgc aggacaccct 73260
ggtctgggcg gccggggcgc cgcgcgcacg ggccgcggga ctggcctgcc gcccgatctc 73320
cgagacggtg cgtgacgcct gggaggtcat ccgggaccag cccgtccctg agcttccgct 73380
cgctgccggc tgcggccttt ccctggcccg ggaaagggag ttgctcgccg cctgggacgc 73440
gcgcggcggt gcggccggct gacgcggccc cggggagtgc ggcgccgttt cccgttcgcg 73500
gggagcggcg tcttccgttt ccgacccatg gggcggcgct ttccggctct tcgcgcggag 73560
ctacaccgtg acggtctcgg cgcgggcgac gatctcgtcg accaacgccg cctgacgcag 73620
ggcggcatac gactcggcgg agatgttctc ggcccgggtc accgcgcggc ggaagaccga 73680
caggatgttc acgaagtgcc ggtccacggg cagcactcgc tcttcgcggt ggtcctggcg 73740
ggacagccgc agtacggggt ggtggctgtc cggagtcgtg aagacgtggt tcagggcgag 73800
cgagccggtg ctgccgtgca gttcgtacgc cgagcggtag ccgtgttcca tgccgaaggc 73860
gaggtgggcg gccacccccg tcggcgcggc cagcaggacg ctgccggaga ccaccacgcc 73920
ccggcgccgc tcgcggcgca gcaccgctcc catcaggcgc agctcgggcc cgaggaagtg 73980
gatcgcggcg cgcagcgggt agacgccgtt gtcgaggagt gcgccgccgc cgatgtcggg 74040
gcggtagcgc atgtcgtcgt cggggcgcgg cgggatggtg aaggcggcgg agaaggtgcg 74100
caggtctccg atggccccgg tctccaacag cactttgacg gtggcgtgtt gcgagtggtg 74160
gaggaacatg aagttctcca tcagcaccag tccgcgctcc cgcgccatgg cgaaaagccg 74220
tgccgcgtcg gcgtggttgg cggcggcggg cttctccacc agtacgtgtt tgcccgcccg 74280
cagcgcggcg gcggcccatt tggcgtgcag catgctgggc acggcgatgt agacggcgtc 74340
cacgtcgggg cgttccagca gtgcctcgta gggcgcgacc gcctcgcagc cgaagtgctc 74400
ccccagggcc ttggcccgtt ccggttcacg gctgccgacg caggtcagca cggtgccggg 74460
ggtggagagc agggcgggca gggtgcggcg gcctgcgatg tcgccgcaac ctatcgctcc 74520
gaagcgcagc accggggacg cttcgggcca cggcgggccg ggtgcggcgg acggttcggc 74580
tggagtaccc agggcggtca tggatggttc cgtcaatcgg tccggatggt cacggcacag 74640
cgtggtgaac ggccggcgcg cacccacgag tcgcttccga caatgggcgg ccctgaagct 74700
acccggccgt ggggcgcgac gacaaggccg atctgacaca gtgccgcgcc aaggggccgc 74760
cgccgccctg cggacccgtt gacctgacac ttcgccaccc aatctgtgga cgggacggtc 74820
gcggtccggg ttaggtgagc gcggcgcccg cggccacgcg acgcctgtcc gaagcggccc 74880
tcggggcacg ccatttgaga gaggagacgc gggtggcaga cgcgatcacg accgagctgg 74940
cggaccgcga actgggccgc agactgcacc ggatacgggg cgcccactgg tacttcggca 75000
accacggcga tccgtatgcg ctcatcctgc gcggccaggc ggacgacccg tcggcgtacg 75060
aggagcgggt acgggacggc ggaccgctgt tccgcagcca catcgggacc tgggtgaccg 75120
cggacccgga ggtgggcgcg gccgtgctgg gcgatccccg gttcggcgcg ctggatcgcg 75180
ccgggcggcg ccccgaggag tacctgcagc cgtcgcccgc ctcgtgcctc gggctggacc 75240
gtgccgcgta cctgcgtctg cggcgggtgg ccgaaccggt gttgggggcg ggcgccgccg 75300
acgagtggcg ccggctcgcc gaggacctcg gtcgtcggct gctcgacggc cgtggttccg 75360
gcttcgacct gacggcggac ttcgcccgcc gactgcccgc gctggtcctg gccgcgtggc 75420
tcggggtgcc ggacgaacgg cgggaggagt gggaggagtt gctgcgggag gcggggccac 75480
tgctcgacag cctgctgtgt ccgcagacgc tggcggccac ccgcgcggcg gactcggccg 75540
ccgaggggct gcgcacgctg ctgggcaagg tggccgtcgc gcgctccgac ggggccggcg 75600
acggcgcgct gggccgcatg gtcgccgccg gggccgcccc ggacgacgcg gtggccgccg 75660
ccatgtgcct ggtgctctcg gccgccgaga cgaccacgac cctggtgtgc gatgcggtcc 75720
gcctgctgct cgaccgcccg cgatggtggc gggcgctgtg cgactccccc gctctggcgc 75780
cggccgcagt ccggcacacc ctgcggtacg tgcccccggt gcggctggag agccgggtgg 75840
cccacgagga cgtggcgccg acggggcacc cattgcccgc cgggagccat gtggtggtgc 75900
tcgtgagcgc cgcgcggcgc ggggccgccc cggacgccgg accggcggac ctgacgaacg 75960
tgcccacggc ggccggggcg ggcctgccgg acgacctgta cttcgcactt tccggggagt 76020
tcgtcgggcg aaccgccgag accgcgttgg gcgtgctggc cgaggtagcc ccccggctgc 76080
ggcgggaggg cgacatcgtc cggcggcgcc gctcccccgt cctcggcagg tatgcgcggt 76140
tccccgtcgc gtactcctga caggcccccg gccggtatcc ccctcagaac ccctcgaagt 76200
ccgatgaaag gagtcccgtg cgcgtcctcg tgacttccat tccgcaccac acgcactact 76260
accacctggt gcctctgatc tgggcgctgc gtgcctcggg gcacgaggtg gtggcggccg 76320
gccagccgtc gctgatcgac gccatcacct ccagcggcat cccggggttc ccgctcgccg 76380
aggaggagtc gctggcccag atcttcgagg aggtcgaggg cgatcttcag ccgtatcagc 76440
acgggatcga cgagttcgac ttcctcggta ccctgcagga cgccctggac tgggagaagt 76500
tgctcgccca gcaggtgatc ctctccggtc tgtggctcga accgctcaac ggcgccacga 76560
ccctcgacag catcgtcgac ttcgccaggt cgtggaagcc cgacctggtg ctctgggagc 76620
cgttcaccta tgcggggccg gtggcggccc gtgcgtgcgg ggcggcgcat gctcgcgtcc 76680
tgtggggtcc ggacacgatc gggctgatgc ggacgaagtt cctccaggcc caggcgcagc 76740
agcccgagga gcaccgggac gacccgatcg cggagtggct gacctgggcg ctggagcgct 76800
acgggtgcga cttccgggag gaggacgtgc tcggccagtg gagcgtggat cccatggcgg 76860
agggcgtcag cctcggcctg gacctgccga ccgtcccgat gcgctacacc ccgtacaacg 76920
gctcggcggt gattcccgac tggctgaccg aggagccgaa gcgcccgcgc gtctgcctga 76980
ccctgggggt gtcctcgcgg gagtacggcg aggacgaggt gccggtgcag aagttcatcg 77040
aagcgctggc cgacctggac atcgagttgg tggcgaccct ggacgacgcc cagcgggacc 77100
tgctgccgcg gatcccggac aacacccgga tcgtcgactt cgtccccatg gacgcgttgc 77160
tgccgacgtg ctcggcgatc atcaaccaca gcggctcggg cacgtgcaac accgcggcgc 77220
tgcacggggt gccgcagatc atcctcggca acatcctgga cgccgccgtg cggcagcaca 77280
tgttcgcgca gtcgtccgcc gccctcacct tcgccccgga ggaggtgacc ggcgagtcgc 77340
tgaggagcgc gctggtgcga ctgctcgggg aaccgaagtt ccgcgacggt gcgcagcggt 77400
tgaaggagcg gatgcgggcc atgcccagtc cggccgggat cgtcccgacc ctggagagcc 77460
tcacggcccg gcaccgccgt gcctgagggg ccgtcaagtg tgtgatgcag caaggctatc 77520
gcgtgacacg actcctgcgc gtaatcgatc tcgtcgactc agccgtggac cggttcgcct 77580
gtccgcgccg gacactggag tgttcatgcg ggcccttttc acgaccgcgc cgctcgccgg 77640
tcacctgctt ccgctcgtgc cgacggcatg ggccctgcgg gcggccggtc acgacgtcct 77700
ggtgacgacc cgggagaact tcgtcccggt cgcgctgcgg tcggggctgc cgtcctcctc 77760
gtgcgggccc gccgtcgatt tcacgggcac ggtcgccgac ggaccgctcg cgccgtctcg 77820
ggacgaggcg gggcagcggg gcgtcctggg cggggcgttg gcgcgcgtcg cccggggcag 77880
cctggccggg gtgcggcggc tggcggacgt ctggcggccg gacttgatcg tcagcgaacg 77940
ggccgagttc gccggaccgc tggtcgcggc ggccctcggc atcccgtggg tccgctacca 78000
ctggtcggtc tcctgtctgg aggagtaccg gcgcgcggcc gaggaggagt tcgcgccgga 78060
gctgaccgcg ctcggcctcg accggttccc ggatcccgcg cgcgtgctcg atccgtggcc 78120
ggtgtccctg cgccggccgg acgcggtcgc ccacgacggc atccggcacg taccggccca 78180
cggggacgcc cccgtgccgg agtgggcgtt cacgcgcggc cgcaggcccc ggatctgcgt 78240
gacgctcggc accatgctgc cccggtacgg cgcgttcggg gtgcgcgact tcctggcgga 78300
gctggtggag gagacgcgcg gatcggactg cgagctgctg atcgcggtcg acgacgacat 78360
cgtcgcgcgg tggccgccgc tgcccgccgc ggtgcggcac gccggccggc tgccgttggc 78420
cgaggtgctg cccgcctgcg acgtggtggt gcaccacggc ggtcagggca cgtccctgac 78480
cgccctggcc gcgggccggc cacaggtcgt catgccgcgg ctcgacgacc agttcgacaa 78540
cgcgcaggca ctggcggcgg cggatgcggc cctgctcgtg ccaccgtccc tggccactcc 78600
cgcggccgtg gccgcggggt gcgccgaact gctggagaac gccctgtatg ccaaggcggc 78660
agccgggctc gccgagacga tggcgctgct gccgtcgccg tcggcggcgg tcggacccct 78720
ggagcacctg gggcctgcac cgggcatgct gcggagccac gcgaacgagg atgcggtgtg 78780
acgtgatttc cgaagtactc aaccgttcga acgatccgcg cgggccgttg atcacggtgg 78840
tcggcgcgtc cggcttcatc ggatccgccc tggtcgccga gttggcgcgc acgccggtgc 78900
ggctgcgggc ggtgtcccga cgcgaggccc ccgtccccgc ggggacgccg gccgccgtcg 78960
aggtccgccg ggcggacctc gcccggccgg gcgaggtccg ggacgccgtc gagggggcgg 79020
acgcggtcgt gcacctcgcc gcccacatcg gcggcgcgca gtcgtggcgc gcggccgacg 79080
agcggtcggc gcgggtgaac gtcggcctgc tgcacgacct ggtcgacgcg ttccggggcc 79140
gctcgggcac cctcccggcc gtggtcttcg ccagtaccct gcaggccggc gccgacgtcg 79200
cccggcaggg cgcgtacgcc cggcagaagt cggccgccga agaggtcctg ctgcgggccg 79260
cgtccgaggg ggtggtccgg ggcgtcgtgc tgcggctgcc gaccgtgtac ggccgcagcc 79320
cgctgaccgg gtggaccggt cgcggggtgg tcgcgtcggt ggcgcggcgg gccgtcgagg 79380
acgggccggt cacgatgtgg cacgacggca cggtcgggcg cgatctgctc cacgtggagg 79440
acgcggcccg cgccttcgtg gcggcgctcg accacgcggc gcggctcgac ggcggcacgt 79500
ggtccgtcgg caccggccgg ctggagccct tgggagaggt gttctcgacc atcgccgggc 79560
tggtgtccga gcggacgggg aggccccccg tcccggtggt ctccacggag ccgcccgacc 79620
atgccgaggc gggcgacttc gacagcccgg tctccgaccc ctccgcgttt cgcgcggtga 79680
ccggatggtc tccccgcgtt ccgttgcagg cggggctcag cgccgtggtg gagacgatgg 79740
tggccgcgga atcgaggggt gggatccgag gttgagcacg gaccggaatc aggccgcgca 79800
cacgcggctc ggccgcagcg cgacgctggt gagccggctc tggctgggca ccgtgaactt 79860
cagcggccgg gtcgaggacg cggacgcgat gcacctgatg gagacggcgg tcgaccgcgg 79920
catcaactgc atcgacacgg cggacatcta cggttggcgg gtccacaagg ggcacaccga 79980
ggagttggtg ggccgttggc tggccaagag cgccgcgcgg cgggaggacg tcctgctggc 80040
caccaaggtc ggcggggaca tgagcgaacg gctcaacgac ggcggcctgt cggcccggca 80100
catcatcacg gcctgcgagc agtcgctgcg gcgtctgagg gtggaccaca tcgacctgta 80160
ccagatgcac cgcatcgacc acgccgctcc ctgggacgag atctggcagg cgatggaccg 80220
tctggtggcg agcggcaagg tgacctacgt ggggtcgtcg aacttcgcgg gctggaacgt 80280
cgccgccgca caggacgccg cgcggcggcg gcggtccctc gggctggtgt ccgagcagtg 80340
cctgtacaac ctggcggtac ggcacgccga gttggagttg ttgccggcgg cgcaggcgta 80400
cgggctggga gtgttcgcct ggtcgccgct gcacggcggg ctgctcagcg gggtgttgcg 80460
caagctggcg gcgggcactg cggtgaagtc ggcgcagggg cgggcccaac tgctgttgcc 80520
cgagctgcac gccacgatcg aggcgtacga ggggttctgc gaccggatcg gggcggaccc 80580
ggccgaggtc ggcctggcct gggtgctgtc ccggccgggg atcagcggtg cggtgatcgg 80640
gccgcgcacg gtggagcagc tggactcggc gctgcgggcc ctggacctgg tcctcgggga 80700
ggccgaactg gccgaactgg acgccatctt cccggccctg ggcaacggcg gccgggcgcc 80760
ggatgcgtgg atcagctgaa gggcggtgca tcggccgacg tcacgccggc cgatgccgcc 80820
ggtcatacga cgtcgagcgc gggcagcggg aagatcagtc ggccgccgcc gtcgaggaag 80880
tcccgttccc gctcgacgaa tccgtcccgg tagatccagg gcaggaccag caattggtcc 80940
ggcttctgtg ccttcgcgtc ctgttcggac acgatgggga tggccgttcc cggggtgaag 81000
cggcccgcct tctcctcgct cacctcaccg atgcagggca ggtcccgctc ggtgatcccg 81060
cagtactgca ggatgacgtt gcccttggtg gaggcgccgt accccagggt cagcctgccc 81120
tcttcgcggg agcggtcgag gaagtcgcgc agggcgcccc gctggttcac gacccggcgg 81180
gcgaagccct cgaacggcgc catgccgtcc agtcccgccg cggcctcccg ggcacggatg 81240
cgggccaggc ccgcatcgtc cttccggtgc tgggagccgc tcctggccag cgtgacgcac 81300
aggctgccgc cgtacacctc ggtgagctcg gccctgatga cagtcaggcc gacccgctct 81360
gccatccact cgatctgccg gagggcgtag tactccaggt gctcgtggca gacgatgtcg 81420
tacgcgtcgg cttcgagcat ggcgggcagg tagctctgct ccatcatcca gatgccgtcc 81480
tcggtgagga cgtcgcggac gtcgctcatg aagcgcagcg ggtccggcag gtcgtagaac 81540
atggctatcg aggtgacgac cttcgcccgc cgcgcgccga accggctctc gaaggtctcg 81600
cgggtgaagt agtcgacgat caactcggcg ttccgcgggt acagttcgcg gaacttcccg 81660
ccggtcgggt cgatgccgac cagttggggg ccgtcggcag ggtagccgct cagcagtgtc 81720
gcgtcgttgc tgccgatgtc gacgaccagg tcgtccgggc cgaggtccac cagctcgcgg 81780
atggcggcga ccttgccgtg gaggtggtcg accatgaacg gccggatgcc cgagcggtag 81840
ccgtagccct ctccgtacat gaggtccgga tcgggggtgt ggcgcagttg cacgaggccg 81900
catccggccg gggaacagac gacgagttcg agcgggaccg acggcacaac ctgttcgcgg 81960
ctcgtcggga acactccggt gagcgcttgt tcgcccaggt cgagtacgga gagcagctcc 82020
ttgttgccgc agacgcggca cgcggtggca atcatggggt cctttcggaa tccgggccgg 82080
ggcgccggcc cggggccagg tcgggggctt cgagacggag ggtgtcgggg gtgggctggg 82140
gggacggcat caggtgcagg cggccgatcg caccggtggg ggcggacgcg tcctggcacg 82200
ggcaggggtc atcggtgaat ccggcgaagc ggtaggccac ttccatcatt cggttgcgtt 82260
cggtggcgcg gaagtccgcg ccgaggtgca ccccggcccg gtgtgcctgg tcggtcagcc 82320
agcgcaggat cgccgtgccg gcgccgaggg acaccacccg gcacgaggtg gccagcagct 82380
tgatccgcca ggcgtcgggg ctgcgccgca gcagcacgac gccgaccgct ccgtaggggc 82440
cgaagcgatc ggtgaccgtg gtgaccagca cctcgtggtc ggggtcgtcg atgagggcgc 82500
gcagatcgtc ctcggagtag tgcactccgg tggcgttcat ctggctggtg cgcagggtga 82560
gttcctcgac ccgggacagc tcgtgggggg tggcgcggct gatccgcatc ctgatgtcca 82620
gcgagcgcag gaagtccgcg tcgggcccgg tgaagtcgga ccgttcggcg tctcgccgga 82680
aggacgcctg gtacatcgag cggcggcgcc gcgagtcgac ggtgacggtg tccgggctga 82740
actccggcag gtcggtcaac ccggtcgcct gtccggcggt gtaggtgcgg acctccggca 82800
actcgtgtgt cacctcggcg cgttcgaagg gctggtcgtc gatgaaggcg agggtgccga 82860
gcgcgaagtt gagccggtcg gcgatctcgc ggaccgactt cgacttcggc ccccagccga 82920
tctgcgggag cacgaagtat tcggcgacgc cgagctgttc cagtttcgcc caggcgtggt 82980
cgtggtcgtt cttgctggcc acggcctgga ggatgccgcg cgcgtccagc tcggcgatgg 83040
tccgcaggac gtccggggtg agccggacct cgtcctcctc caggagtgtg ccctgccaga 83100
gggtgttgtc cagatcccag accaggcatt tgaccagggg ctcggcggcg ttgtcccggt 83160
gcacgtcgtt cctttctctc gatacggcgg atgcgaccgc gactgtctcg atacggcgga 83220
tgcggccgcg actcttcgac aggcggacac cgccgggacc agaaggatta cggcccgttc 83280
atcccgcggc ggacaccgca tgccgggcca ggatcagctc gcagatctcg ttgctgccct 83340
cgatgatttc catgagcttg gcgtcgcggt gcgcccgggc gacgacatgc ccgtcgcggg 83400
ccccggccga cgccagcacc tgcacggccc gctcggcgcc gcgtgcggcg ccggtggccg 83460
cgacgtgctt ggccaggacg gcggcgatca ccatgtcggg gctgccctcg tcccactggg 83520
cgctggcgta ctcgcacgcc ctggcggcgt gctgttcggc gatgaacagt tcggcgaggt 83580
gccgggcgac gagttggtgt tccgaaagcc gcgtgccgaa ctgctcccgt ccgctggtgt 83640
gccgcacggc ggcggccaga cagccgcgca ggatgcccag ggagccccat gccacggaca 83700
tccggccgta gctcagcgcg gtggtgacca gcagggcggg ggtgcggtcg tggccctgca 83760
ggagggcgtc ggccggcagc cggaccccgt ccaggtggat gttcgcatga ccggccgcgc 83820
ggcagccgtg cgcgtcggcg atgcgctcga tccgtacgcc gggggccgag gcgggcacca 83880
cgacggcccc cgcgccctcc tccgtgcgcc cgaagaccac cagcaggtcc gcgtaggcgg 83940
cgttggtcgc ccacaccttg accccgtcga cgacgatctc gtccccgtcg aaggcgatac 84000
gggtccgcaa ggcggacagg tcactgccgg cgccggcttc ggtgaaggcc acggcggcca 84060
gttcgccact ggtcaaccgg gaagtcagcg gggcctgttg gtccgctccg gcgagtcggc 84120
gcagcgtcca ggccgccatg ccctgcgagg tcatgacgct ccgcagggag ctgcacaggg 84180
cgcccacgtg cgcggtgagt tcgccgttgc gccgactgga ccagccgagg ccgccgtggg 84240
ccgcgggcgc ctgcgcgcac agcaggcccc gggagccgag atcgcgcagc agggagaggg 84300
gcagctcgcc cgtacggtcc cactcggccg cccggtcgcc gaccagctcg gtgaacagtt 84360
cctcggcctc ggatgcggcg gcatgcggcg cgtcagccac cggcgggccc ggtcgcctcg 84420
ccggtcggac cgggcgcggc cagccgtccg accagccgga ccatcgcgtc gacggtgcgg 84480
aagttgtcga gcatcaggtc ggcgccgctg atgacgattc cgtgggtctt ctccaggtgc 84540
acgacgagct gcatggcgaa cagcgaggac atgccaccga cggcgaacag gtcctggtcg 84600
cgctcccagg tggtcttggt gttggccgcg aggaaaccga gcagttcctc ggccacctcg 84660
tcgtcggcgg gcgtcgtgcc ggtcgaatcc ggccggccgg aagtcgtggt cattgcatgg 84720
tctcctggta gtcgtagaat ccccggccgc tcttgcggcc gagcaggccc tgccggacct 84780
tgtccagcag cagttcactc gggcggagag ccggatctcc ggtccgttcg tgcatcaccc 84840
gcagcgagtc ggccaggttg tccagcccga tcagatcggc cgtggccagt ggtccggtgc 84900
ggtggccgat gcagtcgcgc atcagcgcgt ccacggtttc cggggtggcc ctgccctcgt 84960
gcaccaccgc gatggcgtcg ttgagcatcc ggtgcaggag gcggctggtc acgaacccgg 85020
cgccgtcgcc gacgacgatg ccccggcggc ccagtccgga cagcagttcc cgggtcgact 85080
ccgcggccgc ctctccgctg cgtggtccca ggaccacctc gaccgtgcgg atcacgtacg 85140
cggggttcat gaagtgcacg ccgaccaggt cctcggggcg ggggacggca tcggccagtt 85200
cgtcgatggg aacgcccgag gtgttgctga tgagcagcgt tccggggcgt gccgcggacg 85260
ccaggtccgc caggacctcc gccttcctct tggggtcctc ggtgacggcc tcgatcacgg 85320
cggtcacggc ggcgatggcg ttcagggcgt cctcgacggt cagttcgccg ggcgggcggt 85380
cgtggggcag cgcgcccatc agccgggccg tccgcagatg gagtgcgacc gtgtcggggg 85440
cggcggcgcg cgcctcgacg gacgtgtcga tcagggtgac cgggtgtccg tgtccgacgg 85500
cgagtgcggc gatggccgtg cccatgacac ccgctccgag cacgacgagc ggagaatttt 85560
cattggaatt gggcacagag cctccagaat cccgggacga cggctgtgcg aaatgctgtc 85620
ccgaatcgct tctgtgctcc atcacttggc cgtgactttg tcacctagga agcggtgcgg 85680
gcctggcgga ggctatgtca tctccggctt gtccaccccg gagttccgta cctaaagtgc 85740
gcccggcgaa cgcgcggcgg aattaccgcc gtttcctgcc aagggcccgt ggtttgaacg 85800
acctcgacgt atgaagggtt tcacatggct catatcgcat tcttcatcct tccggttgcc 85860
gggcatgtga atccgacgct gggagtcgcc gaggagctgg tggcgcgcgg ccaccgggtg 85920
acgtacgcgc tgtccgggga gctcgccgag cgggcccggc tgatcggcgc cgaggtggtc 85980
acctatcccg tggacaagca acggttcctg gaccagatgg tgcctcggca ggacgcggac 86040
gagtacacgg acgagggcga gttcgtacgg gtcctggagt ggctgctgga catgacggcg 86100
cagaccctgg aaccgctgga gcggcacttc gccgagaacc gtcccgatgt cgtcgtcaac 86160
gacccgtcgt cgctgtggac ggggcggctg ctggcggacc ggtgggacat cccggtcatc 86220
cgcagcactc cgacctacgc cgccaacgag cactggtcgc tgcatccgcc cgtcgactcg 86280
gccgagccgc cggacgatcc cgagctgcac aagctgctcg cgcggatcga gcggctgctg 86340
gaggagcagg gcgtcgagca cgacctggcc gccttcaccg gggtcctgca cggcggcccg 86400
gccctgctgt acatgccgcg ctcgttccag tacgcgggcg agaccttcga cgaacagcac 86460
cacttcgtcg gcccctgccc gccccggacc gcgttccacg gcgagtggac gccgacggac 86520
gacgacggcc ggcccttggt gctggtgagc ctgggaaccc tctacaacga ccggccggac 86580
ttcttccgca cctgcctgga ggcgttccgc gacgagccct ggaacgtcct tctggtgctg 86640
ggcggcgggg tgcccgccgc cgacctgggc ccgcttcccg acaacgtccg ggtgcacgac 86700
ttcgtgtcgc tgcgcgatgt gctcccgcac accgccgtgg tggtgaacca cggcgggatg 86760
agcaccgcca tggaggtgtt ctcgcacgag gtgccggtgg tggcgatccc ggtgatgccg 86820
gagcctcggg ccaccgcgcg gcggatcgtc gaactgggtc tcggtgacca gctcctgaac 86880
tcggagctga cggccgagtc cctgcgtgcc accgtgcggc gggtgctgga ggactcccgg 86940
atcccggcga acatgcggaa gatccgtgag cagatcacgg cggccggcgg ggcgaatgcg 87000
gcggccgacg cggtcgaggg actgctgccc caggggagct gaggcgtcct cgcatccgaa 87060
acgcgttcac cttccgaccg gcgggatcgc tccatgctca tcaccgaaac gaccgtgccc 87120
gacgtcttcc gcattgatcc ggagcccatt cccgaccatc ggggccggtt ctacgaagcc 87180
gtgcgccaga ggccgctgga ggctgccgtc ggtcactcga tcgcggtccg gcaggtcaac 87240
ttcaccgtct ccgggcgcaa tgtgctgcgc ggtctccacg ccaccacact gccgccgggc 87300
cagggcaaga tcctcacctg cgtgcggggt tcggtactga ccatggtggt cgacatgagg 87360
gtggggtcgc cgagcttcgg acggtacgag gccgtccggc aggatccgcg gtcgggcacc 87420
gccctctacc tgccggacgg catcggcctg ggctatgtgg cactcgtgga cgacacctgt 87480
atgaactatc tgtgcacaca cgaatacgtc ccgggcatgg tcatcgacgt cgatgcgctg 87540
gaccccgaac tcgacctgcc ctgggacctg gccgacactc cgatccggtc cgccagggac 87600
gccgcggcgc cgtccctgcg ggcggccgtc tccgcgggga tcctgccgac gtacgaggag 87660
tgcctgcggg tccgtgagcc cctacccgcc gctcttgact gaatgcgttc ccaaaaagcc 87720
ttgccggggt cggggtcgac gccgacgccg acgccggcag ggacaaacgc gtaaaagacc 87780
tgcggcgcca tgaaaacagg gcgccaagga aaaggaacgg ttgcgaagtc ggcccgcaac 87840
cgctcatgca attccggaac tgacagccgc cgccccgctg gacgagaacg gccgagttct 87900
tcgcgcagac cgcgcgcgag gacgccgccc ggcattcccc gccgaccgcg cgccactcgt 87960
ccgactcccc ctgcggctgc accagttgcg cggcgggcgc acttcgggcg gcagcagcac 88020
tcgtggagga cggtctccgc cctccacgag tgcaccgggc gactcggccc cgtgcgaacg 88080
acacacgagc tcggccccgt gcgaccggca cgcgtaccgg gccggtcgca cctgccggaa 88140
cgtcacaccg ccgcgacccc acggaagtcg acccgcgcgg agggctgcgc cagccgcagc 88200
gtgtgggcga tggacgccag cgtcacgtgc cggtgccagc cctggaacga ccgtccttcg 88260
aagtcgcgca tgcccacgcc cacactcacc cgttcgaagt cggcgtccac ctgctcggtg 88320
agcatggcca gccgcaacaa cgcgccgcgg tcccaggacg tgaggtcggt cagccacagg 88380
tcggccgggc gccggcggtt gccccgccac acccccatca gcaccagggt ccgcctcggg 88440
accacgcccg gcagcaccac ggcgtgcggg gcgacgagac tgagggagcc ctgccactcc 88500
acggggcgac tcaaccgctt catctgctcc attagttgct gggccgaggt ggtcgcggtg 88560
tggtggtcca ccaggccgcg cccacctgcc gacgccaatt ggaggttccc gcccacacgc 88620
accatgaagg gcagacccac gagactgagc ccacgcacca agcgcggcag aacggcggcg 88680
cgcgcgtcca tcaccacggg tcgcgccgag gtccggctgg cctgggcggc ctcggccacc 88740
aggcgaacga cgttctcctc ctcaccgagc gcaccgggcg cgccgagttg ccgggaaccg 88800
ccgtcgccgc cccggccgcc gcccagcgtc aggtgccagc tgaccggggc cgccgtcgcg 88860
cccgaggcca gccacagtcc gtggctctgc tggcagctca ccacccgccc cagatcgggc 88920
acgaaccgcc ggctcacccc gaccgagcgc acccccgcct tggagaccac catcggccag 88980
atcacccagg cctcggggtt cagcctgtcg tccacgtagc gggccagcgc ggcccgcacc 89040
gcgccccagt cccaggtcga cccggcgacg aaatggtgca ggctctgctc cgccgcgcct 89100
tctccgacga aggcggcgag gttccgggcg gtcttgcgcc cctgggcggt gagcagcccg 89160
cgtatgtact gctcacccct tctgcgctgg tccgcccggc ggagcgagcc gagtaactcc 89220
gcacatccct cggagacgag cgagtcgaag tcgtggcccg cggcggggcc cgtcaggggc 89280
gccgtaccgg cgggttcaag cgtacgaaat ttcat 89315
<210> 2
<211> 2337
<212> DNA
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 2
ggatcatcac tgacgaatcg aggtcgagga accgagcgtc cgaggaacag aggcgcttat 60
cggttggccg cgagattcct gtcgatcctc tcgtgcagcg cgattccgag ggaaacggaa 120
acgttgagag actcggtctg gctcatcatg gggatggaaa ccgaggcgga agacgcctcc 180
tcgaacaggt cggaaggccc acccttttcg ctgccgaaca gcaaggccag ccgatccgga 240
ttgtccccga gttccttcac ggaaatgtcg ccatccgcct tgagcgtcat cagctgcata 300
ccgctgtccc gaatgaaggc gatggcctcc tcgcgaccgg agagaacgac gggaagggag 360
aagacgtaac ctcggctggc cctttggaga cgccggtccg cgatgctggt gatgtcactg 420
tcgaccagga tgatccccga cgctccgagc gcgagcgacg tgcgtactat cgcgccgatg 480
ttcccgacga tcttcacccc gtcgagaacg acgacgtccc cacgccggct cgcgatatcg 540
ccgaacctgg ccgggcgagg gacgcgggcg atgccgaatg tcttggcctt ccgctccccc 600
ttgaacaact ggttgacgat cgaggagtcg atgaggcgga ccggtatgtt ctgccgcccg 660
cacagatcca gcaactcaga tggaaaagga ctgctgtcgc tgccgtagac ctcgatgaac 720
tccaccccgg ccgcgatgct gtgcatgagg ggctcgacgt cctcgatcaa cgttgtcttt 780
atgttggatc gcgacggctt ggtgacatcg atgatccgct gcaccgcggg atcggacgga 840
tttgcgatgg tgtccaactc agtcatggtc gtcctaccgg ctgctgtgtt cagtgacgcg 900
attcctgggg tgtgacaccc tacgcgacga tggcggatgg ctgccctgac cggcaatcac 960
caacgcaagg ggaagtcgtc gctctctggc aaagctcccc gctcttcccc gtccgggacc 1020
cgcgcggtcg atccccgcat atgaagtatt cgccttgatc cccgggggga ccgtcacaga 1080
tccactagtt ctagaaactc cacgggcgct gacgcacacc ggtgcggggc gcgcccgagg 1140
gcgcgccccg caccggtcgt cccgcgtcgg ctacggagtg ccggacgggg cgggttcgga 1200
cctgggtgtc gagccggcgt ccggggaccg ccgcggccgt cccagggttc gcatgaccgg 1260
cttctccacg aagaagtgca ggaacgccga ctgccccagc gccagcgtga aggcgagcag 1320
ggtcagcccg acggcggccg gtgtgtccca ctgccggtaa tagccctgct tcccgccggc 1380
gaagcggtgc ccgtactgga tgatcaggta gtgcacgagg tagaaggcga aggtgagttc 1440
ccccagcagc accatcgtcc tggtccccag ccaggagcgg acgccgcgca catcaccgac 1500
ggccaccgag gcgagcagca gcgcgatcac cgggacggtc aacgcgccgg ggtcgtagtg 1560
gttcggcacc gcgaacgtca ccgcgaacac cgctgagaac agcgcgacgc aggccagggg 1620
acgcgggccc ctccagcgtc cccggatcac gatctgggcc atgagcatcc cgagcacgaa 1680
ctccagcagc cgcaccggcg ggaacatgta gatgaaccac caccgcagct gcggcatgtc 1740
cgggtcccac ggcaggggcg ggctggccgg cagcagcagt gcgaccaggg ggatggagac 1800
ggcggccacg gacaccgcgg cggcccaccg ccagagccgg tccgtacgga ccttggtgaa 1860
gaaggcgaag aggaacggga acatggcgta gaagaacagc tcgcaggaga gcgaccacgc 1920
caccgggttc atgctgccgt actcgtggtg gtcggggaac catgcctgga tcagcagcag 1980
gttcgtgagc agtccgtccc acaccgatcg gcccatgttg ggctcgttga gggccagcac 2040
gatcagcagc gtcaccagca gcacgggcag gtgcagcgag tacgcgcgga ccgtgcgccg 2100
ccgccagaag ttcaccttgg acttgtcggg cagacccgcc caggtgagga cgaaaccgct 2160
gagcatgaag aagaacgaga ccgtcagcgg gcccagccgg ttcagcggga actgcagcgc 2220
ggaattgatc tcggtgttct tgaagaacgg ctgtgtcgat atatgggagg tgaataccag 2280
tagagcggag atgaaacgca tcccgccgag cgcgggaaga tgtttcggca ggggcat 2337
<210> 3
<211> 214
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 3
Met Glu Ser Arg Gly Gly Asp Glu Ala Asp Tyr Ala Ala Leu His Pro
1 5 10 15
Glu Glu Glu Ala Val Val Ala Gln Ala Val Asp Lys Arg Arg Arg Glu
20 25 30
Phe Thr Ala Val Arg Ala Cys Ala Arg Arg Ala Met Glu Lys Leu Gly
35 40 45
Phe Pro Pro Gln Pro Ile Leu Pro Ser Glu Arg Gly Ala Pro Arg Trp
50 55 60
Pro Glu Gly Leu Leu Gly Ser Met Thr His Cys Asp Gly Tyr Arg Ala
65 70 75 80
Ala Ala Leu Val Arg Ala Thr Asp Leu Ala Ser Leu Gly Ile Asp Ala
85 90 95
Glu Pro His Gly Ser Leu Pro Asp Gly Ala Leu His Ser Val Ala Leu
100 105 110
Pro Ala Glu Arg Glu Arg Leu Ala Leu Leu Ala Ala Gly Gln Pro Gly
115 120 125
Val His Trp Asp Arg Leu Leu Phe Ser Ala Lys Glu Ser Val Tyr Lys
130 135 140
Ala Trp Phe Pro Leu Thr Gly Lys Trp Leu Gly Phe Glu Glu Ala Tyr
145 150 155 160
Ile Asp Leu His Gln Asp Ser Gly Thr Ala Gln His Gly Arg Phe Arg
165 170 175
Ala Glu Leu Leu Val Pro Gly Pro Leu Val Gly Gly Arg Arg Ile Lys
180 185 190
His Phe Glu Gly Arg Trp Ile Val Arg Glu Gly Leu Val Thr Thr Ala
195 200 205
Leu Thr Val Pro His Pro
210
<210> 4
<211> 200
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 4
Met Ser Ser His Arg Ala Pro Glu Thr Ala His Arg Ser Arg Arg Ala
1 5 10 15
His Arg Ala Ile Leu Gly Ala Thr Leu Glu Leu Val His Glu Val Gly
20 25 30
Tyr Pro Arg Val Thr Ile Glu Gly Val Ala Ala Arg Ala Gly Val Gly
35 40 45
Lys Gln Thr Ile Tyr Arg Arg Trp Pro Ser Lys Ala Ala Ile Leu Arg
50 55 60
Asp Ala Val Val Ser Leu Thr Glu Asp Ile Ala Arg Ala Gly Gly Ala
65 70 75 80
Val Arg Asp Thr Gly Asp Leu Glu Ala Asp Leu Lys Ala Val Leu Arg
85 90 95
Ser Ala Val Asp Thr Met Thr Asp Pro Gly Tyr Asp Val Pro Ala Arg
100 105 110
Ala Leu Val Ala Ala Gly Ile Ala Asp Pro Ala Leu Gly Lys Glu Leu
115 120 125
Thr Ala Arg Leu Val Glu Pro Pro Leu Arg Leu Cys Leu Glu Arg Leu
130 135 140
Gly Ser Ala Arg Gly Ala Gly Gln Ile Ala Gln Asp Val Asp Pro Arg
145 150 155 160
Ile Ala Val Leu Met Leu Ala Gly Pro Val Ala Gln His Trp Leu Met
165 170 175
Gly Asp Gly Pro Leu Thr His Glu Tyr Thr Asp Ala Leu Val Asp Leu
180 185 190
Ala Leu Arg Gly Leu Ala Pro Arg
195 200
<210> 5
<211> 282
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 5
Met Lys Ser Lys Ser Pro Arg Pro Pro Arg Ser Ala Ser Ala Pro Ala
1 5 10 15
Ala Ser Arg Cys Val Ala Arg Arg Glu Trp Gly Gln Asn Phe Phe Arg
20 25 30
Ala Ala Ala Ala Ala Cys Arg Phe Ser Ala Gln Leu Asp Ser Ser Asp
35 40 45
Ala Ile Ala Pro Gly Ser Pro Asn Asp Leu Leu Thr Val Glu Ile Gly
50 55 60
Ala Gly Ser Gly Arg Val Thr Lys Ala Leu Ala Ser Thr Gly Ser Pro
65 70 75 80
Leu Leu Ala Val Glu Ile Asp Thr Gln Trp Ala Arg Arg Leu Ala Ala
85 90 95
Glu Ser Leu Pro Asp Val Thr Val Val Asn Glu Asp Phe Leu Thr Leu
100 105 110
Gln Leu Pro Gly Gln Pro Val Arg Leu Ile Gly Asn Leu Pro Phe Val
115 120 125
Ser Gly Thr Lys Ile Leu Arg Arg Cys Leu Glu Leu Gly Pro Asp Arg
130 135 140
Met Arg Gln Gly Val Phe Leu Leu Gln Arg Glu Tyr Val Gly Lys Arg
145 150 155 160
Thr Gly Ala Trp Gly Gly Asn Leu Phe Asn Ala Gln Trp Glu Pro Trp
165 170 175
Tyr Ala Phe Glu Lys Gly Leu Ala Phe Ser Arg Gln Glu Phe Asn Pro
180 185 190
Val Pro Arg Ala Asp Thr Gln Thr Leu Met Val Thr Pro His Arg Lys
195 200 205
Pro Pro Val Pro Trp Arg Glu Arg Thr Ala Tyr Gln Arg Phe Thr Gln
210 215 220
Gln Val Phe Asp Thr Gly Gln Met Thr Ile Gly Glu Ala Ala Arg Lys
225 230 235 240
Val Leu Arg Arg Gly His Ala Gln Phe Val Arg Gly Ala Gly Val Arg
245 250 255
Pro Ala Asp Arg Val Lys Asp Leu Thr Val Pro Glu Trp Thr Ala Leu
260 265 270
Phe Arg Ala His Gln Arg Thr Ala Asp Cys
275 280
<210> 6
<211> 408
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 6
Met Leu His Arg Val Asp Leu Ser Ser Leu Thr Gly Leu Arg Trp Tyr
1 5 10 15
Ala Ala Leu Thr Val Phe Ala Cys His Ile Ala Gln Gln Gly Phe Phe
20 25 30
Ala Asp Gln Gln Val Gly Ser Ala Leu Leu His Ile Thr Thr Leu Gly
35 40 45
Ser Met Ala Val Ser Val Phe Phe Ile Leu Ser Gly Phe Val Leu Ala
50 55 60
Trp Ser Ala Arg Asp Glu Asp Ser Thr Pro Thr Phe Trp Arg Arg Arg
65 70 75 80
Ile Ala Lys Ile Tyr Pro Leu His Ile Val Thr Phe Gly Ile Ala Ala
85 90 95
Leu Ile Ile Phe Ser Leu Ser Glu Pro Val Leu Pro Gly Gly Ser Val
100 105 110
Trp Asp Gly Leu Val Pro Asn Ile Leu Leu Val Gln Ser Trp Leu Pro
115 120 125
Asp Ala Ser Leu Ala Ala Ser Phe Asn Thr Pro Ser Trp Ser Leu Ser
130 135 140
Cys Glu Leu Ala Phe Tyr Leu Ser Phe Pro Leu Trp Tyr Arg Leu Val
145 150 155 160
Arg Lys Ile Pro Val Gly Arg Leu Trp Trp Cys Ala Ala Gly Ile Ala
165 170 175
Thr Ala Val Met Cys Val Pro Phe Val Thr Gly Leu Leu Pro Ala Ser
180 185 190
Glu Glu Ala Ala Pro Gly Met Pro Leu Asn Glu Val Trp Phe Ala Tyr
195 200 205
Trp Leu Pro Pro Val Arg Met Leu Glu Phe Val Leu Gly Ile Val Met
210 215 220
Ala Leu Ile Leu Arg Ala Gly Val Trp Arg Gly Pro Arg Ala Gly Thr
225 230 235 240
Cys Thr Leu Leu Leu Ala Ala Ser Tyr Gly Leu Thr Gln Val Val Pro
245 250 255
Pro Met Phe Thr Leu Ala Ala Cys Ser Ile Val Pro Ala Ala Leu Leu
260 265 270
Ile Thr Ala Leu Ala Asp Ala Asp Val His Gly Arg Arg Thr Gly Leu
275 280 285
Arg Ser Ala Met Leu Val Arg Leu Gly Gln Trp Ser Phe Ala Phe Tyr
290 295 300
Leu Val His Phe Met Val Ile Arg Tyr Gly His Arg Leu Met Gly Gly
305 310 315 320
Glu Ser Gly Tyr Glu Arg Gln Trp Ser Thr Pro Ala Ala Ile Ala Leu
325 330 335
Ser Leu Ala Met Leu Met Val Ala Ile Leu Val Gly Gly Leu Leu His
340 345 350
Thr Val Val Glu Gln Pro Cys Met Arg Leu Phe Gly Ser Arg Thr Pro
355 360 365
Ser Ala Val Pro Lys Pro Gly Thr Ala Pro Ala Pro Arg Ser Ser Pro
370 375 380
Gly Pro Asp Val Thr Gly Val Pro Val Val Thr His Thr Pro Asp Val
385 390 395 400
Thr Asn Glu Leu Ser Pro Lys Gly
405
<210> 7
<211> 221
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 7
Met Ala Asp Gln Thr Ala Leu Ser Pro Ala Leu Leu Glu Tyr Ala Arg
1 5 10 15
Ser Val Ala Leu Arg Asp Asp Gly Leu Leu Arg Glu Leu His Gly Val
20 25 30
Thr Ala Gly Leu Pro Gly Gly Arg Ala Met Gln Ile Met Pro Glu Glu
35 40 45
Ala Gln Phe Leu Ala Leu Leu Ile Arg Leu Val Gly Ala Arg Arg Val
50 55 60
Leu Glu Ile Gly Thr Phe Thr Gly Tyr Ser Thr Leu Cys Met Ala Arg
65 70 75 80
Ala Leu Pro Ala Asp Gly Arg Ile Val Thr Cys Asp Ile Ser Asp Lys
85 90 95
Trp Pro Gly Val Gly Ala Pro Phe Trp Arg Arg Ala Gly Val Asp Ser
100 105 110
Leu Ile Asp Leu Arg Val Gly Asp Ala Ala Arg Thr Leu Ala Glu Leu
115 120 125
Arg Glu His Glu Gly Asp Gly Val Phe Asp Leu Val Phe Val Asp Ala
130 135 140
Asp Lys Thr Gly Tyr Pro His Tyr Tyr Glu Gln Ala Leu Ala Leu Val
145 150 155 160
Arg Pro Gly Gly Leu Val Ala Ile Asp Asn Thr Leu Phe Phe Gly Arg
165 170 175
Val Ala Asp Pro Ala Val Asp Asp Ala Asp Thr Val Ala Val Arg Arg
180 185 190
Leu Asn Asp Leu Leu Arg Asp Asp Glu Arg Val Asp Ile Ala Leu Leu
195 200 205
Thr Ile Ala Asp Gly Ile Thr Leu Ala Arg Arg Arg Glu
210 215 220
<210> 8
<211> 449
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 8
Met Pro Glu Ser His Ala Gln Ser Ala Leu Leu Ala Ala Ile Thr Ala
1 5 10 15
Pro Asp Arg Thr Pro Glu Asp Ile Ala Ala Leu Arg Leu Pro Glu Ser
20 25 30
Phe Arg Ala Val Thr Val Arg Lys Glu Asp Thr Asp Met Phe Arg Gly
35 40 45
Met Thr Ser Thr Asp Lys Asp Pro Arg Lys Ser Leu Arg Val Asp Glu
50 55 60
Val Pro Leu Pro Glu Leu Gly Pro Gly Glu Ala Leu Ile Ala Val Met
65 70 75 80
Ala Ser Ser Val Asn Tyr Asn Thr Val Trp Ser Ser Ile Phe Glu Pro
85 90 95
Leu Pro Thr Phe Gly Phe Leu Glu Arg Tyr Gly Arg Thr Ser Pro Ser
100 105 110
Ala Ala Arg His Asp Leu Pro Tyr His Ile Leu Gly Ser Asp Leu Ala
115 120 125
Gly Val Val Leu Arg Thr Gly Pro Gly Val Asn Val Trp Lys Pro Gly
130 135 140
Asp Glu Val Val Ala His Cys Leu Ser Val Glu Leu Glu Ser Ala Asp
145 150 155 160
Gly His Asp Asp Thr Met Leu Asp Pro Ala Gln Arg Ile Trp Gly Phe
165 170 175
Glu Thr Asn Phe Gly Gly Leu Ala Glu Val Ala Leu Val Lys Ser Asn
180 185 190
Gln Leu Met Pro Lys Ala Ala His Leu Thr Trp Glu Glu Ala Ala Ala
195 200 205
Pro Gly Leu Val Asn Ser Thr Ala Tyr Arg Gln Leu Val Ser Arg Asn
210 215 220
Gly Ala Gly Met Lys Gln Gly Asp Asn Val Leu Ile Trp Gly Ala Ser
225 230 235 240
Gly Gly Leu Gly Ser Tyr Ala Thr Gln Leu Ala Leu Ala Gly Gly Ala
245 250 255
Asn Pro Val Cys Val Val Ser Ser Glu Arg Lys Ala Gln Val Cys Arg
260 265 270
Ala Met Gly Ala Glu Ala Ile Ile Asp Arg Ser Ala Glu Asp Tyr Arg
275 280 285
Phe Trp Thr Asp Glu Asp Thr Gln Asn Pro Arg Glu Trp Lys Arg Phe
290 295 300
Gly Gly Arg Ile Arg Glu Leu Thr Gly Gly Glu Asp Val Asp Ile Val
305 310 315 320
Phe Glu His Pro Gly Arg Glu Thr Phe Gly Ala Ser Val Tyr Val Thr
325 330 335
Arg Arg Gly Gly Thr Ile Val Thr Cys Ala Ser Thr Ser Gly Phe Arg
340 345 350
His Glu Phe Asp Asn Arg Tyr Leu Trp Met His Leu Lys Arg Ile Val
355 360 365
Gly Thr His Phe Ala Asn Tyr Arg Glu Ala Trp Glu Ala Asn Arg Leu
370 375 380
Val Ala Lys Gly Lys Ile His Pro Thr Leu Ser Cys Thr Tyr Pro Leu
385 390 395 400
Ala Asp Thr Ala Leu Ala Val His Asp Val His Ser Asn Leu His Gln
405 410 415
Gly Lys Val Gly Val Leu Cys Leu Ala Pro Thr Glu Gly Leu Gly Val
420 425 430
Arg Asp Glu Glu Lys Arg Ala Lys His Ile Asp Ala Ile Asn Arg Phe
435 440 445
Arg
<210> 9
<211> 421
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 9
Met Arg Val Leu Leu Thr Ser Leu Ala His Asn Thr His Tyr Tyr Ser
1 5 10 15
Leu Val Pro Leu Ala Trp Ala Leu Arg Ala Ala Gly His Glu Val Arg
20 25 30
Val Ala Ser Pro Pro Ser Leu Thr Asp Val Ile Thr Ser Thr Gly Leu
35 40 45
Thr Ala Val Pro Val Gly Asp Asp Arg Pro Ala Ala Glu Leu Leu Ala
50 55 60
Glu Met Gly Ser Asp Leu Val Pro Tyr Gln Arg Gly Phe Glu Phe Gly
65 70 75 80
Glu Val Glu Ser Glu Glu Glu Thr Thr Trp Glu Tyr Leu Leu Gly Gln
85 90 95
Gln Ser Met Met Ala Ala Leu Cys Phe Ala Pro Phe Asn Gly Ala Ala
100 105 110
Thr Met Asp Glu Ile Val Asp Phe Ala Arg Gly Trp Arg Pro Asp Leu
115 120 125
Val Val Trp Glu Pro Trp Thr Tyr Ala Gly Pro Val Ala Ala Arg Ala
130 135 140
Cys Gly Ala Ala His Ala Arg Ile Leu Trp Gly Pro Asp Ala Ile Gly
145 150 155 160
Arg Ser Arg Arg Arg Phe Leu Ala Ala Leu Glu Gln Val Pro Glu Glu
165 170 175
Leu Arg Glu Asp Pro Ile Ala Glu Trp Leu Gly Trp Thr Leu Asp Arg
180 185 190
Tyr Gly Tyr Ala Phe Asp Glu Arg Asp Val Leu Gly His Trp Val Ile
195 200 205
Asp Pro Gly Pro Arg Ser Thr Arg Leu Asp Leu Gly Gln Thr Met Val
210 215 220
Pro Met Cys Tyr Val Pro Tyr Asn Gly Arg Ser Val Ile Glu Pro Trp
225 230 235 240
Leu Ala Lys Lys Pro Asp Arg Pro Arg Val Cys Leu Thr Leu Gly Val
245 250 255
Ser Ala Arg Glu Thr Tyr Gly Arg Asp Ala Val Ser Tyr Ser Glu Leu
260 265 270
Leu Glu Ala Leu Gly Arg Leu Asp Ile Glu Val Val Ala Thr Leu Asp
275 280 285
Ala Ser Gln Arg Glu Arg Leu Gly Val Leu Pro Asp Asn Val Val Pro
290 295 300
Val Asp Phe Val Pro Leu Asp Ala Leu Leu Pro Ser Cys Ala Ala Ile
305 310 315 320
Ile His His Gly Gly Ala Gly Thr Trp Ser Thr Ala Leu Leu His Gly
325 330 335
Val Pro Gln Ile Leu Leu Pro Ser Leu Trp Asp Ala Pro Leu Lys Ala
340 345 350
Gln Gln Leu Gln Arg Leu Ser Ala Gly Phe Asp Leu Pro Ala Ala Thr
355 360 365
Leu Thr Ala Arg Gly Leu Ala Asp Ala Val His Thr Ala Val His Asp
370 375 380
Pro Ala Ile Lys Ala Gly Ala Arg Arg Leu Ser Glu Glu Met Leu Ala
385 390 395 400
Asp Pro Thr Pro Ala Gly Ile Val Pro Thr Leu Glu Arg Leu Thr Ala
405 410 415
Leu His Arg Ala Thr
420
<210> 10
<211> 415
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 10
Met Glu Pro Ala Pro Ala Ser Ala Gly Thr Arg Glu Leu Gly Arg Arg
1 5 10 15
Leu Gln Leu Thr Arg Ala Ala His Trp Cys Ala Gly Asn Gln Gly Asp
20 25 30
Pro Tyr Ala Leu Ile Leu Arg Ala Val Ser Asp Pro Glu Pro Leu Glu
35 40 45
Arg Glu Ile Cys Ala Ala Gly Pro Trp Phe His Ser Glu Leu Leu Gly
50 55 60
Ala Trp Val Thr Ala Asp Pro Glu Val Ala Ala Ala Val Leu Ala Asp
65 70 75 80
Pro Arg Phe Gly Thr Leu Asp Arg Ala Gly Arg Arg Pro Asp Glu Glu
85 90 95
Leu Leu Pro Leu Ala Glu Ala Phe Pro Arg His Glu Arg Ala Glu Leu
100 105 110
Val Arg Leu Arg Ala Leu Ala Asp Pro Val Leu Asn Arg Cys Ala Pro
115 120 125
Ala Glu Ala Pro Cys Ala Ala Arg Thr Thr Ala Arg Arg Val Leu Arg
130 135 140
Arg Leu Leu Pro Thr Gly Gly Ala Gly Phe Asp Leu Val Thr Glu Val
145 150 155 160
Ala Arg Pro Tyr Ala Val Glu Leu Val Leu Gly Phe Leu Gly Val Pro
165 170 175
Asp Arg Asp Arg Asp Ala Ala Ala Arg Ala Leu Ala Ala Cys Ala Pro
180 185 190
Gln Leu Asp Ala Arg Leu Ala Pro Gln Ile Leu Ala Val Ala Arg Glu
195 200 205
Ser Ala Asp Ala Val Arg Thr Leu Ala Asp Leu Val Pro Glu Leu Val
210 215 220
Ala Glu Lys Leu Arg Ala Val Glu Ser Gly Gly Pro Arg Pro Asp Asp
225 230 235 240
Val Leu Ala Leu Leu Leu Arg Asp Gly Val Ala Pro Arg Asp Val Glu
245 250 255
Arg Ile Ala Leu Val Leu Ala Ile Gly Ala Pro Glu Pro Ala Ala Thr
260 265 270
Ala Val Ala His Thr Val His Arg Leu Leu Gly Arg Pro Gly Glu Trp
275 280 285
Glu Arg Ala Arg Arg Thr Pro Ala Ala Ala Arg Ala Val Glu Gln Thr
290 295 300
Leu Arg His Arg Pro Pro Ala Arg Leu Glu Ser Arg Val Ala His Thr
305 310 315 320
Asp Leu Glu Leu Gly Gly Arg Arg Ile Ala Ala Asp Glu His Ile Val
325 330 335
Val Leu Ala Ala Ala Gly Arg Glu Thr Pro Gly Pro Glu Pro Leu Gly
340 345 350
Gly Pro Asp Gly Pro His Leu Ala Leu Ala Leu Pro Leu Ile Arg Leu
355 360 365
Ala Thr Thr Thr Ala Val Gln Val Met Ala Gly Arg Leu Pro Gly Leu
370 375 380
Arg Ala Glu Gly Ala Pro Leu Thr Arg Pro Arg Ser Pro Val Val Gly
385 390 395 400
Ala Cys Ala Arg Leu Arg Val His Pro Gly Arg Val His Pro Gly
405 410 415
<210> 11
<211> 237
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 11
Met Tyr Ala Asn Asp Ile Ala Ala Val Tyr Asp Leu Val His Glu Gly
1 5 10 15
Lys Gly Lys Asp Tyr Arg Gln Glu Ala Glu Glu Ile Ala Ala Leu Val
20 25 30
Arg Val His Arg Pro Asp Thr Arg Ser Leu Leu Asp Val Ala Cys Gly
35 40 45
Thr Gly Gln His Leu Arg His Leu Asp Gly Leu Phe Asp His Val Glu
50 55 60
Gly Leu Glu Leu Ser His Asp Met Leu Ala Leu Ala Thr Asp Arg Asn
65 70 75 80
Pro Gly Val Thr Phe His Glu Gly Asp Met Arg Ser Phe Ala Leu Gly
85 90 95
Arg Arg Phe Asp Ala Val Ile Cys Met Phe Ser Ser Ile Gly His Leu
100 105 110
Arg Thr Thr Asp Glu Leu Asp Ser Thr Leu Arg Ser Phe Thr Asp His
115 120 125
Leu Glu Pro Gly Gly Val Ile Val Val Glu Pro Trp Trp Phe Pro Ser
130 135 140
Ser Phe Thr Pro Gly Tyr Val Gly Ala Ser Val Thr Glu Ala Gly Glu
145 150 155 160
Arg Thr Ile Cys Arg Val Ser His Ser Val Arg Glu Gly Asn Ala Thr
165 170 175
Arg Ile Glu Val His Tyr Leu Val Ala Glu Pro Gly Gly Gly Ile Arg
180 185 190
His Leu Thr Glu Asp His Ala Ile Thr Leu Phe Pro Arg Ala Asp Tyr
195 200 205
Glu Ala Ala Phe Glu Arg Ala Gly Cys Asp Val Val Tyr Gln Glu Gly
210 215 220
Gly Pro Ser Gly Arg Gly Leu Phe Ile Gly Thr Arg Arg
225 230 235
<210> 12
<211> 1890
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 12
Met Ser Pro Ser Met Asp Glu Val Leu Gly Ala Leu Arg Thr Ser Val
1 5 10 15
Lys Glu Thr Glu Arg Leu Arg Arg His Asn Arg Glu Leu Leu Ala Ala
20 25 30
Ala His Glu Pro Val Ala Ile Val Gly Met Ala Cys Arg Tyr Pro Gly
35 40 45
Gly Val Thr Thr Pro Asp Asp Leu Trp Glu Leu Ala Ala Asp Gly Val
50 55 60
Asp Ala Ile Thr Arg Phe Pro Ala Asp Arg Gly Trp Asp Glu Ala Ala
65 70 75 80
Val Tyr Ser Pro Asp Pro Asp Thr Pro Gly Thr Thr Tyr Cys Arg Glu
85 90 95
Gly Gly Phe Leu Thr Gly Val Gly Asp Phe Asp Ala Ala Phe Phe Gly
100 105 110
Val Ser Pro Asn Glu Ala Leu Val Met Asp Pro Gln Gln Arg Leu Leu
115 120 125
Leu Glu Thr Ser Trp Glu Ala Leu Glu Arg Ala Gly Val Val Pro Ala
130 135 140
Ser Leu Arg Gly Ser Arg Thr Gly Val Phe Val Gly Ala Ala His Thr
145 150 155 160
Gly Tyr Val Ala Asp Thr Ala Arg Ala Pro Glu Gly Thr Glu Gly Tyr
165 170 175
Leu Leu Thr Gly Asn Ala Asp Ala Val Met Ser Gly Arg Ile Ala Tyr
180 185 190
Thr Leu Gly Leu Glu Gly Pro Ala Leu Thr Ile Glu Thr Ala Cys Ser
195 200 205
Ser Ser Leu Val Ala Leu His Leu Ala Val Gln Ser Leu Arg Arg Gly
210 215 220
Glu Cys Asp Leu Ala Leu Ala Gly Gly Val Ala Val Met Pro Asp Pro
225 230 235 240
Thr Val Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala Ser Asp Gly
245 250 255
Arg Cys Lys Ala Phe Ala Glu Gly Ala Asp Gly Thr Val Trp Ala Glu
260 265 270
Gly Val Gly Val Leu Leu Val Glu Arg Leu Ser Asp Ala Arg Arg Tyr
275 280 285
Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp
290 295 300
Gly Ala Ser Asn Gly Leu Thr Ala Pro Ser Gly Pro Ala Gln Arg Arg
305 310 315 320
Val Ile Arg Glu Ala Leu Ala Asp Ala Gly Leu Ala Pro Gly Asp Val
325 330 335
Asp Ala Val Glu Ala His Gly Thr Gly Thr Ala Leu Gly Asp Pro Ile
340 345 350
Glu Ala Gly Ala Leu Leu Ala Thr Tyr Gly Arg Glu Arg Val Gly Asp
355 360 365
Pro Leu Trp Leu Gly Ser Leu Lys Ser Asn Ile Gly His Ala Gln Ala
370 375 380
Ala Ala Gly Val Gly Gly Val Ile Lys Met Val Glu Ala Met Arg His
385 390 395 400
Ser Ser Leu Pro Arg Thr Leu His Val Asp Ala Pro Ser Ser Lys Val
405 410 415
Glu Trp Gly Ser Gly Ser Val Glu Leu Leu Thr Glu Ala Arg Ser Trp
420 425 430
Pro Arg Arg Ala Gly Arg Val Arg Arg Ala Ala Val Ser Ala Phe Gly
435 440 445
Val Ser Gly Thr Asn Ala His Val Val Ile Glu Glu Pro Pro Ser Glu
450 455 460
Ala Asp Gly Ser Asp Gly Pro Ala Pro Asp Pro Arg Ile Thr Ala Ala
465 470 475 480
Thr Pro Leu Pro Trp Val Ile Ser Ala Arg Ser Glu Glu Ala Leu Arg
485 490 495
Gly Gln Ala Asp Arg Leu Ala Ala Leu Ala Arg Arg Gly Pro Thr Glu
500 505 510
Asp Thr Asp Ala Asp Leu Thr Thr Ala Val Asp Leu Gly Tyr Ser Leu
515 520 525
Ala Thr Thr Arg Glu Ala Leu Glu His Arg Ala Val Ala Leu Val His
530 535 540
Asp Ala Arg Ala Ala Arg Glu Asp Leu Ala Ala Leu Ala Ala Gly Arg
545 550 555 560
Thr Pro Glu Asn Met Val Thr Gly Val Ala Arg Arg Gly Arg Gly Ile
565 570 575
Ala Phe Leu Cys Ser Gly Gln Gly Ala Gln Arg Leu Gly Ala Gly Gln
580 585 590
Glu Leu Arg Arg Arg Phe Pro Val Phe Ala Asp Ala Leu Asp Glu Ile
595 600 605
Ala Ala Glu Phe Asp Ala His Leu Glu Arg Pro Leu Leu Ser Val Met
610 615 620
Phe Ala Glu Pro Ser Ala Pro Asp Ala Thr Leu Leu Asp Arg Thr Asp
625 630 635 640
Tyr Thr Gln Pro Ala Leu Phe Ala Val Glu Thr Ala Leu Phe Arg Leu
645 650 655
Phe Glu Ser Trp Gly Leu Val Pro Asp Val Leu Val Gly His Ser Ile
660 665 670
Gly Gly Leu Val Ala Ala His Ala Ala Gly Val Phe Ser Ala Ala Asp
675 680 685
Ala Ala Arg Leu Val Ala Ala Arg Gly Arg Leu Met Arg Ala Leu Pro
690 695 700
Glu Gly Gly Ala Met Ala Ala Val Gln Ala Thr Glu Arg Glu Val Ala
705 710 715 720
Ala Leu Glu Pro Val Val Ala Gly Gly Ala Val Ile Ala Ala Val Asn
725 730 735
Gly Pro Gln Ala Leu Val Leu Ser Gly Asp Glu Ala Ala Val Leu Ala
740 745 750
Ala Ala Gly Glu Leu Ala Ala Arg Gly Arg Arg Thr Lys Arg Leu Arg
755 760 765
Val Ser His Ala Phe His Ser Pro Arg Met Asp Ala Met Leu Ala Asp
770 775 780
Phe Arg Val Ile Ala Glu Thr Val Asp Tyr His Ala Pro Arg Leu Pro
785 790 795 800
Val Val Ser Glu Val Thr Gly Glu Leu Ala Thr Ala Ala Gln Leu Arg
805 810 815
Asp Pro Gly Tyr Trp Thr Arg Gln Val Arg Glu Pro Val Arg Phe Ala
820 825 830
Asp Ala Val Arg Thr Ala Arg Ala Arg Asp Ala Thr Thr Phe Ile Glu
835 840 845
Leu Gly Pro Asp Ala Val Leu Ser Gly Met Ala Glu Glu Ser Leu Ala
850 855 860
Asp Glu Ala Asp Thr Val Phe Ala Pro Ala Leu Arg Arg Gly Arg Pro
865 870 875 880
Glu Gly Asp Thr Ala Leu Arg Ala Ala Ala Arg Ala Phe Val Arg Gly
885 890 895
Ala Asp Leu Asp Trp Ser Ala Leu Tyr Ser Gly Thr Gly Ala Arg Arg
900 905 910
Thr Asp Leu Pro Thr Tyr Ala Phe Gln His Ser Arg Tyr Trp Leu Ala
915 920 925
Pro Thr Ala Ala Ser Pro Thr Val Ala Pro Ala Thr Ser Ala Pro Ser
930 935 940
Ala Gly Pro Val Ala Glu Ala Glu Gln Asp Asp Ala Leu Trp Ala Ala
945 950 955 960
Val His Ala Gly Asp Ala Ala Ser Ala Ala Ala Arg Leu Gly Ala Asp
965 970 975
Gly Ala Gly Ile Glu Ser Gln Leu Gln Ala Val Leu Pro His Leu Ala
980 985 990
Ala Trp His Asp Arg Arg Arg Thr Thr Ala Gln Thr Ala Gly Leu Arg
995 1000 1005
Tyr Arg Val Ala Trp Gln Ala Ile Ala Pro Asp Ala Val Arg Phe Ser
1010 1015 1020
Pro Ser Asp Arg Trp Leu Met Val Glu His Gly Gln Cys Thr Asp Ser
1025 1030 1035 1040
Ala Asp Ala Ala Glu Arg Ala Leu Arg Ala Ala Gly Ala Glu Val Ile
1045 1050 1055
Arg Leu Val Arg Pro Leu Gly Gln Ala Ala Gly Ala Pro Arg Thr Asp
1060 1065 1070
Ala Leu Asp Arg Asp Ala Leu Ala Ala Arg Leu Ala Glu Leu Ala Arg
1075 1080 1085
Ser Pro Glu Ser Leu Ala Gly Val Leu Leu Leu Pro Asp Thr Gly Gly
1090 1095 1100
Ala Thr Leu Ala Gly His Pro Gly Leu Asp Glu Gly Thr Thr Ala Val
1105 1110 1115 1120
Leu Leu Met Val Gln Ala Met Ala Asp Ala Ala Val Glu Thr Pro Leu
1125 1130 1135
Trp Val Ala Thr Arg Gly Ala Val Ala Val Gly Pro Gly Glu Val Pro
1140 1145 1150
Cys Ala Met Gly Ala Arg Val Trp Gly Leu Gly Arg Val Ala Ala Leu
1155 1160 1165
Glu Ala Pro Val Gln Trp Gly Gly Leu Val Asp Leu Pro Ala Glu Pro
1170 1175 1180
Gly Gly Arg Asp Trp Arg Arg Leu Ala Ala Val Val Ser Gly Arg Gly
1185 1190 1195 1200
Gly Glu Asp Gln Val Ala Ile Arg Gly Ser Gly Leu Phe Gly Arg Arg
1205 1210 1215
Leu Leu Pro Ala Ala Val Pro Ser Ala Ser Arg Ser Trp Arg Pro Arg
1220 1225 1230
Gly Cys Val Leu Val Thr Gly Gly Leu Gly Gly Val Gly Gly His Val
1235 1240 1245
Ala Arg Trp Leu Ala Arg Gly Gly Ala Glu His Val Val Leu Ala Gly
1250 1255 1260
Arg Arg Gly Gly Gly Ala Pro Gly Ala Val Glu Leu Glu Arg Glu Leu
1265 1270 1275 1280
Val Gly Leu Gly Ala Lys Val Thr Phe Val Ala Cys Asp Val Ala Asp
1285 1290 1295
Arg Ala Ser Val Val Gly Leu Leu Gly Val Val Glu Gly Leu Gly Val
1300 1305 1310
Pro Leu Cys Gly Val Phe His Ala Ala Gly Val Ala Gln Val Ser Ala
1315 1320 1325
Leu Gly Glu Val Ser Leu Ala Glu Ala Ala Gly Val Leu Ala Gly Lys
1330 1335 1340
Ala Val Gly Ala Glu Leu Leu Asp Glu Leu Thr Ala Gly Val Asp Leu
1345 1350 1355 1360
Asp Val Phe Val Leu Phe Ser Ser Gly Ala Ala Val Trp Gly Ser Gly
1365 1370 1375
Gly Gln Ser Val Tyr Ala Ala Ala Asn Ala His Leu Asp Ala Leu Ala
1380 1385 1390
Glu Arg Arg Arg Ala Gln Gly Arg Pro Ala Thr Ser Val Ala Trp Gly
1395 1400 1405
Val Trp Asp Gly Gly Gly Met Gly Glu Met Ala Pro Glu Gly Tyr Leu
1410 1415 1420
Ala Arg His Gly Leu Val Pro Leu Arg Pro Glu Thr Ala Leu Thr Ala
1425 1430 1435 1440
Leu His Gln Ala Val Asp Ser Gly Asp Ala Thr Val Thr Val Ala Asp
1445 1450 1455
Leu Asp Trp Glu Arg Phe Ala Pro Gly Phe Thr Ala Phe Arg Pro Ser
1460 1465 1470
Pro Leu Ile Ser Gly Ile Pro Val Ala Arg Thr Ala Leu Ala Ala Ala
1475 1480 1485
Gly Gln Pro Ala Asp Asp Thr Pro Thr Ala Pro Asp Leu Val Arg Ala
1490 1495 1500
Arg Pro Glu Asp Arg Pro Arg Leu Ala Leu Glu Leu Val Leu Arg His
1505 1510 1515 1520
Ile Ala Ala Val Leu Gly His Thr Glu Glu Asn Arg Gly Asp Ala Gln
1525 1530 1535
Ala Pro Phe Arg Asp Ile Gly Phe Asp Ser Leu Ala Ala Val Arg Leu
1540 1545 1550
Arg Gly Arg Leu Ala Glu Asp Thr Gly Leu Asp Leu Pro Ser Thr Leu
1555 1560 1565
Val Phe Asp His Glu Asp Pro Thr Ala Leu Ala His His Leu Ala Gly
1570 1575 1580
Leu Ala Asp Ala Gly Ala Thr Gly Arg His Glu Ser Ala Val Pro Ala
1585 1590 1595 1600
Glu Ser Gly Leu Leu Ala Ser Phe Arg Ala Ala Val Glu Gln Ser Arg
1605 1610 1615
Ser Gly Glu Ala Val Glu Leu Met Ala Ser Leu Ala Ala Phe Arg Pro
1620 1625 1630
Ala Tyr Ser Arg Glu Gln Pro Gly Ser Ala Arg Pro Ala Pro Val Leu
1635 1640 1645
Leu Ala Thr Gly Pro Thr Thr His Pro Thr Leu Tyr Cys Cys Ala Gly
1650 1655 1660
Thr Ala Val Gly Ser Gly Pro Gly Glu Tyr Val Pro Phe Ala Glu Gly
1665 1670 1675 1680
Leu Arg Asp Ser Arg Glu Thr Val Val Leu Pro Leu Ser Gly Phe Gly
1685 1690 1695
Gly Pro Ala Glu Pro Leu Pro Ala Ser Leu Asp Ala Leu Leu Asp Val
1700 1705 1710
Gln Ala Asp Val Leu Leu Glu His Ala Ala Gly Lys Pro Phe Ala Leu
1715 1720 1725
Ala Gly His Ser Ala Gly Ala Asn Val Ala His Ala Leu Ala Ala Arg
1730 1735 1740
Leu Glu Glu Arg Gly Thr Gly Pro Thr Ala Val Val Leu Met Asp Val
1745 1750 1755 1760
Tyr Arg Pro Glu Asp Pro Gly Ala Met Gly Val Trp Arg Asp Asp Leu
1765 1770 1775
Leu Ser Arg Ala Leu Glu Arg Ser Thr Val Pro Leu Glu Asp His Arg
1780 1785 1790
Leu Thr Ala Met Ala Gly Tyr His Arg Leu Leu Leu Gly Ala Arg Leu
1795 1800 1805
Thr Ala Leu Asn Ala Pro Val Leu Leu Val Arg Ala Ser Glu Pro Leu
1810 1815 1820
Arg Glu Trp Pro Val Gly Glu Ala Gln Gly Asp Trp Arg Ser Arg Val
1825 1830 1835 1840
Pro Phe Ala Arg Thr Val Ala Asp Val Pro Gly Asn His Phe Thr Met
1845 1850 1855
Leu Thr Glu His Ala Arg His Thr Ala Ser Val Val His Asp Trp Leu
1860 1865 1870
Glu Ala Val Pro His Pro Ala Gly Pro Pro Ala Leu Leu Thr Gly Gly
1875 1880 1885
Glu His
1890
<210> 13
<211> 1582
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 13
Met Ala Asn Glu Glu Lys Leu Arg Ala Tyr Leu Lys Arg Val Thr Gly
1 5 10 15
Glu Leu His Arg Ala Thr Glu Gln Leu Arg Thr Leu Asp Glu Arg Ala
20 25 30
His Glu Pro Ile Ala Ile Val Gly Ala Ala Cys Arg Leu Pro Gly Gly
35 40 45
Val Arg Ser Pro Asp Glu Leu Trp Asp Leu Leu Leu Ala Gly Thr Asp
50 55 60
Ala Val Ser Leu Ala Pro Ala Asp Arg Gly Trp Asp Val Glu Ala Met
65 70 75 80
Tyr Ser Pro Asp Pro Asp Thr Pro Gly Thr Thr Tyr Cys Arg Glu Gly
85 90 95
Gly Phe Val Gln Gly Ala Asp Arg Phe Asp Pro Gly Leu Phe Gly Ile
100 105 110
Ser Pro Asn Glu Ala Leu Thr Met Asp Pro Gln Gln Arg Leu Leu Leu
115 120 125
Glu Thr Ser Trp Glu Ala Leu Glu Arg Ala Gly Leu Asp Pro Gln Ser
130 135 140
Leu Ala Gly Ser Arg Thr Gly Val Phe Ala Gly Ala Trp Glu Ser Gly
145 150 155 160
Tyr Gln Lys Gly Val Glu Gly Leu Glu Ala Glu Leu Glu Ala Gln Leu
165 170 175
Leu Ala Gly Ile Val Ser Phe Thr Ala Gly Arg Val Ala Tyr Ala Leu
180 185 190
Gly Leu Glu Gly Pro Ala Leu Thr Ile Asp Thr Ala Cys Ser Ser Ser
195 200 205
Leu Val Ala Leu His Leu Ala Val Gln Ser Leu Arg Arg Gly Glu Cys
210 215 220
Asp Leu Ala Leu Ala Gly Gly Ala Thr Val Ile Ala Asp Phe Ala Leu
225 230 235 240
Phe Thr Gln Phe Ser Arg Gln Arg Gly Leu Ala Pro Asp Gly Arg Cys
245 250 255
Lys Ala Phe Ala Glu Ala Ala Asp Gly Phe Gly Pro Ala Glu Gly Ala
260 265 270
Gly Met Leu Leu Val Glu Arg Leu Ser Glu Ala Gln Lys Lys Gly His
275 280 285
Pro Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala
290 295 300
Ser Asn Gly Leu Thr Ala Pro Ser Gly Pro Ala Gln Gln Lys Val Ile
305 310 315 320
Arg Asp Ala Leu Ala Asp Ala Gly Leu Thr Pro Ala Asp Val Asp Ala
325 330 335
Val Glu Ala His Gly Thr Gly Thr Pro Leu Gly Asp Pro Ile Glu Ala
340 345 350
Ser Ala Leu Met Ala Thr Tyr Gly Arg Glu Arg Ala Gly Asp Pro Leu
355 360 365
Trp Leu Gly Ser Leu Lys Ser Asn Ile Gly His Thr Gln Ala Ala Ala
370 375 380
Gly Val Ala Gly Val Ile Lys Met Val Glu Ala Met Arg His Gly Thr
385 390 395 400
Leu Pro Arg Thr Leu His Ala Thr Thr Ala Ser Ser Lys Ile Glu Trp
405 410 415
Gly Ala Gly Ala Val Glu Leu Leu Ala Glu Ala Arg Pro Trp Pro Gln
420 425 430
Arg Ala Asp Gly Pro Arg Arg Ala Ala Ile Ser Ser Phe Gly Ile Ser
435 440 445
Gly Thr Asn Ala His Ile Val Val Glu Glu Ala Pro Thr Ala Arg Ala
450 455 460
Glu Pro Glu Glu Pro Glu Glu Pro Pro Val Ser Pro Thr Thr Val Leu
465 470 475 480
Pro Leu Ser Ala Ala Gly Ala Gln Pro Leu Arg Glu Gln Ala Arg Arg
485 490 495
Leu Ala Ala His Leu Ala Asp His Glu Glu Ile Thr Ala Ala Asp Ala
500 505 510
Ala Tyr Ser Ala Ala Thr Thr Arg Ala Ala Leu Ser Asn Arg Ala Ser
515 520 525
Val Leu Ala Asp Asp Arg Glu Ser Leu Ile Ala Arg Leu Thr Ala Leu
530 535 540
Ala Glu Gly Arg Arg Asp Val Asp Val Ala Val Gly Glu Ala Gly Ser
545 550 555 560
Gly Arg Pro Pro Val Phe Val Phe Pro Gly Gln Gly Ser Gln Trp Thr
565 570 575
Gly Met Gly Ala Glu Leu Leu Glu Ser Ala Pro Ala Phe Arg Val Lys
580 585 590
Ala Glu Glu Cys Ala Arg Ala Leu Ala Ala His Leu Asp Trp Ser Val
595 600 605
Leu Asp Val Leu Arg Gly Gly Pro Asp Ala Pro Pro Ile Asp Arg Ala
610 615 620
Asp Val Val Gln Pro Thr Leu Phe Thr Met Met Val Ser Leu Ala Ala
625 630 635 640
Leu Trp Glu Ala His Gly Val Arg Pro Ala Ala Val Val Gly His Ser
645 650 655
Gln Gly Glu Val Ala Ala Ala Tyr Ala Ala Gly Ala Leu Ser Leu Asp
660 665 670
Asp Ala Ala Arg Val Ile Ala Glu Arg Ser Arg Leu Trp Gly Arg Leu
675 680 685
Ala Gly Asn Gly Gly Met Val Ser Val Met Ala Pro Ala Asp Arg Val
690 695 700
Arg Glu Leu Leu Glu Pro Trp Ala Glu Arg Ile Ser Val Ala Ala Val
705 710 715 720
Asn Gly Pro Ala Ser Val Thr Val Ala Gly Asp Ala Gln Ala Leu Glu
725 730 735
Glu Phe Gly Val Arg Leu Ser Ala Asp Gly Val Leu Arg Trp Pro Leu
740 745 750
Ala Gly Val Asp Phe Ala Gly His Ser Pro Gln Val Glu Gln Phe Arg
755 760 765
Thr Glu Leu Leu Gly Thr Leu Ala Asp Val Arg Pro Thr Ala Ala Arg
770 775 780
Leu Pro Phe Phe Ser Thr Val Thr Ala Gly Ala His Asp Pro Glu Gly
785 790 795 800
Leu Asp Ala Ala Tyr Trp Tyr Arg Asn Thr Arg Glu Pro Val Glu Phe
805 810 815
Glu Ser Thr Leu Arg Ala Leu Leu Arg Gln Gly His Arg Thr Phe Val
820 825 830
Glu Met Gly Pro His Pro Leu Leu Gly Ser Ser Ile Asp Glu Ile Ala
835 840 845
Glu Ala Glu Gly Val His Ala Thr Ala Leu Ser Thr Leu His Arg Gly
850 855 860
Ser Gly Gly Leu Asp Arg Phe Arg Ala Ser Val Gly Ala Ala Phe Ala
865 870 875 880
His Gly Val Arg Val Asp Trp Ser Pro Leu Phe Glu Gly Ala Gly Ala
885 890 895
Arg Arg Val Pro Leu Pro Thr Tyr Ala Phe Arg Arg Asp Arg Phe Trp
900 905 910
Leu Pro Thr Ala Val Gly Arg Arg Thr Ala Lys Ala Pro Ala Asp Glu
915 920 925
Ser Ala Ala Trp Arg Tyr Arg Val Thr Trp Thr Ala Leu Glu Thr Gly
930 935 940
Gly Ser Gly Ala Pro Ser Gly Arg Trp Leu Leu Val Glu Leu Pro Gly
945 950 955 960
Ala Ala Pro Asp Glu Ala Asp Ala Ala Ala Thr Ala Leu Gly Thr Ala
965 970 975
Gly Ala Val Val Glu Arg Cys Pro Leu Asp Pro Ala Glu Val Ala Arg
980 985 990
Val Ala Leu Thr Glu Arg Leu Ala Glu Leu Ala Ala Gly Pro Gln Gly
995 1000 1005
Leu Ala Gly Val Leu Val Leu Pro Gly Arg Ala Ala Asp Ala Ala Pro
1010 1015 1020
Ala Asp Ala Phe Pro Leu Asp Pro Gly Thr Ala Ala Val Leu Leu Val
1025 1030 1035 1040
Thr Gln Ala Val Thr Asp Gly Ala Pro Lys Ala Arg Val Trp Val Ala
1045 1050 1055
Thr Arg Gly Ala Val Ala Val Gly Pro Gly Glu Val Pro Cys Ala Met
1060 1065 1070
Gly Ala Arg Val Trp Gly Leu Gly Arg Val Ala Ala Leu Glu Ala Pro
1075 1080 1085
Val Gln Trp Gly Gly Leu Val Asp Leu Pro Ala Glu Pro Gly Gly Arg
1090 1095 1100
Asp Trp Arg Arg Leu Ala Ala Val Val Ser Gly Arg Gly Gly Glu Asp
1105 1110 1115 1120
Gln Val Ala Ile Arg Gly Ser Gly Leu Phe Gly Arg Arg Met Leu Pro
1125 1130 1135
Ala Ala Pro Gly Val Arg Arg Arg Ser Trp Arg Pro Arg Gly Cys Val
1140 1145 1150
Leu Val Thr Gly Gly Leu Gly Gly Val Gly Gly His Val Ala Arg Trp
1155 1160 1165
Leu Ala Arg Gly Gly Ala Glu His Val Val Leu Ala Gly Arg Arg Gly
1170 1175 1180
Gly Gly Ala Pro Gly Ala Val Glu Leu Glu Arg Glu Leu Val Gly Leu
1185 1190 1195 1200
Gly Ala Lys Val Thr Phe Val Ala Cys Asp Val Ala Asp Arg Ala Ser
1205 1210 1215
Val Val Gly Leu Leu Gly Val Val Glu Gly Leu Gly Val Pro Leu Cys
1220 1225 1230
Gly Val Phe His Ala Ala Gly Val Ala Gln Val Ser Ala Leu Gly Glu
1235 1240 1245
Val Ser Leu Ala Glu Ala Ala Gly Val Leu Ala Gly Lys Ala Val Gly
1250 1255 1260
Ala Glu Leu Leu Asp Glu Leu Thr Ala Gly Val Asp Leu Asp Val Phe
1265 1270 1275 1280
Val Leu Phe Ser Ser Gly Ala Ala Val Trp Gly Ser Gly Gly Gln Ser
1285 1290 1295
Val Tyr Ala Ala Ala Asn Ala His Leu Asp Ala Leu Ala Glu Arg Arg
1300 1305 1310
Arg Ala Gln Gly Arg Pro Ala Thr Ser Val Ala Trp Gly Leu Trp Asp
1315 1320 1325
Gly Gly Gly Met Gly Ala Gly Asp Gly Val Arg Asp Phe Tyr Thr Glu
1330 1335 1340
Arg Gly Leu Ala Pro Met Arg Pro Glu Ser Gly Ile Glu Ala Leu His
1345 1350 1355 1360
Thr Ala Leu Asn Gln Asp Asp Thr Cys Val Thr Val Ala Asp Ile Asp
1365 1370 1375
Trp Glu His Phe Val Thr Gly Phe Thr Ala Phe Arg Pro Ser Pro Leu
1380 1385 1390
Ile Ser Gly Ile Pro Gln Val Arg Ala Leu Arg Ala Ala Gln Pro Thr
1395 1400 1405
Val Gly Ala Ser Asp Asp Leu Arg Arg Arg Ile Asp Ala Ala Leu Thr
1410 1415 1420
Pro Arg Glu Arg Thr Lys Val Leu Val Asp Leu Val Arg Thr Val Ala
1425 1430 1435 1440
Ala Glu Val Leu Gly His Asp Gly Ile Gly Arg Ile Gly His Asp Val
1445 1450 1455
Ala Phe Lys Glu Leu Gly Phe Asp Ser Leu Ala Ala Val Arg Val Arg
1460 1465 1470
Gly Arg Leu Ala Glu Ala Thr Gly Leu Val Leu Pro Ala Thr Ile Ile
1475 1480 1485
Phe Asp His Pro Thr Val Asp Arg Leu Gly Asn Ala Leu Leu Glu Glu
1490 1495 1500
Leu Thr Gly Ala Ser Asp Pro Glu Arg Gly Gly Ala Pro Gly Pro Ala
1505 1510 1515 1520
Gly Thr Gly Gly Asn Asp Ala Ser Pro Pro Ala Pro Glu Pro Ala Ala
1525 1530 1535
His Asp Ala Glu Ile Asp Glu Leu Asp Ala Asp Ala Leu Val Arg Leu
1540 1545 1550
Ala Thr Gly Gly Thr Gly Pro Ala Asp Gly Ala Pro Ala Asn Asp Gly
1555 1560 1565
Ser Thr Glu Ala Gly Thr Thr Arg Gly Gly Ala Pro Glu Gln
1570 1575 1580
<210> 14
<211> 3795
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 14
Val Ser Ala Thr Asn Glu Glu Lys Leu Arg Glu Tyr Leu Arg Arg Ala
1 5 10 15
Met Ala Asp Leu His Ser Ala Arg Glu Arg Leu Arg Glu Val Glu Ser
20 25 30
Ala Ser Arg Glu Pro Ile Ala Ile Val Gly Met Ala Cys Arg Tyr Pro
35 40 45
Gly Gly Val Ala Ser Pro Glu Asp Leu Trp Asp Leu Val Ala Ala Gly
50 55 60
Thr Asp Ala Ile Ser Pro Phe Pro Ala Asp Arg Gly Trp Asp Ala Glu
65 70 75 80
Gly Leu Tyr Asp Pro Glu Pro Gly Val Pro Gly Lys Ser Tyr Val Arg
85 90 95
Glu Gly Gly Phe Leu His Glu Ala Ala Glu Phe Asp Ala Glu Phe Phe
100 105 110
Gly Ile Ser Pro Arg Glu Ala Ala Ala Met Asp Pro Gln Gln Arg Leu
115 120 125
Leu Leu Glu Thr Ser Trp Glu Ala Leu Glu Arg Ala Gly Ile Val Pro
130 135 140
Asp Ser Leu Arg Gly Thr Arg Thr Gly Val Phe Thr Gly Val Met Tyr
145 150 155 160
His Asp Tyr Gly Ser His Gln Val Gly Thr Ala Ala Asp Pro Ser Gly
165 170 175
Gln Leu Gly Leu Gly Thr Ala Gly Ser Val Ala Ser Gly Arg Val Ala
180 185 190
Tyr Thr Leu Gly Leu Gln Gly Pro Ala Val Thr Met Asp Thr Ala Cys
195 200 205
Ser Ser Ser Leu Val Ala Leu His Leu Ala Val Gln Ser Leu Arg Arg
210 215 220
Gly Glu Cys Asp Met Ala Leu Ala Gly Gly Val Thr Val Met Ala Thr
225 230 235 240
Pro Thr Val Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala Ser Asp
245 250 255
Gly Arg Cys Lys Ala Phe Ala Glu Gly Ala Asp Gly Thr Val Trp Ala
260 265 270
Glu Gly Val Gly Val Leu Leu Val Glu Arg Leu Ser Asp Ala Arg Arg
275 280 285
Tyr Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln
290 295 300
Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Ser Gly Pro Ala Gln Arg
305 310 315 320
Lys Val Ile Arg Glu Ala Leu Ala Asp Ala Gly Leu Ala Pro Gly Asp
325 330 335
Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Pro Leu Gly Asp Pro
340 345 350
Ile Glu Ala Gly Ala Leu Met Ala Thr Tyr Gly Ser Glu Arg Gln Gly
355 360 365
Arg Asp Pro Leu Trp Leu Gly Ser Leu Lys Ser Asn Ile Gly His Thr
370 375 380
Gln Ala Ala Ala Gly Ala Ala Gly Val Ile Lys Met Val Glu Ala Ile
385 390 395 400
Arg His Ser Thr Leu Pro Arg Thr Leu His Val Asp Ala Pro Ser Ala
405 410 415
Lys Val Glu Trp Asp Pro Ser Ala Val Glu Leu Leu Thr Asp Ala Arg
420 425 430
Pro Trp Pro Gln Arg Glu His Arg Pro Arg Arg Ala Ala Ile Ser Ala
435 440 445
Phe Gly Val Ser Gly Thr Asn Ala His Val Ile Ile Glu Glu Pro Pro
450 455 460
Ala Glu Thr Ala Thr Gly Gly Ala Ala Ala Ala Gly Asp Ala Pro Val
465 470 475 480
Ala Gly Glu Glu Pro Val Thr Gly Asp Ala Pro Val Thr Gly Glu Val
485 490 495
Pro Ala Ala Gly Ala Ala Ala Gly Thr Ser Val Ser Ser Val Pro Gly
500 505 510
His Ala Ser Val Pro Gly His Ala Ser Ala Pro Arg Val Ala Ser Val
515 520 525
Pro Gly His Ala Ser Ala Pro Arg Val Ala Ser Ala Pro Gly His Ala
530 535 540
Ser Ala Pro Arg Asp Ala Ser Ala Pro Arg Pro Ala Ser Ala Pro Asp
545 550 555 560
Glu Ala Ser Met Thr Gly Asp Thr Pro Ala Thr Pro Ser Thr Val Val
565 570 575
Trp Pro Leu Ser Ala Glu Thr Ala Pro Ala Leu Arg Ala Gln Ala Ala
580 585 590
Arg Leu Arg Ala His Leu Glu Arg Leu Pro Asp Thr Ser Pro Thr Asp
595 600 605
Ile Gly His Ala Leu Ala Ala Asp Arg Ala Ala Leu Thr Gln Arg Ala
610 615 620
Val Leu Leu Gly Asp Asn Gly Ala Pro Val Asp Ala Leu Ala Ala Leu
625 630 635 640
Ala Ala Gly Glu Thr Thr Pro Asp Ala Val His Gly Thr Ala Ala Asp
645 650 655
Ile Arg Arg Val Ala Phe Val Phe Pro Gly Gln Gly Ser Gln Trp Ala
660 665 670
Gly Met Gly Ala Glu Leu Leu Asp Thr Ala Pro Ala Phe Ala Ala Glu
675 680 685
Leu Glu Leu Cys Gln Ser Ala Leu Ser Pro Tyr Val Asp Trp Thr Leu
690 695 700
Ser Asp Val Leu Arg Gly Ala Pro Gly Ala Pro Gly Leu Asp Arg Val
705 710 715 720
Asp Val Val Gln Pro Ala Thr Phe Ala Val Met Val Gly Leu Ala Ala
725 730 735
Leu Trp Arg Ser Leu Gly Val Glu Pro Ala Ala Val Ile Gly His Ser
740 745 750
Gln Gly Glu Ile Ala Ala Ala Cys Val Ala Gly Ala Leu Ser Leu Asp
755 760 765
Asp Ala Ala Arg Ile Val Ala Leu Arg Ser Gln Val Ile Ala Arg Glu
770 775 780
Leu Ala Gly Arg Gly Gly Met Ala Ser Val Ala Leu Pro Ala Thr Asp
785 790 795 800
Val Glu Ala Arg Leu Ala Gly Gly Val Glu Ile Ala Ala Val Asn Gly
805 810 815
Pro Gly Ser Thr Val Val Cys Gly Glu Pro Gly Ala Leu Glu Ala Leu
820 825 830
Leu Val Ala Leu Glu Ala Glu Gly Ser Arg Val Arg Arg Ile Asp Val
835 840 845
Asp Tyr Ala Ser His Ser His Tyr Val Glu Ser Ile Arg Glu Glu Leu
850 855 860
Ala Thr Val Leu Ala Pro Val Arg Pro Tyr Arg Gly Asp Val Pro Phe
865 870 875 880
Tyr Ser Thr Val Glu Ala Ala Leu Leu Asp Thr Ala Ala Leu Asp Ala
885 890 895
Asp Tyr Trp Tyr Arg Asn Leu Arg Leu Pro Val Arg Phe Glu Pro Thr
900 905 910
Val Arg Ala Met Leu Ala Asp Gly Ile Asp Ala Phe Val Glu Cys Ser
915 920 925
Ala His Pro Val Leu Thr Val Gly Val Arg Gln Thr Val Glu Ser Val
930 935 940
Gly Thr Ala Val Pro Ala Val Gly Ser Leu Arg Arg Asp Glu Gly Gly
945 950 955 960
Leu Arg Arg Phe Leu Thr Ser Ala Ala Glu Ala Gln Val Val Gly Val
965 970 975
Pro Val Asp Trp Ala Thr Leu His Pro Gly Ala Gly Arg Val Asn Leu
980 985 990
Pro Thr Tyr Ala Phe Gln Arg Glu Arg Tyr Trp Val Gly Ser Ala Arg
995 1000 1005
Pro Asp Arg Ala Lys Thr Ala Glu Thr Gly Glu Gly Ala Pro Glu Ser
1010 1015 1020
Gly Asp Arg Leu Gly Tyr His Val Glu Trp Lys Gly Leu Arg Ser Ala
1025 1030 1035 1040
Thr Gly Gly Trp Arg Pro Gly Leu Arg Leu Leu Ile Val Pro Thr Gly
1045 1050 1055
Glu Gln His Ala Ala Leu Ala Asp Thr Val Glu Gln Ala Ile Ala Ser
1060 1065 1070
Phe Gly Gly Thr Val Arg Arg Ile Ala Val Asp Pro Ala Arg Thr Gly
1075 1080 1085
Arg Ala Glu Leu Leu Gly Leu Leu Glu Ser Ala Ile Asn Gly Asp Thr
1090 1095 1100
Ala Val Thr Gly Ala Val Ser Leu Leu Gly Leu Cys Thr Asp Gly Arg
1105 1110 1115 1120
Pro Asp His Pro Ala Val Pro Thr Ala Val Thr Ala Thr Leu Ala Leu
1125 1130 1135
Val Gln Ala Leu Ala Asp Leu Gly Ser Thr Ala Pro Leu Trp Thr Val
1140 1145 1150
Thr Cys Gly Ala Val Ala Thr Ala Pro Asp Glu Leu Pro Cys Thr Ala
1155 1160 1165
Gly Ala Gln Leu Trp Gly Leu Gly Arg Val Ala Ala Leu Glu Leu Pro
1170 1175 1180
Glu Val Trp Gly Gly Leu Ile Asp Leu Pro Ala Gln Pro Asp Ala Arg
1185 1190 1195 1200
Val Leu Asp Arg Leu Ala Gly Val Leu Ala Glu Pro Gly Gly Glu Asp
1205 1210 1215
Gln Ile Ala Ile Arg Met Ala Gly Val Phe Gly Arg Arg Val Leu Arg
1220 1225 1230
Asn Pro Ala Asp Ala Gly Ser Pro Ala Trp Arg Ala Arg Gly Thr Val
1235 1240 1245
Leu Ile Ala Gly Asp Ile Thr Thr Val Pro Gly Arg Leu Ile Arg Ser
1250 1255 1260
Leu Leu Glu Asp Gly Ala Asp Arg Val Val Leu Ala Gly Pro Asp Ala
1265 1270 1275 1280
Pro Ala Gln Ala Ala Ala Ala Gly Leu Thr Gly Ala Ser Val Val Pro
1285 1290 1295
Val Arg Cys Asp Val Thr Asp Arg Thr Thr Leu Ala Gly Leu Leu Gly
1300 1305 1310
Glu His Ala Pro Ser Val Val Val His Ala Pro Pro Leu Val Pro Leu
1315 1320 1325
Ala Pro Leu Asn Glu Thr Ala Pro Gly Asp Ile Ala Thr Ala Leu Ala
1330 1335 1340
Ala Lys Thr Thr Ala Ala Gly His Leu Val Asp Leu Ala Pro Ala Ala
1345 1350 1355 1360
Gly Leu Asp Ala Leu Val Leu Phe Ser Ser Val Ser Gly Val Trp Gly
1365 1370 1375
Gly Ala Ala Gln Gly Cys Tyr Ala Ala Ala Thr Ala His Leu Asp Ala
1380 1385 1390
Leu Ala Glu Arg Ala Arg Ala Ala Gly Val Pro Ala Leu Ser Val Ala
1395 1400 1405
Trp Ser Pro Trp Ala Gly Gly Thr Pro Ala Asp Gly Ala Glu Ala Glu
1410 1415 1420
Phe Leu Asn Arg Arg Gly Leu Ala Pro Leu Asp Pro Asp Glu Ala Val
1425 1430 1435 1440
Arg Thr Leu Arg Arg Met Leu Glu Arg Gly Ser Ala Cys Gly Ala Val
1445 1450 1455
Ala Asp Val Glu Trp Asn Arg Phe Ala Ala Ser Tyr Thr Trp Val Arg
1460 1465 1470
Pro Ala Val Leu Phe Asp Asp Ile Pro Asp Val Gln Arg Leu Arg Ala
1475 1480 1485
Val Glu Leu Ala Pro Ser Asn Gly Asp Ser Thr Thr Ser Glu Leu Val
1490 1495 1500
Arg Glu Leu Thr Ala Gln Ser Gly His Lys Arg His Val Thr Leu Leu
1505 1510 1515 1520
Arg Leu Val Arg Ala His Ala Ala Ala Val Leu Gly Gln Ser Ser Gly
1525 1530 1535
Asp Ala Val Asn Ser Ala Arg Ala Phe Arg Asp Leu Gly Phe Asp Ser
1540 1545 1550
Leu Thr Ala Leu Glu Leu Arg Asp Arg Leu Ser Thr Ala Thr Gly Leu
1555 1560 1565
Lys Leu Pro Thr Ser Leu Val Phe Asp His Ser Asn Pro Ala Ala Leu
1570 1575 1580
Ala Arg His Leu Gly Glu Glu Leu Leu Gly Arg Gly Asp Thr Ala Asp
1585 1590 1595 1600
Arg Thr Gly Pro Glu Thr Pro Thr Gln Thr Asp Glu Pro Ile Ala Ile
1605 1610 1615
Ile Gly Met Ala Cys Arg Leu Pro Gly Gly Val Gln Ser Pro Glu Asp
1620 1625 1630
Leu Trp Asp Leu Leu Thr Gly Glu Val Asp Ala Ile Thr Pro Phe Pro
1635 1640 1645
Thr Asp Arg Gly Trp Asn Asn Glu Ala Leu Tyr Asp Pro Asp Pro Gly
1650 1655 1660
Ser Pro Gly His His Thr Tyr Val Arg Glu Gly Gly Phe Leu His Asp
1665 1670 1675 1680
Ala Ala Glu Phe Asp Pro Gly Phe Phe Gly Ile Ser Pro Arg Glu Ala
1685 1690 1695
Leu Ala Met Asp Pro Gln Gln Arg Leu Ile Leu Glu Thr Ser Trp Glu
1700 1705 1710
Ser Phe Glu Arg Ala Gly Ile Asp Pro Val Glu Leu Arg Gly Ser Arg
1715 1720 1725
Thr Gly Val Phe Val Gly Thr Asn Gly Gln His Tyr Val Pro Leu Leu
1730 1735 1740
Gln Asp Gly Asp Glu Ser Phe Asp Gly Tyr Ile Ala Thr Gly Asn Ser
1745 1750 1755 1760
Ala Ser Val Met Ser Gly Arg Leu Ser Tyr Val Phe Gly Leu Glu Gly
1765 1770 1775
Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ala Ser Leu Ala Ala Leu
1780 1785 1790
His Leu Ala Val Gln Ser Leu Arg Arg Gly Glu Cys Asp Tyr Ala Leu
1795 1800 1805
Ala Gly Gly Ala Thr Val Met Ser Thr Pro Glu Met Leu Val Glu Phe
1810 1815 1820
Ala Arg Gln Arg Ala Val Ser Pro Asp Gly Arg Ser Lys Ala Phe Ala
1825 1830 1835 1840
Glu Thr Ala Asp Gly Val Gly Leu Ala Glu Gly Ala Gly Met Leu Leu
1845 1850 1855
Val Glu Arg Leu Ser Glu Ala Gln Lys Lys Gly His Pro Val Leu Ala
1860 1865 1870
Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu
1875 1880 1885
Thr Ala Pro Ser Gly Pro Ala Gln Gln Lys Val Ile Arg Glu Ala Leu
1890 1895 1900
Ala Asp Ala Gly Leu Thr Pro Ala Asp Val Asp Ala Val Glu Ala His
1905 1910 1915 1920
Gly Thr Gly Thr Pro Leu Gly Asp Pro Ile Glu Ala Gly Ala Leu Leu
1925 1930 1935
Ala Thr Tyr Gly Arg Asp Arg Arg Asp Asp Pro Leu Trp Leu Gly Ser
1940 1945 1950
Leu Lys Ser Asn Ile Gly His Thr Gln Ala Ala Ala Gly Val Ala Gly
1955 1960 1965
Val Ile Lys Met Val Leu Ala Leu Arg His Gly Thr Leu Pro Arg Thr
1970 1975 1980
Leu His Ala Thr Thr Ala Ser Ser Lys Ile Glu Trp Asp Ala Gly Ala
1985 1990 1995 2000
Val Glu Leu Leu Asp Glu Ala Arg Pro Trp Pro Gln Arg Ala Asp Gly
2005 2010 2015
Leu Arg Arg Ala Gly Ile Ser Ser Phe Gly Ile Ser Gly Thr Asn Ala
2020 2025 2030
His Val Val Val Glu Glu Pro Pro Glu Pro Thr Ala Pro Glu Leu Leu
2035 2040 2045
Ala Pro Glu Pro Ala Ala Asp Gly Asp Val Trp Ser Glu Glu Trp Trp
2050 2055 2060
His Glu Val Thr Val Pro Leu Met Met Ser Ala His Asn Asp Ala Ala
2065 2070 2075 2080
Leu Arg Asp Gln Ala Arg Arg Leu Arg Ala Asp Leu Leu Ala His Pro
2085 2090 2095
Glu Leu His Pro Ala Asp Val Gly Tyr Thr Leu Ile Thr Thr Arg Thr
2100 2105 2110
Arg Phe Glu Gln Arg Ala Ala Val Val Gly Glu Asn Phe Thr Glu Leu
2115 2120 2125
Ile Ala Ala Leu Asp Asp Leu Val Glu Gly Arg Pro His Pro Leu Val
2130 2135 2140
Leu Arg Gly Thr Ala Gly Thr Ala Asp Gln Val Val Phe Val Phe Pro
2145 2150 2155 2160
Gly Gln Gly Ser Gln Trp Pro Glu Met Ala Asp Gly Leu Phe Asp Arg
2165 2170 2175
Ser Ser Asp Ser Ser Ser Phe Leu Glu Thr Ala Arg Ala Cys Asp Ala
2180 2185 2190
Ala Leu Arg Pro His Leu Gly Trp Ser Val Leu Asp Val Leu Cys Arg
2195 2200 2205
Glu Pro Gly Ala Pro Ser Leu Asp Arg Val Asp Val Val Gln Pro Val
2210 2215 2220
Leu Phe Thr Met Met Val Ser Leu Ala Glu Thr Trp Arg Ser Leu Gly
2225 2230 2235 2240
Val Glu Pro Ala Ala Val Val Gly His Ser Gln Gly Glu Ile Ala Ala
2245 2250 2255
Ala His Val Ala Gly Ala Leu Ser Leu Asp Asp Ala Ala Arg Ile Val
2260 2265 2270
Ala Leu Arg Ser Gln Ala Trp Leu Arg Leu Ala Gly Lys Gly Gly Met
2275 2280 2285
Val Ala Val Thr Met Ser Glu Arg Asp Leu Arg Pro Arg Leu Glu Pro
2290 2295 2300
Trp Ser Asp Arg Leu Ala Val Ala Ala Val Asn Gly Pro Glu Thr Cys
2305 2310 2315 2320
Ala Val Ser Gly Asp Pro Asp Ala Leu Ala Glu Leu Val Ala Glu Leu
2325 2330 2335
Ser Ala Glu Gly Val His Ala Arg Pro Ile Pro Gly Val Asp Thr Ala
2340 2345 2350
Gly His Ser Pro Gln Val Asp Met Leu Glu Glu His Leu Arg Glu Val
2355 2360 2365
Leu Ala Pro Val Ala Pro Arg Ser Ser Asp Ile Pro Phe Tyr Ser Thr
2370 2375 2380
Val Thr Gly Gly Leu Leu Asp Thr Ala Glu Leu Asn Ala Asp Tyr Trp
2385 2390 2395 2400
Tyr Arg Asn Met Arg Glu Pro Val Glu Phe Glu Lys Ala Thr Arg Ala
2405 2410 2415
Leu Ile Ala Asp Gly His Asp Val Phe Leu Glu Ser Ser Pro His Pro
2420 2425 2430
Met Leu Ala Val Ser Leu Gln Glu Thr Ile Ser Asp Ala Gly Ala Ser
2435 2440 2445
Ala Ala Val Leu Gly Thr Leu Arg Arg Gly Gln Gly Gly Pro Arg Cys
2450 2455 2460
Leu Ala Val Ala Val Cys Arg Ala Tyr Thr His Gly Val Glu Ile Asp
2465 2470 2475 2480
Ala Glu Ala Ile Phe Gly Pro Asp Ser Arg His Val Glu Leu Pro Thr
2485 2490 2495
Tyr Pro Phe Gln Arg Glu Arg Tyr Trp Tyr Ser Pro Thr Ser Arg Gly
2500 2505 2510
Asp Asp Pro Ala Ser Leu Gly Leu Asp Ala Ala Asp His Pro Leu Leu
2515 2520 2525
Gly Gly Gly Val Glu Leu Pro Asp Ser Gly Ala Gln Met Tyr Thr Ala
2530 2535 2540
Arg Leu Gly Thr Asp Ala Thr Pro Trp Leu Ala Asp His Ala Leu Met
2545 2550 2555 2560
Gly Ala Ala Leu Leu Pro Gly Ala Ala Phe Ala Asp Leu Ala Leu Trp
2565 2570 2575
Ala Gly Arg Gln Ala Gly Thr Gly Arg Ile Glu Glu Leu Thr Leu Ala
2580 2585 2590
Ala Pro Leu Ala Leu Pro Glu Ser Gly Gly Val Arg Leu Arg Leu Asn
2595 2600 2605
Val Gly Ala Pro Gly Ala Asp Asp Ala Arg Arg Phe Ala Val His Ala
2610 2615 2620
Arg Ala Glu Gly Ala Ala Asp Trp Thr Leu His Ala Glu Gly Leu Leu
2625 2630 2635 2640
Thr Ala Glu Asp Ala Ala Asp Val Pro Asp Ala Ser Ala Thr Ala Pro
2645 2650 2655
Pro Pro Gly Ala Glu Gln Leu Asp Thr Gly Asp Phe Tyr Glu Arg Phe
2660 2665 2670
Ala Glu Leu Gly Tyr Gly Tyr Gly Pro Phe Phe Arg Gly Leu Val Ser
2675 2680 2685
Ala His Arg Ser Gly Ser Asp Ile His Ala Glu Val Ala Leu Pro Val
2690 2695 2700
Gln Ala Gln Gly Asp Ala Ala Arg Phe Gly Ile His Pro Ala Leu Leu
2705 2710 2715 2720
Asp Ala Ala Leu Gln Thr Met Ser Leu Gly Gly Phe Phe Pro Glu Asp
2725 2730 2735
Gly Arg Ile Arg Met Pro Phe Ala Leu Arg Gly Val Arg Leu Tyr Arg
2740 2745 2750
Thr Gly Ala Glu Arg Leu His Val Arg Ile Ser Pro Val Ser Gln Asp
2755 2760 2765
Ala Val Arg Ile Arg Cys Ala Asp Thr Glu Gly Arg Ala Val Ala Glu
2770 2775 2780
Ile Asp Ser Phe Leu Met Arg Pro Val Asp Pro Glu Gln Leu Leu Gly
2785 2790 2795 2800
Gly Arg Pro Val Gly Ala Asp Ala Leu Phe Arg Ile Ala Trp Arg Glu
2805 2810 2815
Leu Thr Ser Gly Ser Gly Thr Gly Leu Arg Thr Gly Asn Gly Ala Gly
2820 2825 2830
Ala Ala Ser Ser Val Arg Trp Val Val Ala Gly Pro Asp Val Leu Gly
2835 2840 2845
Leu Ala Glu Ala Ala Asp Ala His Leu Pro Asp Ala Leu Gly Pro Asp
2850 2855 2860
Gly Pro Leu Pro Thr Ala Ala Gly Glu Ala Ala Pro Asp Ala Phe Val
2865 2870 2875 2880
Phe Gly Val Pro Thr Gly Thr Gly Asp Val Ala Ala Asp Ala His Ala
2885 2890 2895
Val Ala Cys Gln Val Leu Asp Leu Val Gln Arg Arg Leu Ala Ala Pro
2900 2905 2910
Asp Ala Pro Glu Gly Ala Arg Leu Val Val Ala Thr Arg Gly Ala Val
2915 2920 2925
Ala Val Arg Gly Asp Ala Glu Val Ser Asp Pro Ala Ala Ala Ala Ala
2930 2935 2940
Trp Gly Leu Leu Arg Ser Ala Gln Ala Glu Glu Pro Asp Arg Phe Leu
2945 2950 2955 2960
Leu Val Asp Leu Asp Asp Asp Pro Ala Ser Ala Arg Ala Leu Pro Thr
2965 2970 2975
Ala Leu Ala Ser Gly Glu Pro Gln Thr Ala Val Arg Ala Gly Arg Val
2980 2985 2990
Tyr Val Pro Arg Leu Glu Arg Ala Ala Asp Ser Thr Asp Gly Pro Leu
2995 3000 3005
Thr Pro Pro Glu Lys Gly Ala Trp Arg Leu Gly Arg Gly Ala Asp Leu
3010 3015 3020
Thr Leu Asp Gly Leu Ala Leu Val Pro Ala Pro Asp Ala Glu Ala Pro
3025 3030 3035 3040
Leu Glu His Gly Gln Val Arg Val Ala Val Arg Ala Ala Gly Val Asn
3045 3050 3055
Phe Arg Asp Ala Leu Ile Ala Leu Gly Met Tyr Pro Cys Glu Ala Glu
3060 3065 3070
Met Gly Thr Glu Gly Ala Gly Thr Val Val Glu Val Gly Pro Gly Val
3075 3080 3085
Thr Gly Val Ala Pro Gly Asp Arg Val Leu Gly Leu Trp Asn Gly Gly
3090 3095 3100
Leu Gly Pro Val Cys Val Ala Asp His Arg Leu Leu Val Pro Ile Pro
3105 3110 3115 3120
Asp Gly Trp Ser Tyr Ala Arg Ala Ala Ser Val Pro Ala Val Phe Leu
3125 3130 3135
Ser Ala Tyr Tyr Gly Leu Val Thr Leu Ala Asp Leu Arg Pro Gly Glu
3140 3145 3150
Lys Val Leu Val His Ala Ala Ala Gly Gly Val Gly Met Ala Ala Val
3155 3160 3165
Gln Ile Ala Arg His Leu Gly Ala Glu Val Leu Ala Thr Ala Ser Thr
3170 3175 3180
Gly Lys Trp Asp Val Leu Arg Ala Met Gly Ile Thr Asp Glu His Leu
3185 3190 3195 3200
Ala Ser Ser Arg Thr Leu Asp Phe Ala Thr Ala Phe Ala Gly Thr Asp
3205 3210 3215
Gly Thr Ser Arg Ala Asp Val Val Leu Asn Ser Leu Thr Lys Glu Phe
3220 3225 3230
Val Asp Ala Ser Leu Gly Leu Leu Arg Pro Gly Gly Arg Phe Leu Glu
3235 3240 3245
Leu Gly Lys Thr Asp Val Arg Asp Pro Glu Gln Val Gly Ala Asp His
3250 3255 3260
Pro Gly Val Arg Tyr Arg Ala Phe Asp Leu Asn Glu Ala Gly Pro Asp
3265 3270 3275 3280
Glu Leu Gly Arg Leu Leu Arg Lys Leu Met Glu Leu Phe Ala Ala Gly
3285 3290 3295
Val Leu His Pro Leu Pro Val Val Thr His Asp Val Arg Arg Ala Ala
3300 3305 3310
Asp Ala Leu Arg Thr Ile Ser Gln Ala Arg His Thr Gly Lys Leu Val
3315 3320 3325
Leu Thr Met Pro Pro Ala Trp His Pro Tyr Gly Thr Val Leu Ile Thr
3330 3335 3340
Gly Gly Thr Gly Ala Leu Gly Gly Arg Ile Ala Arg His Leu Ala Thr
3345 3350 3355 3360
His His Gly Val Arg Gln Leu Leu Ile Ala Ala Arg Arg Gly Pro Asp
3365 3370 3375
Gly Glu Gly Ala Ala Glu Leu Val Ala Asp Leu Thr Ala Leu Gly Ala
3380 3385 3390
Ser Ala Thr Val Val Ala Cys Asp Val Ser Asp Ala Asp Ala Val Arg
3395 3400 3405
Arg Leu Leu Ala Gly Val Pro Ala Glu His Pro Leu Thr Ala Val Val
3410 3415 3420
His Ser Ala Gly Val Leu Asp Asp Gly Val Leu Pro Thr Leu Thr Pro
3425 3430 3435 3440
Glu Arg Met Arg Arg Val Leu Arg Pro Lys Val Glu Ala Ala Val His
3445 3450 3455
Leu Asp Glu Leu Thr Arg Asp Leu Asp Leu Ser Ala Phe Val Leu Phe
3460 3465 3470
Ser Ser Ser Ala Gly Leu Leu Gly Ser Pro Ala Gln Gly Asn Tyr Ala
3475 3480 3485
Ala Ala Asn Ala Thr Leu Asp Ala Leu Ala Val Arg Arg Arg Ala Leu
3490 3495 3500
Gly Leu Pro Ala Val Ser Leu Ala Trp Gly Leu Trp Ser Asp Thr Ser
3505 3510 3515 3520
Arg Met Ala Gly Gly Leu Asp Gln Glu Ser Leu Gln Arg Arg Phe Ala
3525 3530 3535
Arg Asn Gly Phe Pro Pro Leu Ser Ala Thr Leu Gly Ala Ala Leu Phe
3540 3545 3550
Asp Ala Ala Leu Arg Val Asp Glu Ala Val Gln Ile Pro Met Arg Phe
3555 3560 3565
Asp Pro Ala Ala Leu Arg Ala Thr Gly Thr Val Pro Ala Leu Leu Ser
3570 3575 3580
Asp Leu Val Gly Pro Ala Pro Ala Ala Gly Ser Ala Thr Pro Ala Ala
3585 3590 3595 3600
Gly Pro Tyr Pro Thr Pro Asp Ala Gly His Thr Gly Glu Pro Leu Ala
3605 3610 3615
Glu Arg Leu Ala Arg Leu Ser Ala Glu Glu Arg His Asp Gln Leu Leu
3620 3625 3630
Ser Leu Val Ser Glu His Val Ala Ala Val Leu Gly His Gly Ser Ala
3635 3640 3645
Ala Glu Val Arg Ser Asp Arg Pro Phe Arg Glu Val Gly Phe Asp Ser
3650 3655 3660
Leu Thr Ala Val Glu Leu Arg Asn Arg Met Gly Ala Val Thr Gly Val
3665 3670 3675 3680
Arg Leu Pro Ala Thr Leu Val Phe Asp His Pro Thr Pro Ala Ala Leu
3685 3690 3695
Ala Ala His Leu Asp Gly Leu Leu Ala Pro Gln Arg Pro Pro Thr Thr
3700 3705 3710
Ala Pro Leu Leu Ser Glu Leu Asp Arg Ile Glu Glu Ala Leu Ala Ala
3715 3720 3725
Leu Thr Pro Glu Gly Leu Ala Ala Val Ala Pro Ala Pro Asp Ala Arg
3730 3735 3740
Ala Glu Val Ala Leu Arg Leu Asp Ala Leu Ala Asp Arg Trp Arg Ala
3745 3750 3755 3760
Leu His Asp Gly Ala Ala Gly Val Asp Asp Asp Ile Ala Asp Val Leu
3765 3770 3775
Ser Thr Ala Asp Asp Asp Glu Ile Phe Ala Phe Ile Asp Glu Arg Tyr
3780 3785 3790
Gly Ala Ser
3795
<210> 15
<211> 2004
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 15
Met Thr Ala Glu Asn Asp Lys Ile Arg Ser Tyr Leu Lys Arg Ala Thr
1 5 10 15
Ala Glu Leu His Lys Thr Lys Ser Arg Leu Ala Glu Val Glu Ser Ala
20 25 30
Ser Arg Glu Pro Ile Ala Ile Val Gly Met Ala Cys Arg Tyr Pro Gly
35 40 45
Gly Val Ala Ser Pro Glu Asp Leu Trp Asp Leu Ala Ala Ala Gly Ala
50 55 60
Asp Ala Ile Ser Pro Phe Pro Val Asp Arg Gly Trp Asp Val Glu Gly
65 70 75 80
Leu Tyr Asp Pro Asp Pro Glu Ala Val Gly Arg Ser Tyr Val Arg Glu
85 90 95
Gly Gly Phe Leu His Gly Ala Ala Glu Phe Asp Ala Glu Phe Phe Gly
100 105 110
Ile Ser Pro Arg Glu Ala Ala Ala Met Asp Pro Gln Gln Arg Leu Leu
115 120 125
Leu Glu Thr Ser Trp Glu Ala Leu Glu Arg Ala Gly Ile Val Pro Asp
130 135 140
Ser Leu Arg Gly Thr Arg Thr Gly Val Phe Thr Gly Val Met Tyr Asp
145 150 155 160
Asp Tyr Gly Ser Gln Phe Asp Ser Ala Pro Pro Glu Tyr Glu Gly Tyr
165 170 175
Leu Val Asn Gly Ser Ala Gly Ser Ile Ala Ser Gly Arg Val Ala Tyr
180 185 190
Val Leu Gly Leu Glu Gly Pro Ala Leu Thr Val Asp Thr Ala Cys Ser
195 200 205
Ser Ser Leu Val Ala Leu His Leu Ala Val Gln Ser Leu Arg Arg Gly
210 215 220
Glu Cys Asp Met Ala Leu Ala Gly Gly Val Thr Val Met Ala Thr Pro
225 230 235 240
Thr Val Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala Ser Asp Gly
245 250 255
Arg Cys Lys Ala Phe Ala Glu Gly Ala Asp Gly Thr Val Trp Ala Glu
260 265 270
Gly Val Gly Val Leu Leu Val Glu Arg Leu Ser Asp Ala Arg Arg Tyr
275 280 285
Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp
290 295 300
Gly Ala Ser Asn Gly Leu Thr Ala Pro Ser Gly Ala Ala Gln Arg Arg
305 310 315 320
Val Ile Arg Glu Ala Leu Ala Asp Ala Gly Leu Ala Pro Gly Asp Val
325 330 335
Asp Ala Val Glu Ala His Gly Thr Gly Thr Ala Leu Gly Asp Pro Ile
340 345 350
Glu Ala Gly Ala Leu Leu Ala Thr Tyr Gly Arg Glu Arg Val Gly Asp
355 360 365
Pro Leu Trp Leu Gly Ser Leu Lys Ser Asn Ile Gly His Ala Gln Ala
370 375 380
Ala Ala Gly Val Gly Gly Val Ile Lys Met Val Glu Ala Met Arg His
385 390 395 400
Ser Ser Leu Pro Arg Thr Leu His Val Asp Ala Pro Ser Ser Arg Val
405 410 415
Glu Trp Gly Ser Gly Ala Val Glu Leu Leu Thr Glu Ala Arg Ser Trp
420 425 430
Pro Arg Arg Ala Gly Arg Val Arg Arg Ala Ala Val Ser Ala Phe Gly
435 440 445
Val Ser Gly Thr Asn Ala His Val Val Ile Glu Glu Pro Ser Val Glu
450 455 460
Glu Ser Ala Glu Ala Glu Ala Val Val Thr Ala Ala Ala Glu Ser Ser
465 470 475 480
Ser Val Leu Ala Trp Pro Val Ser Ala Arg Ser Glu Glu Ala Leu Arg
485 490 495
Gly Gln Ala Val Arg Leu Arg Glu His Val Glu Arg Val Gly Ala Asp
500 505 510
Pro Val Asp Val Ala His Ser Leu Val Val Ser Arg Ala Ser Phe Gly
515 520 525
Glu Arg Ala Val Val Val Gly Arg Glu Arg Gly Glu Leu Leu Ala Gly
530 535 540
Leu Asp Ala Val Ala Ala Gly Val Val Ala Ala Gly Gly Ala Ala Ser
545 550 555 560
Gly Val Val Arg Gly Ser Ala Val Arg Gly Arg Arg Val Gly Val Leu
565 570 575
Phe Thr Gly Gln Gly Ala Gln Trp Val Gly Met Gly Arg Glu Leu Tyr
580 585 590
Gly Ala Gly Gly Val Phe Ala Gly Val Leu Asp Glu Val Leu Gly Val
595 600 605
Val Gly Glu Val Gly Gly Arg Ser Leu Arg Glu Val Met Phe Ala Glu
610 615 620
Ala Gly Ser Val Asp Ala Gly Leu Leu Gly Cys Thr Glu Phe Ala Gln
625 630 635 640
Pro Ala Leu Phe Ala Leu Glu Val Ala Leu Phe Arg Ala Leu Glu Ala
645 650 655
Arg Gly Val Gly Val Ser Val Val Leu Gly His Ser Val Gly Glu Val
660 665 670
Ala Ala Ala Tyr Val Ala Gly Val Phe Ser Leu Ala Asp Ala Val Arg
675 680 685
Leu Val Val Ala Arg Gly Arg Leu Met Gly Ala Leu Pro Val Gly Gly
690 695 700
Ala Met Val Ser Val Gly Ala Ser Glu Ala Glu Leu Ala Gly Leu Val
705 710 715 720
Ala Gly Leu Gly Gly Arg Val Ser Val Ala Ala Val Asn Gly Pro Ala
725 730 735
Ser Val Val Leu Ser Gly Glu Ala Gly Val Leu Asp Gly Val Val Ala
740 745 750
Gly Leu Val Gly Arg Gly Val Glu Cys Arg Trp Leu Glu Val Ser His
755 760 765
Ala Phe His Ser Val Leu Met Asp Pro Met Leu Glu Glu Phe Arg Arg
770 775 780
Val Ala Ala Ser Val Glu Phe His Arg Pro Arg Ser Gly Val Ala Val
785 790 795 800
Val Ser Ser Val Thr Gly Ala Val Ala Gly Leu Asp Glu Leu Gly Asp
805 810 815
Pro Glu Tyr Trp Val Arg His Val Arg Glu Ala Val Arg Phe Ala Asp
820 825 830
Gly Val Gly Ala Ala Arg Asp Val Gly Val Asp Thr Phe Val Glu Val
835 840 845
Gly Pro His Ala Val Leu Thr Val Met Ala Gly Gln Cys Leu Asp Gly
850 855 860
Asp Glu Gly Asp Leu Ala Phe Val Pro Val Leu Arg Arg Asp Arg Pro
865 870 875 880
Glu Leu Glu Thr Phe Thr Thr Ala Leu Ala Thr Leu Tyr Ala Arg Gly
885 890 895
Leu Pro Val Pro Pro Ala Pro Ser Glu Pro Ala Gly Arg Arg Val Asp
900 905 910
Leu Pro Thr Tyr Ala Phe His Arg Asp Arg Tyr Trp Leu Ala Ala Leu
915 920 925
Pro Arg Leu Thr Thr Gly Gly Val Ser Ala Ala Gly Leu His Gly Val
930 935 940
Glu His Pro Leu Leu Ala Ala Ala Val Glu Leu Pro Gly Ala Glu Thr
945 950 955 960
Glu Val Trp Thr Gly Arg Ile Ser Ala Ala Asp Leu Pro Trp Leu Ala
965 970 975
Asp His Leu Val Trp Asp Arg Gly Val Val Pro Gly Ser Ala Leu Leu
980 985 990
Glu Met Leu Leu Gln Val Gly Ser Arg Ile Gly Leu Pro Arg Val Ala
995 1000 1005
Glu Leu Ala Phe Glu Thr Ala Leu Thr Trp Ala Ala Asp Asn Pro Val
1010 1015 1020
Gln Ile Arg Val Val Val Ala Ala Pro Ala Ser Gly Pro Gly Gly Ala
1025 1030 1035 1040
Arg Glu Val Ser Leu His Ser Arg Pro Glu Pro Val Ala Asp Pro Ser
1045 1050 1055
His Ser Thr Arg Ser Pro His Leu Ala Ala Gln Asp Arg Asp Asn Gly
1060 1065 1070
Trp Thr Arg His Ala Ser Gly Leu Leu Ala Pro Ala Ala Asp His Ala
1075 1080 1085
Asp His Thr His Glu Ala Gly His Pro His Gly Ala Pro His Pro His
1090 1095 1100
Glu Ser Gly His Pro His Gly Ala Asp Arg Thr Gly Ala Asp Ala Phe
1105 1110 1115 1120
Ala Glu Leu Thr Gly Ala Trp Pro Pro Ala Gly Ala Glu Pro Leu Asp
1125 1130 1135
Ile Ala Gly Gln Tyr Pro Leu Phe Ala Ala Ala Gly Val Arg Tyr Glu
1140 1145 1150
Gly Ala Phe Arg Gly Leu Arg Ala Ala Trp Arg Arg Gly Asp Glu Ile
1155 1160 1165
Phe Ala Glu Val Arg Leu Pro Asp Ala His Ala Ala Asp Ala Ala Arg
1170 1175 1180
Tyr Gly Val His Pro Ala Leu Leu Asp Ala Ala Leu His Pro Ile Ala
1185 1190 1195 1200
Leu Leu Asp Pro Leu Gly Asp Gly Gly His Gly Leu Leu Pro Phe Ser
1205 1210 1215
Trp Thr Asp Val Arg Arg His Asp Ala Ala Gly His Ala Leu Arg Val
1220 1225 1230
Arg Val Ala Ala Val Asp Gly Gly Ala Val Ser Ile Ala Ala Val Asp
1235 1240 1245
Arg Glu Gly Ser Pro Val Leu Ser Ala Arg Ser Leu Ala Leu Arg Arg
1250 1255 1260
Ile Pro Ala Asp Arg Leu Pro Ala Ala Pro Ala Ala Pro Leu Tyr Arg
1265 1270 1275 1280
Val Asp Trp Val Pro Leu Pro Gly Arg Val Ser Val Ala Ala Val Thr
1285 1290 1295
Arg Trp Ala Val Val Gly Pro Glu Ala Glu Ala Thr Ala Ala Gly Leu
1300 1305 1310
Arg Ala Val Gly Ile Asp Ala Arg Thr His Val Leu Pro Phe Asp Glu
1315 1320 1325
Pro Leu Pro Pro Gln Val Gly Ala Asp Ala Glu Val Ile Leu Leu Asp
1330 1335 1340
Leu Thr Thr Ala Thr Ala Thr Ala Thr Ala Thr Ala Ser Arg Thr Ala
1345 1350 1355 1360
Pro His Gly Arg Leu Leu Gly Leu Leu Asp Glu Leu Arg Ala Thr Val
1365 1370 1375
Arg Arg Thr Leu Glu Ala Val Gln Ala Arg Leu Ala Asp Thr Asp Thr
1380 1385 1390
Asp Thr Asp Thr Asn Ala Asp Ala Gly Ala Asp Ser Gly Val Arg Thr
1395 1400 1405
Asp Ala Arg Thr Ala Thr Arg Pro Gly Gly Arg Pro Arg Leu Val Val
1410 1415 1420
Leu Thr Arg Gly Ala Ala Gly Pro Glu Gly Gly Ala Ala Asp Pro Ala
1425 1430 1435 1440
Gly Ala Ala Val Trp Gly Leu Val Arg Val Ala Gln Ala Glu Gln Pro
1445 1450 1455
Gly Arg Phe Thr Leu Val Asp Val Asp Gly Ala Gln Ala Ser Leu Arg
1460 1465 1470
Ala Leu Pro Gly Leu Leu Ala Thr Asp Thr Ala Gln Leu Ala Val Arg
1475 1480 1485
Asp Gly Arg Ala Ala Val Pro Arg Leu Val Arg Val Ala Asp Val Ala
1490 1495 1500
Asp Val Ala Asp Leu Asp Thr Gly Ser Asp Thr Ala Ala Asp Glu Thr
1505 1510 1515 1520
Gly Ala Gly Glu Pro Ala Glu Thr Leu Asp Pro Asn Gly Thr Val Leu
1525 1530 1535
Ile Thr Gly Gly Thr Gly Ala Leu Ala Ala Glu Thr Ala Arg His Leu
1540 1545 1550
Val Glu Arg His Lys Ala Arg His Leu Leu Leu Val Ser Arg Arg Gly
1555 1560 1565
Pro Asp Ala Pro Gly Ala Ala Glu Leu Ala Ala Glu Leu Thr Asn Leu
1570 1575 1580
Gly Ala Glu Val Thr Val Arg Ala Cys Asp Val Ala Asp Arg Asp Ala
1585 1590 1595 1600
Leu Arg Arg Leu Leu Gly Glu Leu Pro Ala Glu His Pro Leu Thr Cys
1605 1610 1615
Val Val His Thr Ala Gly Val Leu Asp Asp Gly Val Leu Ser Val Gln
1620 1625 1630
Thr Ala Glu Arg Ile Asp Ala Val Leu Arg Pro Lys Ala Asp Ala Ala
1635 1640 1645
Val His Leu Asp Glu Leu Thr Arg Glu Leu Gly Pro Val Pro Leu Val
1650 1655 1660
Leu Tyr Ser Ser Val Ser Ala Ala Leu Gly Ser Ala Gly Gln Ala Gly
1665 1670 1675 1680
Tyr Ala Ala Ala Asn Ala Phe Leu Asp Ala Leu Ala Ala Arg Arg Arg
1685 1690 1695
Ala Ala Gly His Pro Ala Leu Ser Leu Gly Trp Gly Trp Trp Ser Gly
1700 1705 1710
Leu Gly Leu Ala Thr Gly Leu Glu Arg Ala Asp Ala Ala Arg Ile Arg
1715 1720 1725
Arg Ser Gly Val Ala Pro Leu Asp Pro Arg Ala Ala Leu Glu Leu Phe
1730 1735 1740
Asp Arg Ala Leu Val Arg Pro Glu Pro Ala Leu Leu Pro Val Arg Leu
1745 1750 1755 1760
Asp Leu Arg Ala Ala Ala Arg Ala Thr Val Leu Pro Glu Val Leu Arg
1765 1770 1775
Asp Leu Val Gly Val Pro Ala Asp Gly Gly Ser Ala Pro Gly Ala Val
1780 1785 1790
Ala Gly Ala Gly Gly Glu Ala Gly Thr Gly His Arg Pro Pro Ala Pro
1795 1800 1805
Ala Asp Ala Ala Ala Ala Leu Ala Thr Arg Leu Ala Gly Arg Ser Ala
1810 1815 1820
Pro Glu Arg Thr Ala Leu Leu Leu Asp Leu Val Arg Thr Glu Val Ala
1825 1830 1835 1840
Ala Val Leu Gly His Gly Asp Thr Ala Ala Val Gly Ala Ala Arg Ser
1845 1850 1855
Phe Lys Asp Ala Gly Phe Asp Ser Leu Thr Ala Val Asp Leu Arg Asn
1860 1865 1870
Arg Leu Asn Ala Arg Thr Gly Leu Arg Leu Pro Ala Thr Leu Val Phe
1875 1880 1885
Asp His Pro Thr Pro Leu Ser Leu Ala Glu Leu Leu Leu Gly Glu Leu
1890 1895 1900
Thr Ala Ala Gly Arg Ala Glu Pro Ala Gly Pro Val Pro Asp Glu Pro
1905 1910 1915 1920
Ala Gly Ala Glu Asp Leu Ser Ser Ala Phe Asp Arg Leu Glu Arg Ser
1925 1930 1935
Leu Ala Ala Thr Asp Asp Gly Asp Ala Arg Val Arg Ala Ala Gln Arg
1940 1945 1950
Leu Arg Gly Leu Leu Ala Ala Leu Thr Val Gly Ser Gly Glu Gln Ser
1955 1960 1965
Gly Pro Gly Ala Gly Glu Ser Pro His Gly Pro Gly Asp Val Val Ile
1970 1975 1980
Asp Arg Leu Arg Ser Ala Ser Asp Asp Asp Leu Phe Asp Leu Leu Asp
1985 1990 1995 2000
Ser Asp Phe Gln
<210> 16
<211> 4538
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 16
Met Ser Cys Arg Phe Pro Ser Ala Pro Gly Ile Gln Glu Phe Trp Lys
1 5 10 15
Leu Leu Thr Asp Gly Thr Glu Ala Ile Gly Arg Ala Ala Asp Gly Arg
20 25 30
Arg Arg Gly Met Ile Glu Ala Val Gly Asp Phe Asp Ala Ala Phe Phe
35 40 45
Gly Met Ser Pro Arg Glu Ala Ala Glu Thr Asp Pro Gln Gln Arg Leu
50 55 60
Met Leu Glu Leu Gly Trp Glu Ala Leu Glu Asp Ala Gly Ile Val Pro
65 70 75 80
Gly Ser Leu Arg Gly Glu Ala Val Gly Val Phe Val Gly Ala Met Asn
85 90 95
Asp Asp Tyr Ala Thr Leu Leu His Arg Ala Gly Ala Pro Ile Gly Ala
100 105 110
His Thr Ala Thr Gly Leu Gln Arg Ala Met Leu Ala Asn Arg Leu Ser
115 120 125
Tyr Val Leu Gly Thr Arg Gly Pro Ser Leu Ala Val Asp Thr Ala Gln
130 135 140
Ser Ser Ser Leu Val Ala Val Ala Leu Ala Val Glu Ser Leu Arg Ala
145 150 155 160
Gly Thr Ser Arg Ile Ala Val Ala Gly Gly Val Asn Leu Ile Leu Ala
165 170 175
Asp Glu Gly Ser Ala Ala Met Glu Arg Leu Gly Ala Leu Ser Pro Asp
180 185 190
Gly Arg Cys His Thr Phe Asp Ala Arg Ala Asn Gly Tyr Val Arg Gly
195 200 205
Glu Gly Gly Ala Ala Val Val Leu Lys Pro Leu Ala Asp Ala Leu Ala
210 215 220
Asp Gly Asp Pro Val Tyr Cys Val Val Arg Gly Val Ala Ile Gly Asn
225 230 235 240
Asp Gly Gly Gly Pro Gly Leu Thr Ala Pro Asp Arg Glu Gly Gln Glu
245 250 255
Ala Val Leu Arg Ser Ala Cys Ala Gln Ala Gly Val Asp Pro Ala Glu
260 265 270
Val His Phe Val Glu Leu His Gly Thr Gly Thr Pro Val Gly Asp Pro
275 280 285
Val Glu Ala His Ala Leu Gly Ala Val His Gly Ser Gly Arg Ser Ala
290 295 300
Asp Thr Pro Leu Leu Val Gly Ser Val Lys Thr Asn Ile Gly His Leu
305 310 315 320
Glu Gly Ala Ala Gly Ile Ala Gly Leu Val Lys Ala Val Leu Cys Leu
325 330 335
Arg Glu Arg Thr Leu Pro Gly Ser Leu Asn Phe Asp Thr Pro Asn Pro
340 345 350
Ala Ile Pro Leu Asp Arg Leu Arg Leu Lys Val Gln Thr Ala Pro Thr
355 360 365
Glu Leu His Pro Gly Pro Ser Gly Ala Pro Leu Leu Ala Gly Val Ser
370 375 380
Ser Phe Gly Ile Gly Gly Thr Asn Cys His Val Val Leu Glu His Leu
385 390 395 400
Pro Gln Pro Ala Pro Ala Gly Pro Asp Ala Ile Pro Ser Ser Ala Ser
405 410 415
Glu Ala Ala Ala Pro His Pro Ala Pro Pro Leu Leu Leu Ser Ala Arg
420 425 430
Ser Arg Ala Ala Leu Arg Ala Gln Ala Ala Arg Leu His Asp His Leu
435 440 445
Gly Arg Thr Gly Ala Asp Pro Arg Asp Ile Ala Tyr Ser Leu Ala Thr
450 455 460
Thr Arg Thr Leu Phe Glu His Arg Ala Ala Leu Arg Cys Gly Asp Arg
465 470 475 480
Glu Glu Leu Ala Ala Ser Leu Asp Ala Phe Ala Arg Gly Lys Thr Ser
485 490 495
Ala Gly Val Arg Thr Gly Thr Ala Val Ser Gly Gly Thr Ala Val Leu
500 505 510
Phe Thr Gly Gln Gly Ala Gln Trp Val Gly Met Gly Arg Glu Leu Tyr
515 520 525
Gly Ala Gly Gly Val Phe Ala Gly Val Leu Asp Glu Val Leu Gly Val
530 535 540
Val Gly Glu Val Gly Gly Arg Ser Leu Arg Glu Val Met Phe Ala Glu
545 550 555 560
Ala Gly Ser Val Gly Ala Gly Leu Leu Gly Cys Thr Glu Phe Ala Gln
565 570 575
Pro Ala Leu Phe Ala Leu Glu Val Ala Leu Phe Arg Ala Leu Glu Ala
580 585 590
Arg Gly Val Gly Val Ser Val Val Leu Gly His Ser Val Gly Glu Val
595 600 605
Ala Ala Ala Tyr Val Ala Gly Val Phe Ser Leu Ala Asp Ala Val Arg
610 615 620
Leu Val Val Ala Arg Gly Arg Leu Met Gly Ala Leu Pro Val Gly Gly
625 630 635 640
Ala Met Val Ser Val Gly Ala Ser Glu Ala Glu Leu Ala Gly Leu Val
645 650 655
Ala Gly Leu Gly Gly Arg Val Ser Val Ala Ala Val Asn Gly Pro Ala
660 665 670
Ser Val Val Leu Ser Gly Glu Ala Gly Val Leu Asp Gly Val Val Ala
675 680 685
Gly Leu Val Gly Arg Gly Val Glu Cys Arg Trp Leu Glu Val Ser His
690 695 700
Ala Phe His Ser Val Leu Met Asp Pro Met Leu Glu Glu Phe Arg Arg
705 710 715 720
Val Ala Ala Ser Val Glu Phe His Arg Pro Arg Ser Gly Val Ala Val
725 730 735
Val Ser Ser Val Thr Gly Ala Val Ala Gly Leu Asp Glu Leu Gly Asp
740 745 750
Pro Glu Tyr Trp Val Arg His Val Arg Glu Ala Val Arg Phe Ala Asp
755 760 765
Gly Val Gly Ala Ala Arg Asp Val Gly Val Asp Thr Phe Val Glu Val
770 775 780
Gly Pro His Ala Val Leu Thr Val Met Ala Gly Gln Cys Leu Asp Gly
785 790 795 800
Asp Glu Gly Asp Leu Ala Phe Val Pro Val Leu Arg Arg Asp Arg Pro
805 810 815
Glu Leu Glu Thr Phe Thr Thr Ala Leu Ala Thr Leu Tyr Thr Arg Asp
820 825 830
Ala Glu Leu Asp Val Ala Ala Leu His Ser Gly Phe Gly Gly Arg Arg
835 840 845
Val Asp Leu Pro Thr Tyr Pro Phe Gln Arg Arg Thr His Trp Ser Pro
850 855 860
Ala Leu Ser Arg Gly Ile Ala Ala Asp Ala Gly Pro Gly Leu Thr Thr
865 870 875 880
Thr Asp Ala Ala Gly Asn Thr Ala Pro Pro Glu Ser Thr Glu Ala Pro
885 890 895
Leu Arg Asp Pro Asp Asp Glu Pro Leu Thr Ala Ser Pro Glu Pro Met
900 905 910
Ser Pro Glu Gln Leu Val Arg Leu Val Arg Glu Thr Thr Ala Thr Val
915 920 925
Leu Gly His Asp Asp Pro Asp Glu Ile Ala Leu Asp Arg Thr Phe Thr
930 935 940
Ser Gln Gly Leu Glu Ser Ala Thr Ala Val Glu Leu His Asp Leu Leu
945 950 955 960
Asn Arg Ala Thr Gly Leu Thr Leu Ala Ala Thr Leu Val Tyr Asp Leu
965 970 975
Pro Thr Pro Arg Ala Val Ala Glu His Leu Val Ala Ala Leu His Gly
980 985 990
Thr Lys Ser Ala His Pro Gly Glu His Glu Ala Val Gly Ala Ala Ala
995 1000 1005
Ala Arg Gly Gly Thr Arg Asp Asp Asp Pro Ile Ala Ile Val Gly Val
1010 1015 1020
Gly Cys Arg Leu Pro Gly Gly Val Asp Ser Arg Ala Ala Leu Trp Asp
1025 1030 1035 1040
Leu Leu Ala Ser Gly Thr Asp Ala Ile Ser Ser Phe Pro Ala Asp Arg
1045 1050 1055
Gly Trp Asp Leu Asp Gly Leu Tyr Asp Ala Glu Pro Gly Val Pro Gly
1060 1065 1070
Lys Thr Tyr Val Arg Gln Gly Gly Phe Leu His Gln Ala Ala Glu Phe
1075 1080 1085
Asp Ala Glu Phe Phe Gly Ile Ser Pro Arg Glu Ala Thr Ala Met Asp
1090 1095 1100
Pro Gln Gln Arg Leu Leu Leu Glu Thr Ser Trp Glu Ala Leu Glu Asp
1105 1110 1115 1120
Ala Gly Val Leu Pro Glu Ser Leu Arg Gly Gly Asp Thr Gly Val Phe
1125 1130 1135
Ile Gly Ala Val Ala Pro Glu Tyr Gly Pro Arg Leu His Glu Gly Ala
1140 1145 1150
Asp Gly Tyr Glu Gly Tyr Leu Leu Thr Gly Thr Thr Ala Ser Val Ala
1155 1160 1165
Ser Gly Arg Ile Ala Tyr Thr Leu Gly Thr Arg Gly Pro Ala Leu Thr
1170 1175 1180
Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Val
1185 1190 1195 1200
Gln Ala Leu Arg Arg Gly Glu Cys Gly Leu Ala Leu Ala Gly Gly Ala
1205 1210 1215
Thr Val Met Ser Gly Pro Gly Met Phe Val Glu Phe Ser Arg Gln Arg
1220 1225 1230
Gly Leu Ala Pro Asp Gly Arg Cys Met Pro Phe Ser Ala Asp Ala Asp
1235 1240 1245
Gly Thr Ala Trp Ser Glu Gly Val Ala Val Leu Ala Leu Glu Arg Leu
1250 1255 1260
Ser Asp Ala Arg Arg Ala Gly His Arg Val Leu Ala Val Val Arg Gly
1265 1270 1275 1280
Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn
1285 1290 1295
Gly Ser Ala Gln Glu Gly Val Ile Arg Ala Ala Leu Ala Asp Ala Gly
1300 1305 1310
Leu Ala Pro Gly Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr
1315 1320 1325
Ala Leu Gly Asp Pro Ile Glu Ala Gly Ala Leu Leu Ala Thr Tyr Gly
1330 1335 1340
Arg Glu Arg Val Gly Glu Pro Leu Trp Leu Gly Ser Leu Lys Ser Asn
1345 1350 1355 1360
Val Gly His Thr Gln Ala Ala Ala Gly Ala Ala Gly Val Ile Lys Met
1365 1370 1375
Leu Leu Ala Met Arg His Gly Thr Leu Pro Arg Thr Leu His Ala Asp
1380 1385 1390
Arg Pro Ser Thr His Val Asp Trp Ser Ser Gly Thr Val Glu Leu Leu
1395 1400 1405
Ala Glu Ala Arg Arg Trp Pro Glu Arg Ala Gly Arg Pro Arg Arg Ala
1410 1415 1420
Ala Val Ser Ser Phe Gly Ile Ser Gly Thr Asn Ala His Leu Val Ile
1425 1430 1435 1440
Glu Glu Ala Pro Ala Glu Thr Pro Thr Glu Pro Pro Thr Val Thr Ala
1445 1450 1455
Pro Thr Ala Glu Leu Ala Pro Thr Leu Ala Trp Pro Val Ser Ala Arg
1460 1465 1470
Ser Glu Glu Ala Leu Arg Ala Gln Ala Ala Arg Leu Arg Glu His Val
1475 1480 1485
Glu Arg Val Gly Ala Asp Pro Val Asp Val Ala His Ser Leu Ala Val
1490 1495 1500
Thr Arg Glu Ser Phe Gly Glu Arg Ala Val Val Val Gly Gly Asp Arg
1505 1510 1515 1520
Ala Glu Leu Met Ala Gly Leu Asp Ala Leu Ala Ala Gly His Thr Arg
1525 1530 1535
Pro Lys Thr Val Arg Gly Thr Ala Val Ser Gly Gly Thr Ala Val Leu
1540 1545 1550
Phe Thr Gly Gln Gly Ala Gln Trp Val Gly Met Gly Arg Glu Leu Tyr
1555 1560 1565
Gly Ala Gly Gly Val Phe Ala Gly Val Leu Asp Glu Val Leu Gly Val
1570 1575 1580
Val Gly Glu Val Gly Gly Arg Ser Leu Arg Glu Val Met Phe Ala Glu
1585 1590 1595 1600
Ala Gly Ser Val Asp Ala Gly Leu Leu Gly Cys Thr Glu Phe Ala Gln
1605 1610 1615
Pro Ala Leu Phe Ala Leu Glu Val Ala Leu Phe Arg Ala Leu Glu Ala
1620 1625 1630
Arg Gly Val Gly Val Ser Val Val Leu Gly His Ser Val Gly Glu Val
1635 1640 1645
Ala Ala Ala Tyr Val Ala Gly Val Phe Ser Leu Ala Asp Ala Val Arg
1650 1655 1660
Leu Val Val Ala Arg Gly Arg Leu Met Gly Ala Leu Pro Val Gly Gly
1665 1670 1675 1680
Ala Met Val Ser Val Gly Ala Ser Glu Ala Glu Leu Ala Gly Leu Val
1685 1690 1695
Ala Gly Leu Gly Gly Arg Val Ser Val Ala Ala Val Asn Gly Pro Ala
1700 1705 1710
Ser Val Val Leu Ser Gly Glu Ala Gly Val Leu Asp Gly Val Val Ala
1715 1720 1725
Gly Leu Val Gly Arg Gly Val Glu Cys Arg Trp Leu Glu Val Ser His
1730 1735 1740
Ala Phe His Ser Val Leu Met Asp Pro Met Leu Glu Glu Phe Arg Arg
1745 1750 1755 1760
Val Ala Ala Ser Val Glu Phe His Arg Pro Arg Ser Gly Val Ala Val
1765 1770 1775
Val Ser Ser Val Thr Gly Ala Val Ala Gly Leu Asp Glu Leu Gly Asp
1780 1785 1790
Pro Glu Tyr Trp Val Arg His Val Arg Glu Ala Val Arg Phe Ala Asp
1795 1800 1805
Gly Val Gly Ala Ala Arg Asp Val Gly Val Asp Thr Phe Val Glu Val
1810 1815 1820
Gly Pro His Ala Val Leu Thr Val Met Ala Gly Gln Cys Leu Asp Gly
1825 1830 1835 1840
Asp Glu Gly Asp Leu Ala Phe Val Pro Val Leu Arg Arg Asp Arg Pro
1845 1850 1855
Glu Leu Glu Thr Phe Thr Thr Ala Leu Ala Thr Leu Tyr Ala Arg Gly
1860 1865 1870
Ala Gln Ile Asp Trp Asp Ala Pro Asn Arg Lys Arg Asp Ala Arg Arg
1875 1880 1885
Ile Asp Leu Pro Thr Tyr Pro Phe Gln Arg Ala Arg Phe Trp Leu Asp
1890 1895 1900
Pro Ala Pro Ala Ala Val Pro Thr Ala Met Ala Ala Gly Ser Ser Glu
1905 1910 1915 1920
Asp Val Pro Thr Ala Ala Gln Gly Val Thr Ser Ala Thr Ala Gly Leu
1925 1930 1935
Arg Tyr Arg Val Thr Trp Gln Pro Ala Ala Val Gly Cys Gly Val Pro
1940 1945 1950
Arg Pro Ala Gly Arg Met Leu Leu Leu Ala Ser Asp Asp Asp Thr Thr
1955 1960 1965
Asp Ser Gly Leu Ala Thr Ala Ile Ala Arg Glu Leu Ala Val Arg Gly
1970 1975 1980
Thr Glu Val His Thr Ala Val Val Pro Val Gly Thr Gly Arg Glu Ala
1985 1990 1995 2000
Ala Ala Asp Leu Leu Arg Ala Ala Gly Asp Gly Ala Ala Arg Ser Thr
2005 2010 2015
His Val Leu Trp Leu Ala Pro Ala Glu Pro Asp Thr Ala Asp Ala Val
2020 2025 2030
Ala Leu Ile Gln Ala Leu Gly Glu Ala Gly Pro Asp Ala Pro Leu Trp
2035 2040 2045
Ile Thr Thr Arg Asp Ala Val Ala Ala Gln Pro Gly Glu Ala Pro Ser
2050 2055 2060
Val Ala Gly Ala Gln Leu Trp Gly Leu Gly Gln Val Ala Ala Leu Glu
2065 2070 2075 2080
Leu Ala Gln Arg Trp Gly Gly Leu Ala Asp Leu Pro Gly Glu Pro Ser
2085 2090 2095
Pro Ala Ala Leu Arg Ala Phe Val Gly Thr Leu Leu Ala Glu Gly Glu
2100 2105 2110
Asp Asn Gln Phe Ala Val Arg Pro Ser Gly Val His Val Arg Arg Val
2115 2120 2125
Val Pro Val Pro Val Arg Ala Ala Thr Thr Ala Ala Ala Arg Asp Ala
2130 2135 2140
Gln Gly Asp Thr Pro Asp Gly Val Val Pro Gly Asn Arg Arg Ser Ser
2145 2150 2155 2160
Gly Thr Val Leu Ile Thr Gly Gly Thr Gly Ala Leu Gly Ala Gln Val
2165 2170 2175
Ala Arg Arg Leu Ala Arg Ala Gly Ala Pro His Leu Leu Leu Val Gly
2180 2185 2190
Arg Arg Gly Ala Ala Gly Pro Gly Ala Gly Glu Leu Val Glu Glu Leu
2195 2200 2205
Thr Ala Leu Gly Thr Glu Val Thr Val Ala Ala Cys Asp Val Ala Asp
2210 2215 2220
Arg Asp Ala Leu Ala Ala Leu Leu Ala Gly Ile Pro Glu Asp Arg Pro
2225 2230 2235 2240
Leu Ala Ala Val Leu His Ala Ala Gly Val Leu Asp Asp Gly Val Leu
2245 2250 2255
Asp Ser Leu Thr Ser Asp Arg Ile Asp Ala Val Leu Arg Ala Lys Val
2260 2265 2270
Thr Ala Ala Arg His Leu Asp Glu Leu Thr Ala Asp Leu Pro Leu Asp
2275 2280 2285
Ala Phe Val Leu Phe Ser Ser Ile Val Gly Val Trp Gly Asn Gly Gly
2290 2295 2300
Gln Ala Ala Tyr Ala Ala Ala Asn Ala Ala Leu Asp Ala Leu Ala His
2305 2310 2315 2320
Arg Arg Arg Ala Arg Gly Gly Arg Ala Thr Ser Ile Ala Trp Gly Pro
2325 2330 2335
Trp Ala Gly Ala Gly Met Ala Ser Gly Thr Ala Thr Lys Ser Phe Glu
2340 2345 2350
Arg Asp Gly Val Ala Ala Leu Asp Pro Glu His Ala Leu Asp Val Leu
2355 2360 2365
Asp Asp Ala Val Gly Ala Gly Gly Thr Ser Ala Ala Ala Gly Ala Ser
2370 2375 2380
Ala Ala Val Ala Thr Ser Leu Ile Val Ala Asp Val Asp Trp Glu Thr
2385 2390 2395 2400
Phe Val Gly Arg Ser Val Thr Arg Arg Thr Trp Ala Leu Phe Asp Gly
2405 2410 2415
Val Pro Ala Ala Arg Ser Ala Arg Ser Ala Arg Ala Ala Gln Gly Arg
2420 2425 2430
Ala Thr Leu Pro Arg Gly Thr Arg Pro Gly His Gly Gly Pro Gly Gly
2435 2440 2445
Ser Gly Ala Gly Ala Asp Glu Gly Arg Pro Trp Leu Ser Val Gly Pro
2450 2455 2460
Ser Ser Thr Glu Arg Arg Arg Ala Leu Leu Asp Leu Val Cys Ser Glu
2465 2470 2475 2480
Ala Ala Glu Ile Leu Arg His Ala Ser Ala Asp Ala Val Asp Pro Glu
2485 2490 2495
Ile Ala Phe Arg Ser Ala Gly Phe Asp Ser Leu Thr Val Leu Glu Leu
2500 2505 2510
Arg Asn Arg Leu Thr Ala Ala Thr Gly Leu Asn Leu Pro Ser Thr Leu
2515 2520 2525
Leu Phe Asp His Pro Asn Pro Thr Ser Leu Ala Ala His Leu His Asp
2530 2535 2540
Glu Leu Phe Gly Thr Asp Ser Glu Ala Glu Pro Val Ala Asp Thr Arg
2545 2550 2555 2560
Ala Arg Ala Thr Ala Asp Glu Arg Glu Pro Ile Ala Ile Val Gly Met
2565 2570 2575
Ala Cys Arg Tyr Pro Gly Gly Val Ser Ser Pro Glu Asp Leu Trp Arg
2580 2585 2590
Leu Val Ala Glu Asp Gly His Thr Leu Ser Pro Phe Pro Val Asp Arg
2595 2600 2605
Gly Trp Asp Val Glu Gly Leu Tyr Asp Pro Asp Pro Glu Ala Val Gly
2610 2615 2620
Arg Ser Tyr Val Arg Glu Gly Gly Phe Leu His Gly Ala Ala Glu Phe
2625 2630 2635 2640
Asp Ala Glu Phe Phe Gly Ile Ser Pro Arg Glu Ala Ala Ala Met Asp
2645 2650 2655
Pro Gln Gln Arg Leu Leu Leu Glu Thr Ser Trp Glu Ala Leu Glu Arg
2660 2665 2670
Ala Gly Ile Val Pro Asp Ala Leu Arg Gly Thr Arg Thr Gly Val Phe
2675 2680 2685
Thr Gly Ile Ser Gln Gln Asp Tyr Ala Ser Gln Leu Gly Asp Ala Ala
2690 2695 2700
Glu Thr Tyr Gly Gly His Val Leu Thr Gly Thr Leu Gly Ser Val Ile
2705 2710 2715 2720
Ser Gly Arg Val Ala Tyr Val Leu Gly Leu Glu Gly Pro Ala Leu Thr
2725 2730 2735
Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Val
2740 2745 2750
Gln Ser Leu Arg Arg Gly Glu Cys Asp Met Ala Leu Ala Gly Gly Val
2755 2760 2765
Thr Val Met Ala Thr Pro Thr Val Phe Val Glu Phe Ser Arg Gln Arg
2770 2775 2780
Gly Leu Ala Ser Asp Gly Arg Cys Lys Ala Phe Ala Glu Gly Ala Asp
2785 2790 2795 2800
Gly Thr Val Trp Ala Glu Gly Val Gly Val Leu Leu Val Glu Arg Leu
2805 2810 2815
Ser Asp Ala Arg Arg Tyr Gly His Arg Val Leu Ala Val Val Arg Gly
2820 2825 2830
Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Ser
2835 2840 2845
Gly Ala Ala Gln Arg Arg Val Ile Arg Glu Ala Leu Ala Asp Ala Gly
2850 2855 2860
Leu Ala Pro Gly Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr
2865 2870 2875 2880
Ala Leu Gly Asp Pro Ile Glu Ala Gly Ala Leu Leu Ala Thr Tyr Gly
2885 2890 2895
Arg Glu Arg Val Gly Asp Pro Leu Trp Leu Gly Ser Leu Lys Ser Asn
2900 2905 2910
Ile Gly His Ala Gln Ala Ala Ala Gly Val Gly Gly Val Ile Lys Met
2915 2920 2925
Val Glu Ala Met Arg His Ser Ser Leu Pro Arg Thr Leu His Val Asp
2930 2935 2940
Ala Pro Ser Ser Arg Val Glu Trp Gly Ser Gly Ala Val Glu Leu Leu
2945 2950 2955 2960
Thr Glu Ala Arg Ser Trp Pro Arg Arg Ala Gly Arg Val Arg Arg Ala
2965 2970 2975
Ala Val Ser Ala Phe Gly Val Ser Gly Thr Asn Ala His Val Val Ile
2980 2985 2990
Glu Glu Pro Ser Val Glu Glu Ser Ala Glu Ala Glu Ala Val Val Thr
2995 3000 3005
Ala Ala Ala Glu Ser Ser Ser Val Leu Ala Trp Pro Val Ser Ala Arg
3010 3015 3020
Ser Glu Glu Ala Leu Arg Gly Gln Ala Val Arg Leu Arg Glu His Val
3025 3030 3035 3040
Glu Arg Val Gly Ala Asp Pro Val Asp Val Ala His Ser Leu Val Val
3045 3050 3055
Ser Arg Ala Ser Phe Gly Glu Arg Ala Val Val Val Gly Arg Glu Arg
3060 3065 3070
Gly Glu Leu Leu Ala Gly Leu Asp Ala Val Ala Ala Gly Val Val Ala
3075 3080 3085
Ala Gly Gly Ala Ala Ser Gly Val Val Arg Gly Ser Ala Val Arg Gly
3090 3095 3100
Arg Arg Val Gly Val Leu Phe Thr Gly Gln Gly Ala Gln Trp Val Gly
3105 3110 3115 3120
Met Gly Arg Glu Leu Tyr Gly Ala Gly Gly Val Phe Ala Gly Val Leu
3125 3130 3135
Asp Glu Val Leu Gly Val Val Gly Glu Val Gly Gly Arg Ser Leu Arg
3140 3145 3150
Glu Val Met Phe Ala Glu Ala Gly Ser Val Asp Ala Gly Leu Leu Gly
3155 3160 3165
Cys Thr Glu Phe Ala Gln Pro Ala Leu Phe Ala Leu Glu Val Ala Leu
3170 3175 3180
Phe Arg Ala Leu Glu Ala Arg Gly Val Gly Val Ser Val Val Leu Gly
3185 3190 3195 3200
His Ser Val Gly Glu Val Ala Ala Ala Tyr Val Ala Gly Val Phe Ser
3205 3210 3215
Leu Ala Asp Ala Val Arg Leu Val Val Ala Arg Gly Arg Leu Met Gly
3220 3225 3230
Ala Leu Pro Val Gly Gly Ala Met Val Ser Val Gly Ala Ser Glu Ala
3235 3240 3245
Glu Leu Ala Gly Leu Val Ala Gly Leu Gly Gly Arg Val Ser Val Ala
3250 3255 3260
Ala Val Asn Gly Pro Ala Ser Val Val Leu Ser Gly Glu Ala Gly Val
3265 3270 3275 3280
Leu Asp Gly Val Val Ala Gly Leu Val Gly Arg Gly Val Glu Cys Arg
3285 3290 3295
Trp Leu Glu Val Ser His Ala Phe His Ser Val Leu Met Asp Pro Met
3300 3305 3310
Leu Glu Glu Phe Arg Arg Val Ala Ala Ser Val Glu Phe His Arg Pro
3315 3320 3325
Arg Ser Gly Val Ala Val Val Ser Ser Val Thr Gly Ala Val Ala Gly
3330 3335 3340
Leu Asp Glu Leu Gly Asp Pro Glu Tyr Trp Val Arg His Val Arg Glu
3345 3350 3355 3360
Ala Val Arg Phe Ala Asp Gly Val Gly Ala Ala Arg Asp Val Gly Val
3365 3370 3375
Asp Thr Phe Val Glu Val Gly Pro His Ala Val Leu Thr Val Met Ala
3380 3385 3390
Gly Gln Cys Leu Asp Gly Asp Glu Gly Asp Leu Ala Phe Val Pro Val
3395 3400 3405
Leu Arg Arg Asp Arg Pro Glu Leu Glu Thr Phe Thr Thr Ala Leu Ala
3410 3415 3420
Thr Leu Tyr Thr Arg Asp Ala Glu Leu Asp Val Ala Ala Leu His Ser
3425 3430 3435 3440
Gly Phe Gly Gly Arg Arg Val Asp Leu Pro Thr Tyr Pro Phe Gln Arg
3445 3450 3455
Arg Gly Tyr Trp Ala Thr Gly Ser Val Ser Gly Ser Thr Gly Ser Ser
3460 3465 3470
Ala Ala Ala Arg Phe Gly Leu Glu Trp Lys Asp His Pro Phe Leu Ser
3475 3480 3485
Gly Ala Thr Pro Ile Val Gly Ser Gly Ala Leu Leu Leu Thr Gly Arg
3490 3495 3500
Val Ala Leu Ser Thr His Pro Trp Leu Ala Asp His Ala Ile Ser Gly
3505 3510 3515 3520
Thr Val Leu Leu Pro Gly Thr Ala Ile Ala Asp Leu Leu Leu Arg Ala
3525 3530 3535
Ala Glu Glu Val Gly Ala Gly Gly Val Glu Glu Leu Thr Leu His Ala
3540 3545 3550
Pro Leu Leu Leu Pro Glu Gln Gly Gly Leu Arg Leu Gln Val Leu Val
3555 3560 3565
Glu Ala Ala Asp Gly Gln Gly Arg Arg Ala Val Ala Leu Ala Ala Arg
3570 3575 3580
Pro Glu Thr Pro Gly Trp Asp Gly Glu Glu Pro Glu Trp Thr Lys His
3585 3590 3595 3600
Ala Glu Gly Val Leu Ala Pro Ala Glu Pro Ala Val Pro Asp Thr Ala
3605 3610 3615
Trp Ala Ala Gly Ala Trp Pro Pro Pro Gly Ala Glu Pro Val Asp Val
3620 3625 3630
Gly Glu Leu Tyr Glu Gly Phe Ala Ala Asp Gly Tyr Asp Tyr Gly Pro
3635 3640 3645
Ala Phe Ser Gly Leu Ser Gly Ala Trp Arg Leu Gly Asn Glu Leu Phe
3650 3655 3660
Ala Glu Val Arg Leu Ser Ala Thr Gly Thr Ala Gly Asp Gly Phe Gly
3665 3670 3675 3680
Ile His Pro Ala Leu Phe Asp Ala Ala Leu His Pro Trp Arg Ala Gly
3685 3690 3695
Gly Leu Leu Pro Asp Thr Gly Gly Thr Thr Leu Ala Pro Phe Ser Trp
3700 3705 3710
Gln Gly Ile Ala Leu His Ala Thr Gly Ala Glu Thr Leu Arg Val Arg
3715 3720 3725
Leu Ala Pro Ala Gly Ser Gly Ala Glu Ser Ala Phe Ser Val Arg Ala
3730 3735 3740
Ala Asp Pro Ala Gly Ala Pro Val Leu Thr Leu Asp Ala Leu Leu Leu
3745 3750 3755 3760
Arg Pro Val Ala Leu Gly Thr Ala Gly Ala Pro Glu Pro Leu Tyr Arg
3765 3770 3775
Val Asp Trp Gln Pro Val Pro Gln Arg Ser Asp Thr Pro Gly Ala His
3780 3785 3790
Gly Trp Thr Val Leu Gly Pro Ala Ala Gly Glu Thr Ala Ala Glu Gln
3795 3800 3805
Ala Ala Thr Glu Glu Cys Ala Thr Leu Arg Ala Leu Pro Gly Ala Glu
3810 3815 3820
Pro Ala Ala His Ala Asp Leu Ala Ala Leu Arg Thr Ala Leu Thr Ala
3825 3830 3835 3840
Gly Thr Pro Val Pro Gly Leu Val Val Val Pro Ala Thr Asp Ile Arg
3845 3850 3855
Pro Ala Glu Ser Ser Ala Gly Ala Gly Ala Gly Val Asp Ala Gly Ala
3860 3865 3870
Asp Ala Arg Val Arg Arg Gly Lys Ala His Val Arg Thr Ala Thr Ala
3875 3880 3885
His Ala Arg Thr Gly Thr Asp Trp Gly Asp Asp Pro Val Arg Val Ala
3890 3895 3900
Leu Gly Arg Gly Leu Ala Leu Val Arg Glu Trp Thr Glu Asp Glu Arg
3905 3910 3915 3920
Leu Ala Asp Ser Arg Leu Val Val Leu Thr Arg Gly Ala Val Glu Ala
3925 3930 3935
Gly Ser Gly Glu Val Pro Asp Leu Ala Gly Ala Ala Leu Trp Gly Leu
3940 3945 3950
Leu Arg Ser Ala Gln Ser Glu Tyr Pro Asp Arg Phe Thr Leu Val Asp
3955 3960 3965
Val Asp Asp Ser Pro Glu Ser Arg Ala Ala Leu Pro Arg Ala Leu Glu
3970 3975 3980
Ser Gly Glu Pro Gln Leu Ala Leu Arg Ala Gly Ala Leu Leu Ala Pro
3985 3990 3995 4000
Ala Leu Val Pro Ile Thr Thr Pro Ala Thr Ala Ala Thr Pro Ala Thr
4005 4010 4015
Ala Val Asp Ser Ala Ala Ala Ala Val Ala Ala Gln Ser Val Ala Pro
4020 4025 4030
Glu Ala Ala Gly Pro Ala Glu Arg Gly Gly Ala Ala Thr Gly Gly Pro
4035 4040 4045
Ala Ser Asp Gly Ala Phe Asp Pro Asp Gly Ser Ala Val Asp Ala Val
4050 4055 4060
Phe Asp Pro Ala Gly Thr Val Leu Ile Thr Gly Cys Thr Gly Ala Leu
4065 4070 4075 4080
Gly Arg Arg Val Ala Pro His Leu Ala Arg Arg His Gly Val Arg His
4085 4090 4095
Met Leu Leu Val Ser Arg Arg Gly Pro Asp Ala Pro Glu Ala Ala Leu
4100 4105 4110
Leu Glu Arg Glu Leu Val Gly Leu Gly Val Thr Ala Thr Phe Leu Ala
4115 4120 4125
Cys Asp Leu Ala Asp Pro Ala Ala Val Arg Lys Ala Val Val Ala Val
4130 4135 4140
Ser Pro Glu His Pro Leu Thr Gly Val Val His Thr Ala Gly Val Leu
4145 4150 4155 4160
Asp Asp Gly Ala Leu Thr Gly Leu Thr Gln Glu Arg Leu Asp Thr Val
4165 4170 4175
Leu Arg Ser Lys Ala Asp Ala Val Arg Asn Leu His Glu Ala Thr Leu
4180 4185 4190
Asp Arg Pro Leu Arg Ala Phe Val Leu Phe Ser Ala Ala Ala Gly Leu
4195 4200 4205
Leu Gly Arg Pro Gly Gln Gly Ser Tyr Ala Ala Ala Asn Ala Val Leu
4210 4215 4220
Asp Ala Leu Ala Gly Ala Arg Arg Ala Ala Gly Leu Pro Ala Val Ser
4225 4230 4235 4240
Leu Ala Trp Gly Leu Trp Asp Glu Arg Ala Gly Met Ala Gly Gly Leu
4245 4250 4255
Asp Asp Val Ala Leu His Arg Leu Arg Arg Glu Gly Ile Ala Ala Met
4260 4265 4270
Pro Pro Glu Gln Gly Leu Gly Leu Leu Asp Gln Ala Leu Thr Ala His
4275 4280 4285
Arg Asp Gly Pro Ala Val Leu Val Pro Leu Leu Leu Asp Gly Ala Ala
4290 4295 4300
Leu Arg Arg Thr Ala Lys Glu Arg Gly Ala Ala Ala Val Pro Pro Leu
4305 4310 4315 4320
Leu Arg Gly Leu Leu Pro Ala Ala Leu Arg His Ser Ser Thr Gly Thr
4325 4330 4335
Pro Ala Ala Ala Asp Arg His Gly Lys Gly Ala Glu Ser Gly Thr Gly
4340 4345 4350
Arg Ile Ala Arg Ile Val Ala Leu Asp Ala Ala Glu Arg Ser Thr Ala
4355 4360 4365
Val Leu Asp Leu Val Thr Glu Gln Val Ala Glu Val Leu Gly His Ala
4370 4375 4380
Ser Ala Ala Glu Ile Glu Pro Glu Arg Pro Phe Arg Glu Ile Gly Val
4385 4390 4395 4400
Asp Ser Leu Ala Ala Val Glu Leu Arg Asn Arg Leu Ser Arg Leu Val
4405 4410 4415
Gly Leu Arg Leu Pro Thr Thr Leu Ala Phe Asp His Pro Thr Pro Lys
4420 4425 4430
Asp Met Ala Glu Trp Ile Asp Gly Glu Leu Pro Arg Pro Ala Gly Ala
4435 4440 4445
Pro Val Val Asp Ala Ala Leu Glu Gly Ile Gly Glu Leu Ala Arg Ala
4450 4455 4460
Val Ala Leu Leu Gly Ser Asp Asp Ala Arg Arg Val Glu Val Arg Gln
4465 4470 4475 4480
Arg Leu Val Gly Leu Leu Thr Ala Leu Asp Thr Pro Gly Arg Gly Val
4485 4490 4495
Val Gly Pro Gln Gly Arg Thr Ala Pro Ala Ala Pro Ala Ala Ala Asp
4500 4505 4510
Gly Ala Gly Ala Thr Val Thr Asp Arg Leu Asp Glu Ala Thr Asp Asp
4515 4520 4525
Glu Ile Phe Ala Phe Leu Asp Glu Gln Leu
4530 4535
<210> 17
<211> 403
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 17
Met Gly Glu Ala Val Ser Gly Pro Met Glu Leu Ser Lys Asp Ala Asp
1 5 10 15
Ala Arg Gly Leu Leu Asp Trp Phe Ala Phe Asn Arg Thr Arg His Pro
20 25 30
Val Phe Trp Asp Glu Gly Arg Gln Ala Trp Gln Val Phe Gly Tyr Asp
35 40 45
Asp Tyr Val Thr Val Ser Asn Asn Pro Gln Phe Phe Ser Ser Asp Phe
50 55 60
Asn Met Val Met Pro Thr Pro Pro Glu Leu Glu Met Ile Ile Gly Pro
65 70 75 80
Gly Thr Ile Gly Ala Leu Asp Pro Pro Ala His Gly Pro Met Arg Lys
85 90 95
Leu Val Ser Gln Ala Phe Thr Pro Arg Arg Ile Ala Arg Leu Glu Pro
100 105 110
Arg Val Arg Ala Ile Thr Glu Glu Leu Leu Asp Lys Val Arg Glu Gln
115 120 125
Asn Val Ile Asp Ala Val Gly Asp Leu Ser Tyr Ala Leu Pro Val Ile
130 135 140
Val Ile Ala Glu Leu Leu Gly Val Pro Thr Gly Asp Arg Asp Leu Phe
145 150 155 160
Arg Glu Trp Val Asp Thr Leu Leu Thr Asn Glu Gly Leu Glu Tyr Pro
165 170 175
Asn Leu Pro Asp Asn Phe Thr Glu Thr Ile Ala Pro Ala Leu Lys Glu
180 185 190
Met Thr Asp Tyr Leu Leu Glu Gln Ile His Ala Lys Arg Glu Ala Pro
195 200 205
Ala Asp Asp Leu Ile Ser Gly Leu Val Gln Ala Glu Gln Asp Gly Arg
210 215 220
Arg Leu Thr Asp Val Glu Ile Val Asn Ile Val Ala Leu Leu Leu Thr
225 230 235 240
Ala Gly His Val Ser Ser Ser Thr Leu Leu Ser Asn Leu Phe Leu Val
245 250 255
Leu Glu Glu Asn Pro Gln Ala Leu Glu Asp Leu Arg Ala Asp Arg Thr
260 265 270
Leu Val Pro Gly Ala Ile Glu Glu Thr Leu Arg Tyr Arg Ser Pro Phe
275 280 285
Asn Asn Ile Phe Arg Phe Val Lys Gln Asp Thr Thr Ile Leu Gly Pro
290 295 300
Leu Met Glu Lys Gly Gln Met Val Ile Ala Trp Ser Gln Ser Ala Asn
305 310 315 320
Arg Asp Pro Arg His Phe Pro Asp Pro Asp Thr Phe Asp Ile Arg Arg
325 330 335
Ser Asp Gly Thr Arg His Met Ala Phe Gly His Gly Ile His His Cys
340 345 350
Leu Gly Ala Ala Leu Ala Arg Leu Glu Gly Lys Val Met Leu Glu Leu
355 360 365
Leu Leu Glu Arg Val Asp Gly Phe Arg Ile Asp His Glu Asn Thr Leu
370 375 380
Phe Tyr Glu Ala Asp Gln Leu Thr Pro Lys Tyr Leu Pro Val Arg Val
385 390 395 400
Asp Trp Asn
<210> 18
<211> 116
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 18
Met Val Glu Ser Gly Val Thr Val Asp Phe Pro Val Gln Arg Val Tyr
1 5 10 15
Tyr Met His Gly Gln Thr Gln Ser Ser Pro Pro Arg Gly Leu His Ala
20 25 30
His Arg Thr Leu Glu Gln Leu Val Ile Ala Val His Gly Ala Phe Ser
35 40 45
Ile Thr Leu Asp Asp Gly Phe Gln His Ala Thr Tyr Arg Leu Asp Glu
50 55 60
Pro Gly Ala Gly Leu Cys Ile Gly Pro Met Val Trp Arg Val Leu Lys
65 70 75 80
Asp Phe Ala Pro Asp Thr Val Ala Leu Val Leu Ala Ser Gln His Tyr
85 90 95
Glu Glu Ser Asp Tyr Tyr Arg Asp Tyr Asp Thr Phe Leu His Asp Ala
100 105 110
Arg Ser Leu Thr
115
<210> 19
<211> 399
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 19
Met Thr Ile Pro Phe Leu Asp Ala Gly Ala Gly Tyr Arg Glu Leu Arg
1 5 10 15
Ala Asp Ile Asp Ala Ala Leu Gln Arg Val Ser Ala Ser Gly Arg Tyr
20 25 30
Leu Leu Gly Ala Glu Leu Glu Gly Phe Glu Glu Glu Phe Ala Ala Tyr
35 40 45
Cys Asp Asn Gly His Cys Val Ala Val Gly Ser Gly Cys Asp Ala Leu
50 55 60
Glu Leu Ser Leu Arg Ala Leu Asp Ile Gly Pro Gly Asp Glu Val Val
65 70 75 80
Val Pro Ala His Thr Phe Ile Gly Thr Trp Leu Ala Val Ser Ala Thr
85 90 95
Gly Ala Gln Pro Val Ala Val Asp Pro Thr Pro Asp Gly Leu Ser Leu
100 105 110
Asp Pro Ala Leu Val Glu Ala Ala Val Thr Pro Arg Thr Lys Ala Leu
115 120 125
Met Pro Val His Leu His Gly His Pro Ala Asp Leu Asp Pro Leu Leu
130 135 140
Ala Val Ala Glu Arg His Gly Leu Ala Val Val Glu Asp Ala Ala Gln
145 150 155 160
Ala His Gly Ala Arg Tyr Arg Gly Arg Arg Ile Gly Ser Gly His Val
165 170 175
Val Ala Phe Ser Phe Tyr Pro Gly Lys Asn Leu Gly Ala Met Gly Asp
180 185 190
Gly Gly Ala Val Val Thr Arg Asp Ala Gly Val Ala Asp Arg Ile Arg
195 200 205
Leu Leu Arg Asn Cys Gly Ser Arg Glu Lys Tyr Arg His Glu Val Arg
210 215 220
Ala Thr Asn Ser Arg Leu Asp Glu Leu Gln Ala Ala Val Leu Arg Ala
225 230 235 240
Lys Leu Pro Arg Leu Asp Ala Trp Asn Ala Arg Arg Ala Arg Thr Ala
245 250 255
Glu Arg Tyr Thr Arg Ala Leu Gly Ser Leu Pro Gln Ile Ala Val Pro
260 265 270
Val Thr Ala Arg Trp Ala Asp Pro Ala Trp His Leu Tyr Val Ile Arg
275 280 285
Cys Ala Glu Arg Asp Glu Leu Arg Arg Arg Leu Glu Arg Ala Gly Val
290 295 300
Gln Thr Leu Ile His Tyr Pro Val Pro Pro His Arg Ser Pro Ala Tyr
305 310 315 320
Ala Asp Ala Pro Ala Gly Ala Pro Ala Gly Ala His Pro Arg Ser Glu
325 330 335
Arg Leu Ala Ala Gln Ser Leu Ser Leu Pro Leu Gly Pro His Leu Gly
340 345 350
Asp Asp Glu Ser Arg Ala Val Val Ala Ala Val Arg Ala Ala Ala Ala
355 360 365
Gly Leu Ala Ala Tyr Pro Thr Pro Asp Gly Thr Pro Arg Thr Pro Arg
370 375 380
Thr Thr Pro Asp Gly Gln Arg Phe Pro Leu Ala Thr Glu Lys Arg
385 390 395
<210> 20
<211> 302
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 20
Met Thr Glu Val Met Ser Gly Arg Ser Gly Met Lys Gly Ile Ile Leu
1 5 10 15
Ala Gly Gly Gly Gly Thr Arg Leu Arg Pro Leu Thr Gly Thr Leu Ser
20 25 30
Lys Gln Leu Leu Pro Val Tyr Asp Lys Pro Met Ile Tyr Tyr Pro Leu
35 40 45
Ser Val Leu Met Leu Gly Gly Ile Arg Glu Ile Leu Val Ile Ser Ser
50 55 60
Thr Gln His Ile Glu Leu Phe Gln Gln Leu Leu Gly Asp Gly Ser Arg
65 70 75 80
Leu Gly Leu Asp Ile Thr Tyr Ala Glu Gln Pro Glu Pro Gln Gly Ile
85 90 95
Ala Gln Ala Leu Thr Ile Gly Thr Asp His Ile Gly Asp Ser Pro Val
100 105 110
Ala Leu Ile Leu Gly Asp Asn Ile Phe His Gly Pro Gly Phe Ser Ser
115 120 125
Val Leu Arg Gly Ser Ile Arg His Leu Asp Gly Cys Val Leu Phe Gly
130 135 140
Tyr Pro Val Ser Asp Pro Gln Arg Tyr Gly Val Gly Glu Ile Asp Asp
145 150 155 160
Gln Gly Met Leu Leu Ser Leu Glu Glu Lys Pro Ala Arg Pro Arg Ser
165 170 175
Asn Leu Ala Val Thr Gly Leu Tyr Leu Tyr Asp Asn Asp Val Val Asp
180 185 190
Ile Ala Lys Asn Ile Arg Pro Ser Ala Arg Gly Glu Leu Glu Ile Thr
195 200 205
Asp Val Asn Gln Val Tyr Leu Glu Gln Lys Arg Ala Arg Leu Ile Glu
210 215 220
Leu Gly His Gly Phe Ala Trp Leu Asp Met Gly Thr His Asp Ser Leu
225 230 235 240
Leu Gln Gly Gly Gln Tyr Val Gln Leu Leu Glu Gln Arg Gln Gly Val
245 250 255
Arg Ile Ala Cys Ile Glu Glu Ile Ala Leu Arg Met Gly Phe Ile Asp
260 265 270
Ala Asp Thr Leu Tyr Trp Leu Gly Arg Glu Leu Gly Thr Ser Gly Tyr
275 280 285
Gly Ala Tyr Leu Met Glu Val Ala Thr His Ala Gly Ala Ala
290 295 300
<210> 21
<211> 345
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 21
Met Gln Ala Pro His Glu Ser Pro His Arg Pro Thr Arg Phe Ala Asp
1 5 10 15
Gly Arg Gln Pro Ala Arg Ile Leu Val Thr Gly Gly Ala Gly Phe Ile
20 25 30
Gly Ser Arg Phe Val Asn Ala Leu Leu Asp Gly Ser Leu Pro Glu Phe
35 40 45
Gly Lys Pro Glu Val Arg Val Leu Asp Ala Leu Thr Tyr Ala Gly Asn
50 55 60
Leu Ala Asn Leu Ala Pro Val Gly Asp Cys Pro Arg Leu Arg Ile Phe
65 70 75 80
Gln Gly Asp Ile Cys Asp Arg Ser Ala Val Ala Gln Ala Met Ala Gly
85 90 95
Val Asp Leu Val Val His Phe Ala Ala Glu Ser His Val Asp Arg Ser
100 105 110
Ile Asp Asp Ala Asp Ala Phe Val Arg Thr Asn Val Leu Gly Thr Gln
115 120 125
Val Leu Leu Gln Glu Ala Leu Ala Ile Arg Pro Gly Leu Phe Val His
130 135 140
Val Ser Thr Asp Glu Val Tyr Gly Ser Ile Pro Val Gly Ser Trp Pro
145 150 155 160
Glu Asp His Pro Leu Ser Pro Asn Ser Pro Tyr Ala Ala Ser Lys Ala
165 170 175
Ser Ser Asp Leu Leu Ala Leu Ala Tyr His Arg Thr His Gly Leu Pro
180 185 190
Val Cys Val Thr Arg Cys Ser Asn Asn Tyr Gly Pro Tyr Gln Tyr Pro
195 200 205
Glu Lys Ile Ile Pro Leu Phe Thr Ser Asn Leu Leu Asp Gly Arg Thr
210 215 220
Val Pro Leu Tyr Gly Asp Gly Gly Asn Arg Arg Asp Trp Leu His Val
225 230 235 240
Asn Asp His Cys Arg Gly Ile Ala Leu Val Ala Arg Gly Gly Arg Pro
245 250 255
Gly Glu Val Tyr Asn Ile Gly Gly Gly Ala Glu Leu Thr Asn Val Glu
260 265 270
Leu Thr Glu Arg Leu Leu Lys Leu Cys Gly Ala Asp Trp Ser Ala Val
275 280 285
Arg Gln Val Pro Asp Arg Lys Gly His Asp Gln Arg Tyr Ser Val Asp
290 295 300
Tyr Thr Lys Ile Ala Thr Glu Leu Gly Tyr Ala Pro Arg Ile Thr Ile
305 310 315 320
Asp Glu Gly Leu Glu Gln Thr Val Arg Trp Tyr Arg Glu Asn His Ala
325 330 335
Trp Trp Thr Pro Val Lys Arg Gly Arg
340 345
<210> 22
<211> 745
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 22
Met Val Asp Ala Cys Glu Glu Gly Thr Met Thr Leu Met Ser Ala Ser
1 5 10 15
Val Asp Pro Arg Asp Leu Trp Leu Arg Arg Tyr Gln Pro Ser Ala Ser
20 25 30
Pro Ala Val Arg Leu Val Cys Phe Pro His Ala Gly Gly Ser Ala Ser
35 40 45
Ser Phe Leu Pro Phe Thr Arg Gln Leu Pro Asp Arg Ile Glu Val Ser
50 55 60
Ala Val Gln Tyr Pro Gly Arg Gln Asp Arg Arg Ser Glu Pro Leu Ile
65 70 75 80
Asp Thr Ile Glu Gly Leu Ala Lys Pro Leu Ala Asp Met Leu Glu Thr
85 90 95
Arg Ala Gly Pro Pro Val Val Leu Phe Gly His Ser Met Gly Ala Leu
100 105 110
Val Ala Tyr Glu Val Ala Arg Val Leu Gln Gln Arg Gly Ala Ala Pro
115 120 125
Val Arg Leu Val Val Ser Gly Arg Arg Ala Pro Ala Ser Asp Arg Pro
130 135 140
Met Thr Val His Leu Tyr Asp Asp Asp Arg Leu Val Glu Glu Leu Arg
145 150 155 160
Thr Leu Asp Gly Thr Asp Ser Gln Val Phe Ala Asp Pro Glu Leu Leu
165 170 175
Gln Leu Val Leu Pro Ala Ile Arg Asn Asp Tyr Arg Ala Val Gly Thr
180 185 190
Tyr Thr His Arg Pro Gly Ala Pro Leu Asp Cys Pro Leu Thr Val Phe
195 200 205
Thr Gly Ala Asp Asp Pro Thr Val Thr Ala Ala Glu Ala Ala Ala Trp
210 215 220
His Glu Val Ala Ala Ala Gly Ala Glu Met Arg Thr Phe Pro Gly Gly
225 230 235 240
His Phe Phe Pro Tyr Gln Arg Thr Ala Glu Val Cys Gly Ala Leu Val
245 250 255
Asp Thr Leu Ala Pro Leu Leu Ser Thr Gly Thr Arg Gly Val Arg Arg
260 265 270
Val Arg Pro Gly Asp Val Gly Thr Val Glu Tyr Ala Gly His Arg Arg
275 280 285
Thr Ala Glu Arg Val Leu Leu Ser Ala Asp Thr Leu Asp Ser Pro Val
290 295 300
Thr Ser Leu Ala Asp Val Pro Arg Trp Leu Glu Ala Tyr Arg Arg Ala
305 310 315 320
His Arg Phe His Val Glu Pro Ile Pro Phe Asp Arg Leu Arg Arg Trp
325 330 335
Ser Phe Glu Pro Gly Thr Gly Asp Leu Arg His Glu Thr Gly Arg Phe
340 345 350
Phe Ser Val Glu Gly Leu Arg Thr Ser Ser Asp Ala Asp Pro Val Ala
355 360 365
Arg Val Gln Pro Ile Ile Val Gln Pro Glu Val Gly Leu Leu Gly Ile
370 375 380
Leu Ala Arg Glu Phe Asp Gly Val Leu His Phe Leu Met Gln Ala Lys
385 390 395 400
Pro Glu Pro Gly Asn Val Asn Gly Leu Gln Leu Ser Pro Thr Val Gln
405 410 415
Ala Thr Arg Ser Asn Phe Asp Glu Val His His Gly Arg Ser Thr Pro
420 425 430
Phe Leu Asp His Phe Ile His Arg Pro Gly Arg Arg Val Leu Ile Asp
435 440 445
Thr Ile Gln Ser Glu Gln Gly Asp Trp Phe Leu His Lys Arg Asn Arg
450 455 460
Asn Met Val Val Glu Ile Asp Thr Asp Ile Glu Ala Asp Ala Thr Phe
465 470 475 480
Arg Trp Leu Thr Leu Gly Gln Ile Arg Arg Leu Met Leu Gln Asp Asp
485 490 495
Leu Val Asn Met Asp Thr Arg Ser Val Leu Ala Cys Leu Pro Thr Ala
500 505 510
His Gly Ala Pro Asp Asp Asp Glu Asp Phe Pro Ala Ala Leu Arg Arg
515 520 525
Ser Phe Tyr Gly Glu Ala Ala Pro Leu His Asp Leu His Ala Ile Thr
530 535 540
Ser Cys Leu Thr Asp Val Arg Ala Leu Arg Val Leu Arg Gln Gln Ser
545 550 555 560
Val Pro Leu Asp Asp Ala Arg Arg Asp Gly Trp Glu Arg Thr Glu Ser
565 570 575
Thr Ile Arg His Arg Ser Gly Lys His Phe Glu Ile Met Ala Val Glu
580 585 590
Val Thr Ala Glu Arg Arg Glu Val Ala Ser Trp Thr Gln Pro Leu Leu
595 600 605
Arg Pro Cys Ser Gln Gly Leu Val Ala Leu Ile Thr Arg Arg Ile Asn
610 615 620
Gly Val Leu His Ala Leu Val Glu Ala Arg Ser Asp Val Gly Thr Leu
625 630 635 640
Asn Val Ala Glu Phe Gly Pro Thr Val Gln Cys Arg Pro Ala Glu Ser
645 650 655
Asp Gly Met Ser Pro Pro Tyr Leu Asp Gln Val Leu Thr Ala Gly Ala
660 665 670
Asp Arg Ile Arg Tyr Asp Val Val Gln Ser Glu Glu Gly Gly Arg Phe
675 680 685
Tyr His Ala Arg Asn Arg Tyr Met Val Val Glu Ala Gly Pro Glu Leu
690 695 700
Asp Thr Gly Cys Pro Pro Gly Phe Cys Trp Ala Thr Phe Gly Gln Leu
705 710 715 720
Thr Glu Leu Leu Ala His Gly Asn Tyr Leu Asn Val Glu Leu Arg Thr
725 730 735
Leu Val Ala Cys Ala His Ala Ser Tyr
740 745
<210> 23
<211> 382
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 23
Met Ile Asn Leu Phe Gln Pro Gln Met Gly Ala Glu Glu Leu Ala Ala
1 5 10 15
Ile Ala Gly Val Phe Asp Asp Gln Trp Leu Gly His Gly Pro Arg Thr
20 25 30
Lys Ala Phe Glu Ser Ala Phe Ala Asp His Leu Gly Val Gly Pro Glu
35 40 45
His Val Val Phe Leu Asn Ser Gly Thr Ala Gly Leu Phe Leu Ala Leu
50 55 60
Glu Ser Leu Gly Leu Gln Pro Asp Asp Glu Val Val Leu Pro Ser Pro
65 70 75 80
Ser Phe Leu Ala Ala Ala Asn Ala Val Gln Leu Thr Gly Ala Arg Pro
85 90 95
Val Phe Cys Asp Val Asp Pro Arg Thr Leu Asn Pro Ala Leu Glu His
100 105 110
Ile Glu Gln Ala Val Thr Ala Arg Thr Arg Ala Val Ile Ala Leu His
115 120 125
Tyr Gly Gly Tyr Pro Gly Asp Ile Val Arg Ile Ala Glu His Cys Arg
130 135 140
Asn Gln Gly Ile Thr Leu Ile Glu Asp Ala Ala Cys Ser Val Ala Ser
145 150 155 160
Arg Ile Asp Gly Arg Val Val Gly Thr Phe Gly Asp Leu Ala Met Trp
165 170 175
Ser Phe Asp Ala Met Lys Val Leu Val Thr Gly Asp Gly Gly Met Ile
180 185 190
Tyr Val Lys Asp Pro Gly Ala Ala Ala Arg Ile Arg Arg Leu Ala Tyr
195 200 205
His Gly Leu Thr Gln Ser Ser Gly Leu Gly Tyr Ala Arg Val Ser Ala
210 215 220
Arg Trp Trp Glu Met Asp Val Pro Glu Pro Gly Arg Arg Val Ile Gly
225 230 235 240
Asn Asp Leu Thr Ala Ala Ile Gly Ala Val Gln Leu Arg Arg Leu Pro
245 250 255
Asp Phe Val Ala Arg Arg Lys Glu Ile Val Ala Leu Tyr Glu Ser Glu
260 265 270
Leu Arg Thr Met Glu Gly Val Ser Thr Pro Pro Ala Leu Pro Glu Gly
275 280 285
His Glu Ser Thr His Tyr Phe Tyr Trp Ile Gln Leu Pro Pro Gly Val
290 295 300
Arg Asp Arg Val Ala Arg Asp Leu Leu Thr Asp Gly Ile Tyr Thr Thr
305 310 315 320
Phe Arg Tyr Ala Pro Leu His Lys Val Pro Ala Tyr Gly His Ala Gly
325 330 335
Arg Glu Leu Pro Gly Val Glu Trp Ala Ser Glu Arg Thr Leu Cys Leu
340 345 350
Pro Leu His Pro Gly Leu Ser Asp Ala Asp Val Leu Thr Val Val Ser
355 360 365
Ser Leu Arg Lys Ala Leu Asn Ala Gly Ala Gln Ala Pro Ala
370 375 380
<210> 24
<211> 239
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 24
Met Tyr Glu Asn Asp Ser Ala Ala Glu Val Tyr Asp Leu Leu Tyr Gln
1 5 10 15
Asp Arg Lys Asp Tyr Ala Gly Glu Ala Ala Arg Val Thr Gly Leu Ile
20 25 30
Arg Glu Arg Thr Pro Asn Ala Ser Ser Leu Leu Asp Ile Ala Cys Gly
35 40 45
Thr Gly Thr His Leu Glu Ala Phe Ala Lys Leu Tyr Asp Arg Val Ser
50 55 60
Gly Leu Glu Leu Ser Glu Trp Met Ala Ala Arg Ala Glu Glu Arg Leu
65 70 75 80
Ser Asp Val Thr Leu His Arg Gly Asp Met Arg Ser Phe Asn Leu Gly
85 90 95
Glu Thr Phe Asp Ala Val Val Cys Met Phe Ser Ser Ile Gly Tyr Leu
100 105 110
Glu Thr Ala Ala Asp Leu Glu Asp Ala Ile Ala Ala Met Ser Arg His
115 120 125
Leu Ser Ala Asp Gly Val Leu Ala Val Glu Pro Trp Tyr Phe Pro Asp
130 135 140
Thr Phe Leu Asp Gly Tyr Val Ser Thr His Ala Leu Arg Thr Glu Ser
145 150 155 160
Gly Asp Gln Gly Val Ala Arg Val Ala His Ser Thr Arg Glu Gly Lys
165 170 175
Lys Thr Arg Met Glu Ile His Tyr Leu Ile Ala His Thr Thr Asp Gly
180 185 190
Ile Arg His Arg Ser Glu Val Asp Tyr Leu Thr Leu Phe Ser Arg Ala
195 200 205
Glu Tyr Glu Thr Ala Tyr Arg Lys Ala Gly Leu His Val Glu Tyr Val
210 215 220
Glu Thr Gly Asn Gly Ser Pro Gly Phe Phe Leu Gly Thr Arg Ala
225 230 235
<210> 25
<211> 670
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 25
Met Ser Tyr Leu Asp Tyr Gly Glu Glu Ala Ser Glu Glu Asp Glu Ser
1 5 10 15
Asp Asp Ala Leu Thr Phe Leu Glu Phe Val Ala Arg Ser Ala Pro Arg
20 25 30
Ser Glu Tyr Asp Arg Leu Met Ala Arg Ala Glu Arg Ala Gly Ala Asp
35 40 45
Glu Glu Arg Met Arg Arg Leu Glu Arg Phe Asn Arg Leu Ala Leu Thr
50 55 60
Ala Gln Ser Met Ile Glu Tyr Arg Arg Asp Arg Glu Ala Glu Leu Ala
65 70 75 80
Ala Leu Val Asp Ala Ala His Glu Phe Val Ala Ala Gln Gln Tyr Lys
85 90 95
Asp Leu Leu Glu Ser Val Ala Arg Arg Ala Arg Leu Leu Leu Lys Leu
100 105 110
Asp Val Ala Tyr Val Ser Leu His Gln Glu Asp Leu His His Glu Asp
115 120 125
Arg Pro Gly Thr Val Val Leu Ser Ala Asp Gly Asn Ala Val Lys Val
130 135 140
Ala Asp Ser Tyr Arg Leu Pro Ala Asp Gly Gly Leu Gly Gly Met Val
145 150 155 160
Arg Thr Cys His Ala Pro Phe Trp Thr Pro Asp Tyr Leu Gly Asp Ser
165 170 175
Ser Phe Val His Val Glu Thr Val Asp Asp Ile Val Arg Ala Glu Gly
180 185 190
Leu Arg Ala Val Leu Ala Val Pro Leu Cys Val Gly Asp Asp Ser Val
195 200 205
Gly Val Leu Tyr Val Ala Asp Arg Gln Val Arg His Leu Thr Pro Asn
210 215 220
Glu Val Thr Leu Leu Cys Ser Leu Ala Asp Leu Ala Ala Val Ala Ile
225 230 235 240
Glu Arg Ile Arg Leu Val Glu Glu Leu Arg Asp Thr Ile Gly Arg Leu
245 250 255
Arg Glu Asp Val Gly Glu Ala Arg Ala Ala Leu Ala Gly Thr Arg Arg
260 265 270
Ser Ala Asp Leu Gln Ser His Leu Ile Thr Gln Val Leu Glu Arg Arg
275 280 285
Gly Ala Asp Ala Leu Leu Ala Ala Ala Ala Glu Ser Leu Gly Gly Gly
290 295 300
Thr Ser Leu Cys Ser Pro Leu Gly Arg Pro Leu Ala Glu Tyr Gly Asn
305 310 315 320
Leu Arg Pro Val Ala Pro Ala Asp Leu Arg Ala Ala Cys Arg Arg Ala
325 330 335
Ala Glu Thr Gly Arg Pro Thr Pro Val Ala Pro Gly Tyr Trp Thr Val
340 345 350
Pro Leu Tyr Pro Gly Glu Tyr Asn Ala Gly Phe Leu Leu Thr Asp Val
355 360 365
Gly Pro Glu Ala Asp His Thr Val Val Pro Leu Leu Pro Met Val Ala
370 375 380
Arg Thr Leu Ala Leu His Leu Arg Ile Gln Arg Asn Asp Ser Thr Lys
385 390 395 400
Ala Gln Ser His Gln Asp Phe Phe Asp Asp Leu Val Gly Ala Pro Arg
405 410 415
Ser Pro Ala Leu Leu Arg Glu Arg Ala Leu Leu Phe Ser Leu Ser Phe
420 425 430
Arg Arg Pro His Val Val Leu Val Ala Ser Gly Pro His Gly Ala Ser
435 440 445
Ala Arg Leu Glu Ser Ser Gly Ala Asp Tyr Ala Lys Glu Leu Gly Gly
450 455 460
Leu Cys Ser Val Arg Asp Gly Ala Val Val Leu Leu Leu Pro Gly Asp
465 470 475 480
Asp Pro Val Ala Val Ala Gln Thr Ala Ala Pro Glu Leu Thr Asp Arg
485 490 495
Val Gly His Pro Val Thr Val Gly Ala Ala Gly Pro Ala Ser Thr Val
500 505 510
Asp Gly Ile Ser Asp Ala His Arg Glu Ala Ala Gln Cys Leu Glu Thr
515 520 525
Leu Arg Ala Leu Gly Gly Asp Gly Gly Thr Ala Cys Ala Ser Asp Leu
530 535 540
Gly Phe Leu Gly Met Leu Leu Ala Glu Glu Asn Asp Val Pro Gly Tyr
545 550 555 560
Ile Lys Thr Thr Ile Gly Pro Val Ile Asp Tyr Asp Thr His Arg Phe
565 570 575
Thr Asp Leu Ile Pro Thr Leu Arg Val Tyr Leu Glu Ser Gly Arg Ser
580 585 590
Pro Thr Arg Ala Ala Glu Thr Leu Arg Val His Pro Asn Thr Val Ser
595 600 605
Arg Arg Leu Glu Arg Ile Gly Gln Leu Leu Gly Glu Asp Trp Gln Gly
610 615 620
Pro Glu Arg Val Leu Asp Ile Gln Leu Ala Leu Arg Leu Tyr Gln Val
625 630 635 640
Arg Ser Ala Leu Ser Ser Arg Ser Ala Ser Ala Ser Leu Pro Pro Arg
645 650 655
Pro Ala Pro Ala Ser Arg Thr Val Leu Gly Ser Gln Arg Glu
660 665 670
<210> 26
<211> 354
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 26
Met His Arg Arg Val Gln Arg Arg Leu Ser His Ala Leu Thr Arg Ala
1 5 10 15
Arg Asp Leu Val Pro Lys Gly Pro Arg Ser Arg Leu Lys Thr Arg Pro
20 25 30
Pro Asp Gly Asp Pro Arg Arg Arg Ala Gly Ala Gly Ala Leu Ala Ala
35 40 45
Pro Leu Phe Pro Glu Pro Gly Arg Leu Arg Lys Arg Gln Asp Leu Pro
50 55 60
Met Asn Gly Cys Gln Val Ala Val Gly Ala Val Val Arg Pro Arg Asn
65 70 75 80
Phe Ala Arg Leu Arg Ala Pro Ser Cys Gly Lys Gly Glu Ala Ser Val
85 90 95
Asn Phe Arg Arg Arg Tyr Gly Asn Ser Cys Pro Pro Val Arg Cys Ala
100 105 110
Gly Ser Gly Arg Arg Phe Arg Gln Arg Arg Pro Leu Cys His Val Arg
115 120 125
Leu Ala Asp Cys Leu Gly Ala Ser Tyr Val Pro Leu Thr Ser Thr Gly
130 135 140
Ser Asp Ala Gly Ser Arg Thr Pro Asp Arg Val His Arg Ser Thr Arg
145 150 155 160
Ala Thr Ser Ser Leu Arg Ser Thr Cys Pro Ser Ala Ser Thr Gly Thr
165 170 175
Glu Pro Glu Gly Ser Val Pro Gly Pro Gly Pro Ser Arg Ala Gly Arg
180 185 190
Gly Pro His Asp Arg Pro Ile Arg Ser Ala Ala Ile Ala Glu Asn Thr
195 200 205
Ala Glu Pro Pro Ala Arg Arg Val Gly Arg Ile Lys Pro Cys Arg Leu
210 215 220
Ile Arg Leu Glu Gln His Ile Asp Pro Arg Gly Ser Leu Ser Val Val
225 230 235 240
Glu Ser Gly Val Thr Val Asp Phe Pro Val Gln Arg Val Tyr Tyr Met
245 250 255
His Gly Gln Thr Gln Ser Ser Pro Pro Arg Gly Leu His Ala His Arg
260 265 270
Thr Leu Glu Gln Leu Val Ile Ala Val His Gly Ala Phe Ser Ile Thr
275 280 285
Leu Asp Asp Gly Phe Gln His Ala Thr Tyr Arg Leu Asp Glu Pro Gly
290 295 300
Ala Gly Leu Cys Ile Gly Pro Met Val Trp Arg Val Leu Lys Asp Phe
305 310 315 320
Ala Pro Asp Thr Val Ala Leu Val Leu Ala Ser Gln His Tyr Glu Glu
325 330 335
Ser Asp Tyr Tyr Arg Asp Tyr Asp Thr Phe Leu His Asp Ala Arg Ser
340 345 350
Leu Thr
<210> 27
<211> 550
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 27
Met Ser Ile Ala Gln Phe Ala Leu His Asp Val Ile Lys Arg Tyr His
1 5 10 15
Asp Cys Val Val Leu Asp Arg Val Gly Phe Ser Ile Lys Pro Gly Glu
20 25 30
Lys Val Gly Val Ile Gly Asp Asn Gly Ser Gly Lys Ser Thr Leu Leu
35 40 45
Lys Val Leu Ala Gly Arg Glu Gln Pro Asp Asn Gly Met Leu Thr Val
50 55 60
Val Ala Pro Gly Gly Ile Gly Tyr Leu Ala Gln Thr Leu Glu Leu Pro
65 70 75 80
Leu Asp Ala Thr Val Gln Asp Ala Val Asp Leu Ala Leu Ser Asp Leu
85 90 95
Arg Glu Leu Glu Ala Ser Met His Glu Val Glu Ala Glu Leu Thr Glu
100 105 110
Arg Asp Glu Asp Gly Ser Glu Arg Glu Leu Ser Ala Leu Leu Gln Arg
115 120 125
Tyr Ala Gly Leu Val Glu Gln Tyr Gln Ala Arg Gly Gly Tyr Glu Ala
130 135 140
Asp Val Arg Val Glu Val Ala Leu His Gly Leu Gly Leu Pro Ser Leu
145 150 155 160
Asp Arg Asp Arg Lys Leu Gly Thr Leu Ser Gly Gly Glu Arg Ser Arg
165 170 175
Leu Ala Leu Ala Ala Thr Leu Ala Ser Ala Pro Glu Leu Leu Leu Leu
180 185 190
Asp Glu Pro Thr Asn Asp Leu Asp Asp Arg Ala Met Glu Trp Leu Glu
195 200 205
Asn His Leu Gln Gly His Arg Gly Thr Val Ile Ala Val Thr His Asp
210 215 220
Arg Val Phe Leu Asp Arg Leu Thr Thr Thr Ile Leu Glu Val Asp Ser
225 230 235 240
Gly Arg Val Thr Arg Tyr Gly Asn Gly Tyr Glu Gly Tyr Leu Thr Ala
245 250 255
Lys Ala Val Glu Arg Glu Arg Arg Leu Arg Glu Tyr Glu Glu Trp Arg
260 265 270
Ala Glu Leu Glu Arg Asn Gln Gly Leu Ile Thr Ser Asn Val Ala Arg
275 280 285
Met Asp Asn Ile Pro Arg Lys Met Ser Leu Ser Val Phe Gly His Gly
290 295 300
Ala Tyr Arg Arg Arg Gly Arg Asp His Gly Ala Met Val Arg Ile Arg
305 310 315 320
Asn Ala Lys Gln Arg Val Ala Gln Leu Thr Glu Asn Pro Ala Leu Ala
325 330 335
Pro Ala Asp Pro Leu Ser Phe Ala Ala Arg Ile Asp Thr Ala Gly Pro
340 345 350
Glu Ala Glu Glu Ala Val Ala Glu Leu Thr Asp Val Arg Val Ala Asp
355 360 365
Arg Leu Asp Val Asp Ser Leu Lys Ile Arg Pro Gly Glu Arg Leu Leu
370 375 380
Ile Thr Gly Pro Asn Gly Ala Gly Lys Ser Thr Leu Leu Arg Val Leu
385 390 395 400
Ser Gly Glu Leu Ala Pro Asp Ser Gly Ser Val Arg Val Gly Cys Arg
405 410 415
Val Gly His Leu Arg Gln Asp Glu Thr Pro Trp Ser Pro Glu Leu Thr
420 425 430
Val Leu Arg Ala Phe Ala His Gly Arg Glu Gly Tyr Leu Glu Asp His
435 440 445
Ala Glu Lys Leu Leu Ser Leu Gly Leu Phe Ser Pro Ser Asp Leu Arg
450 455 460
Arg Arg Val Lys Asp Leu Ser Tyr Gly Gln Arg Arg Arg Ile Glu Ile
465 470 475 480
Ala Arg Leu Val Ser Asp Pro Met Asp Leu Leu Leu Leu Asp Glu Pro
485 490 495
Thr Asn His Leu Thr Pro Val Leu Val Glu Glu Leu Glu Gln Ala Leu
500 505 510
Val Asp Tyr Arg Gly Ala Val Val Val Val Thr His Asp Arg Arg Met
515 520 525
Arg Ser Arg Phe Thr Gly Ala Arg Leu Ala Met Asp His Gly Cys Ile
530 535 540
Ala Glu Phe Ser Ala Gly
545 550
<210> 28
<211> 433
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 28
Met Gly Glu Thr Lys Asn Arg Ile Thr Glu Leu Val Arg Ala Tyr His
1 5 10 15
Arg Glu Gln Ala Thr Gly Asn Phe Val Pro Gly Thr Thr His Val Pro
20 25 30
Val Ser Gly Ala Val Leu Ser Glu Asp Asp Arg Leu Ala Leu Val Glu
35 40 45
Thr Ala Leu Glu Met Arg Ile Ala Ala Gly Pro Ala Ser Arg Ser Phe
50 55 60
Glu Arg Gln Phe Ala Arg Tyr Leu Gly Leu Arg Lys Ala His Leu Thr
65 70 75 80
Asn Ser Gly Ser Ser Ala Asn Leu Leu Ala Leu Ser Ala Leu Thr Ser
85 90 95
Pro Gln Leu Glu Asp Arg Arg Leu Lys Pro Gly Asp Glu Val Val Thr
100 105 110
Val Ala Ala Gly Phe Pro Thr Thr Val Asn Pro Ile Phe His Asn Glu
115 120 125
Leu Val Pro Val Phe Val Asp Val Glu Leu Gly Thr Tyr Asn Thr Thr
130 135 140
Pro Glu Arg Ile Glu Arg Ala Ile Gly Pro Arg Thr Arg Ala Ile Met
145 150 155 160
Ile Ala His Ala Leu Gly Asn Pro Phe Glu Ala Glu Glu Val Ala Arg
165 170 175
Leu Ala Asp Glu Arg Gly Leu Phe Leu Val Glu Asp Asn Cys Asp Ala
180 185 190
Val Gly Ser Arg Tyr Arg Gly Arg Leu Thr Gly Ser Phe Gly Asp Leu
195 200 205
Ser Thr Val Ser Phe Tyr Pro Ala His His Ile Ala Met Gly Glu Gly
210 215 220
Gly Cys Val Leu Thr Asp Asn Leu Ala Leu Ala Arg Ile Val Glu Ser
225 230 235 240
Leu Arg Asp Trp Gly Arg Asp Cys Trp Cys Glu Pro Gly Glu Asp Asn
245 250 255
Arg Cys Leu Lys Arg Phe Asp Gln Lys Met Gly Asp Leu Pro Pro Gly
260 265 270
Tyr Asp His Lys Tyr Ile Phe Ser His Val Gly Tyr Asn Leu Lys Ser
275 280 285
Thr Asp Leu Gln Ala Ala Leu Gly Leu Ser Gln Leu Thr Arg Ile Glu
290 295 300
Glu Phe Thr Asp Ala Arg Arg Ala Asn Trp Arg Arg Met Arg Glu Thr
305 310 315 320
Leu Asp Gly Leu Pro Gly Leu Leu Leu Pro Glu Ala Thr Pro Gly Ser
325 330 335
Asp Pro Ser Trp Phe Gly Phe Leu Ile Thr Val Asp Pro Asp Ala Thr
340 345 350
Tyr Ser Arg Ala Ala Leu Val Asp His Leu Glu Ser Arg Arg Ile Ser
355 360 365
Thr Arg Arg Leu Phe Gly Gly Asn Leu Val Arg His Pro Ala Tyr Thr
370 375 380
Gly Arg Gln Tyr Arg Val Ser Gly Ala Leu Glu Asn Ser Asp Leu Ile
385 390 395 400
Thr Asp Gln Thr Phe Trp Ile Gly Val Phe Pro Gly Ile Thr Thr Glu
405 410 415
Met Val Asp Tyr Val Thr Asp Thr Val Arg Glu Phe Val Leu Lys His
420 425 430
Ser
<210> 29
<211> 482
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 29
Met Thr His Pro Glu Asp Ser Ala Gly Thr Ser Gln Arg Ala Asp Ala
1 5 10 15
Leu Met Asn Asp Thr Leu Ala Ala Ala Asp Ala Glu Gly Trp Asp Gly
20 25 30
Glu Gln Phe Asp Arg Glu Asp Arg Ala Ser Leu Arg Arg Val Ala Gly
35 40 45
Leu Ser Thr Glu Leu Thr Asp Val Ser Glu Val Glu Tyr Arg Lys Leu
50 55 60
Arg Leu Glu Arg Val Val Leu Val Gly Ile Trp Thr Ser Gly Thr Ala
65 70 75 80
Ala Glu Ala Glu Ser Ser Leu Ala Glu Leu Ala Ala Leu Ala Glu Thr
85 90 95
Ala Gly Ala Leu Val Leu Asp Gly Val Val Gln Arg Arg Gln Lys Pro
100 105 110
Asp Pro Ala Thr Tyr Ile Gly Ser Gly Lys Ala Ser Gln Leu Arg Asp
115 120 125
Ile Val Glu Glu Thr Gly Ala Asp Thr Val Val Cys Asp Gly Glu Leu
130 135 140
Ser Pro Ser Gln Leu Met His Leu Glu Glu Val Val Gly Val Lys Val
145 150 155 160
Val Asp Arg Thr Ala Leu Ile Leu Asp Ile Phe Ala Gln His Ala Gln
165 170 175
Ser Arg Glu Gly Lys Ala Gln Val Ala Leu Ala Gln Met Gln Tyr Met
180 185 190
Leu Pro Arg Leu Arg Gly Trp Gly Gln Ser Leu Ser Arg Gln Met Gly
195 200 205
Gly Gly Gly Gly Gly Gly Met Ala Thr Arg Gly Pro Gly Glu Thr Lys
210 215 220
Ile Glu Thr Asp Arg Arg Arg Ile Asn Asp Lys Met Ala Arg Leu Arg
225 230 235 240
Arg Glu Leu Glu Gln Leu Lys Thr Gly Arg Asp Val Lys Arg Glu Glu
245 250 255
Arg Arg Arg Asn Lys Val Leu Ser Val Ala Leu Ala Gly Tyr Thr Asn
260 265 270
Ala Gly Lys Ser Ser Leu Leu Asn Arg Leu Thr Gly Ala Gly Val Leu
275 280 285
Val Glu Asn Ala Leu Phe Ala Thr Leu Asp Thr Thr Val Arg Arg Ala
290 295 300
Thr Thr Pro Ser Gly Arg Thr Tyr Thr Ile Ala Asp Thr Val Gly Phe
305 310 315 320
Val Arg His Leu Pro His His Leu Val Glu Ala Phe Arg Ser Thr Ile
325 330 335
Glu Glu Val Ala Asp Ala His Leu Val Leu His Val Val Asp Gly Ser
340 345 350
His Pro Asp Pro Gly Ala Gln Leu Ala Ser Val Arg Glu Val Leu Arg
355 360 365
Asp Val Gly Ala Ala Glu Ser Thr Glu Ile Val Val Val Asn Lys Ala
370 375 380
Asp Val Ala Asp Pro Asp Val Leu Ala Arg Leu Leu Glu Gln Glu Pro
385 390 395 400
Asp Ala Ile Val Val Ser Ala Arg Ser Gly Gln Gly Ile Asp Glu Leu
405 410 415
Gln Glu Leu Ile Asp Arg Leu Leu Pro His Pro Ala Val Glu Val Glu
420 425 430
Val Val Ile Pro Tyr Asp Glu Gly Gly Leu Val Ala Arg Ala His Asp
435 440 445
Glu Gly Glu Val Leu Ser Ala Glu His Thr Pro Glu Gly Thr Leu Leu
450 455 460
Thr Ala Leu Val His Pro Asp Leu Ala Ser Glu Leu Gln Ala His Pro
465 470 475 480
Arg Pro
<210> 30
<211> 346
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 30
Met Arg Val Leu Ile Ile Gly Gly Ser Gln Phe Val Gly Arg Ala Tyr
1 5 10 15
Ala Ala Glu Ala Leu Ala Ala Gly His Glu Val Thr Thr Phe Asn Arg
20 25 30
Gly Val Ser Gly Thr Asp Leu Pro Gly Val Glu Ala Val Arg Gly Asp
35 40 45
Arg Glu Ala Ala Gly Asp Leu Glu Arg Leu Val Ser Gly Arg Arg Trp
50 55 60
Asp Ala Val Val Asp Thr Cys Gly Tyr Val Pro Arg Thr Val Gly Ala
65 70 75 80
Ser Ala Ala Ala Leu Ser Gly His Ala Asp Ala Tyr Leu Tyr Val Ser
85 90 95
Ser Ile Ala Cys Leu Pro Asp Trp Thr Gln Ala Val Arg Pro Val Asp
100 105 110
Asp Asp Ser Pro Ala Tyr Asp Cys Pro Pro Asp Ala Gly Pro Asp His
115 120 125
Ala Asp Gly Asp Tyr Gly Thr Leu Lys Ala Gly Cys Glu Arg Ala Val
130 135 140
Asp Gln His Phe Val Gly Arg Thr Leu His Leu Arg Ala Gly Val Ile
145 150 155 160
Leu Gly Pro His Asp Asn Met Arg Met Leu Asp Ala Trp Leu Trp Arg
165 170 175
Met Arg Ala Ala Glu Gly Glu His Arg Arg Val Leu Ala Pro Gly Gly
180 185 190
Pro Glu Val Gly Met Arg Leu Ile Asp Val Arg Asp Val Ala Ala Phe
195 200 205
Gly Leu Asp Cys Leu Ala Glu Gly Arg Thr Gly Ala Tyr Ile Val Asn
210 215 220
Pro Pro Glu Lys Asn Thr Thr Phe Gly Asn Leu Leu Thr Glu Cys Val
225 230 235 240
Lys Ala Thr Gly Ser Ala Ala Glu Pro Val Trp Val Asp Asp Arg Phe
245 250 255
Phe Ala Asp His Gly Val Ser Pro Trp Thr Asp Leu Pro Leu Trp Val
260 265 270
Pro Asp Thr Ala Gln Asp Thr Leu Val Trp Ala Ala Gly Ala Pro Arg
275 280 285
Ala Arg Ala Ala Gly Leu Ala Cys Arg Pro Ile Ser Glu Thr Val Arg
290 295 300
Asp Ala Trp Glu Val Ile Arg Asp Gln Pro Val Pro Glu Leu Pro Leu
305 310 315 320
Ala Ala Gly Cys Gly Leu Ser Leu Ala Arg Glu Arg Glu Leu Leu Ala
325 330 335
Ala Trp Asp Ala Arg Gly Gly Ala Ala Gly
340 345
<210> 31
<211> 346
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 31
Met Thr Ala Leu Gly Thr Pro Ala Glu Pro Ser Ala Ala Pro Gly Pro
1 5 10 15
Pro Trp Pro Glu Ala Ser Pro Val Leu Arg Phe Gly Ala Ile Gly Cys
20 25 30
Gly Asp Ile Ala Gly Arg Arg Thr Leu Pro Ala Leu Leu Ser Thr Pro
35 40 45
Gly Thr Val Leu Thr Cys Val Gly Ser Arg Glu Pro Glu Arg Ala Lys
50 55 60
Ala Leu Gly Glu His Phe Gly Cys Glu Ala Val Ala Pro Tyr Glu Ala
65 70 75 80
Leu Leu Glu Arg Pro Asp Val Asp Ala Val Tyr Ile Ala Val Pro Ser
85 90 95
Met Leu His Ala Lys Trp Ala Ala Ala Ala Leu Arg Ala Gly Lys His
100 105 110
Val Leu Val Glu Lys Pro Ala Ala Ala Asn His Ala Asp Ala Ala Arg
115 120 125
Leu Phe Ala Met Ala Arg Glu Arg Gly Leu Val Leu Met Glu Asn Phe
130 135 140
Met Phe Leu His His Ser Gln His Ala Thr Val Lys Val Leu Leu Glu
145 150 155 160
Thr Gly Ala Ile Gly Asp Leu Arg Thr Phe Ser Ala Ala Phe Thr Ile
165 170 175
Pro Pro Arg Pro Asp Asp Asp Met Arg Tyr Arg Pro Asp Ile Gly Gly
180 185 190
Gly Ala Leu Leu Asp Asn Gly Val Tyr Pro Leu Arg Ala Ala Ile His
195 200 205
Phe Leu Gly Pro Glu Leu Arg Leu Met Gly Ala Val Leu Arg Arg Glu
210 215 220
Arg Arg Arg Gly Val Val Val Ser Gly Ser Val Leu Leu Ala Ala Pro
225 230 235 240
Thr Gly Val Ala Ala His Leu Ala Phe Gly Met Glu His Gly Tyr Arg
245 250 255
Ser Ala Tyr Glu Leu His Gly Ser Thr Gly Ser Leu Ala Leu Asn His
260 265 270
Val Phe Thr Thr Pro Asp Ser His His Pro Val Leu Arg Leu Ser Arg
275 280 285
Gln Asp His Arg Glu Glu Arg Val Leu Pro Val Asp Arg His Phe Val
290 295 300
Asn Ile Leu Ser Val Phe Arg Arg Ala Val Thr Arg Ala Glu Asn Ile
305 310 315 320
Ser Ala Glu Ser Tyr Ala Ala Leu Arg Gln Ala Ala Leu Val Asp Glu
325 330 335
Ile Val Ala Arg Ala Glu Thr Val Thr Val
340 345
<210> 32
<211> 415
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 32
Met Ala Asp Ala Ile Thr Thr Glu Leu Ala Asp Arg Glu Leu Gly Arg
1 5 10 15
Arg Leu His Arg Ile Arg Gly Ala His Trp Tyr Phe Gly Asn His Gly
20 25 30
Asp Pro Tyr Ala Leu Ile Leu Arg Gly Gln Ala Asp Asp Pro Ser Ala
35 40 45
Tyr Glu Glu Arg Val Arg Asp Gly Gly Pro Leu Phe Arg Ser His Ile
50 55 60
Gly Thr Trp Val Thr Ala Asp Pro Glu Val Gly Ala Ala Val Leu Gly
65 70 75 80
Asp Pro Arg Phe Gly Ala Leu Asp Arg Ala Gly Arg Arg Pro Glu Glu
85 90 95
Tyr Leu Gln Pro Ser Pro Ala Ser Cys Leu Gly Leu Asp Arg Ala Ala
100 105 110
Tyr Leu Arg Leu Arg Arg Val Ala Glu Pro Val Leu Gly Ala Gly Ala
115 120 125
Ala Asp Glu Trp Arg Arg Leu Ala Glu Asp Leu Gly Arg Arg Leu Leu
130 135 140
Asp Gly Arg Gly Ser Gly Phe Asp Leu Thr Ala Asp Phe Ala Arg Arg
145 150 155 160
Leu Pro Ala Leu Val Leu Ala Ala Trp Leu Gly Val Pro Asp Glu Arg
165 170 175
Arg Glu Glu Trp Glu Glu Leu Leu Arg Glu Ala Gly Pro Leu Leu Asp
180 185 190
Ser Leu Leu Cys Pro Gln Thr Leu Ala Ala Thr Arg Ala Ala Asp Ser
195 200 205
Ala Ala Glu Gly Leu Arg Thr Leu Leu Gly Lys Val Ala Val Ala Arg
210 215 220
Ser Asp Gly Ala Gly Asp Gly Ala Leu Gly Arg Met Val Ala Ala Gly
225 230 235 240
Ala Ala Pro Asp Asp Ala Val Ala Ala Ala Met Cys Leu Val Leu Ser
245 250 255
Ala Ala Glu Thr Thr Thr Thr Leu Val Cys Asp Ala Val Arg Leu Leu
260 265 270
Leu Asp Arg Pro Arg Trp Trp Arg Ala Leu Cys Asp Ser Pro Ala Leu
275 280 285
Ala Pro Ala Ala Val Arg His Thr Leu Arg Tyr Val Pro Pro Val Arg
290 295 300
Leu Glu Ser Arg Val Ala His Glu Asp Val Ala Pro Thr Gly His Pro
305 310 315 320
Leu Pro Ala Gly Ser His Val Val Val Leu Val Ser Ala Ala Arg Arg
325 330 335
Gly Ala Ala Pro Asp Ala Gly Pro Ala Asp Leu Thr Asn Val Pro Thr
340 345 350
Ala Ala Gly Ala Gly Leu Pro Asp Asp Leu Tyr Phe Ala Leu Ser Gly
355 360 365
Glu Phe Val Gly Arg Thr Ala Glu Thr Ala Leu Gly Val Leu Ala Glu
370 375 380
Val Ala Pro Arg Leu Arg Arg Glu Gly Asp Ile Val Arg Arg Arg Arg
385 390 395 400
Ser Pro Val Leu Gly Arg Tyr Ala Arg Phe Pro Val Ala Tyr Ser
405 410 415
<210> 33
<211> 422
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 33
Met Arg Val Leu Val Thr Ser Ile Pro His His Thr His Tyr Tyr His
1 5 10 15
Leu Val Pro Leu Ile Trp Ala Leu Arg Ala Ser Gly His Glu Val Val
20 25 30
Ala Ala Gly Gln Pro Ser Leu Ile Asp Ala Ile Thr Ser Ser Gly Ile
35 40 45
Pro Gly Phe Pro Leu Ala Glu Glu Glu Ser Leu Ala Gln Ile Phe Glu
50 55 60
Glu Val Glu Gly Asp Leu Gln Pro Tyr Gln His Gly Ile Asp Glu Phe
65 70 75 80
Asp Phe Leu Gly Thr Leu Gln Asp Ala Leu Asp Trp Glu Lys Leu Leu
85 90 95
Ala Gln Gln Val Ile Leu Ser Gly Leu Trp Leu Glu Pro Leu Asn Gly
100 105 110
Ala Thr Thr Leu Asp Ser Ile Val Asp Phe Ala Arg Ser Trp Lys Pro
115 120 125
Asp Leu Val Leu Trp Glu Pro Phe Thr Tyr Ala Gly Pro Val Ala Ala
130 135 140
Arg Ala Cys Gly Ala Ala His Ala Arg Val Leu Trp Gly Pro Asp Thr
145 150 155 160
Ile Gly Leu Met Arg Thr Lys Phe Leu Gln Ala Gln Ala Gln Gln Pro
165 170 175
Glu Glu His Arg Asp Asp Pro Ile Ala Glu Trp Leu Thr Trp Ala Leu
180 185 190
Glu Arg Tyr Gly Cys Asp Phe Arg Glu Glu Asp Val Leu Gly Gln Trp
195 200 205
Ser Val Asp Pro Met Ala Glu Gly Val Ser Leu Gly Leu Asp Leu Pro
210 215 220
Thr Val Pro Met Arg Tyr Thr Pro Tyr Asn Gly Ser Ala Val Ile Pro
225 230 235 240
Asp Trp Leu Thr Glu Glu Pro Lys Arg Pro Arg Val Cys Leu Thr Leu
245 250 255
Gly Val Ser Ser Arg Glu Tyr Gly Glu Asp Glu Val Pro Val Gln Lys
260 265 270
Phe Ile Glu Ala Leu Ala Asp Leu Asp Ile Glu Leu Val Ala Thr Leu
275 280 285
Asp Asp Ala Gln Arg Asp Leu Leu Pro Arg Ile Pro Asp Asn Thr Arg
290 295 300
Ile Val Asp Phe Val Pro Met Asp Ala Leu Leu Pro Thr Cys Ser Ala
305 310 315 320
Ile Ile Asn His Ser Gly Ser Gly Thr Cys Asn Thr Ala Ala Leu His
325 330 335
Gly Val Pro Gln Ile Ile Leu Gly Asn Ile Leu Asp Ala Ala Val Arg
340 345 350
Gln His Met Phe Ala Gln Ser Ser Ala Ala Leu Thr Phe Ala Pro Glu
355 360 365
Glu Val Thr Gly Glu Ser Leu Arg Ser Ala Leu Val Arg Leu Leu Gly
370 375 380
Glu Pro Lys Phe Arg Asp Gly Ala Gln Arg Leu Lys Glu Arg Met Arg
385 390 395 400
Ala Met Pro Ser Pro Ala Gly Ile Val Pro Thr Leu Glu Ser Leu Thr
405 410 415
Ala Arg His Arg Arg Ala
420
<210> 34
<211> 391
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 34
Met Arg Ala Leu Phe Thr Thr Ala Pro Leu Ala Gly His Leu Leu Pro
1 5 10 15
Leu Val Pro Thr Ala Trp Ala Leu Arg Ala Ala Gly His Asp Val Leu
20 25 30
Val Thr Thr Arg Glu Asn Phe Val Pro Val Ala Leu Arg Ser Gly Leu
35 40 45
Pro Ser Ser Ser Cys Gly Pro Ala Val Asp Phe Thr Gly Thr Val Ala
50 55 60
Asp Gly Pro Leu Ala Pro Ser Arg Asp Glu Ala Gly Gln Arg Gly Val
65 70 75 80
Leu Gly Gly Ala Leu Ala Arg Val Ala Arg Gly Ser Leu Ala Gly Val
85 90 95
Arg Arg Leu Ala Asp Val Trp Arg Pro Asp Leu Ile Val Ser Glu Arg
100 105 110
Ala Glu Phe Ala Gly Pro Leu Val Ala Ala Ala Leu Gly Ile Pro Trp
115 120 125
Val Arg Tyr His Trp Ser Val Ser Cys Leu Glu Glu Tyr Arg Arg Ala
130 135 140
Ala Glu Glu Glu Phe Ala Pro Glu Leu Thr Ala Leu Gly Leu Asp Arg
145 150 155 160
Phe Pro Asp Pro Ala Arg Val Leu Asp Pro Trp Pro Val Ser Leu Arg
165 170 175
Arg Pro Asp Ala Val Ala His Asp Gly Ile Arg His Val Pro Ala His
180 185 190
Gly Asp Ala Pro Val Pro Glu Trp Ala Phe Thr Arg Gly Arg Arg Pro
195 200 205
Arg Ile Cys Val Thr Leu Gly Thr Met Leu Pro Arg Tyr Gly Ala Phe
210 215 220
Gly Val Arg Asp Phe Leu Ala Glu Leu Val Glu Glu Thr Arg Gly Ser
225 230 235 240
Asp Cys Glu Leu Leu Ile Ala Val Asp Asp Asp Ile Val Ala Arg Trp
245 250 255
Pro Pro Leu Pro Ala Ala Val Arg His Ala Gly Arg Leu Pro Leu Ala
260 265 270
Glu Val Leu Pro Ala Cys Asp Val Val Val His His Gly Gly Gln Gly
275 280 285
Thr Ser Leu Thr Ala Leu Ala Ala Gly Arg Pro Gln Val Val Met Pro
290 295 300
Arg Leu Asp Asp Gln Phe Asp Asn Ala Gln Ala Leu Ala Ala Ala Asp
305 310 315 320
Ala Ala Leu Leu Val Pro Pro Ser Leu Ala Thr Pro Ala Ala Val Ala
325 330 335
Ala Gly Cys Ala Glu Leu Leu Glu Asn Ala Leu Tyr Ala Lys Ala Ala
340 345 350
Ala Gly Leu Ala Glu Thr Met Ala Leu Leu Pro Ser Pro Ser Ala Ala
355 360 365
Val Gly Pro Leu Glu His Leu Gly Pro Ala Pro Gly Met Leu Arg Ser
370 375 380
His Ala Asn Glu Asp Ala Val
385 390
<210> 35
<211> 330
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 35
Met Ile Ser Glu Val Leu Asn Arg Ser Asn Asp Pro Arg Gly Pro Leu
1 5 10 15
Ile Thr Val Val Gly Ala Ser Gly Phe Ile Gly Ser Ala Leu Val Ala
20 25 30
Glu Leu Ala Arg Thr Pro Val Arg Leu Arg Ala Val Ser Arg Arg Glu
35 40 45
Ala Pro Val Pro Ala Gly Thr Pro Ala Ala Val Glu Val Arg Arg Ala
50 55 60
Asp Leu Ala Arg Pro Gly Glu Val Arg Asp Ala Val Glu Gly Ala Asp
65 70 75 80
Ala Val Val His Leu Ala Ala His Ile Gly Gly Ala Gln Ser Trp Arg
85 90 95
Ala Ala Asp Glu Arg Ser Ala Arg Val Asn Val Gly Leu Leu His Asp
100 105 110
Leu Val Asp Ala Phe Arg Gly Arg Ser Gly Thr Leu Pro Ala Val Val
115 120 125
Phe Ala Ser Thr Leu Gln Ala Gly Ala Asp Val Ala Arg Gln Gly Ala
130 135 140
Tyr Ala Arg Gln Lys Ser Ala Ala Glu Glu Val Leu Leu Arg Ala Ala
145 150 155 160
Ser Glu Gly Val Val Arg Gly Val Val Leu Arg Leu Pro Thr Val Tyr
165 170 175
Gly Arg Ser Pro Leu Thr Gly Trp Thr Gly Arg Gly Val Val Ala Ser
180 185 190
Val Ala Arg Arg Ala Val Glu Asp Gly Pro Val Thr Met Trp His Asp
195 200 205
Gly Thr Val Gly Arg Asp Leu Leu His Val Glu Asp Ala Ala Arg Ala
210 215 220
Phe Val Ala Ala Leu Asp His Ala Ala Arg Leu Asp Gly Gly Thr Trp
225 230 235 240
Ser Val Gly Thr Gly Arg Leu Glu Pro Leu Gly Glu Val Phe Ser Thr
245 250 255
Ile Ala Gly Leu Val Ser Glu Arg Thr Gly Arg Pro Pro Val Pro Val
260 265 270
Val Ser Thr Glu Pro Pro Asp His Ala Glu Ala Gly Asp Phe Asp Ser
275 280 285
Pro Val Ser Asp Pro Ser Ala Phe Arg Ala Val Thr Gly Trp Ser Pro
290 295 300
Arg Val Pro Leu Gln Ala Gly Leu Ser Ala Val Val Glu Thr Met Val
305 310 315 320
Ala Ala Glu Ser Arg Gly Gly Ile Arg Gly
325 330
<210> 36
<211> 335
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 36
Met Ser Thr Asp Arg Asn Gln Ala Ala His Thr Arg Leu Gly Arg Ser
1 5 10 15
Ala Thr Leu Val Ser Arg Leu Trp Leu Gly Thr Val Asn Phe Ser Gly
20 25 30
Arg Val Glu Asp Ala Asp Ala Met His Leu Met Glu Thr Ala Val Asp
35 40 45
Arg Gly Ile Asn Cys Ile Asp Thr Ala Asp Ile Tyr Gly Trp Arg Val
50 55 60
His Lys Gly His Thr Glu Glu Leu Val Gly Arg Trp Leu Ala Lys Ser
65 70 75 80
Ala Ala Arg Arg Glu Asp Val Leu Leu Ala Thr Lys Val Gly Gly Asp
85 90 95
Met Ser Glu Arg Leu Asn Asp Gly Gly Leu Ser Ala Arg His Ile Ile
100 105 110
Thr Ala Cys Glu Gln Ser Leu Arg Arg Leu Arg Val Asp His Ile Asp
115 120 125
Leu Tyr Gln Met His Arg Ile Asp His Ala Ala Pro Trp Asp Glu Ile
130 135 140
Trp Gln Ala Met Asp Arg Leu Val Ala Ser Gly Lys Val Thr Tyr Val
145 150 155 160
Gly Ser Ser Asn Phe Ala Gly Trp Asn Val Ala Ala Ala Gln Asp Ala
165 170 175
Ala Arg Arg Arg Arg Ser Leu Gly Leu Val Ser Glu Gln Cys Leu Tyr
180 185 190
Asn Leu Ala Val Arg His Ala Glu Leu Glu Leu Leu Pro Ala Ala Gln
195 200 205
Ala Tyr Gly Leu Gly Val Phe Ala Trp Ser Pro Leu His Gly Gly Leu
210 215 220
Leu Ser Gly Val Leu Arg Lys Leu Ala Ala Gly Thr Ala Val Lys Ser
225 230 235 240
Ala Gln Gly Arg Ala Gln Leu Leu Leu Pro Glu Leu His Ala Thr Ile
245 250 255
Glu Ala Tyr Glu Gly Phe Cys Asp Arg Ile Gly Ala Asp Pro Ala Glu
260 265 270
Val Gly Leu Ala Trp Val Leu Ser Arg Pro Gly Ile Ser Gly Ala Val
275 280 285
Ile Gly Pro Arg Thr Val Glu Gln Leu Asp Ser Ala Leu Arg Ala Leu
290 295 300
Asp Leu Val Leu Gly Glu Ala Glu Leu Ala Glu Leu Asp Ala Ile Phe
305 310 315 320
Pro Ala Leu Gly Asn Gly Gly Arg Ala Pro Asp Ala Trp Ile Ser
325 330 335
<210> 37
<211> 410
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 37
Met Ile Ala Thr Ala Cys Arg Val Cys Gly Asn Lys Glu Leu Leu Ser
1 5 10 15
Val Leu Asp Leu Gly Glu Gln Ala Leu Thr Gly Val Phe Pro Thr Ser
20 25 30
Arg Glu Gln Val Val Pro Ser Val Pro Leu Glu Leu Val Val Cys Ser
35 40 45
Pro Ala Gly Cys Gly Leu Val Gln Leu Arg His Thr Pro Asp Pro Asp
50 55 60
Leu Met Tyr Gly Glu Gly Tyr Gly Tyr Arg Ser Gly Ile Arg Pro Phe
65 70 75 80
Met Val Asp His Leu His Gly Lys Val Ala Ala Ile Arg Glu Leu Val
85 90 95
Asp Leu Gly Pro Asp Asp Leu Val Val Asp Ile Gly Ser Asn Asp Ala
100 105 110
Thr Leu Leu Ser Gly Tyr Pro Ala Asp Gly Pro Gln Leu Val Gly Ile
115 120 125
Asp Pro Thr Gly Gly Lys Phe Arg Glu Leu Tyr Pro Arg Asn Ala Glu
130 135 140
Leu Ile Val Asp Tyr Phe Thr Arg Glu Thr Phe Glu Ser Arg Phe Gly
145 150 155 160
Ala Arg Arg Ala Lys Val Val Thr Ser Ile Ala Met Phe Tyr Asp Leu
165 170 175
Pro Asp Pro Leu Arg Phe Met Ser Asp Val Arg Asp Val Leu Thr Glu
180 185 190
Asp Gly Ile Trp Met Met Glu Gln Ser Tyr Leu Pro Ala Met Leu Glu
195 200 205
Ala Asp Ala Tyr Asp Ile Val Cys His Glu His Leu Glu Tyr Tyr Ala
210 215 220
Leu Arg Gln Ile Glu Trp Met Ala Glu Arg Val Gly Leu Thr Val Ile
225 230 235 240
Arg Ala Glu Leu Thr Glu Val Tyr Gly Gly Ser Leu Cys Val Thr Leu
245 250 255
Ala Arg Ser Gly Ser Gln His Arg Lys Asp Asp Ala Gly Leu Ala Arg
260 265 270
Ile Arg Ala Arg Glu Ala Ala Ala Gly Leu Asp Gly Met Ala Pro Phe
275 280 285
Glu Gly Phe Ala Arg Arg Val Val Asn Gln Arg Gly Ala Leu Arg Asp
290 295 300
Phe Leu Asp Arg Ser Arg Glu Glu Gly Arg Leu Thr Leu Gly Tyr Gly
305 310 315 320
Ala Ser Thr Lys Gly Asn Val Ile Leu Gln Tyr Cys Gly Ile Thr Glu
325 330 335
Arg Asp Leu Pro Cys Ile Gly Glu Val Ser Glu Glu Lys Ala Gly Arg
340 345 350
Phe Thr Pro Gly Thr Ala Ile Pro Ile Val Ser Glu Gln Asp Ala Lys
355 360 365
Ala Gln Lys Pro Asp Gln Leu Leu Val Leu Pro Trp Ile Tyr Arg Asp
370 375 380
Gly Phe Val Glu Arg Glu Arg Asp Phe Leu Asp Gly Gly Gly Arg Leu
385 390 395 400
Ile Phe Pro Leu Pro Ala Leu Asp Val Val
405 410
<210> 38
<211> 370
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 38
Met His Arg Asp Asn Ala Ala Glu Pro Leu Val Lys Cys Leu Val Trp
1 5 10 15
Asp Leu Asp Asn Thr Leu Trp Gln Gly Thr Leu Leu Glu Glu Asp Glu
20 25 30
Val Arg Leu Thr Pro Asp Val Leu Arg Thr Ile Ala Glu Leu Asp Ala
35 40 45
Arg Gly Ile Leu Gln Ala Val Ala Ser Lys Asn Asp His Asp His Ala
50 55 60
Trp Ala Lys Leu Glu Gln Leu Gly Val Ala Glu Tyr Phe Val Leu Pro
65 70 75 80
Gln Ile Gly Trp Gly Pro Lys Ser Lys Ser Val Arg Glu Ile Ala Asp
85 90 95
Arg Leu Asn Phe Ala Leu Gly Thr Leu Ala Phe Ile Asp Asp Gln Pro
100 105 110
Phe Glu Arg Ala Glu Val Thr His Glu Leu Pro Glu Val Arg Thr Tyr
115 120 125
Thr Ala Gly Gln Ala Thr Gly Leu Thr Asp Leu Pro Glu Phe Ser Pro
130 135 140
Asp Thr Val Thr Val Asp Ser Arg Arg Arg Arg Ser Met Tyr Gln Ala
145 150 155 160
Ser Phe Arg Arg Asp Ala Glu Arg Ser Asp Phe Thr Gly Pro Asp Ala
165 170 175
Asp Phe Leu Arg Ser Leu Asp Ile Arg Met Arg Ile Ser Arg Ala Thr
180 185 190
Pro His Glu Leu Ser Arg Val Glu Glu Leu Thr Leu Arg Thr Ser Gln
195 200 205
Met Asn Ala Thr Gly Val His Tyr Ser Glu Asp Asp Leu Arg Ala Leu
210 215 220
Ile Asp Asp Pro Asp His Glu Val Leu Val Thr Thr Val Thr Asp Arg
225 230 235 240
Phe Gly Pro Tyr Gly Ala Val Gly Val Val Leu Leu Arg Arg Ser Pro
245 250 255
Asp Ala Trp Arg Ile Lys Leu Leu Ala Thr Ser Cys Arg Val Val Ser
260 265 270
Leu Gly Ala Gly Thr Ala Ile Leu Arg Trp Leu Thr Asp Gln Ala His
275 280 285
Arg Ala Gly Val His Leu Gly Ala Asp Phe Arg Ala Thr Glu Arg Asn
290 295 300
Arg Met Met Glu Val Ala Tyr Arg Phe Ala Gly Phe Thr Asp Asp Pro
305 310 315 320
Cys Pro Cys Gln Asp Ala Ser Ala Pro Thr Gly Ala Ile Gly Arg Leu
325 330 335
His Leu Met Pro Ser Pro Gln Pro Thr Pro Asp Thr Leu Arg Leu Glu
340 345 350
Ala Pro Asp Leu Ala Pro Gly Arg Arg Pro Gly Pro Asp Ser Glu Arg
355 360 365
Thr Pro
370
<210> 39
<211> 373
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 39
Met Ala Asp Ala Pro His Ala Ala Ala Ser Glu Ala Glu Glu Leu Phe
1 5 10 15
Thr Glu Leu Val Gly Asp Arg Ala Ala Glu Trp Asp Arg Thr Gly Glu
20 25 30
Leu Pro Leu Ser Leu Leu Arg Asp Leu Gly Ser Arg Gly Leu Leu Cys
35 40 45
Ala Gln Ala Pro Ala Ala His Gly Gly Leu Gly Trp Ser Ser Arg Arg
50 55 60
Asn Gly Glu Leu Thr Ala His Val Gly Ala Leu Cys Ser Ser Leu Arg
65 70 75 80
Ser Val Met Thr Ser Gln Gly Met Ala Ala Trp Thr Leu Arg Arg Leu
85 90 95
Ala Gly Ala Asp Gln Gln Ala Pro Leu Thr Ser Arg Leu Thr Ser Gly
100 105 110
Glu Leu Ala Ala Val Ala Phe Thr Glu Ala Gly Ala Gly Ser Asp Leu
115 120 125
Ser Ala Leu Arg Thr Arg Ile Ala Phe Asp Gly Asp Glu Ile Val Val
130 135 140
Asp Gly Val Lys Val Trp Ala Thr Asn Ala Ala Tyr Ala Asp Leu Leu
145 150 155 160
Val Val Phe Gly Arg Thr Glu Glu Gly Ala Gly Ala Val Val Val Pro
165 170 175
Ala Ser Ala Pro Gly Val Arg Ile Glu Arg Ile Ala Asp Ala His Gly
180 185 190
Cys Arg Ala Ala Gly His Ala Asn Ile His Leu Asp Gly Val Arg Leu
195 200 205
Pro Ala Asp Ala Leu Leu Gln Gly His Asp Arg Thr Pro Ala Leu Leu
210 215 220
Val Thr Thr Ala Leu Ser Tyr Gly Arg Met Ser Val Ala Trp Gly Ser
225 230 235 240
Leu Gly Ile Leu Arg Gly Cys Leu Ala Ala Ala Val Arg His Thr Ser
245 250 255
Gly Arg Glu Gln Phe Gly Thr Arg Leu Ser Glu His Gln Leu Val Ala
260 265 270
Arg His Leu Ala Glu Leu Phe Ile Ala Glu Gln His Ala Ala Arg Ala
275 280 285
Cys Glu Tyr Ala Ser Ala Gln Trp Asp Glu Gly Ser Pro Asp Met Val
290 295 300
Ile Ala Ala Val Leu Ala Lys His Val Ala Ala Thr Gly Ala Ala Arg
305 310 315 320
Gly Ala Glu Arg Ala Val Gln Val Leu Ala Ser Ala Gly Ala Arg Asp
325 330 335
Gly His Val Val Ala Arg Ala His Arg Asp Ala Lys Leu Met Glu Ile
340 345 350
Ile Glu Gly Ser Asn Glu Ile Cys Glu Leu Ile Leu Ala Arg His Ala
355 360 365
Val Ser Ala Ala Gly
370
<210> 40
<211> 106
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 40
Met Thr Thr Thr Ser Gly Arg Pro Asp Ser Thr Gly Thr Thr Pro Ala
1 5 10 15
Asp Asp Glu Val Ala Glu Glu Leu Leu Gly Phe Leu Ala Ala Asn Thr
20 25 30
Lys Thr Thr Trp Glu Arg Asp Gln Asp Leu Phe Ala Val Gly Gly Met
35 40 45
Ser Ser Leu Phe Ala Met Gln Leu Val Val His Leu Glu Lys Thr His
50 55 60
Gly Ile Val Ile Ser Gly Ala Asp Leu Met Leu Asp Asn Phe Arg Thr
65 70 75 80
Val Asp Ala Met Val Arg Leu Val Gly Arg Leu Ala Ala Pro Gly Pro
85 90 95
Thr Gly Glu Ala Thr Gly Pro Ala Gly Gly
100 105
<210> 41
<211> 288
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 41
Met Pro Asn Ser Asn Glu Asn Ser Pro Leu Val Val Leu Gly Ala Gly
1 5 10 15
Val Met Gly Thr Ala Ile Ala Ala Leu Ala Val Gly His Gly His Pro
20 25 30
Val Thr Leu Ile Asp Thr Ser Val Glu Ala Arg Ala Ala Ala Pro Asp
35 40 45
Thr Val Ala Leu His Leu Arg Thr Ala Arg Leu Met Gly Ala Leu Pro
50 55 60
His Asp Arg Pro Pro Gly Glu Leu Thr Val Glu Asp Ala Leu Asn Ala
65 70 75 80
Ile Ala Ala Val Thr Ala Val Ile Glu Ala Val Thr Glu Asp Pro Lys
85 90 95
Arg Lys Ala Glu Val Leu Ala Asp Leu Ala Ser Ala Ala Arg Pro Gly
100 105 110
Thr Leu Leu Ile Ser Asn Thr Ser Gly Val Pro Ile Asp Glu Leu Ala
115 120 125
Asp Ala Val Pro Arg Pro Glu Asp Leu Val Gly Val His Phe Met Asn
130 135 140
Pro Ala Tyr Val Ile Arg Thr Val Glu Val Val Leu Gly Pro Arg Ser
145 150 155 160
Gly Glu Ala Ala Ala Glu Ser Thr Arg Glu Leu Leu Ser Gly Leu Gly
165 170 175
Arg Arg Gly Ile Val Val Gly Asp Gly Ala Gly Phe Val Thr Ser Arg
180 185 190
Leu Leu His Arg Met Leu Asn Asp Ala Ile Ala Val Val His Glu Gly
195 200 205
Arg Ala Thr Pro Glu Thr Val Asp Ala Leu Met Arg Asp Cys Ile Gly
210 215 220
His Arg Thr Gly Pro Leu Ala Thr Ala Asp Leu Ile Gly Leu Asp Asn
225 230 235 240
Leu Ala Asp Ser Leu Arg Val Met His Glu Arg Thr Gly Asp Pro Ala
245 250 255
Leu Arg Pro Ser Glu Leu Leu Leu Asp Lys Val Arg Gln Gly Leu Leu
260 265 270
Gly Arg Lys Ser Gly Arg Gly Phe Tyr Asp Tyr Gln Glu Thr Met Gln
275 280 285
<210> 42
<211> 405
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 42
Met Ala His Ile Ala Phe Phe Ile Leu Pro Val Ala Gly His Val Asn
1 5 10 15
Pro Thr Leu Gly Val Ala Glu Glu Leu Val Ala Arg Gly His Arg Val
20 25 30
Thr Tyr Ala Leu Ser Gly Glu Leu Ala Glu Arg Ala Arg Leu Ile Gly
35 40 45
Ala Glu Val Val Thr Tyr Pro Val Asp Lys Gln Arg Phe Leu Asp Gln
50 55 60
Met Val Pro Arg Gln Asp Ala Asp Glu Tyr Thr Asp Glu Gly Glu Phe
65 70 75 80
Val Arg Val Leu Glu Trp Leu Leu Asp Met Thr Ala Gln Thr Leu Glu
85 90 95
Pro Leu Glu Arg His Phe Ala Glu Asn Arg Pro Asp Val Val Val Asn
100 105 110
Asp Pro Ser Ser Leu Trp Thr Gly Arg Leu Leu Ala Asp Arg Trp Asp
115 120 125
Ile Pro Val Ile Arg Ser Thr Pro Thr Tyr Ala Ala Asn Glu His Trp
130 135 140
Ser Leu His Pro Pro Val Asp Ser Ala Glu Pro Pro Asp Asp Pro Glu
145 150 155 160
Leu His Lys Leu Leu Ala Arg Ile Glu Arg Leu Leu Glu Glu Gln Gly
165 170 175
Val Glu His Asp Leu Ala Ala Phe Thr Gly Val Leu His Gly Gly Pro
180 185 190
Ala Leu Leu Tyr Met Pro Arg Ser Phe Gln Tyr Ala Gly Glu Thr Phe
195 200 205
Asp Glu Gln His His Phe Val Gly Pro Cys Pro Pro Arg Thr Ala Phe
210 215 220
His Gly Glu Trp Thr Pro Thr Asp Asp Asp Gly Arg Pro Leu Val Leu
225 230 235 240
Val Ser Leu Gly Thr Leu Tyr Asn Asp Arg Pro Asp Phe Phe Arg Thr
245 250 255
Cys Leu Glu Ala Phe Arg Asp Glu Pro Trp Asn Val Leu Leu Val Leu
260 265 270
Gly Gly Gly Val Pro Ala Ala Asp Leu Gly Pro Leu Pro Asp Asn Val
275 280 285
Arg Val His Asp Phe Val Ser Leu Arg Asp Val Leu Pro His Thr Ala
290 295 300
Val Val Val Asn His Gly Gly Met Ser Thr Ala Met Glu Val Phe Ser
305 310 315 320
His Glu Val Pro Val Val Ala Ile Pro Val Met Pro Glu Pro Arg Ala
325 330 335
Thr Ala Arg Arg Ile Val Glu Leu Gly Leu Gly Asp Gln Leu Leu Asn
340 345 350
Ser Glu Leu Thr Ala Glu Ser Leu Arg Ala Thr Val Arg Arg Val Leu
355 360 365
Glu Asp Ser Arg Ile Pro Ala Asn Met Arg Lys Ile Arg Glu Gln Ile
370 375 380
Thr Ala Ala Gly Gly Ala Asn Ala Ala Ala Asp Ala Val Glu Gly Leu
385 390 395 400
Leu Pro Gln Gly Ser
405
<210> 43
<211> 202
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 43
Met Leu Ile Thr Glu Thr Thr Val Pro Asp Val Phe Arg Ile Asp Pro
1 5 10 15
Glu Pro Ile Pro Asp His Arg Gly Arg Phe Tyr Glu Ala Val Arg Gln
20 25 30
Arg Pro Leu Glu Ala Ala Val Gly His Ser Ile Ala Val Arg Gln Val
35 40 45
Asn Phe Thr Val Ser Gly Arg Asn Val Leu Arg Gly Leu His Ala Thr
50 55 60
Thr Leu Pro Pro Gly Gln Gly Lys Ile Leu Thr Cys Val Arg Gly Ser
65 70 75 80
Val Leu Thr Met Val Val Asp Met Arg Val Gly Ser Pro Ser Phe Gly
85 90 95
Arg Tyr Glu Ala Val Arg Gln Asp Pro Arg Ser Gly Thr Ala Leu Tyr
100 105 110
Leu Pro Asp Gly Ile Gly Leu Gly Tyr Val Ala Leu Val Asp Asp Thr
115 120 125
Cys Met Asn Tyr Leu Cys Thr His Glu Tyr Val Pro Gly Met Val Ile
130 135 140
Asp Val Asp Ala Leu Asp Pro Glu Leu Asp Leu Pro Trp Asp Leu Ala
145 150 155 160
Asp Thr Pro Ile Arg Ser Ala Arg Asp Ala Ala Ala Pro Ser Leu Arg
165 170 175
Ala Ala Val Ser Ala Gly Ile Leu Pro Thr Tyr Glu Glu Cys Leu Arg
180 185 190
Val Arg Glu Pro Leu Pro Ala Ala Leu Asp
195 200
<210> 44
<211> 390
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 44
Met Lys Phe Arg Thr Leu Glu Pro Ala Gly Thr Ala Pro Leu Thr Gly
1 5 10 15
Pro Ala Ala Gly His Asp Phe Asp Ser Leu Val Ser Glu Gly Cys Ala
20 25 30
Glu Leu Leu Gly Ser Leu Arg Arg Ala Asp Gln Arg Arg Arg Gly Glu
35 40 45
Gln Tyr Ile Arg Gly Leu Leu Thr Ala Gln Gly Arg Lys Thr Ala Arg
50 55 60
Asn Leu Ala Ala Phe Val Gly Glu Gly Ala Ala Glu Gln Ser Leu His
65 70 75 80
His Phe Val Ala Gly Ser Thr Trp Asp Trp Gly Ala Val Arg Ala Ala
85 90 95
Leu Ala Arg Tyr Val Asp Asp Arg Leu Asn Pro Glu Ala Trp Val Ile
100 105 110
Trp Pro Met Val Val Ser Lys Ala Gly Val Arg Ser Val Gly Val Ser
115 120 125
Arg Arg Phe Val Pro Asp Leu Gly Arg Val Val Ser Cys Gln Gln Ser
130 135 140
His Gly Leu Trp Leu Ala Ser Gly Ala Thr Ala Ala Pro Val Ser Trp
145 150 155 160
His Leu Thr Leu Gly Gly Gly Arg Gly Gly Asp Gly Gly Ser Arg Gln
165 170 175
Leu Gly Ala Pro Gly Ala Leu Gly Glu Glu Glu Asn Val Val Arg Leu
180 185 190
Val Ala Glu Ala Ala Gln Ala Ser Arg Thr Ser Ala Arg Pro Val Val
195 200 205
Met Asp Ala Arg Ala Ala Val Leu Pro Arg Leu Val Arg Gly Leu Ser
210 215 220
Leu Val Gly Leu Pro Phe Met Val Arg Val Gly Gly Asn Leu Gln Leu
225 230 235 240
Ala Ser Ala Gly Gly Arg Gly Leu Val Asp His His Thr Ala Thr Thr
245 250 255
Ser Ala Gln Gln Leu Met Glu Gln Met Lys Arg Leu Ser Arg Pro Val
260 265 270
Glu Trp Gln Gly Ser Leu Ser Leu Val Ala Pro His Ala Val Val Leu
275 280 285
Pro Gly Val Val Pro Arg Arg Thr Leu Val Leu Met Gly Val Trp Arg
290 295 300
Gly Asn Arg Arg Arg Pro Ala Asp Leu Trp Leu Thr Asp Leu Thr Ser
305 310 315 320
Trp Asp Arg Gly Ala Leu Leu Arg Leu Ala Met Leu Thr Glu Gln Val
325 330 335
Asp Ala Asp Phe Glu Arg Val Ser Val Gly Val Gly Met Arg Asp Phe
340 345 350
Glu Gly Arg Ser Phe Gln Gly Trp His Arg His Val Thr Leu Ala Ser
355 360 365
Ile Ala His Thr Leu Arg Leu Ala Gln Pro Ser Ala Arg Val Asp Phe
370 375 380
Arg Gly Val Ala Ala Val
385 390
<210> 45
<211> 269
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 45
Met Thr Glu Leu Asp Thr Ile Ala Asn Pro Ser Asp Pro Ala Val Gln
1 5 10 15
Arg Ile Ile Asp Val Thr Lys Pro Ser Arg Ser Asn Ile Lys Thr Thr
20 25 30
Leu Ile Glu Asp Val Glu Pro Leu Met His Ser Ile Ala Ala Gly Val
35 40 45
Glu Phe Ile Glu Val Tyr Gly Ser Asp Ser Ser Pro Phe Pro Ser Glu
50 55 60
Leu Leu Asp Leu Cys Gly Arg Gln Asn Ile Pro Val Arg Leu Ile Asp
65 70 75 80
Ser Ser Ile Val Asn Gln Leu Phe Lys Gly Glu Arg Lys Ala Lys Thr
85 90 95
Phe Gly Ile Ala Arg Val Pro Arg Pro Ala Arg Phe Gly Asp Ile Ala
100 105 110
Ser Arg Arg Gly Asp Val Val Val Leu Asp Gly Val Lys Ile Val Gly
115 120 125
Asn Ile Gly Ala Ile Val Arg Thr Ser Leu Ala Leu Gly Ala Ser Gly
130 135 140
Ile Ile Leu Val Asp Ser Asp Ile Thr Ser Ile Ala Asp Arg Arg Leu
145 150 155 160
Gln Arg Ala Ser Arg Gly Tyr Val Phe Ser Leu Pro Val Val Leu Ser
165 170 175
Gly Arg Glu Glu Ala Ile Ala Phe Ile Arg Asp Ser Gly Met Gln Leu
180 185 190
Met Thr Leu Lys Ala Asp Gly Asp Ile Ser Val Lys Glu Leu Gly Asp
195 200 205
Asn Pro Asp Arg Leu Ala Leu Leu Phe Gly Ser Glu Lys Gly Gly Pro
210 215 220
Ser Asp Leu Phe Glu Glu Ala Ser Ser Ala Ser Val Ser Ile Pro Met
225 230 235 240
Met Ser Gln Thr Glu Ser Leu Asn Val Ser Val Ser Leu Gly Ile Ala
245 250 255
Leu His Glu Arg Ile Asp Arg Asn Leu Ala Ala Asn Arg
260 265
<210> 46
<211> 388
<212> PRT
<213> 可利霉素基因工程菌(Streptomyces spiramyceticus WSJ-1)
<400> 46
Met Pro Leu Pro Lys His Leu Pro Ala Leu Gly Gly Met Arg Phe Ile
1 5 10 15
Ser Ala Leu Leu Val Phe Thr Ser His Ile Ser Thr Gln Pro Phe Phe
20 25 30
Lys Asn Thr Glu Ile Asn Ser Ala Leu Gln Phe Pro Leu Asn Arg Leu
35 40 45
Gly Pro Leu Thr Val Ser Phe Phe Phe Met Leu Ser Gly Phe Val Leu
50 55 60
Thr Trp Ala Gly Leu Pro Asp Lys Ser Lys Val Asn Phe Trp Arg Arg
65 70 75 80
Arg Thr Val Arg Ala Tyr Ser Leu His Leu Pro Val Leu Leu Val Thr
85 90 95
Leu Leu Ile Val Leu Ala Leu Asn Glu Pro Asn Met Gly Arg Ser Val
100 105 110
Trp Asp Gly Leu Leu Thr Asn Leu Leu Leu Ile Gln Ala Trp Phe Pro
115 120 125
Asp His His Glu Tyr Gly Ser Met Asn Pro Val Ala Trp Ser Leu Ser
130 135 140
Cys Glu Leu Phe Phe Tyr Ala Met Phe Pro Phe Leu Phe Ala Phe Phe
145 150 155 160
Thr Lys Val Arg Thr Asp Arg Leu Trp Arg Trp Ala Ala Ala Val Ser
165 170 175
Val Ala Ala Val Ser Ile Pro Leu Val Ala Leu Leu Leu Pro Ala Ser
180 185 190
Pro Pro Leu Pro Trp Asp Pro Asp Met Pro Gln Leu Arg Trp Trp Phe
195 200 205
Ile Tyr Met Phe Pro Pro Val Arg Leu Leu Glu Phe Val Leu Gly Met
210 215 220
Leu Met Ala Gln Ile Val Ile Arg Gly Arg Trp Arg Gly Pro Arg Pro
225 230 235 240
Leu Ala Cys Val Ala Leu Phe Ser Ala Val Phe Ala Val Thr Phe Ala
245 250 255
Val Pro Asn His Tyr Asp Pro Gly Ala Leu Thr Val Pro Val Ile Ala
260 265 270
Leu Leu Leu Ala Ser Val Ala Val Gly Asp Val Arg Gly Val Arg Ser
275 280 285
Trp Leu Gly Thr Arg Thr Met Val Leu Leu Gly Glu Leu Thr Phe Ala
290 295 300
Phe Tyr Leu Val His Tyr Leu Ile Ile Gln Tyr Gly His Arg Phe Ala
305 310 315 320
Gly Gly Lys Gln Gly Tyr Tyr Arg Gln Trp Asp Thr Pro Ala Ala Val
325 330 335
Gly Leu Thr Leu Leu Ala Phe Thr Leu Ala Leu Gly Gln Ser Ala Phe
340 345 350
Leu His Phe Phe Val Glu Lys Pro Val Met Arg Thr Leu Gly Arg Pro
355 360 365
Arg Arg Ser Pro Asp Ala Gly Ser Thr Pro Arg Ser Glu Pro Ala Pro
370 375 380
Ser Gly Thr Pro
385

Claims (9)

1.一种可利霉素生物合成基因簇，其特征是，所述生物合成基因簇的基因至少包括：
(1)聚酮合酶基因orf10-14，共5个基因；
(2)与糖基合成相关基因orf9、16-22、24、26、28、29、33-35、41，共16个基因；
(3)与糖基转移相关基因orf7、8、30-32、40，共6个基因，选自6个基因中的至少5个；
(4)外源引入的碳霉糖4”-O-异戊酰转移酶基因orf44，共1个基因。
2.如权利要求1所述生物合成基因簇，其特征是，所述的5个聚酮合酶基因编码聚酮体生物合成酶，所述聚酮体生物合成酶催化可利霉素16元内酯环的合成，所述5个聚酮合酶基因orf10-14的核苷酸序列或互补序列所对应的氨基酸序列为IA-W10、IA-W11、IA-W12、IA-W13和IA-W14。
3.如权利要求1或2所述的生物合成基因簇，其特征是，5个聚酮合酶包含模块或结构域，即酮基合成酶(KS)、酰基转移酶(AT)、酮基还原酶(KR)、脱水酶(DH)、烯酰基还原酶(ER)、酰基载体蛋白(ACP)、硫酯酶结构域的核苷酸序列或互补序列所对应的氨基酸序列。
4.如权利要求1所述的生物合成基因簇，其特征是，所述糖基合成相关基因orf9、16-22、24、26、28、29、33-35、41的核苷酸序列或互补序列所对应的氨基酸序列为IA-W9、IA-W16、IA-W17、IA-W18、IA-W19、IA-W20、IA-W21、IA-W22、IA-W24、IA-W26、IA-W28、IA-W29、IA-W33、IA-W34、IA-W35、IA-W41。
5.如权利要求1或4所述的生物合成基因簇，其特征是，糖基合成相关基因中，orf18，19和28编码参与可利霉素基本糖基单元合成、脱水和异构化酶；orf9、20、21、24、26和29编码参与福洛糖胺合成中NDP-氨基己糖N-二甲基化、2,3脱水、氨基化、异构化、脱水和酮基还原酶；orf16、17、22编码参与碳霉糖胺NDP-氨基己糖异构化、氨基化和N-二甲基化酶；orf33、34、35和41编码碳霉糖NDP-氨基己糖酮基还原、甲基化和异构化酶。
6.如权利要求1所述的生物合成基因簇，其特征是，所述糖基转移相关基因orf7、8、30-32、40的核苷酸序列或互补序列所对应的氨基酸序列为IA-W7、IA-W8、IA-W30、IA-W31、IA-W32、和IA-W40。
7.如权利要求1或6所述的生物合成基因簇，其特征是，糖基转移相关基因中：orf7编码碳霉糖胺糖基化酶；orf8编码其糖基化辅助蛋白；orf31和32编码福洛糖胺糖基化酶；orf30编码其糖基化辅助蛋白；orf40编码碳霉糖糖基化酶。
8.如权利要求1所述的生物合成基因簇，其特征是，外源引入的碳霉糖4”-O-异戊酰转移酶基因orf44的核苷酸序列或互补序列所对应的氨基酸序列为IA-W44。
9.一种具有如权利要求1-8任意一项权利要求所述的生物合成基因簇的可利霉素生产菌。
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