CN1298447A - 生产刺糖噻杀虫剂所用的生物合成基因 - Google Patents
生产刺糖噻杀虫剂所用的生物合成基因 Download PDFInfo
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Abstract
本发明涉及刺糖噻生物合成基团,用该生物合成基因转化的产刺糖噻微生物,用生物合成基因增加刺糖噻杀虫大环内酯类化合物的产生的方法,以及用所述基因或其片段改变由产刺糖噻微生物产生的产物的方法。
Description
本发明提供了新的生物合成基因,包含该生物合成基因的载体,被该生物合成基因转化的刺糖多孢菌(Saccharopolyspora spinosa)菌株,使用所述基因增加刺糖噻(Spinosyn)杀虫大环内酯产量的方法,和使用所述基因或其片段改变生产刺糖噻的刺糖多孢菌菌株所生产的产物的方法。
如美国专利5,362,634所述,发酵产物A83543是由刺糖多孢菌生产的相关化合物家族。该家族的已知成员被称为因子或组分,每一个成员都有一个识别用的字母标识。下文将这些化合物称为刺糖噻A,B等。刺糖噻化合物可用于防治蜘蛛刚动物、线虫和昆虫,尤其是鳞翅目(Lepidoptera)和双翅目(Diptera)昆虫,它们不会污染环境,并具有理想的毒理学分布图。表1和2鉴定了多种已知刺糖噻化合物的结构:
表1
天然产生的刺糖噻化合物由融合于12-员大环内酯的5,6,5-三环体系、中性糖(鼠李糖)和氨基糖(forosamine)组成(见Kirst等(1991))。如果不含氨基糖,可将化合物称为假苷元A,D等,如果不含中性糖,可将化合物称为逆向假苷元A,D等。更优选的命名是将假苷元称为刺糖噻A17-Psa,刺糖噻D17-Psa等,将逆向假苷元A,D称为刺糖噻A9-Psa,刺糖噻D9-Psa等。
通过发酵培养物NRRL 18395,18537,18538,18539,18719,18720,18743和18823可产生天然的刺糖噻化合物,这些培养物已被保藏于美国农业部农业研究服务中心下属的中西部北方研究中心原种培养物保藏中心(1815 North University Street,Peoria,IL 61604)。
美国专利5,362,634和相应的欧洲专利申请375316 A1描述了刺糖噻A,B,C,D,E,F,G,H和J。这些化合物是通过培养新的微生物刺糖多孢菌菌株产生的,所述菌株选自NRRL 18395,NRRL 18537,NRRL18538和NRRL18539。
WO93/09126描述了刺糖噻L,M,N,Q,R,S和T。其中还描述了两个刺糖噻J生产菌株:NRRL 18719和NRRL 18720,以及一个生产刺糖噻Q,R,S和T的菌株:NRRL 18823。
WO94/20518和US 5,6704,486描述了刺糖噻K,O,P,U,V,W和Y及其衍生物。还描述了刺糖噻-K生产菌株NRRL 18743。
生产刺糖噻化合物的困难在于很大的发酵体积仅能生产很少量的刺糖噻。非常需要增加刺糖噻的生产效率,籍此增加刺糖噻的产率,同时降低其花费。含有刺糖噻生物合成酶基因的经克隆的DNA片段能复制编码刺糖噻生产过程中的限速酶的基因。当其中一个编码活性可限制所需刺糖噻的合成时,在任何情况下都可使用上述DNA片段来增加产量。通过复制编码限速酶(将大菌素转变为泰乐菌素的甲基转移酶)的基因,可在弗氏链霉菌(Streptomyces fradiae)的发酵过程中获得这种类型的产量增加(Baltz等,1997)。在另一个例子中,WO97/06266描述了将第二个eryG拷贝插入红色糖多孢菌(Sac.erythraea)染色体的非必需区域,以改良6-脱氧红霉素D向6,12-双脱氧红霉素A的转变过程。
克隆的生物合成基因也可提供生产新的具有不同杀虫活性谱的刺糖噻衍生物的方法。之所以需要新的衍生物是因为:尽管已知的刺糖噻具有广谱的抗虫活性,但它们不能控制所有的害虫。生物合成的刺糖噻中间体或其在体内产生的衍生物或其在体外经化学修饰所得的衍生物可提供不同的控制模式。通过突变的刺糖多孢菌菌株可合成特定的中间体(或其天然衍生物),所述突变菌株中的某些编码刺糖噻生物合成所用酶的基因已被破坏。通过经由同源重组整合含有靶基因内部片段的诱变质粒可产生上述突变菌株。通过质粒整合形成了两个不完全的生物合成基因拷贝,从而消除了该基因所编码的酶的功能。通过发酵该突变菌株应能积累该酶的底物或所述底物的某些天然衍生物。使用该策略可有效产生生产新的6-脱氧红霉素衍生物所用的红色糖多孢菌菌株(Weber & McAlpine,1992)。
通过刺糖多孢菌突变菌株也可合成新的中间体,所述突变菌株中某些编码刺糖噻生物合成之酶的基因部分已被在体外经特异性突变的相同基因部分(或得自其它生物体的相应基因部分)所取代。通过经由双重同源重组与诱变质粒交换靶区域即可产生该突变菌株,所述诱变质粒在侧翼于靶区域的非突变序列之间含有新的片段。杂合基因可产生功能有所变化的蛋白质,该蛋白质或者缺乏活性或者能进行新的酶促转化。通过发酵突变菌株可积累新的衍生物,使用该策略可产生生产新的脱水红霉素衍生物所用的红色糖多孢菌菌株(Donadio等,1993)。本发明的核酸可用于生产WO93/13663和US5,824,513中所述类型的经改造的聚酮化合物合酶,WO98/01546,WO98/49315和WO98/51695中所述类型的杂合聚酮化合物合酶,并可用于构建WO96/40968,WO98/49315,WO98/27203,US 5,783,431,US 5,824,485和US5,811,238中所述的聚酮化合物合酶文库和聚酮化合物文库。
通过逐步缩合和修饰2-和3-碳羧酸前体,产生线性聚酮化合物,环化并桥连所述化合物以产生四环苷元即可进行刺糖噻的生物合成。接着形成假苷元(含有三-O-甲基化鼠李糖),再加入二-N-甲基化forosamine即可完成生物合成(Broughton等,1991)。其它大环内酯,如抗生素红霉素、抗寄生虫剂除虫菌素和免疫抑制剂纳巴霉素也是以类似的方式合成的。在生产这些化合物的细菌中,大多数大环内酯生物合成基因簇集在基因组的70-80kb区域(Donadio等,1991;MacNeil等,1992;Schwecke等,1995)。这些簇的中心是3-5个高度保守的基因,所述基因编码很大的多功能的Ⅰ型聚酮化合物合酶(Polyketide synthasePKS)蛋白质。多肽合在一起形成了由一个起始组件和几个延伸组件组成的复合物,各个组件为正在生成的聚酮化合物链添加了特定的脂酰-CoA前体,并以特殊的方式修饰β-酮基,因此,PKS中各组件的组成和顺序决定了聚酮化合物的结构。组件含有几个各自行使其特殊功能的结构域。起始组件由酰基转移酶(AT)结构域组成,该结构域负责将前体的酰基基团添加至酰基载体蛋白(ACP)结构域。延伸组件含有上述结构域以及通过脱羧缩合将预先存在的聚酮化合物链添加至新的酰基-ACP的β-酮基合酶(KS)结构域。延伸组件中还可含有其它组件以进行特定的β-酮基修饰:β-酮基还原酶(KR)结构域将β-酮基还原为羟基,脱水酶(DH)结构域除去羟基留下双键,烯脂酰还原酶(ER)结构域还原双键留下饱和的碳。最后一个延伸组件以硫酯酶(TE)结构域终止,该结构域以大环的内酯的形式从PKS酶上释放出聚酮化合物。
通过另加修饰(如甲基化和还原态的改变)并添加不寻常的糖即可由大环的内酯衍生得到大环内酯。上述修饰以及合成和结合糖所需的大多数基因都簇集在PKS基因的周围。在大环内酯类抗生素,如红霉素和泰乐菌素的生产菌株(Donadio等,1993;Merson-Davies &Cundliffe,1994)以及胞外多糖,如沙门氏菌属和耶尔森氏菌属的O-抗原的生产菌株(Jiang等,1991;Kessler等,1993)中,编码脱氧糖生物合成酶的基因相似。所有这些合成涉及通过添加核苷酸二磷酸,接着进行脱水,还原和/或差向异构来激活葡萄糖。所得糖可经一次或多次修饰,如脱氧,转氨基和甲基化,这取决于大环内酯中存在的糖组成成分的类型。通过特定糖基转移酶的作用将糖掺入大环内酯。参与合成和结合糖的基因紧密簇集,甚至作为单个操纵子被转录,但它们也可以是分散的(Decker & Hutchinson,1993;Jarvis & Hutchinson,1994)。刺糖噻的合成还包括内酯核的桥连,该活性在大环内酯生产菌株中很少见。因此,刺糖噻生物合成基因簇独一无二地另外还含有编码具有此功能之酶的基因。
本文所用术语的定义如下:
AmR-赋予阿泊拉霉素抗性的基因
ApR-赋予氨苄青霉素抗性的基因
ACP-酰基载体蛋白
AT-酰基转移酶
bp-碱基对
克隆-将DNA区段掺入重组DNA克隆载体并用重组DNA转化宿主细胞的方法
CmR-赋予氯霉素抗性的基因
密码子偏好-使用特殊密码子指定特定氨基酸的偏好,对刺糖多孢菌而言,其偏爱使用胞嘧啶或鸟嘌呤作为第三个碱基的密码子
互补-通过克隆基因使突变菌株回复至其正常表型
接合-遗传物质由一个细菌细胞转移至另一个细菌细胞的过程
COS-λ粘端序列
粘粒-重组DNA克隆载体,它是质粒,不仅能以质粒的方式在宿主细胞中复制,也可被包装入噬菌体头部
DH-脱水酶
ER-烯脂酰还原酶
接合后体-由接合交配得到的重组菌株
基因-编码多肽的DNA序列
基因组文库-一系列重组DNA克隆载体,其中已克隆了基本上能代表特定生物体之所有DNA序列的DNA区段
同源性-序列之间的相似程度
杂交-两个单链DNA分子退火形成双链DNA分子的过程,它可以是也可以不是完全的碱基配对
体外包装-体外将DNA包裹在外被蛋白内以产生病毒样颗粒,所述病毒样颗粒可通过感染将DNA导入宿主细胞
kb-千碱基对
KR-β-酮基还原酶
KS-酮基合酶
诱变-使DNA序列发生变化,它们可以是随机的或靶向的,可以在体内或体外产生,突变可以是沉默的,或导致翻译产物之氨基酸序列的变化,所述变化可改变蛋白质的特性并产生突变的表型
NmR-赋予新霉素抗性的基因
ORF-开放阅读框
ori-质粒的复制起点(oriR)或转移起点(oriT)
PKS-聚酮化合物合酶
启动子-介导转录起始的DNA序列
重组DNA克隆载体-任何自主复制或整合的载体,包括但不限于质粒,其中含有DNA分子,该DNA分子中能添加或已添加了一个或多个其它的DNA分子
重组DNA方法学-用于产生,表征和修饰克隆至重组DNA载体中的DNA区段的技术
限制性片段-通过一个或多个限制性酶的作用而产生的任何线性DNA分子
刺糖噻-由利用所有或大多数刺糖噻基因的微生物产生的,特征在于融合于12-员大环内酯的5,6,5-三环体系,中性糖(鼠李糖)和氨基糖(forosamine)的发酵产物,或类似的大环内酯发酵产物
刺糖噻基因-编码刺糖噻生物合成所需产物的DNA序列,更具体地为如下文所述的基因spnA,spnB,spnC,spnB,spnE,spnF,spnG,spnH,spnI,spnJ,spnK,spnL,spnM,spnN,spnO,spnP,spnQ,spnR,spnS,刺糖多孢菌gtt,刺糖多孢菌gdh,刺糖多孢菌epi和刺糖多孢菌kre,或其功能等同物
亚克隆-具有插入DNA的克隆载体,所述DNA衍生自另一个同样大小或更大的DNA
TE-硫酯酶
转化-将DNA(异源或同源)导入受体宿主细胞以改变表型并导致受体细胞发生变化
附图简述
图1图示了刺糖噻的生物合成途径。
图2图示了刺糖多孢菌DNA之克隆区域的BamHⅠ片段排列和开放阅读框。
图3是粘粒pOJ436的限制性位点和功能图谱。
图4是粘粒pOJ260的限制性位点和功能图谱。
图5是pDAB1523的限制性位点和功能图谱。
发明简述
克隆了刺糖噻生物合成基因和相关的ORF,并测定了它们的DNA序列。下文将克隆的基因和ORF称为spnA,spnB,spnC,spnD,spnE,spnF,spnG,spnH,spnI,spnJ,spnK,spnL,spnM,spnN,spnO,spnP,spnQ,spnR,spnS,ORFL15,ORFL16,ORFR1,ORFR2,刺糖多孢菌gtt,刺糖多孢菌gdh,刺糖多孢菌epi和刺糖多孢菌kre。在图1和下文的讨论中鉴定了克隆的基因在刺糖噻生物合成中的功能。
在本发明的一个方面,提供了分离的DNA分子,其含有编码刺糖噻生物合成酶的DNA序列,其中所述酶由选自SEQ ID NO:2-5,7-24,26,27,29和33的氨基酸序列限定,或者所述酶由上述氨基酸序列中的一个来限定,该氨基酸序列中具有一个或多个氨基酸取代,但不会影响到编码酶的功能特性。在优选的实施方案中,DNA序列选自基因spnA,spnB,spnC,spnD,spnE,spnF,spnG,spnH,spnI,spnJ,spnK,spnL,spnM,spnN,spnO,spnP,spnQ,spnR,spnS,ORFL15,ORFL16,ORFR1,ORFR2,刺糖多孢菌gtt,刺糖多孢菌gdh,刺糖多孢菌epi和刺糖多孢菌kre,所述基因分别描述于SEQ ID NO:1的碱基21111-28898,28916-35374,35419-44931,44966-59752,59803-76569,20168-20995,18541-19713,17749-18501,16556-17743,14799-16418,13592-14785,12696-13547,11530-12492,10436-11434,8967-10427,7083-8450,5363-6751,4168-5325,3416-4165,2024-2791,1135-1971,76932-77528和77729-79984,SEQ ID NO:27的碱基334-1119,SEQ ID NO:24的碱基88-1077,SEQ ID NO:31的碱基226-834,和SEQ ID NO:24的碱基1165-1992。
本发明的另一方面提供了分离的DNA分子,其含有编码选自KSi,ATi,ACPi,KS1,AT1,KR1和ACP1的刺糖噻PKS结构域的DNA序列,所述结构域分别描述于SEQ ID NO:2的氨基酸6-423,528-853,895-977,998-1413,1525-1858,2158-2337和2432-2513。在优选的实施方案中,DNA序列选自SEQ ID NO:1的碱基21126-22379,22692-23669,23793-24041,24102-25349,25683-26684,27582-28121和28404-28649。
本发明的另一方面提供了分离的DNA分子,其含有编码选自KS2,AT2,DH2,ER2,KR2和ACP2的刺糖噻PKS结构域的DNA序列,所述结构域分别描述于SEQ ID NO:3的氨基酸1-424,536-866,892-1077,1338-1683,1687-1866和1955-2034。在优选的实施方案中,DNA序列选自SEQID NO:1的碱基29024-30295,30629-31621,31697-32254,33035-34072,34082-34621,34886-35125。
本发明的另一方面提供了分离的DNA分子,其含有编码选自KS3,AT3,KR3,ACP3,KS4,AT4,KR4和ACP4的刺糖噻PKS结构域的DNA序列,所述结构域分别描述于SEQ ID NO:4的氨基酸1-423,531-280,1159-1337,1425-1506,1529-1952,2066-2396,2700-2880和2972-3053。在优选的实施方案中,DNA序列选自SEQ ID NO:1的碱基35518-36786,37108-38097,38992-39528,39790-40035,40102-41373,41713-42705,43615-44157和44431-44676。
本发明的另一方面提供了分离的DNA分子,其含有编码选自KS5,AT5,DH5,KR5,ACP5,KS6,AT6,KR6,ACP6,KS7,AT7,KR7和ACP7的刺糖噻PKS结构域的DNA序列,所述结构域分别描述于SEQ ID NO:5的氨基酸1-424,539-866,893-1078,1384-1565,1645-1726,1748-2172,2283-2613,2916-3095,3188-3269,3291-3713,3825-4153,4344-4638和4725-4806。在优选的实施方案中,DNA序列选自SEQ ID NO:1的碱基45077-46348,46691-47674,47753-48310,49226-49771,50009-50254,50318-51592,51923-52915,53822-54361,54638-54883,54947-56215,56549-57535,58106-58990和59249-59494。
本发明的另一方面提供了分离的DNA分子,其含有编码选自KS8,AT8,DH8,KR8,ACP8,KS9,AT9,DH9,KR9,ACP9,KS10,AT10,DH10,KR10,ACP10和TE10的刺糖噻PKS结构域的DNA序列,所述结构域分别描述于SEQ ID NO:6的氨基酸1-424,530-848,883-1070,1369-1552,1648-1726,1749-2173,2287-2614,2640-2800,3157-3341,3422-3500,3534-3948,4060-4390,4413-4597,4900-5078,5172-5253和5302-5555。在优选的实施方案中,DNA序列选自SEQ ID NO:1的碱基59902-61173,61489-62445,62548-63111,64006-64557,64843-65079,65146-66420,66760-67743,67819-68301,69370-69924,70165-70401,70471-71745,72079-73071,73138-73692,74599-75135,75415-75660和75805-76566。
本发明的另一方面提供了分离的DNA分子,其含有编码刺糖噻PKS组件的DNA序列,所述组件选自SEQ ID NO:2的氨基酸6-1413,SEQ IDNO:2的1525-2513,SEQ ID NO:3的1-2034,SEQ ID NO:4的1-1506,SEQID NO:4的1529-3053,SEQ ID NO:5的1-1726,SEQ ID NO:5的1748-3269,SEQ ID NO:5的3291-4806,SEQ ID NO:5的1-1726,SEQ ID NO:6的1-1726,SEQ ID NO:6的1749-3500和SEQ ID NO:6的35434-5555。在优选的实施方案中,DNA序列选自SEQ ID NO:1的碱基21126-24041,24102-28649,29024-35125,35518-40035,40102-44676,45077-50254,50318-54883,54947-59494,59902-65079,65146-70401和70471-76566。
本发明的另一方面提供了重组DNA载体,其含有如上所述的本发明的DNA序列。
本发明的另一方面提供了被上述本发明重组载体转化的宿主细胞。
本发明的另一方面提供了提高刺糖噻生产微生物之刺糖噻生产能力的方法,所述方法包括下列步骤:
1)用重组DNA载体或其部分转化利用生物合成途径生产刺糖噻或刺糖噻前体的微生物,所述载体或其部分含有如上所述的本发明的DNA序列,所述DNA序列编码所述途径中限速活性的表达,和
2)在适于细胞生长和分裂,表达所述DNA序列和生产刺糖噻的条件下培养被所述载体转化的所述微生物。
本发明的另一方面提供了生产刺糖噻的微生物,其含有可操纵的刺糖噻生物合成基因,其中至少一个刺糖噻生物合成基因spnA,spnB,spnC,spnD,spnE,spnF,spnG,spnH,spnI,spnJ,spnK,spnL,spnM,spnN,spnO,spnP,spnQ,spnR,spnS刺糖多孢菌gTT,刺糖多孢菌gdh,刺糖多孢菌epi或刺糖多孢菌kre已被复制。
本发明的另一方面提供了生产刺糖噻的微生物,所述微生物的基因组中含有刺糖噻生物合成基因,其中所述生物合成基因中的至少一个基因已通过与该基因的内部片段重组而被破坏,其余所述基因可有效产生刺糖噻,而不是被破坏的基因有效时产生的产物。优选微生物是刺糖多孢菌突变菌株。
本发明还提供了生产刺糖噻的微生物,所述微生物的基因组中含有可操作的刺糖噻生物合成基因,其中所述基因a)包括至少一个可操作的PKS组件,所述组件比SEQ ID NO:1中的所述组件少一个以上或至少少一个;或b)包括通过缺失,失活或添加KR,DH或ER结构域,或通过取代AT结构域而与SEQ ID NO:1所述的相应组件有所不同的PKS组件。优选微生物是刺糖多孢菌突变菌株。
本发明还提供了通过培养本发明的新微生物而产生的刺糖噻。
本发明的另一方面提供了分离刺糖噻生物合成基因的方法,所述方法包括制备刺糖噻生产微生物的基因组文库,并将长度至少为20个碱基的经标记的SEQ ID NO:1片段用作杂交探针。发明详述
由通过用Sau3AⅠ部分消化产生的片段构建刺糖多孢菌(NRRL18395)DNA的粘粒文库。将它们克隆至载体pOJ436的BamHⅠ位点(见图3)(Bierman等,1992),并通过体外包装和转导将其导入大肠杆菌细胞。通过使用Solenberg & Burgett(1989)的方法进行杂交,从所得重组细菌的文库中筛选与两个经放射性标记的DNA探针的同源性。一个探针是400kb的SpeⅠ片段,在通过转化或用N-甲基-N'-硝基-N-亚硝基胍诱变得到的不能生产刺糖噻的刺糖多孢菌菌株中,该SpeⅠ片段经常被缺失(Matsushima等,1994)。第二个探针是300bp的刺糖多孢菌DNA片段,该片段编码不参与刺糖噻生物合成的酮基合酶部分(B.E.Schoner,个人通讯)。它包括在所有聚酮化合物和脂肪酸合酶基因中高度保守的区域,因此预期可与刺糖噻PKS基因交叉杂交。粘粒9A6和2C10是与两个探针都能杂交的7个克隆中的两个。通过与粘粒9A6经放射性标记的SgrAⅠ-BamHⅠ片段(SEQ ID NO:1的碱基26757-26936)杂交,可从基因组文库中筛选出粘粒3E11。为了测定粘粒9A6中插入物的核苷酸序列,将BamHⅠ片段亚克隆至质粒pOJ260的BamHⅠ位点(见图4)(Bierman等,1992)。通过两种方法中的任一种测定所述质粒之插入物的序列。在一个方法中,用Sau3AⅠ部分消化经亚克隆的片段,将选定大小的片段克隆至噬菌体M13mp19 DNA的BamHⅠ位点。由随机选择的重组子制备单链DNA,根据Burgett &Rosteck(1994)的方法,使用购自ABI(Applied Biosystems公司,Foster,CA)的试剂和仪器通过荧光循环测序法进行测序。各个质粒的噬菌体亚克隆的序列被装配成一个邻接的序列。在另一个测序方法中,用经设计可与以前测定的序列末端附近的区域互补的单链寡核苷酸反复引发双链质粒DNA。因此,一系列部分重叠的序列可汇集成完整的序列。根据厂商说明,使用Prism-Ready测序试剂盒(ABI),并在ABI373A测序仪上进行分析。对穿过双链9A6 DNA之BamHⅠ位点的序列使用相同的策略。使用MacVector程序的AssemblyLIGN组件(OxfordMolecular,Campbell,KY),用上述数据排列经亚克隆的序列,并确定各序列相互之间的方向,从而组装出粘粒9A6中刺糖多孢菌DNA的完整的核苷酸序列。通过对克隆至噬菌体M13(SeqWright,Houston,TX)的随机DNA片段进行荧光循环测序以测定粘粒2C10和3E11的完整序列。粘粒2C10和3E11中的插入物重叠,3E11中的插入物与粘粒9A6中的插入物末端重叠。见图2,这三个粘粒插入物合在一起跨越了约80kb长的独特的序列(SEQ ID NO:1)。下表3鉴定了包括在上述各个插入物中的SEQ ID NO:1部分。表3
图2图示了3个插入物与80kb序列的关系。
插入物 | SEQIDNO:1中的碱基 |
粘粒9A6 | 1-26941 |
粘粒3E11 | 23489-57287 |
粘粒2C10(经校正) | 41429-80161 |
应注意的是粘粒2C10缺失了SEQ ID NO:1的G41877,C45570,C57845和G73173。将这些缺失确定为克隆假象。缺失产生了截短的PKS多肽的框内终止密码子,其中一个出现在粘粒3E11的克隆区域,但不存在于已得到序列的3E11区域。因此,可直接由刺糖多孢菌(NRRL 18395)基因组中的PCR-扩增区域测定跨越PKS区域中的所有8个终止密码子的未经克隆的DNA的序列。未经克隆的DNA的序列证明ACP结构域的末端存在4个终止密码子,并证明其它编码区内的4个移码是粘粒2C10所独有的克隆假象。PKS基因
SEQ ID NO:1包括约55kb的中间区域,该区域与编码已知大环内酯生产微生物之聚酮化合物合酶的DNA具有显著的同源性(Donadio等,1991;MacNeil等,1992;Schwecke等,1995;Dehoff等,1997)。刺糖噻PKS DNA区域由5个ORF组成,在ACP结构域的末端具有框内终止密码子,这与其它大环内酯生产细菌中的PKS ORF类似。5个刺糖噻PKS基因按头-对-尾的方式排列(见图2),而对非PKS功能,如红霉素PKS基因AⅠ和AⅡ之间的插入元件(Donadio等,1993)没有任何干扰。将它们称为spnA,spnB,spnC,spnD,spnE。下表4鉴定了5个刺糖噻PKS基因各自的核苷酸序列和对应的多肽。表4
spnA编码起始组件(SEQ ID NO:1,碱基21126-24041)和延伸组件1(SEQ ID NO:1,碱基24102-28649)。下表5鉴定了起始组件和延伸组件1中的各个功能域的核苷酸序列和对应的氨基酸序列。
基因 | SEQIDNO:1中的碱基 | 对应的多肽 |
spnA | 21111-28898 | SEQIDNO:2 |
spnB | 28916-35374 | SEQIDNO:3 |
spnC | 35419-44931 | SEQIDNO:4 |
spnD | 44966-59752 | SEQIDNO:5 |
spnE | 59803-76569 | SEQIDNO:6 |
表5
spnB编码延伸组件2(SEQ ID NO:1,碱基29024-35125)。下表6鉴定了延伸组件2中的各个功能域的核苷酸序列和对应的氨基酸序列。
表6
spnC编码延伸组件3(SEQ ID NO:1,碱基35518-40035)和延伸组件4(SEQ ID NO:1,碱基40102-44676)。下表7鉴定了延伸组件3和4中的各个功能域的核苷酸序列和对应的氨基酸序列。
spnD编码延伸组件5(SEQ ID NO:1,碱基45077-50254),延伸组件6(SEQ ID NO:1,碱基50318-54883)和延伸组件7(SEQ ID NO:1,碱基54947-59494)。下表8鉴定了延伸组件5,6和7中的各个功能域的核苷酸序列和对应的氨基酸序列。
表8
spnE编码延伸组件8(SEQ ID NO:1,碱基59902-65079),延伸组件8(SEQ ID NO:1,碱基65146-70401)和延伸组件10(SEQ ID NO:1,碱基70471-76566)。下表9鉴定了延伸组件8,9和10中的各个功能域的核苷酸序列和对应的氨基酸序列。
表9
上表5-9中鉴定的50个结构域的边界及功能是根据与其它聚酮化合物合酶,尤其是红霉素聚酮化合物合酶之结构域的保守氨基酸序列的相似性推测的(Donadio等,1992)。假定位于起始组件氨基末端的非预期的KSi结构域是非功能性的,因为它在氨基酸172处含有谷氨酰胺残基而不是β-酮基合酶活性所需的半胱氨酸(Siggard-Andersen,1993)。在泰乐菌素PKS的起始组件中也发现了类似的非功能性KS结构域(Dehoff等,1997)。其它刺糖噻PKS结构域是功能性的。它们无一具有红霉素和纳巴霉素PKS基因之失活结构域的序列特征(Donadio等,1992;Aparicio等,1996)。其中的这些基因被破坏的刺糖多孢菌菌株不能发酵产生刺糖噻的现象表明:克隆的PKS基因是刺糖噻生物合成所必需的。通过使用本领域技术人员众所周知的方法,将基因的内部片段克隆至质粒pOJ260(图4)即可破坏基因。然后,使用Matsushima等(1994)的方法通过接合将得自大肠杆菌的重组质粒导入刺糖多孢菌,并选择阿泊拉霉素抗性接合后体。基于pOJ260的质粒不能在刺糖多孢菌中独立复制,通过经由克隆DNA和基因组中该DNA的同源序列之间的重组,将质粒整合至染色体中,即可稳定维持该质粒。整合在染色体中产生了两个不完整的靶基因形式(一个缺乏5’序列,一个缺乏3’序列),它们之间是pOJ260 DNA。通过用分别对应于下列区段SEQ ID NO:1:21365-22052,22052-24338或24338-26227的BamHⅠ片段V,N或K破坏spnA ORF即可阻断刺糖噻生物合成。用分别对应于下列区段SEQ ID NO:1:碱基48848-50578,50578-52467或55207-55888的BamHI片段G,E或K破坏spnD ORF也可阻断刺糖噻生物合成。用分别对应于下列区段SEQ ID NO:1:63219-63989,65406-66733,66733-68997,69369-70731和70731-72675的BamHⅠ片段J,I,D,H和F破坏spnE ORF也可阻断刺糖噻生物合成。经由BamHⅠ片段C(SEQ IDNO:1的碱基44612-47565)或B(SEQ ID NO:1的碱基55936-63219)整合不能阻断刺糖噻生物合成,因为它们对任何一个基因而言都不是内部片段;BamHⅠ片段C跨越了spnC和spnD之间的连接部分,BamHⅠ片段B跨越了spnD和spnE之间的连接部分。在这些情况下,整合留下了各个基因的一个完整的版本。与PKS邻接的负责其它修饰的基因
在PKS基因上游的DNA(克隆至粘粒9A6)中,有16个开放阅读框(ORF),各由至少100个密码子组成,以ATG或GTG开始,以TAA,TAG或TGA终止,生物体之蛋白质编码区的预期密码子偏好为:其DNA含有高百分比的鸟嘌呤和胞嘧啶残基(Bibb等,1984)。图2的右下方图示了9A6中的16个ORF。根据下文中将要讨论的证据,将其中14个ORF称为刺糖噻生物合成基因,即spnF,spnG,spnH,spnl,spnJ,spnK,spnL,spnM,spnN,spnO,spnP,spnQ,spnR和spnS(图2中以F-S表示)。在下表10中,鉴定了所述各个基因以及紧接spnS上游的2个ORF(ORFL15和ORFL16)的DNA序列和相应多肽的氨基酸序列。表10中还鉴定了位于PKS基因下游的ORFR1和ORFR2(克隆至粘粒2C10)的核苷酸序列以及相应的氨基酸序列。
表10
基因 | SEQIDNO:1中的碱基 | 多肽 |
spnF | 20168-20995 | SEQIDNO:7 |
spnG | 18541-19713(C) | SEQIDNO:8 |
spnH | 17749-18501(C) | SEQIDNO:9 |
spnI | 16556-17743 | SEQIDNO:10 |
spnJ | 14799-16418(C) | SEQIDNO:11 |
spnK | 13592-14785(C) | SEQIDNO:12 |
spnL | 12696-13547(C) | SEQIDNO:13 |
spnM | 11530-12492(C) | SEQIDNO:14 |
spnN | 10436-11434 | SEQIDNO:15 |
spnO | 8967-10427 | SEQIDNO:16 |
spnP | 7083-8450 | SEQIDNO:17 |
spnQ | 5363-6751(C) | SEQIDNO:18 |
spnR | 4168-5325(C) | SEQIDNO:19 |
spnS | 3416-4165(C) | SEQIDNO:20 |
ORFL15 | 2024-2791 | SEQIDNO:21 |
ORFL16 | 1135-1971(C) | SEQIDNO:22 |
ORFR1 | 76932-77528 | SEQIDNO:23 |
ORFR 2 | 77729-79984 | SEQIDNO:24 |
(C)表示序列表中给出互补链。
为了确定表10中鉴定的多肽的功能,利用了三条证据线索:与已知功能之序列的相似性,靶基因破坏实验的结果和生物转化实验的结果。
使用BLAST算法规则将推测多肽的氨基酸序列与国立生物技术信息中心(NCBI,华盛顿)的数据库中采集的序列相比较以确定它们与已知蛋白质的相关程度。周期性重复对NCBI数据库的BLAST检索,以从其它同源性中得到新的线索。表11是根据1998年1月12日的基本BLAST检索结果给出的最佳匹配。表11*较高的相似性与较高的BLAST评分相关(Altschul等,1990)。
在破坏靶基因时,通过PCR扩增由粘粒DNA产生内部片段并克隆至质粒pOJ260。然后将所得质粒接合至刺糖多孢菌(NRRL18395),分离并发酵阿泊拉霉素-抗性接合后体。如上所述,破坏实验的基础是当携有内部基因片段的质粒被整合时,产生两个不完整的生物合成基因拷贝,从而消除了酶功能。分析所得发酵产物以确定积累了何种刺糖噻。表12概述了靶基因破坏实验的结果。
在生物转化研究中,检测刺糖噻合成被改变的菌株将可用的刺糖噻中间体转变为其它刺糖噻的能力。所用中间体是刺糖噻A苷元(AGL),刺糖噻P(P),刺糖噻K(K)和刺糖噻A 9-Psa(PSA)。表12概述了生物转化实验的结果。
表12
下面将在逐个基因的基础上详细讨论由BLAST检索,基因破坏实验和生物转化研究得出的结论。
PKS上游的11个基因参与刺糖噻生物合成,这是因为所述11个基因被破坏的菌株中不能积累主要的刺糖噻A和D(表12)。再往上游的2个基因(ORFL15,ORFL16)和PKS下游的大基因(ORFR2)对刺糖噻生产没有贡献,这是因为将它们破坏不会影响发酵(表12)。未尝试破坏紧接PKS基因下游的ORF(ORFR1),这是因为它太小以致于不能产生以可接受的频率重组的内部片段。也未尝试破坏spnQ,spnR和spnS基因,这是因为早期BLAST检索的结果表明:这些基因与已知参与不同寻常的脱氧糖的生物合成之酶具有显著的相似性。spnQ的基因产物与参与合成肠沙门氏菌细胞表面脂多糖的阿比可糖组成成分的CDP-4-酮基-6-脱氧-D-葡萄糖-3-脱水酶之间,具有53%的同一性(Jiang等,1991);spnR的基因产物与一组据称有脱氧糖转氨酶功能的蛋白质之间的同一性达40%(Thorson等,1993);spnS的基因产物与合成含forosamine的抗生素螺旋霉素的微生物产二素链霉菌的SrmX产物之间的同一性为42%(Geistlich等,1992)。从最近的BLAST检索结果看,相似性甚至更强(表11)。根据这些相似性和这些基因与其它刺糖噻生物合成基因的紧密联系,可以得出下列结论,即spnQ,spnR和spnS参与生产刺糖噻的forosamine组成成分。spnF,spnJ,spnL,spnM
spnF,spnJ,spnL或spnM基因被破坏的菌株不会将任何刺糖噻积累至显著的水平(spnM突变株中低水平的刺糖噻A可能是由其羧基末端缺失的基因产物的某些残留活性引起的)。然而,它们将外源提供的苷元生物转化为刺糖噻A,因此,它们含有刺糖噻生物合成的后序步骤所必需的所有酶。这些特定的基因必定参与由PKS基因的推定的大环内酯产物产生苷元的步骤。spnF和spnL在碳-碳桥形成过程中的作用同其与使碳原子甲基化的酶的相似性(表11)是一致的。引起被阻断的突变株中经部分修饰的中间体缺乏的原因可能是:化合物的不稳定性,或者与泰乐菌素途径类似,由于缺乏起正调节剂作用的糖基化分子而使生物合成降低(Fish & Cundliffe,1997)。spnG,spnH,spnI,spnK
破坏spnG也可防止刺糖噻产生,但突变菌株不能生物转化苷元,因此刺糖噻生物合成途径的后序步骤需要该基因(表12)。该基因的序列与已知糖基转移酶基因的相似性(表11)暗示spnG编码向苷元添加第一个糖所需的鼠李糖基转移酶。spnG被破坏的突变菌株也缺乏功能性的4’-O-甲基转移酶(OMT),原因是它将3’,4’-双脱甲基刺糖噻(P)转变为4’-脱甲基刺糖噻(K),而不是完全甲基化的刺糖噻A。4’-OMT活性可能不在突变菌株中表达,原因是编码基因(spnH)位于相同操纵子中处于破坏中的整合的下游。通过破坏BamHⅠ片段T可证实该操纵子的存在,所述片段跨越spnG和spnH之间的连接部分,但对任何开放阅读框而言都不是内部片段。然而,该片段的破坏改变了刺糖噻合成,因此该片段对包含两个基因的单个转录物而言必定是内部片段。除了预期的由spnH编码的4’-OMT活性丧失外,该破坏还可使非预期的3’-OMT功能丧失,导致刺糖噻P积累(表12)。3’-OMT活性似乎由汇集于下游的基因spnI编码。该基因的大多数序列与黑胡桃链霉菌的ORF Y基因相似(表11)。ORF Y产物的功能未知,但黑胡桃链霉菌产生了与刺糖噻A的三-甲基化鼠李糖相似的异常的四-甲基化脱氧糖(nogalose),因此这两个基因可能都参与糖的甲基化。与该假说一致的是,破坏spnI产生的突变体将刺糖噻P只生物转化成3’-脱甲基刺糖噻(J)而不是刺糖噻A(表12)。破坏作用可防止刺糖噻在任何未补料的发酵中积累。spnK序列类似于spnI和ORF Y,可能编码2’-OMT。破坏该基因也可防止刺糖噻在任何未补料的发酵中积累(表12)。spnN,spnO,spnP
破坏基因spnN,spnO和spnP导致假苷元积累(表12),因此,这些基因参与生物合成或添加forosamine糖。spnP与糖基转移酶的相似性(表11)表明:它编码刺糖噻forosamyl转移酶。spnO和2,3脱水酶之间的高水平的相似性(表11)说明spnO参与forosamine合成的2’-脱氧步骤。鼠李糖基因
克隆至粘粒9A6,3E11和2C10的重叠插入物不含编码由葡萄糖生产鼠李糖所需的4种酶的基因(Liu & Thorson,1994)。第一种酶是葡萄糖胸苷酸转移酶(gtt)或功能等同的酶,该酶通过添加核苷酸基二磷酸(NDP)激活葡萄糖。第二种酶是葡萄糖脱水酶(gdh),该酶可产生很多脱氧糖生物合成途径所共有的中间体NDP-4-酮基-6-脱氧-葡萄糖。还需要鼠李糖合成所特有的差向异构酶(epi)和酮基还原酶(kre)以将NDP-4-酮基-6-脱氧-葡萄糖转变为NDP-L-鼠李糖,该激活糖是糖基转移酶将鼠李糖添加至苷元所需的底物。刺糖多孢菌中编码这些酶的基因克隆自λ载体ZAP ExpressTM(Stratagene,LaJolla,CA)中的7-12kb部分Sau3AⅠ片段的独立文库。通过随机引物延伸(Boehringer Mannheim,Indianapolis,IN)含有红色糖多孢菌gdh(Linton等,1995)和gtt基因的质粒pESCl的片段来制备经放射性标记的探针。在严紧洗涤条件(0.5×SSC,0.1%SDS,65℃,1小时)下进行噬斑杂交以筛选噬菌体文库。从3个杂交噬菌体中的2个中切下含有插入物的载体的质粒(pDAB1620和pDAB1621)部分,使用Prism-Ready测序试剂盒(ABI)和多个引物进行部分测序。pDAB1620之插入物的测序部分(SEQ IDNO:25)包括编码329-氨基酸多肽(SEQ ID NO:26)的ORF,所述多肽与红色糖多孢菌的gdh产物具有82%的同一性。与该基因邻接的是编码275-氨基酸多肽(SEQ ID NO:27)的ORF,所述多肽与红色糖多孢菌的kre基因产物具有72%的同一性。pDAB1621之插入物的测序部分(SEQID NO:28)含有编码261-氨基酸多肽(SEQ ID NO:29)的ORF,所述多肽与红色糖多孢菌gtt的基因产物具有83%的同一性。使用基于已知epi蛋白之保守氨基酸区域(Jiang等,1991;Linton等,1995)的简并寡核苷酸引物(SEQ ID NO:30和SEQ ID NO:31),通过PCR扩增刺糖多孢菌基因组DNA以制备鼠李糖基因的第二个探针。在GeneAmp 9600热循环仪中,用AmpliTaq聚合酶(Perkin-Elmer)进行共30轮PCR反应循环,每个循环的具体反应条件为94℃30秒,60℃30秒和72℃45秒。探针与7-12kb文库中的一个噬菌体杂交;切下含有该插入物之载体的质粒部分(pDAB1622)并进行部分测序(SEQ ID NO:32)。它包括编码202-氨基酸多肽(SEQ ID NO:33)的ORF,所述多肽与红色糖多孢菌的epi蛋白具有57%的同源性。通过与含有内部片段(SEQ ID NO:25的碱基382-941,SEQ ID NO:25的1268-1867,SEQ ID NO:28的447-994或SEQ ID NO:32的346-739)的质粒重组可破坏基因。在所有情况下都能得到阿泊拉霉素-抗性接合后体,但它们仅能在渗透性稳定化的培养基,如添加有200g/L蔗糖的CSM或R6中生长(Matsushima等,1994)。甚至在这些条件下,它们也比刺糖多孢菌亲本菌株(NRRL18395)生长缓慢,形态也有所不同,它们具有高度片段化的菌丝体。这些结果的成因是:刺糖多孢菌细胞壁中存在鼠李糖,该微生物正常的细胞壁合成需要这4个基因。这些基因被破坏的突变体生长得非常缓慢以致于不能在已知可生产刺糖噻的条件下发酵。然而,刺糖多孢菌基因组DNA与红色糖多孢菌的gtt/gdh探针(洗涤条件为2×SSC,0.1%SDS,65℃,1小时)或简并epi探针(洗涤条件为0.1×SSC,0.1%SDS,65℃,1小时)的Southern杂交结果表明:刺糖多孢菌基因组中不存在这些基因的其它同系物。因此,这4个克隆的刺糖多孢菌基因必定是细胞壁形成和刺糖噻生物合成所需鼠李糖的唯一来源。
下表13鉴定了产生鼠李糖所需的4个刺糖多孢菌基因各自的核苷酸序列和相应的氨基酸序列。
表13
基因 | DNA序列 | 氨基酸序列 |
刺糖多孢菌gtt | SEQID NO:28,碱基334-1119 | SEQ ID NO:29 |
刺糖多孢菌gdh | SEQ ID NO:25,碱基88-1077 | SEQ ID NO:26 |
刺糖多孢菌epi | SEQ ID NO:32,碱基226-834 | SEQ ID NO:33 |
刺糖多孢菌kre | SEQ ID NO:25,碱基1165-1992 | SEQ ID NO:27 |
因此,可确定刺糖多孢菌的23个基因在生物合成刺糖噻过程中的作用:5个PKS基因产生大环内酯,4个基因将大环内酯修饰为苷元,5个基因合成并添加鼠李糖,3个基因使鼠李糖甲基化,6个基因合成并添加forosamine。假拟的生物合成途径概述于图1。实用性
克隆的刺糖多孢菌DNA有很多用途。可使用克隆的基因改善刺糖噻的产量并生产新的刺糖噻。通过将双份拷贝的基因整合至特定菌株的基因组中即可使产量提高,其中所述基因编码该菌株中的任一限速酶。当特定突变菌株中的生物合成途径因缺乏所需的酶而被阻断的极端条件下,通过整合一拷贝所需基因即可恢复所需刺糖噻的生产。下文实施例1-3和6将阐明通过整合多拷贝刺糖噻基因而获得的产量改善。
使用克隆DNA的片段破坏刺糖噻的生物合成步骤即可生产新的刺糖噻。这种破坏作用可导致前体或“支路”产物(前体经天然加工的衍生物)积累。可用于进行破坏的片段是基因的内部片段,也即基因的5’和3’末端碱基被除去的片段。利用所述片段的同源重组事件导致两个部分拷贝的基因:一个缺失了5’末端除去的碱基,一个缺失了3’末端除去的碱基。片段每个末端被除去的碱基数目必须足够大以使部分拷贝的基因都不能保留活性。一般从每个末端至少除去50个碱基,更优选从每个末端除去至少100个碱基。部分基因片段的长度必须足够大以使重组频率高得足以进行实际的实验。用于破坏的片段必须至少为300个碱基长,更优选至少约为600个碱基长。由破坏基因产生的经修饰的刺糖噻自身可以是昆虫控制剂,或可用作其它化学修饰的底物,产生新的半合成的具有独特特性和活性谱的刺糖噻。下文实施例4阐明了破坏的用途。
通过诱变克隆的基因,用突变基因取代刺糖噻生产微生物中未经突变的该基因对应物也可生产新的刺糖噻。诱变包括例如:1)缺失或灭活KR,DH或ER结构域以使一个或多个所述功能被阻断,菌株产生的刺糖噻具有内酯核,该内酯核具有刺糖噻A的核中不存在的双键,羟基或酮基(见Donadio等,1993);2)取代AT结构域以使不同的羧酸掺入内酯核(见Ruan等,1997);3)在现存的PKS组件中添加KR,DH或ER结构域以使菌株产生的刺糖噻具有内酯核,该内酯核具有刺糖噻A的核中不存在的饱和键,羟基或双键;或4)添加或除去完整的PKS组件以使环状内酯核具有较多或较少数目的碳原子。实施例5阐明了使用诱变产生具有经修饰之功能性的刺糖噻。
可将刺糖噻基因簇区域的DNA用作杂交探针以鉴定同源序列,因此,可使用此处克隆的DNA确定得自刺糖多孢菌基因文库,与此处所述的区域重叠但也含有得自邻接区域的以前未被克隆的DNA的其它质粒在刺糖多孢菌基因组中的位置。另外,也可使用得自此处克隆的区域的DNA鉴定其它生物体中不相同但相似的序列。杂交探针一般至少约20个碱基长,并被标记以进行检测。
可使用如美国专利5,362,634所述的常规方法培养本发明提供的经改良的菌株以提供刺糖噻。
提供下列实施例是为了更完整地理解本发明,不应将它们看成是对本发明的限制。实施例1通过用粘粒9A6转化改善刺糖噻A和D的产量
于30℃,在250ml Erlenmeyer烧瓶中的50ml CSM培养基(胰胨豆胨培养液30g/l,酵母提取物3g/l,硫酸镁2g/l,葡萄糖5g/l,麦芽糖4g/l)中,以300rpm的振荡速度将刺糖多孢菌菌株NRRL18538的营养培养物培养48小时。发酵培养物中含有分散在7ml INF202中的1ml该营养培养物的接种物,INF202是与Strobel & Nakatsukasa(1993)所述类似的适宜培养基。在30℃的恒温室中,用按10×10个模件安排的30ml塑料瓶以300rpm的振荡速度将培养物培养3,5或7天。用4倍体积的乙腈提取培养液,然后通过流过C-18反相柱的等度高压液相层析(HPLC)分析刺糖噻A+D(Strobel & Nakatsukasa(1993))。由250nm下的光吸收值测定刺糖噻的量。对每个时间点而言,由10个发酵瓶测定刺糖噻A+D。另外通过稍加改动的HPLC系统分析每套重复实验中的2个代表性样品中的假苷元(PSA),假苷元是缺乏forosamine的刺糖噻前体。在该系统中,流动相是35∶35∶30的乙腈/甲醇/0.5%(w/v)醋酸铵水溶液(R.wijayaratne,未公开)。
培养物中不仅含有具有杀昆虫活性的刺糖噻A和D,还含有假苷元(表14)。表14菌株NRRL18538中的刺糖噻生产
上述数值是平均值±95%置信水平。
时间 | A+D(μg/ml) | PSA(μg/ml) |
3天5天7天 | 101±3269±14334±32 | 109±11155±26110±53 |
假苷元(forosamine缺失的刺糖噻A前体)的积累表明:在这些条件下培养的该菌株中,forosamine的供应和/或添加限制了刺糖噻A+D的产量。
使用Matsushima等(1994)的方法将大肠杆菌S17-1中的粘粒9A6(Simon等,1983)接合至刺糖多孢菌菌株NRRL 18538中。随后,在上述发酵条件下培养6个被粘粒9A6转化的独立的分离物并分析刺糖噻因子的生产情况。发酵3天后这些菌株的刺糖噻A+D平均产量高于其亲本菌株达35μg/ml,发酵5天后高37μg/ml。在整个发酵过程中,转化培养物中的假苷元的量低于其亲本菌株(表15)。表15被粘粒9A6转化的NRRL18538衍生物中的刺糖噻生产
上述数值是平均值±95%置信水平。
时间 | A+D(μg/ml) | PSA(μg/ml) |
3天5天7天 | 136±4306±5365±7 | 31±27±27±1 |
在发酵过程中的不同时间分析菌株NRRL18538和6个被粘粒9A6转化的独立的分离物中的刺糖噻含量。对每个菌株而言,由10个发酵瓶测定刺糖噻A+D(表16)。另外对每套重复实验中的2个样品中的假苷元含量进行分析(表17)。表16粘粒9A6对NRRL18538中的刺糖噻A+D的作用
上述数值是μg/ml平均值±95%置信水平。表17粘粒9A6对NRRL18538中的假苷元积累的作用
上述数值是μg/ml平均值±95%置信水平。
时间 | -9A6 | +9A6 | 9A6的作用 |
3天5天7天9天 | 101±3269±14334±32414±17 | 136±4306±5365±7411±8 | +35%+14%+9%-1% |
时间 | -9A6 | +9A6 | 9A6的作用 |
3天5天7天9天 | 109±11155±26110±53119±11 | 31±27±27±15±1 | -72%-95%-94%-96% |
因此阐明:用粘粒9A6转化能改善将前体假苷元加工为刺糖噻的效率。在NRRL18538中,发酵3天后刺糖噻A+D产量增加35%,发酵5天后增加14%(表15)。限速方法似乎是供应和/或添加forosamine,因为在整个发酵过程中,亲本中存在的假苷元约为120μg/ml,但在转接合子中,3天降低为约30μg/ml,随后基本上耗尽(表15)。尽管未用数量表示转变,但该数据与被粘粒9A6转化的菌株中将假苷元加工为刺糖噻A+D的效率有所改善的结果是一致的。该效果可能是由复制forosamine生物合成基因,即forosaminyl转移酶基因或联合改善所引起的。发酵7或9天后,用或未用粘粒9A6转化的NRRL18358菌株的刺糖噻A+D产量在统计学上没有显著差异。转接合子中的假苷元仍在减少,但在通过此发酵阶段积累的刺糖噻的较高背景之下,检测不到通过由假苷元转变产生的额外的刺糖噻A+D。实施例2通过粘粒9A6修正菌株NRRL18823中的甲基化缺陷
尽管菌株NRRL18823中的forosamine供应/添加可限制刺糖噻合成,其它生物合成功能在其它菌株中也被限制。刺糖多孢菌菌株NRRL18823积累刺糖噻H(2’-脱甲基-刺糖噻A;Kirst等,1992)而不是刺糖噻A。刺糖噻H不是刺糖噻A生物合成途径中的中间体,而是在未发生2’-O-甲基化时天然合成的“支路”产物。使用上述方法将大肠杆菌菌株S17-1中的粘粒9A6接合至菌株NRRL 18823中。当2个所得接合后体发酵时可产生显著水平的刺糖噻A,而仅产生极少量的刺糖噻H(表18)。表18
菌株 | H(μg/ml) | A+D(μg/ml) |
NRRL 18823NRRL 18823/9A6-2NRRL 18823/9A6-5 | 3233645 | 0551646 |
表18表明:用粘粒9A6进行转化能克服对刺糖噻生产的第二种限制,即菌株NRRL 18823中的甲基化缺陷。实施例3通过粘粒9A6修正菌株NRRL18743中的4’-O-甲基化缺陷
刺糖多孢菌菌株NRRL18743积累刺糖噻K(4’-脱甲基-刺糖噻A)。刺糖噻K是刺糖噻A生物合成途径中的中间体。含有粘粒9A6的菌株NRRL18743的2个接合后体产生显著水平的刺糖噻A,而仅产生极少量的刺糖噻K,第3个接合后体未产生可测水平的刺糖噻K(表19)。
表19
菌株 | K(μg/ml) | A+D(μg/ml ) |
NRRL 18743NRRL 18743/9A6-1NRRL 18743/9A6-2NRRL 18743/9A6-3 | 48838220 | 0829725706 |
表19表明:用粘粒9A6进行转化能克服对刺糖噻生产的第三种限制,即菌株NRRL 18743中的甲基化缺陷。实施例4通过破坏spnP导致刺糖噻前体积累
在使用SEQ ID NO:34和SEQ ID NO:35中给出的引物的聚合酶链反应中扩增spnP的内部片段(碱基7391-8159)。根据厂商说明,在100μl含有20pmol各种引物和1μg 9A6 DNA的反应溶液中使用AmpliTaq聚合酶(Perkin Elmer,Foster City,CA)。将混合物在94℃ 60秒,37℃60秒和72℃120秒的条件下进行25轮PCR循环。将扩增产物作为EcoRⅠ-HindⅢ片段克隆至质粒载体pOJ260(Bierman等,1992),然后由大肠杆菌S17-1接合至刺糖多孢菌NRRL 18538中。由质粒携有的序列和染色体序列之间的单次同源重组事件产生的稳定的接合后体,在两个不完整的spnP拷贝之间含有一拷贝整合至染色体中的载体DNA。当这些接合后体发酵时可积累forosamine-缺失的前体假苷元,而不是终产物刺糖噻A和D(表20)。表20
假苷元是用于制备已知杀虫剂的中间体(国际申请WO93/09126)。实施例5修饰PKS结构域ER2之后积累新的刺糖噻
菌株 | PSA(μg/ml) | A+D(μg/ml) |
NRRL 18538NRRL 18538/1614-2NRRL 18538/1615-1NRRL 18538/1615-2NRRL 18538/1615-5NRRL 18538/1615-6 | 79416372543476504 | 2842221211918 |
设计重叠,互补的寡核苷酸SEQ ID NO:36和SEQ ID NO:37以修饰编码刺糖噻PKS之组件2中的烯酯酰还原酶功能的基因。这些诱变引物可用序列TCACC取代SEQ ID NO:1的碱基33563-33567处的GGTGG,以使序列编码推定NAD(P)H-结合基元中的丝氨酸-脯氨酸二肽而不是甘氨酸-甘氨酸二肽。类似的取代被成功用于灭活红霉素ER而不会影响任何其它PKS功能(Donadio等,1993)。取代同时还导入了新的PinAⅠ限制性位点并消除了SgrAⅠ位点,以便于检测重组生物体中经改造的DNA。
在诱变的第一个步骤中,进行两个独立的PCR扩增,一个使用诱变引物SEQ ID NO:36和侧翼引物SEQ ID NO:38,另一个使用诱变引物SEQ ID NO:37和侧翼引物SEQ ID NO:39;第二步,将第一步反应的产物稀释100倍,合并后仅用侧翼引物SEQ ID NO:38和SEQ IDNO:39进行扩增;第三步,根据厂商说明(InVitrogen,San Diego,CA)将第二步PCR反应的产物克隆至质粒pCRⅡ中。以Van911-NheⅠ片段的形式切下突变的ER2结构域部分(跨越SEQ ID NO:1的碱基33424-33626),插入以取代克隆至质粒pBluescript SK-(Stratagene)中的粘粒3E11之3.5kb EcoRⅠ片段中的野生型Van911-NheⅠ片段(SEQ ID NO:1的碱基32162-35620)。然后将经突变的EcoRⅠ片段转移至接合质粒pDAB1523(图5),所述质粒是pOJ260的衍生物,其中含有玫瑰孢链霉菌的rpsL基因,该基因可赋予反向选择的氯霉素-敏感表型(Hosted& Baltz,1997)。使用Matsushima等(1994)的方法,将所得的含有突变EcoRⅠ片段的质粒由大肠杆菌S17-1(Simon等,1983)中接合至刺糖多孢菌菌株NRRL18538之自发链霉素-抗性衍生物SS15中。(本领域技术人员易于分离刺糖多孢菌菌株NRRL18538之自发链霉素-抗性衍生物)。通过使用经地高辛配基标记的探针(Boehringer Mannheim)进行Southern杂交,证明阿泊拉霉素-抗性接合后体含有野生型和突变形式的ER2结构域。它们也含有玫瑰孢链霉菌rpsL基因,因此,它们在含有150mg/L链霉素的BHI琼脂(Difco,Detroit,MI)上生长缓慢并且不能产生气生菌丝体。基于它们在含有150mg/L链霉素的BHI琼脂上生长并产生白色的气生菌丝体的能力,选择自发回复为链霉素抗性的回复体。Southern分析表明这些菌株不再含有玫瑰孢链霉菌rpsL基因或任何其它pDAB1523序列。一些菌株失去了整簇刺糖噻生物合成基因,包括ER2结构域以及pDAB1523。在其它菌株中,pDAB1523序列与突变的ER2结构域一起被切下,重新产生亲本基因结构。在第三种类型的链霉素抗性菌株中,pDAB1523与野生型ER2结构域一起被切下,后一位置上只剩下突变形式的ER2结构域。当第三种类型的菌株发酵时,可产生新的代谢物,通过使用乙腈∶甲醇∶2%醋酸铵(44∶44∶12)为流动相,在C18柱(ODS-AQ,YMC,Wilmington,NC)上进行液相层析即可将该代谢物与刺糖噻A分开。通过电喷射离子化和使用三联四极质谱仪(TSQ700,Finnigan MAT,San Jose,CA)的串联质谱术(Balcer等,1996)分析新的代谢物实体。预期其具有C18∶C19-无水刺糖噻A的特性,分子量为729.5道尔顿,并产生142道尔顿的forosamine片段。我们的结论是:修饰编码PKS结构域的DNA导致产生新的发酵产物。实施例6通过用鼠李糖生物合成基因转化NRRL 18538以改善刺糖噻A和D的产量
将含有鼠李糖生物合成基因的片段独自克隆至接合载体pOJ260(Bierman等,1992)中。所得质粒列于表21。
表21
质粒 | 基因 |
pDAB1632pDAB1634pDAB1633 | gttgdh+kreepi |
通过Matsushima等(1994)的方法,将各个质粒由大肠杆菌S17-1(Simon等,1983)中接合至刺糖多孢菌菌株NRRL18538中。选择并发酵可能含有通过同源重组整合至染色体中的质粒的阿泊拉霉素抗性接合后体(表22)。表22被鼠李糖基因转化的NRRL 15328衍生物中刺糖噻的产生
数值为平均值±95%置信限。
菌株 | 复制的基因 | A+D(μg/ml) | |
实验 1 | 实验 2 | ||
NRRL 18538NRRL 18538/1632-1NRRL 18538/1634-1NRRL 18538/1633-1 | 无gttgdh+kreepi | 344±39410±21351±27318±29 | 405±25418±38360±21315±18 |
在被gtt或epi转化或者被gdh和kre联合转化的NRRL 15328衍生物中,刺糖噻的产量没有一致的增加。
将含有gtt和gdh+kre基因的片段同时放在一个质粒中。分离出2个含有gtt,gdh和kre基因组合的质粒(pDAB1654和pDAB1655),通过Matsushima等(1994)的方法,将各个质粒由大肠杆菌S17-1(Simon等,1983)中接合至刺糖多孢菌菌株NRRL18538中。选择并发酵阿泊拉霉素抗性接合后体(表23)。表23被鼠李糖基因转化的NRRL 15328衍生物中刺糖噻的产生数值为平均值±95%置信限。
在被gtt,gdh和kre基因转化的NRRL 15328衍生物中,观察到刺糖噻的产量显著增加,这可能是由通过同时增加gtt和gdh基因产物(刺糖噻生物合成所必需的酶)的量而克服了NDP-4-酮基-6-脱氧-葡萄糖的限速供应所引起的(见图1)。提供较多的NDP-4-酮基-6-脱氧-葡萄糖中间体可使鼠李糖和forosamine的产量增加,因此将苷元转变为刺糖噻A+D的能力更强。与此假说一致的是,在NRRL 18538中,脱氧糖的供应限制刺糖噻的产生,很多forosamine合成或添加被阻断的突变菌株能将PSA积累至很高水平。还可制备更多的此类中间体,因为它仅需要一个脱氧糖,而相比之下刺糖噻A或D需要2个脱氧糖。
本发明并不限于含有本发明的刺糖噻基因的特定载体,还包括位于能将基因导入重组宿主细胞中的任何载体上的生物合成基因。
另外,由于遗传密码的简并性,本领域技术人员熟知制备编码与天然基因序列相同或功能上相同之活性的DNA序列的合成方法。类似地,本领域技术人员熟知修饰或突变基因序列以制备编码与天然序列相同或基本上相同之多肽活性的新序列的技术。因此,本发明还包括这些合成的突变体和经修饰的基因形式以及这些基因的表达产物。
上述所有专利和文献都列入本文作为参考。
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Broughton,Mary C
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Madduri,Krishnamurthy
Treadway,Patti J
Turner,Jan R
Waldron,Clive<120>刺糖噻杀虫剂生物合成基因<130>50489<140><141><150>US 09/36987<151>1998-03-09<160>39<170>PatentIn Ver.2.0<210>1<211>80161<212>DNA<213>刺糖多孢菌<400>1gatctccatg aagctcaacg taggcacgga cggtcaggtg gactgggtga tcgcccgcga 60cctgctggcc gacgggctga tcgccgaggc aggcgaaggc gatgtgcgga tcggccctcg 120acggggtttt ccggggttgg tcgtgatcga gatgagctcg ccgtcggggc aggcctcctt 180cgaggtgaat gctgaccagc ttgcggactt cttgaacgac acctacgacg tggtcgaacc 240tggtgatgaa caccggtgga tgaacgtcga cgaggtgctg agccagctgc tctcgccaac 300ctgtaatggc ccagctctcc cgaagcgccg cacgccaaag cgctggctgc gggacctggc 360ggcgctgaac accgccacgc tgtgtctccg agctccagct ggaccacgtc ggtgccgtgc 420gcccggctcg gtcaggccga aggtgctgat cttctccagg cgcgccatcg gcgcaggaag 480cgctgcttct gctcccgccg cagtaccgtc gtgtcatggc cacggacagc ttcgattcct 540cgaagctaca ggcggccgtg gcatcgagcg tcgcgtcgtg cgtctcggaa gtcagccgag 600acgtctacac gcacctgatt accgaggctc cgcagttgcg agccgatgag atcgtcctca 660gcattctacg gacgagtgtt gaggaaaata tcgccacatt gccgcacgtt ctcgaattcg 720agattccgtt gggatattcg ccgggtcctg ctgcggtgtt ggagtatccg cgacgactgg 780cgaaacattt ccatcaacgc gctgatcagg gccaaccgca tcgggcactt ccgcttcctg 840tagtgatgcc tcgacgagat ccgccgccaa tgcgccgacg aggccgtatc cgcagcgacc 900acgcaacgaa tgctcgcaac cagcttcggc tacatcgacc gcgtcacgga gcagatcgcc 960gaaacctacc agctcgaacg ggaccgctgg ctcctggcga cgggacggcc gtgaggtctc 1020tgcggcatcc gcatagcgtc ttctcccgct gaggcacatg aggtgttgcg cgcggtcgtt 1080tccggcagtc gcacggcatt cgtcctagct gcgggcaatt gagggagcga agatttagag 1140gagtgtggcc acgcggacca agccggcgag tgctcgggag cggctgtggg gcggccaggc 1200gatgactgtc gtcacgtccg gcgcgtctag aaccggtacg gcggcgaggc cttcgagcag 1260gttgacgcga ctggattcgg gcatgaccac ggtagtgcgg ccgagtgcga tcatttggaa 1320cagttgcgtc tggttgcgta cttccacgcc ggggccatct ggatagacgc cgtcggggcc 1380gggccagcgc gcaagcggga gatccggcag tgagctgaca tccgccatcc gtacatgggg 1440ctcgctggca agcggatgcg aggtcggaag aatggcgact tgttgctcgg tgttcagaat 1500ttcgatgtcg agttcggccg tcgggtcgaa gggttgatgc aacagcgcca cgtcggcccg 1560gccgtcatgc agcgttttct ggggctggga ttcgcagagc agcaggtcga cggccacggc 1620tcccggctcg gcggcgtacg cgtcgagcaa cttcgccagc agctcaccgg aggcgccggc 1680cttggcagcc aggactagcg agggctggct cgtcgcggca cgctgggtgc gtcgctcggc 1740tgctgccagc gcgccgagga tcgcccggcc ttcggtcagc agcattgccc cggcttcggt 1800gagcgagact ttgcggctgg tgcgttgcag caacacgact ccgagtcgtt gctcgagctg 1860ggcgatcgtc cgcgacagcg gcggctgggc gatgcccagg cgctgggcgg cccggccgaa 1920gtgcaactcc tcggcgactg caacgaagta ccgcaactcc cgcgtctcca tccgtcgagc 1980ctaccgctga ttcatatcag ctgggtatcg gtgtgagacc tagatggtgt tggttccccg 2040ccggtttcgg gccacgctag aaagcatgag cgaacagacg attgcactgg tcaccggcgc 2100aaacaaggga atcggatacg agatcgcggc cgggctcggc gcgctggggt ggagcgtcgg 2160aatcggggca cgggaccacc agcgcgggga ggatgccgtg gcgaaattgc gtgcggacgg 2220cgtcgatgcg ttcgcggtat ccctggacgt gacagacgac gcgagcgtcg cggctgctgc 2280ggctctgctc gaggagcgcg ccggccggct cgatgtgctg gttaataacg ccggcatcgc 2340cggggcatgg ccggaggagc cctcgaccgt cacaccggcg agcctccggg cggtggtgga 2400gaccaacgtg atcggcgtcg ttcgggttac caacgctatg ctgccgttgc tacgccgctc 2460cgagcgcccg cggatcgtca accagtccag ccacgtcgct tccctgacct tgcaaaccac 2520gccgggcgtc gacctcggcg ggatcagcgg agcctactca ccgtcgaaga cgttcctcaa 2580cgcgatcacc atccagtacg ccaaggaact cagcgatacc aacatcaaaa tcaacaacgc 2640ctgccccggc tacgtcgcga ccgaccttaa cggcttccac ggaaccagca cgccggcaga 2700cggtgccagg atcgccattc ggctcgccac gctgccagac gacggcccga ccggaggcat 2760gttcgacgac gccgggaatg tgccctggtg aggcgctcag tcggcgatgg tgcaatcgaa 2820gtcggagagg ctcgctgcga ccgggtacgc cgaacaacac ctgttcctgt gggtacggat 2880gtcggccttc gccgtctcgg tcattgacaa cctgtacttc gggcgccgtt accgccggtg 2940cgccgcggtt gcctggcgac actgggccag ccgtggctca ccggcggctt aggtcaggcg 3000tgggcggttg ccagcatggc gggtgcggct ttgcgtaggt cgggtaggcg catccggcgc 3060gggagccggt cgagttcttc gccgatggcc ggtgctttgg ggctgctcag gagccgaaca 3120cctcccagcc gcaggtgccg ggctgaaccg agtggttctc gtcggctcgg atcacaacgt 3180ctgccggaac agctgcggcg aggtggtcgc agattcgagg cgggatcgtc ctcggcgacc 3240ttgccgacga tcgcggctag ggcccagggc ttcgtcgacc tggttggcac ctagatcacg 3300acggtcaaaa cttgccggca tcagagacgatcgaagtgat cccgggtcac gtcggcttat 3360cggtcgagtg agtcccgggg cctgcccagc caggtcttgc gtcgttgttc cgggctcagt 3420tgcggattcc gacgaacagg cctcggccgt tcggtgctcc aggaaggtat tccgcgcgga 3480tccctgcgtc ttcgagcgcg gcggtgtact cgtcctcagt gaacagcgag aggatttcga 3540actctgtgaa gtcccggatc ccggtgggtt cggcgactgt gtagcggacg gtcatccggc 3600tcgtacggcc ctccaggacc gagtgcgata gccggctgat cacccgctcg ccgtggtgcg 3660cgacggctcc ggtgacgaac ccgtcgatga acttgtcggg aaaccaccag ggttcgatga 3720ccgcgactcc accaggggcc aggtgccggg ccatgttccg cgtcacgcgt cgcaggtcgt 3780caacggtccg catgtaagcc gcggtaaagc acaggcaggt gatgacgtcg aatggctcgc 3840cgaggtcgaa atcgcggatg tcaccgatgt gaatcggtac ctcagggact cgtctgatcg 3900cgatctcccg catcgcatcg gacagttcaa gccccgcgac cttcgcgtat tcggcacgga 3960atcgctctag gtgcgccccg gtcccacagg cgacgtcgag tagggactgt gcttcgggca 4020gcctggtgcg tacgagctgg actacttccc cggcctcggc tgcccagtcc cggccacgcg 4080cggagtggat cgcgtcgtag atgtcggcat gatctgggct gtataccgag gaggtttctg 4140cgaatgtgtc gctcacgcgc gacatcctca ctttcggagt ggtgatcttt ggctgatgtg 4200gtgttcgacg gccttctgga actcgtcagc caccgtgcgc acctcggcgt cgtcaaggct 4260tgggtgcagt ggtagcagga gtgttctgcg gcaggcgtcc tccgcagaag gcagcttgca 4320gtccgcgcgg tagatgggga ccttgtgcag gggcgggtag cggtagctcg tgtagatgcc 4380gcgttccagc atttgctgcg ccacctggtc gcggatctcc ggagccagct ggacccagta 4440gaagtagtgt gacgagacgt gcccatccgg tagcgtcggc ggtaggagga cacccggcac 4500atcggaaagc aaccggtcgt actgcgtagc gatttctcta cgcctgttga tgaattctgg 4560cagtttgcgc agctgcacgc tgccaagcgc tgccgtcatg tcgttcccga tcagccgctg 4620gccgatgtct tcgacgcgaa tatcccacca gcggttggaa gacttggccg aatcgaatcc 4680gctcatctgc tcaagaccgt ggtaggcgag tcgtcttgcg cggtgcgcca gctccggatc 4740cgccgcgtag aacatgtccc catccccggt gaccaggatc ttcatcgcat cgaaactcca 4800cgtggccagg tcaccaaagg ttccgcaagc ggtgccgtgc acggacgatg ccaccgcgca 4860ggcggagtcc tcgatgagca tgaggccctt ttcacggcag aaatcggcga tcgcggtgac 4920ttctcccggc gatcctccat agtggagcag caatacggcc ttggtcgccg gcgtgatggc 4980cctcgccaca tcatccagcg tggggttcaa cgtccggggg tcgacgtcgc agaacaccgg 5040gcgggcaccg gaggatgcga tggcgttggc cgccgccacg aagcttatcg aaggaagtac 5100cacgtcgtcg cctgggccga ggtcgagcac ctgcacggta aggaacagcg cggcagtccc 5160cgagttgagg aacacgacct gttcgggatc cactcccagg tggtgggcga attcggcctc 5220gaacgtccgg gtgcgcggcc cgagcccgat ccagttggag gcgaacacct ccgcgatcgc 5280gtcgagttct tcggtgccga ggatcggctg gtgcaggttg atcacgttgc tgaaatcctc 5340cgagatgccg ccatgctgga tgctaggaac tcttggccac gaattcagcg attgattcga 5400cgacgtagtc gatcatttgg tccgttatgc ctgggtagac gccgacccag aaggttcggt 5460cggtgacgat gtcgctgttg gtgagcgcgt cggcgatccg gtaccgcacc tgctcgaagg 5520ccgggtgccg ggtgatgtta ccgccgaaca gcagtcgggt gccgatgttg cgggattcca 5580ggaagttcac cagggcggca cgggtgaacc cggcgtccgc actgatggtg atcgcaaacc 5640cgaaccagct cgggtcgctg tgcggtgtgg ctaccggcag cagcaggccc ggcaacccgg 5700acagcccttc gcgcaaccgt cgccagttac ggcggcgtgc cgacccgaat gcggaaatct 5760tgctcaactg gctcagcgca agtgcggcct gcaggtcggt ggtcttgagg ttgtaaccga 5820cgtgggagaa cgtgtacttg tggtcgtagc ccggtggaag ggtaccgagg tggtagtcga 5880acctcttgcg gcaggtgttg tccacgccgg gctcgcacca gcaatcccgt ccccagtcac 5940gcagcgactc gatgatgcga gccaattcca ggctgccggt caacacgcag ccaccctcgc 6000cgctggtgat gtgatgggca ggatagaagc tgaccgttgt caggtcgccg aaggttccgg 6060tcagccgtcc ccggtaggtg gatcccaccg catcacagtt gtcttcgacg aggaacagct 6120cgtgttcttt tgcgatctcc gcgatttcgt cagcggcgaa ggggttgccc agggtgtgcg 6180ccagcatgat ggctcgcgtc cgttccgtga cggcggcctt gatgcggtct ggcgttgcgt 6240tgtaggtgcc cagttccacg tcgacgaata ccgggacgag tccgttttgg accgccggat 6300tgatcgtcgt ggggaagccg accgccgcag tgatcacttc gtcgccgggc cgcagtcgtg 6360cctcgccgag tttgggggag gtaagcgaac tcagtgccag gagattggcc gacgaaccgg 6420agttgacgag atgagccttg cggaggccga agaagcgggc gaactcgctc tcgaatcgcc 6480gtgcattccc gcccgcggcg atccggagct ccagcgcggc ttccaccagt gccacccggt 6540cgtcctcgtc gagcacggcg cccgatggcc ggatcggcgt cgatccagcc acgaaggtcg 6600gggattcctg ttcgcggtgg taatcgcgta cggatgccaa tatccggtcc ttggcatccg 6660gcaccatctc agtagcggta gcgcaagtgt cgtcacacga agtcactctg gcgcgccctt 6720tccccagcgc tctggttttc cggctctgca tgcaggcgac gatcagtctt cgcgccttgc 6780cttcaggaga tgagcgatgc ccgtggcgaa tcgcgttatg acgtcccagc gggacagtgt 6840gctgtctcgg cgccttacac cttcctgccc tggttcgatg cggtgcggga catcaggaca 6900gcggagcaag gagaagcgct cattgactca gaaatcctcg atctacccgg cacacccgac 6960tcggtagagc ccaggctagc gggaacgacc tgctcgcgct tgtcaagatc gctaccatca 7020cctggaaggc ctaagatttg gcttgcgaaa gcggcgtttc ccgggggata tcagagattt 7080ctgtgattct tggcatgctt cccgggtgtt caattgcgat cggagagttc atgcgtgtcc 7140tgttcacccc gctgccggcg agttcgcact tcttcaacct ggtgccgttg gcgtgggcgt 7200tgcgtgccgc ggggcacgag gtccgtgtcg ccatctgccc gaatatggtg tcgatggtca 7260ccggagcagg actcaccgcg gttcccgtcg gcgacgagct cgacctcatc tccttggcgg 7320ccaagaacga actcgttctc ggcagcgggg tctcgttcga cgagaagggg cggcatccgg 7380aactcttcga cgagctgctg tcaatcaact ccggcagaga cacggacgcc gtggagcaac 7440tccaccttgt ggatgaccga tcgctggacg atctcatggg gttcgccgag aaatggcagc 7500ctgatctcgt tgtgtgggac gctatggtgt gttcggggcc agttgtggcg cgagcgctcg 7560gcgcacgaca cgtgcggatg ctcgtcgccc tcgatgtgtc ggggtggctg cggtccggtt 7620tcctcgaata ccaggaatcg aagccgcctg agcagcgcgt cgacccgctc gggacgtggc 7680tgggagcgaa gctcgccaag ttcggagcca cgttcgatga agagatcgtg acgggccaag 7740cgaccataga tccgattcca tcctggatgc gcctgcctgt ggacttggac tacatctcga 7800tgcgtttcgt gccgtacaac ggtccggcgg tgttgccgga gtggttgcgc gaacgaccga 7a60cgaagccgcg cgtctgcatc acgcgcgggc tgaccaagcg gcggctgagc agggtgaccg 7920aacagtacgg ggagcaaagt gaccaggaac aagcaatggt ggaaaggttg ttgcgcggcg 7980cggccaggct cgacgtcgag gtgatcgcca ccttgtctga cgacgaagta cgggagatgg 8040gggagttgcc ctcgaacgtc cgggtccacg aatacgtacc gctcaacgaa ctgctggagt 8100cgtgttcagt gatcatccat catggctcga cgacgacgca ggaaaccgcc acggtcaacg 8160gcgtaccgca gttgattctc cctgggacct tctgggacga atctcgtagg gcggagctcc 8220tagccgatcg gggagccggt ctggtcctcg accccgcgac gtttaccgaa gacgacgtgc 8280gaggtcagct ggcccgcctg ctcgacgagc cgtcgttcgc tgccaacgcg gcgctgatcc 8340gccgtgaaat cgaggaaagt cccagcccgc acgacatcgt tccacgtctg gaaaagctag 8400ttgccgaacg tgagaaccgc cgcactgggc agtctgatgg ccatccgtga gcaacgtgtg 8460gccggaaaca tggacgccgg ggtttggcag gtgttcatcg ctgttgcgtc gactcggatt 8520ccgccgtgac cgggacgatg ccaggcgagt cccgaagtca gattcttgtc cagaatcgtc 8580caatggggtg ttgatctccc cagaggtttg cgctccaacc gatttccgac gaggatcgtg 8640gcgcccgctg agcaacgact accgtgcggt cgagacatac cgctgtgcgc caggagcgaa 8700ggtgggttgc ccgatcaccg tgctggtggt agatgccgag ccgaaggtca ccttggatga 8760ggcggaagcc tggcgagagc acaccgaggc cgtggccgac gtccgtgtct tctccggcgg 8820gcatttcttc atgaccgaac gccaggacga ggtgctcgcg gtccttacgg gcggatcgct 8880tcgatgatcc tcgccaggcc gctggaccag accgcgacgc ccctgggagc cggcgtgcac 8940atcgtcacgg cagtgaggga ttgggcatga gcagttctgt cgaagctgag gcaagtgctg 9000ctgcgccgct cggcagcaac aacacgcggc ggttcgtcga ctctgcgctg agcgcttgca 9060atggcatgat tccgaccacg gagttccact gctggctcgc cgatcggctg ggcgagaaca 9120gcttcgagac caatcgcatc ccgttcgacc gcctgtcgaa atggaaattc gatgccagca 9180cggagaacct ggttcatgcc gacggtaggt tcttcacggt agaaggcctg caggtcgaga 9240ccaactatgg cgcggcaccc agctggcacc agccgatcat caaccaggct gaagtaggta 9300tcctcggcat tctcgtcaag gagatcgacg gcgtgctgca ctgcctcatg tcagcaaaga 9360tggaaccggg caacgtcaac gtcctgcagc tctcgccgac ggttcaggca actcggagca 9420actacacgca ggcacaccgt ggcagcgttc cgccctatgt ggactacttc ctcgggcggg 9480gccgcggccg cgtgctggta gacgtgctcc agtctgaaca ggggtcctgg ttctaccgga 9540agcgcaaccg gaacatggtg gtggaagtcc aggaggaagt gccagtcctg ccagacttct 9600gctggttgac gctcggccag gtgctggctc tccttcgtca ggacaacatc gtcaacatgg 9660acacccggac ggtgctgtct tgcatcccgt tccacgattc cgccaccgga cccgaactag 9720ccgcctcgga ggagcccttc cgacaggcgg tggccaggtc gctctcgcac ggcatcgatt 9780cgtcgagtat ctccgaggcg gtcggttggt tcgaggaagc caaggcccgc taccgcttgc 9840gggcaacgcg cgttccgctg agcagggtcg acaagtggta ccgcaccgat accgagatcg 9900cccaccagga cggcaagtac ttcgcggtga tcgcggtgtc ggtgtccgcg accaatcgtg 9960aggtcgccag ctggacgcag ccgatgatcg aaccgcgaga acaaggtgag atcgcactgt 10020tggtcaagcg gatcggcgga gtgctgcacg gtttggtcca cgctcgggtg gaggctgggt 10080ataagtggac tgcggaaatc gctcccacgg tccagtgcag tgtggccaac taccaaagca 10140ccccgtcgaa cgactggccg ccgttcttgg acgacgtgct caccgccgat cccgaaaccg 10200tgcggtacga atcgatcctg tccgaagaag gcggtcggtt ctaccaggcg cagaacaggt 10260accggatcat cgaggtgcat gaggacttcg cggcacgacc tcccagcgac ttccggtgga 10320tgactttggg acagttgggc gagctgctcc ggagcaccca cttcttgaac atccaggcgc 10380gcagcttggt cgcctccctg catagcttgt gggcgttggg gcgatgacca gctcgatgcg 10440aaagccggtg cgcatcggtg tgctcgggtg cgcttccttc gcgtggcgac ggatgctgcc 10500cgcgatgtgc gacgtggccg aaacagaggt ggtggcggtg gcgagccgtg atccggcgaa 10560agccgaacgg ttcgcagcgc gattcgaatg cgaggcggtg ctgggttacc agcggctcct 10620ggagcggccg gacatcgatg ccgtctacgt gccgttgccg cctggcatgc atgcagagtg 10680gatcggcaag gcgcttgagg cagacaaaca cgtgcttgcg gagaaaccgc tgacgacgac 10740ggcgtccgac accgctcgcc tggtcgggct ggccaggagg aagaacctgc tgctgcggga 10800gaattacctg ttcctccacc acggccggca cgacgtggtc cgcgacctgc tgcaatccgg 10860ggagatcggt gagctccggg agttcaccgc cgtgttcgga attccgccgc ttcccgacac 10920ggacatccgc tatcgcaccg aactcggtgg cggagcgttg ctggacatcg gtgtctatcc 10980cgcccgtgcc gctcggcact ttctcctcgg tccgctcacg gttctcggcg caagctcgca 11040cgaggcccag gagtcgggcg tcgacttgtc gggcagcgtg ctgctccaat cggaaggtgg 11100caccgttgcc cacctcggat acggtttcgt gcaccactac cgcagcgcgt acgagctgtg 11160ggggagtcgt gggcgaatcg tcgtcgaccg ggcgttcacg ccgcccgccg agtggcaggc 11220cgtgatccga atcgagcgga agggcgttgt cgacgagttg tccttgccag cggaagatca 11280ggttcgcaag gcggtcaccg ccttcgcacg cgacatcaga gcagggacag gcgtggacga 11340ccctgcggtg gccggagatt cgggcgaatc gatgatccag caggccgcgc tggtggaggc 11400gatcggtcag gcccgtcggt gcgggtccac atagccgccc ggcatccgcg ggtagtagtt 11460cgcctcgaag cctgaccggg catccggaag ccagcgggga agccgctgga gaggctcacc 11520gccatccgct cacctggcat ctcgcggacc gctgatcgcg gacggctcgg agaagtgctc 11580gtcgaaccac gagacgacca ctcgcgagct ggccagggcg gcgggaaagt gagccaatcc 11640ggagagcgga tgccaccgca ctggcgtacc cgccgcgcgg tagctgtccc ggagtcgctc 11700gccgaatgcg aacggaacga tctcgtcgtc cgtgctgtgg tagacgagcg tggggaccac 11760cgggccaccg ttcctacctg cgacgctttc ggccagtcgt gcgcgccatc gaggttgctc 11820gaaaaggccg gaagtgtcga ggaagtcgct cagctcgcgg ccgaggaagc gggtgacgag 11880ctccggtgca ccgagctcgc gcacttgatc aacggcggta cgacccgctt cggtgagaag 11940ctcgtcgaat ggcagatcgg ggtaggcagc ggcatgcccg accaggccgg ccagcaccgg 12000cccggtgaac accccgtcat ttcggtggat gatgtccagc agatcgatcg gcaccgcacc 12060tgcggccgca gcgcggattc gcagttcagg tgcgtaggtg gggtgcagtt cgccggcgaa 12120ggccgacgct tgcccaccct gcgcatagcc ccagatgccg accgggcagt cggtcgtcag 12180gccggagccc ggtagccgtt gcgcagcgcg ggcggcatcg agcatggcgt gtccctgcgc 12240cctgccgacg gtgtaggtgt gggttccagg agtaccgagg ccttcgtagt cggtgatgac 12300cacggcccac ccgcggtcga gggccacggc gatcagctcg gtctccggct cggttccggt 12360tcgaagcagg tacgacgggg caacttggct accgaggccg tgggtgccca ctgcgaaagt 12420gatgatgggg cgatcttcgc gcggccacgg gatgttcggc accagaacgg tgccggagac 12480ggcgttcggc atgccaaggg cggagttgga ccggtagagg atttgccagg ccttggctgc 12540gacgggttcg cccgtgccgc gcagtgccga gacgggccgg gccctgagga gcgtgcccgg 12600gacacccggc ggtagcggcg tcggcggtcg gtagaaggga tcatccgcgg gtgcccgcag 12660atcgtcgccg accaggctgg cgtgctcgga ggccatcagg actgcttctt tcgagcctgc 12720aggagcatga aacccatgct ttcctcgttt ctggcgtaat ccggatgttt ccggtattcc 12780gcaaccgcgg cgatcagctg tgctggtccc ggtccgtgct tcgccgcgat gtctcccaag 12840tagcgttgct ggtaggtgcc gacagccgca ggctcgacgc cggcgagctc atcgagtttc 12900cggagcaact cgtcgacgta ccaggagacc atgcacctgg tctgtgccgt gaggtcggtg 12960acttcgagaa tctcgaaccc ggcttcgctg accagcgccg tgaagctgtt caaggtatgg 13020gcggtcgtgc ccgtccaaac cgccgcgtac tcttccggga gtcgaacccg agtgatgatg 13080tctccgagga cgaaccggcc gccgggttcc aggattcggt ggacctcgcg gatcgcggcg 13140gcctggtcca cgatctgcac gacggactgc atcgcccatg cggcctgaaa gaaaccgtcc 13200gggtagggca gctgggcgcc gtcgactaga tcgaactcaa gactgccggc cagtccggtc 13260tcgttggcga gcctggtggc ggcggcgaga tgctgggcgt tcacggtgat tccggtgact 13320cgaacgccgc tggcgcatgc cgcacggact acgggctgcc cattgccgca gcccaggtcg 13380aacaggtgcg ctccgggacg gagcgcggcc ttgtcgatga acaggtcggt cagttggtcg 13440gcagcatccg accacggtgt ggcaccggca tcctcccgat acccgcccgc ccagtaaccg 13500tggtgcaggg gacgcccgtg cgccaacgca tcgaagatgg actccacctg atccgcggtc 13560ggaaatgcct gtgtgttcgc ccctctgctg ttcactcgtc ctccgcgctg ttcacgtcgg 13620ccaggtgcaa tatgtcgtcc agactccttg gcacccaagc aggaacgccg ccttcggcgt 13680tgacgccttt ctccaggaac gcgatgttgt ggtaggtgtg gaggccgacc aaattgcgtt 13740ccaggtagct cggctcgtac gagcccgcat gcggctgctc ctcgtgctga acgccttcca 13800acaggttctt gagcaggctg accgtggtgc cgggtgcggc cgggcactgc gcctgcccgc 13860cgaatccggg agcataggtc gtccacagat cctcgatcac gtatacgcca ccgctgcgca 13920accgggggaa cagcgtttcc agggatgtgc gcacgtgtcc gttgatgtgg ctgccatcgt 13980cgatgatgat gtcgaacggt ccgtacttgt cgtcaacggc ggccagctcc tcgggcttgc 14040tctggtcggc gcggacggtg cagagcctct gctggtcgag gaaggacttg tcgaaaacgt 14100ccatcccgaa cacgaggccg cggtggaagt agcgcttcca catcttcagg gattcgccgc 14160cgccaccgtc gaagttgtag ccaccgacac cgatctccag gatgcgcacc gggcgatcac 14220ggaactcgcc gaggtgtcgc tcgtatagcg gggtgaacca gtgcaggccg ccccacttgt 14280ccgtgcggta gtgggaggcg agcaagttga ggtcgggacg tcggtgcccg cagccggcga 14340ccactgcgga gatggcctgg aagccatcgg acagttccga cggaccgggt atcgaaccgg 14400atgtggtggt tcggaggaag ttggtgctcc gggcgccgac ggccctggga gctcctgggc 14460cgaacaactc ggcgatgaga tcggtgagct cgtaaccgat ccgcagcggg acgtctccga 14520ccggtcgttg ctcggccttg atcagctcac cggactgtag cgtcaggacg aagtcaacgg 14580tctcgcctcg gtgggtgatc tggaccgcga cctcggtccg ttcgatgtcg ggggccggtt 14640ccgcgcggaa gaggatctcg tcgatcagca cgggtgcgat cctggcgagt ccgagttcgg 14700tggtcaggtc ggccaggctc gccgcactgg atccggcggc gaggatgatg cgttccacgg 14760tttcgatctc gtgcgttgtg gacatcgtga tgagctcctc atggctgacc gggtgaaagc 14820cgtgccggcg gtttgatcga caggccgtgc tggaagatgt tctgcggatc ccaccgcgct 14880ttggcccgct gcagccgcgg gtagttgtct ttgtagtaca ggtcgtgcca ggcaacaccg 14940gaggtgttcc acaatggatc ggccaagtcg gtgtccgggt agttgatgta ggagccgtcg 15000acacgggtac ctggcaccgg aactccgccg gtttcggcgt acatctcgcg gtagaaaccg 15060cgaatccagg tcagatgccg ctcgtcctcg gcgggctccg accagttcgt gacgaacagc 15120gctttgagaa ccgagtcgcg ctgagcgagt gcggtggccg acggagccac ggcattcgcc 15180ataccgccgt aaccgagcag caacagcgcc gccgcagggt tgtcgtatcc gtagacggtc 15240agccgccggt aaaccgtggc tagttgagct tcggacagcc cggtgcgcaa gtaggcggct 15300ttgaccttgg tccgttgcat gcccggttcg ccgccttcgg cgatcgcccc ggccacctgg 15360gtcgatcgca accacggcag ggtttcccgc agcccttcgg ctggagtcac gccgacctgg 15420gcgttgatcg ccgacaggtg ttcggccagg gtgcgttccg cgttcggatc cgtgccgtcc 15480aggtgaacgt tcagcgtgac gtagccagct tgccggtgtg cgcagacgag cgtgctgaac 15540aacccgagtt gcgtggattc aggcgcgctg tgctgctcgt accaattgcc gaagttctgt 15600aggagcacgg cgaatgactg ctctgtcagt tcgtgccacg gccagtggaa cgatcggagc 15660agcactgtcg cgggcggccg tggcaggagc tctgcggcgt cggtgctgac cacgtccggc 15720gttcggagcc aaaacctggt gacgatcccg aagttgccgc caccgccacc ggtgtgcgcc 15780caccacaagt cgtgaccggc gcccgtggag ttccggtcgg cctcgacgat gtgcacttca 15840ccggcctggt cgaccacgac gacctcgacg ccttgaaggt agtcgacgac cgaaccgaat 15900cggcgcgaca gcgggccgta tcccccgccg aggatgtgcc cgcctgcgcc caccccggga 15960catgcgccgg tcgggatcgt cacgccccag ttcttgaaca gggttcggta cacctgcccg 16020agggcggcgc ccgcctcgat cgcgaatgcc ccgcgcgtgc tgtcgtagta cacgcggttg 16080agctcggaga ggtcgacgag cactcggatc gccgggtccg caacgagatt ctcgaagcag 16140tgcccgccgc tgcggacccc tacccgcctg ccggtgcgca cggcgtcggc gacggcgtgc 16200acgacgtctt cggcggagct ggcgatgtgg atgcgttcgg gttttccggt gaaacggggg 16260ttgtgcccga cgacgaggtc cggataacga ggatcgtcgg gctcgacggt gatctctgtt 16320cctggggttc gacgattcat gggtgccggg tcatggaatt cgggcaccgc ccctcctttt 16380ctgactggtc cactttgttc gcccgcagcc gagatcatct acgcgtccgg gtgattatct 16440gtgtgtttca gctcatacgt gaaacccggt cgcctccgcc ggctctactt tgtggatcga 16500tatcgcggtg cgcatggtgc cgtatgcgct ggaaccgaaa aggtgatgac ttaccatgag 16560tgagatcgca gttgccccct ggtcggtggt ggagcgtttg ctgctcgcgg cgggtgcggg 16620cccggcgaag ctccaggaag cagtgcaggt ggccggactg gacgcggtgg ccgacgccat 16680cgtcgacgaa ctcgtcgtac gctgcgatcc gctgtcgttg gacgagtcgg tgcgaatcgg 16740cctggagatc acttctggcg ctcagctggt ccggagaacc gttgagctcg atcacgcagg 16800cctgcggctc gcggcggtcg ccgaagcagc tgctgttctc cggttcgacg cggtggatct 16860gctggaaggg ctcttcggcc cggttgacgg caggcggcac aacagccgtg aagtccgctg 16920gtcggacagc atgacgcagt tctcgcccga ccagggcctc gccggcgcgc agcgcctgct 16980ggcgttccgg aacagggtgt ccaccgcggt gcacgccgtg ctggccgcag ccgccaccag 17040gcgcgcggac ctcggtgcgc tggcagtccg ctacggatcc gacaaatggg cggacctgca 17100ctggtacacc gaacactacg agcaccactt ctcccgattc caggatgccc cggtgcgagt 17160gttggaaata ggaatcggtg gttatcacgc acccgaactc ggtggtgctt cgctgcgcat 17220gtggcagcgg tacttccggc gaggtctcgt ttacgggctg gacattttcg agaaagccgg 17280gaacgaaggg caccgagtgc gaaagctgcg aggtgaccag agcgatgcgg aattcctgga 17340agacatggtg gcgaagatcg gcccgttcga cattgtcatc gacgacggca gccatgtcaa 17400cgaccacgtc aagaaatcct tccaatccct gtttccgcac gtccgcccag gtggtttgta 17460cgtcatcgag gatctccaga cggcgtactg gcccggctac ggcggtcgcg atggggaacc 17520cgcggcccag cgcacctcga tcgacatgct caaagaactg atcgacggcc tgcattatca 17580ggagcgcgaa tcgcggtgcg ggaccgagcc ctcctacacg gaacggaacg tggcggccct 17640gcacttctac cacaacctgg tattcgtgga gaaagggctc aacgctgaga ctgccgcgcc 17700ggggttcgtg ccccggcaag cgctcggcgt cgagggcggc tgagccgttc accagctgcg 17760gcgccagtag gcgcccgtgc cgtcgatgtc gtggatgggt tccgtgatcc cgagttccgc 17820gcggaacccc ttcaccgcgt cctggcagga cggcagaaaa tagtcgtcga tgatgacgaa 17880tccgcccggc gagagcttcg ggtacaggtt ccgcaatgag tccattgtgg attcgtagag 17940gtcgccgtcg agtcgtagca cggcgagttc ctggatgggg gcggtgggca aggtgtcccg 18000gaaccagccg gggaggaacc tgacctgttc gtcgagcagc ccgtagcggg cgaagttctg 18060ccggacggtc tcaagcgata cgccaagcac gtcgttgtac tcgtgcagcg ccatagcctg 18120gtccgcttgg tggtcttgcg cagagctttc cggcattccc tggaaggaat ccactaccca 18180gacggtacgt ccggtatctc cgaatgcctg gagaaccgcg cgcatgaaga tgcatgcgcc 18240gccccgccag acaccggtct cggcgaaatc cccgggaaca ccgtctgcga gcacggcttc 18300cacgcagtgc tggaggttgt ccagccgctc cagaccgatc atcgtgtgcg cgacagttgg 18360ccagtccgtg cctttggccc gagcggcctg cctgtagtcg gtgttgtcct gccaggcgtt 18420cggatgcggc cgatcactgt aaatcgtgtt ggtgagtacc ttcttgagca ggtccaggta 18480cagcgcgttc tgggagggca tcggttctcc ggatccagct gttctcgggt gactagttca 18540tcaggcacgg atggccgcag tgttctccag tgtccgcacc agcgcggcgg gatggggcat 18600ggccgtgatc tcgtcgctga gtttgattgc cgcagaagcg aagccggtgt cgccgagcac 18660cgttgcgatt gagtcggtga actgttcgtg gtcggactgg gcctgctcat ccggcaagca 18720gatgcccgcc ccggcagcgg cgaggttgcg cgcgtagtcg aactggtcga agtactgggg 18780aagcacgagt tgcgggatgc cgagtcgggt cgcggtgaat gccgttcccg agccgcccgc 18840gcagatgacc agctcgcagg tacgcaggaa caggttgagc gggaccgatt cggcgatccg 18900ggcgttgtcg ggtaggtcgg tgagaagtgc ccggtgctcg gggggaacgg cgatcacggc 18960ctcgacgccg ggcaactcgg tggcagccgc tactgcgcgc agcagcggag ccggcccggt 19020ggcgttcagc accatgcggc ccatgcagat gcagacccgc cgtgctgagg tgcgcgccgc 19080gccccatgcc gggaatgcgc cgcttccgtt gtacggcacg tactggaccg gtgcgccttg 19140cggcgcgtcg cttgcttgca ggctcggcgg acagggatcg aggatgagct cgggagtggg 19200caggccggtc agtccgtggt gccggcacac cgggtcaagc aactcgtggg ctcgatcgct 19260gaaggggcct gcggtggggt cgactcccca gcggtgcagc acgaccggca ggtcgagcaa 19320tccgccgagc acccggccga tcagcgcgca gacgtcgacc aacagcactg acggtcgcca 19380ggcctcggcc agtcgaaggt attcggggag ctgatcgagc gagctttgcg cgacattgga 19440cgcggtctgc tcccacagtt gccggcctgc ctcggtgtcg cgctgaccga acgccggatt 19500gggaaagcgc agctgcgtgg ttccacccgt atcgccggtc ctgtcgttcc cgcggatccc 19560ggccgtggtg agacctgcac catgcgcggt cgcctgcagc tctggtggtg cggcgatcag 19620gacctcgtgc ccggatgctt gcagcgccca gcacagcggc accattgcca tgagatgcgt 19680cggatagggc aagggaacga cgagtacgcg catacttcgg accccagtct ctttcccccg 19740attagcgcag cagcccctac tcccattggc caggatttgg aaaatgcgct gcgtatgtcg 19800atcgccgttg acgtccaacg gacttccggc ggcaacaata gtgtgtcacg gcaggaatgt 19860cacgcgacca tcgaagatct ttgggtcgcc gcacctggtt tcacgcgaac gagtgaaatg 19920cgcgagctcc gctcgatcgg ggtgggccgg acctgtacgg tgatcaccgt tggttctgcg 19980gggattcatg gggaagattt gcgctggctg tttgcctcct ggccggatag ttatagtcgg 20040taccgccgca tgcggcggta accgcgaatt aactgacggc tagtttgccg tcttttctct 20100ctgtgtgttt cctgctcggt tccagaaaat tacgagaagg tgaacgttgc agagatcagg 20160cataccggtg ttgccaggtg gcgcaccaac atcgcagcag gttgggcaga tgtatgacct 20220ggtcacgccg ttgctgaact cggtcgcggg cggcccctgc gccatccacc acggctactg 20280ggagaacgac gggcgggctt cctggcagca ggccgccgac cggctcaccg accttgtcgc 20340cgaacggacc gtgctcgatg gcggcgttcg actgctcgat gtggggtgcg gtaccggaca 20400accagcgctg cgcgtcgcgc gcgacaacgc gatccagatc accggcatca ccgtcagcca 20460ggtgcaagtg gccatcgccg ctgattgcgc acgcgaacgc ggactaagcc accgggtgga 20520cttctcgtgc gtcgatgcca tgtccctgcc gtacccggac aatgctttcg acgccgcctg 20580ggccatgcag tcgctgttgg agatgtccga accggaccgt gccatccggg aaatccttcg 20640agtactcaaa cccggtggca tcctcggcgt caccgaggtc gtcaaacgag aagcgggcgg 20700cgggatgccg gtgtccgggg acaggtggcc gaccggcctt cggatctgcc tggctgagca 20760acttctggaa tcgctgcgtg cagcggggtt cgagatcctc gattgggagg acgtgtcgtc 20820gaggacccgg tacttcatgc cgcagttcgc cgaagagctc gctgcgcacc agcacgggat 20880cgcggacagg tacgggccgg ctgtcgccgg ctgggccgcc gcggtctgcg attatgagaa 20940atatgcccac gacatgggct atgcgattct gacggcgcgg aagccggtcg gctgagggcg 21000cgccgcaatt cgatgacgtt catgcgccgt gtcggagaat cgccggtggc ggcgccagca 21060gaggctgaac ttactggtgg tgtgtccagg aatcggaggg gcagtaccga atgagcgaag 21120ccgggaacct gatagccgtc atcggactgt cctgccgcct accccaggcg cctgacccgg 21180cttccttctg gcggttgctg cgcaccggaa cggacgccat caccacggtc ccggaagggc 21240ggtggggcga cccgttgcct ggtcgggatg cgcccaaggg cccggaatgg ggtggtttcc 21300tggctgatgt cgactgcttc gatcccgagt tcttcgggat ctcgccgcga gaagcggcaa 21360ccgtggatcc ccagcagagg ctggctctgg agctcgcctg ggaggcactc gaagacgccg 21420gtatccccgc cggcgagctg cgcggtactg ccgccggtgt gttcatgggg gcgatctctg 21480acgactacgc cgccctgctg cgcgagagcc cgccggaagt ggctgcgcag taccgcctca 21540ccggcaccca tcgaagcctg atcgccaacc gcgtgtccta tgtgctcggc ctgcgcgggc 21600caagcctgac ggtggattca ggtcagtcct cgtccctggt cggcgtgcat ctcgccagcg 21660agagcctgcg acggggtgag tgcacgatcg cactcgccgg cggcgtgaac ctcaacctgg 21720ccgccgagag caacagcgct ctgatggact tcggcgcgct ctccccggac ggtcgctgct 21780tcaccttcga tgtgcgggcg aacggttacg tccgtggtga gggcggcggc cttgtcgtgc 21840tgaagaaggc cgatcaggcg cacgccgatg gcgaccggat ctactgcctc atccgcggca 21900gcgcggtcaa caacgatggg ggcggtgccg ggctcaccgt tccggcggcg gacgcccagg 21960cggagctgct gcgccaggca taccggaacg cgggcgtcga cccggccgcc gtgcagtatg 22020tcgagctcca cggcagcgcg accagggtcg gggatcccgt cgaagcagca gccctcggag 22080ctgtcctggg ggcggcgaga cggcccggcg acgagctgcg tgtggggtcg gcgaagacca 22140acgtcggcca tctggaagca gcggcgggcg tcaccgggtt gctgaagacc gcactcagca 22200tctggcaccg cgaactgccg ccgagtcttc atttcaccgc ccccaacccg gaaatcccgc 22260tggacgaatt gaacctacgc gtccagcgtg atctgcggcc gtggccggag agcgaggggc 22320cgctgctggc cggcgtcagc gccttcggaa tgggaggcac gaactgccac ctggtgctct 22380ccggcacgtc ccgggtggag cgacggcgca gtggacccgc tgaggcgacc atgccgtggg 22440tcttgtcggc cagaacaccg gtcgcattgc gtgcgcaggc ggcgcgcttg cacacgcacc 22500tcaatacggc cggtcaaagt ccgttggacg tcgcctactc actggcgacc actcgatccg 22560cgctaccgca ccgggccgcg ctggtcgcgg acgacgaacc gaaactgctc gccgggttga 22620aggccctcgc tgacggcgac gacgcgccca cgctgtgcca cggcgcgact tccggcgagc 22680gggcagcggt cttcgtcttt cccggacagg gcagccagtg gatcgggatg ggtaggcagc 22740tgctcgaaac ctccgaggtt ttcgcggcgt cgatgtcgga ctgcgccgac gcattggcgc 22800cacacctgga ttggtccctg ctggatgtgc tgcgcaacgc ggccggcgct gcgcaccttg 22860accacgacga tgtcgtccag cccgcgctgt tcgccatcat ggtctcgctc gcggagctct 22920ggcgttcgtg gggcgtgcgt ccggtggcgg tcgtcgggca ctcgcagggg gagatcgcgg 22980cggcctgcgt cgccggggcc ctgtccgtcc gcgatgccgc cagggtggtg gcggtgcgca 23040gcaggcttct gacggcgctg gccggcagtg gcgcgatggc ctcgttgcag catcccgccg 23100aagaggtgcg gcaaatcctg ttgccctggc gcgatcggat cggcgtggcg ggggtgaacg 23160gaccgtcgtc gaccctggtg tcaggggacc gggaggcgat ggcggaactg ctggccgagt 23220gcgcagaccg agagctccgg atgcgccgga ttcccgttga atacgcctcc cattcgcctc 23280acatcgaggt tgtccgggat gagctgctgg ggctgttggc gccggtcgaa cccaggacgg 23340gaagcatccc gatctattcg acgacgaccg gggacctgct ggaccggccg atggacgccg 23400actactggta ccgcaacctt cgtcaaccgg tgctgttcga agcggccgtc gaggccctgt 23460tgaagcgggg gtacgacgca ttcatcgaga tcagcccaca cccggtgctg actgcgaaca 23520tccaggaaac cgccgtgcga gcagggcggg aggtagtggc gctcgggaca ctccgccgcg 23580gcgaaggtgg catgcggcag gcgctgacgt cgctggccag agcacacgta cacggagtgg 23640ccgcggactg gcacgcggtc ttcgccggta ccggggcgca gcgggtcgac ctgccgacgt 23700acgcctttca gcgacagcgc tactggctgg acgcgaagct tcccgacgtc gccatgcccg 23760agagcgacgt gtcgacggcg ttgcgggaaa agctgcggtc ttcgccgagg gcggacgtgg 23820actcgacgac cctcacgatg atccgggcac aggcagccgt ggtcctcggc cactccgatc 23880cgaaagaggt ggacccggat cggacgttca aggacctggg cttcgattcc tcgatggtgg 23940tcgagctgtg cgaccgccta aacgccgcca caggtctgcg actcgcaccg agcgtcgttt 24000tcgactgtcc tacgccggac aagctcgccc gccaggtacg gacgtrgttg ttgggcgagc 24060cggctcccat gacgtcacac cggccggact ccgatgcgga cgagcctatc gccgtgatcg 24120ggatgggctg tcggtttccg ggtggggtgt cctcgcccga ggagttgtgg cagttggtcg 24180ccgctgggcg ggacgtcgtg tccgagttcc cggctgaccg aggttgggac ctggagcgtg 24240cggggacatc gcacgtgcgc gccggcgggt tcttgcatgg cgccccggat tttgaccccg 24300ggttcttccg gatttcgccg cgcgaggcgt tggcgatgga tccacagcag cggttgctgc 24360tggaaatcgc ctgggaagca gtcgaacgag gcgggatcaa cccgcagcac ctgcacggaa 24420gtcaaaccgg ggtcttcgtc ggcgcgacct ccctggacta cgggccacgc ctgcacgaag 24480cgtccgagga ggcggccggg tacgtgctca ccggcagcac cacgagtgtg gcgtcgggtc 24540gggttgcgta ttcgttcggg ttcgagggcc ctgcggtgac ggtggatacg gcgtgttcgt 24600cgtcgttggt ggccctgcat ttggcgtgtc agtcgttgcg ttcgggtgag tgtgatctgg 24660cgttggccgg tggtgtgacc gtgatggcca cgccggggat gttcgtggag ttttcgcggc 24720agcgtggttt ggcgccggat gggcggtgca agtcgttcgc ggaggccgcc gacggcaccg 24780gctggtccga gggtgctggc ctggttctac tggagcggtt gtcggatgcc cggcggaatg 24840ggcatgaggt gctggcggtt gttcgtggta gtgcggtgaa tcaggacggt gcgtcgaatg 24900gtttgaccgc gccgaatggt tcgtcgcagc agcgggtgat tgcccaggca ttggcgagtg 24960cggggttgtc ggtgtccgat gtggatgctg tggaggcgca tgggacgggc acgcggcttg 25020gtgatccgat cgaggcgcag gcgctgatcg ccacctacgg ccagggccgg cttccggaac 25080ggccattgtg gttgggctcg atgaagtcga acatcggtca cgcgcaggca gctgcgggga 25140tagccggcgt catgaagatg gtgatggcga tgcggcacgg gcagctaccg cgcacgttgc 25200acgtggatga gccgacttct ggggtggatt ggtcggcggg gacggttcaa ctccttacgg 25260agaacacgcc ctggcccggg agtggtcgtg ttcgtcgggt gggggtgtcg tcgttcggga 25320tcagtggtac taacgcgcac gtcatcctcg aacagccccc gggagtgccg agtcagtctg 25380cggggccggg ttcgggctct gtcgtggatg ttccggtggt gccgtggatg gtgtcgggca 25440aaacacccga agcgctatcc gcgcaggcaa cggcgttgat gacctatctg gacgagcgac 25500ctgatgtctc ctcgctggat gttgggtact cgctggcgtt gacacggtcg gcgctggatg 25560agcgagcggt ggtgctgggg tcggaccgtg aaacgttgtt gtgcggtgtg aaagcgctgt 25620ctgccggtca tgaggcttct gggttggtga ccggatctgt gggggctggg ggccgcatcg 25680ggtttgtgtt ttccggtcag ggtggtcagt ggctggggat gggccggggg ctttaccggg 25740cttttccggt gttcgctgct gcctttgacg aagcttgtgc cgagctggat gcgcatctgg 25800gccaggaaat cggggttcgg gaggtggtgt ccggttcgga tgcgcagttg ctggatcgga 25860cgttgtgggc gcagtcgggt ttgttcgcgt tgcaggtggg cttgctgaag ttgctggatt 25920cgtggggggt tcggccgagt gtggtgttgg ggcattcggt gggcgagttg gcggcggcgt 25980tcgcggcggg tgtggtgtcg ttgtcgggtg cggctcggtt ggtggcgggt cgtgcccggt 26040tgatgcaggc gttgccgtct ggcggtggga tgctggcggt gcctgctggt gaggagctgt 26100tgtggtcgtt gttggccgat cagggtgatc gtgtggggat cgccgcggtc aacgctgcgg 26160ggtcggtggt gctctctggt gatcgggatg tgctcgatga ccttgccggt cggctggacg 26220ggcaagggat ccggtcgagg tggttgcggg tgtcgcatgc gtttcattcg tatcggatgg 26280atccgatgct ggcggagttc gccgaattgg cacgaaccgt ggattaccgg cgttgtgaag 26340tgccgatcgt gtcgaccttg accggagacc tcgatgacgc tggcaggatg agcgggcccg 26400actactgggt gcgtcaggtg cgagagccgg tccgcttcgc cgacggtgtc caggcgctgg 26460tcgagcacga tgtggccacc gttgtcgagc tcggtccgga cggggcgttg tcggcgctga 26520tccaggaatg tgtcgccgca tccgatcacg ccgggcggct gagcgcggtc ccggcgatgc 26580gcaggaacca ggacgaggcg cagaaggtga tgacggccct ggcacacgtc cacgtacgtg 26640gtggtgcggt ggactggcgg tcgttcttcg ccggtacaag ggcgaagcaa atcgagctgc 26700ccacctacgc cttccaacga cagcggtact ggctgaacgc gctgcgtgaa tcttccgccg 26760gcgacatggg caggcgtgtc gaagcgaagt tctggggcgc cgtcgagcac gaagatgtgg 26820aatcgcttgc acgcgtattg ggcattgtgg acgacggcgc tgctgtggat tccctgagaa 26880gcgcccttcc ggtgttggcc ggttggcagc gaacccgcac caccgagtcc attatggatc 26940agcggtgtta ccgaattggc tggcggcagg tagccggact cccgccgatg ggaactgttt 27000tcggtacctg gctggtcttc gcgcctcatg gctggtccag cgaaccggag gtggtggact 27060gcgttacggc actgcgggca cgtggtgcct cggtggtgtt ggtggaagct gatcccgacc 27120cgacctcctt cggcgaccgg gtacgaaccc tgtgttcggg ccttccggat cttgttggcg 27180tgttgtcaat gttgtgcttg gaagaatcgg tccttccggg attttctgcg gtgtcacggg 27240gttttgcgtt gaccgtggag ttggtgcggg ttttgcgggc agctggtgcg actgcccggt 27300tgtggttgct gacgtgtggt ggcgtgtcgg tgggagatgt accggttcgt ccagcgcagg 27360ccctggcgtg ggggttgggg cgtgttgtgg ggttggagca tccggactgg tggggcggct 27420tgatcgatat tccggtcttg ttcgacgaag acgctcaaga gcggttgtcg attgtgctgg 27480caggtctcga tgaggacgag gtcgcgatcc gtcctgacgg catgttcgcg cgtcggttgg 27540tacgccacac tgtctcagct gatgtgaaga aggcgtggcg ccccagggga tcggtgctgg 27600tgacgggcgg cacgggtggt ttgggggcgc acgttgctcg ctggctggcc gacgccggag 27660ccgaacatgt ggcgatggtg agtcgacgcg gcgagcaggc accgagtgct gagaagttgc 27720ggacggaact ggaggatctg ggtacccggg tgtcgatcgt gtcatgcgat gtgaccgatc 27780gcgaggcgct cgccgaagtg ctgaaagccc ttccggctga aaacccgttg accgcggtag 27840tgcatgcggc aggcgtgatc gagactggtg atgcggcggc aatgagcctg gctgatttcg 27900atcacgtgtt gtccgcaaag gtggccggtg ccgcgaatcc ggatgccttg ttggccgatg 27960tggaattgga cgcgttcgtc ttgttctcat cggtgtcagg agtttggggc gctgggggac 28020acggggctta cgcagcggcg aatgcctatc tggatgcgct cgcggaacag cgtcggtcgc 28080gagggctggt cgcgactgcg gtggcctggg ggccgtgggc cggcgagggc atggcctccg 28140gagaaacagg agaccagctg cgccgatacg gcctttcccc aatggctccg cagcacgcca 28200tcgccggaat ccggcaggcc gtggaacagg acgaaatttc cctggtagtg gccgatgtcg 28260attgggcacg tttcagcgcg ggattgctgg cggctaggcc gcggccgctg ctgaacgaac 28320tggccgaggt caaggaactc ctcgtcgatg cccagcccga ggcgggagtc cttgccgacg 28380cgtcgttgga atggcggcag cgattgtccg cggcaccgag gccgacacag gaacagctga 28440tcctggagct ggtacgcggc gaaaccgctc tggtgctggg acaccccggg gcagcggccg 28500ttgcatcgga acgagccttc aaggacagcg gattcgactc gcaggccgcg gtcgaactcc 28560gcgttcggct caatcgagct accggcctcc agttgccatc gacaattatc ttcagccatc 28620ccacgcctgc ggaactggct gcggagctgc gggcgaggct tcttcccgag tccgcaggag 28680caggcattcc cgaggaggac gaggcgcgaa tcagagcggc actgacgtcg atcccgttcc 28740cggccttgcg cgaggcaggc ttggtgagtc cgctgctcgc acttgccgga cacccggtcg 28800actccggtat ctcctcggac gatgcggccg cgacctcgat cgatgcgatg gatgtagccg 28860gcctcgtcga agcagcgctg ggcgaacgcg agtcctgaga ccgccgacct gggagatgac 28920ggtgaccacc agttacgaag aagttgtcga ggcactgcga gcatcgctca aggagaacga 28980acgcctccgg cgcggcaggg atcggttctc cgcggagaag gacgatccca tcgcgatcgt 29040ggcgatgagt tgtcgttatc ccggtcaggt ctcctcgccg gaggacctgt ggcaactggc 29100tgccggcggt gtggacgcga tctccgaagt tccgggggat cgcggatggg acctggatgg 29160cgtgttcgtt ccggactccg atcgtcctgg cacgtcgtat gcctgcgcgg gcggttttct 29220tcagggcgtg tcggagttcg acgcgggttt cttcgggatt tcgccgcgtg aggcgctggc 29280gatggatccg cagcagcggt tgctgctgga agtcgcgtgg gaggtcttcg agcgggctgg 29340gctggagcag cggtcgacac gcggttcccg cgttggcgtg ttcgtcggca ccaatggcca 29400ggactacgcg tcgtggttgc ggacgccgcc gcctgcggtg gcaggtcatg tgctgacggg 29460cggtgcggca gcggttcttt cgggccgggt tgcgtattcg ttcgggttcg agggtcctgc 29520ggtgacggtg gatacggcgt gttcgtcgtc gttggtggcg ttgcacctgg cggggcaagc 29580actgcgggcc ggtgagtgcg accttgccct tgccggtggc gtcacggtga tgtcgacgcc 29640gaaggtgttc ctggagttct cccgccaacg gggtctcgcg ccggatgggc ggtgcaagtc 29700gttcgcggcg ggtgcggatg gcactggatg gggtgagggt gccggactgt tgttgctgga 29760gcggttgtcg gatgcccggc ggaatgggca tgaggtgctg gcggttgttc gtggtagtgc 29820ggtgaatcag gacggtgcgt cgaatggttt gaccgcgccg aatggttcgt cgcagcagcg 29880ggtgattacc caggcgttgg cgagtgcggg gttgtcggtg tccgatgtgg atgctgtgga 29940ggcgcatggg acgggcacgc ggcttggtga tccgatcgag gcgcaggcgc tgatcgccac 30000ctacggccgt gatcgtgatc ctggccggcc gttgtggttg gggtcggtca agtcgaacat 30060cggtcatacg caagcggcgg cgggtgtggc tggtgtgatc aagatggtga tggcgatgcg 30120gcacgggcag ctgccacgca cgttgcacgt ggaatcgccg tcgccggagg tggattggtc 30180ggcggggacg gttcaactcc ttacggagaa cacgccctgg cccaggagtg gtcgtgttcg 30240tcgggtgggg gtgtcgtcgt tcgggatcag tggtactaac gcgcacgtca tcctcgaaca 30300gcccccggga gtgccgagtc agtctgcggg gccgggttcg ggttctgtcg tggatgttcc 30360ggtggtgccg tggatggtgt cgggcaaaac acccgaagcg ctatccgcgc aggcaacggc 30420gttgatgacc tatctggacg agcgacctga tgtctcctcg ctggatgttg ggtactcgct 30480ggcgttgaca cggtcggcgc tggatgagcg agcggtggtg ctggggtcgg accgtgaaac 30540gttgttgtgc ggtgtgaaag cgctgtctgc cggtcatgag gcttctgggt tggtgaccgg 30600atctgtgggg gctgggggcc gcatcgggtt tgtgttttcc ggtcagggtg gtcagtggct 30660ggggatgggc cgggggcttt accgggcttt tccggtgttc gctgctgcct ttgacgaagc 30720ttgtgccgag ctggatgcac atctgggcca ggaaatcggg gttcgggagg tggtgtccgg 30780ttcggatgcg cagttgctgg atcggacgtt gtgggcgcag tcgggtttgt tcgcgttgca 30840ggtgggcttg ctgaagttgc tggattcgtg gggggttcgg ccgagtgtgg tgttggggca 30900ttcggtgggc gagttggcgg cggcgttcgc ggcgggtgtg gtgtcgttgt cgggtgcggc 30960tcggttggtg gcgggtcgtg cccggttgat gcaggcgttg ccgtctggcg gtgggatgct 31020ggcggtgcct gctggtgagg agctgttgtg gtcgttgttg gccgatcagg gtgatcgtgt 31080ggggatcgcc gcggtcaacg ctgcggggtc ggtggtgctc tctggtgatc gggatgtgct 31140cgatgacctt gccggtcggc tggacgggca agggatccgg tcgaggtggt tgcgggtgtc 31200gcatgcgttt cattcgtatc ggatggatcc gatgctggcg gagttcgccg aattggcacg 31260aaccgtggat taccggcgtt gtgaagtgcc gatcgtgtcg accttgaccg gagacctcga 31320tgacgctggc aggatgagcg ggcccgacta ctgggtgcgt caggtgcgag agccggtccg 31380cttcgccgac ggtgtccagg cgctggtcga gcacgatgtg gccactgttg tcgagctcgg 31440tccggacggg gcgttgtcgg cgctgatcca ggaatgtgtc gccgcatccg atcacgccgg 31500gcggctgagc gcggtcccgg cgatgcgcag gaaccaggac gaggcgcaga aggtgatgac 31560ggccctggca cacgtccacg tacgtggtgg tgcggtggac tggcggtcgt tcttcgccgg 31620tacgggagcg aaacaaatcg agctgcccac ctacgccttc caacgacagc ggtactggct 31680ggtgccatcg gattccggtg atgtgacagg tgccggtctg gccggggcgg agcatccgct 31740gttgggtgct gtggtgccgg tcgcgggtgg tgacgaggtg ttgctgaccg gcaggatttc 31800ggtgcggacg catccgtggc tggccgaaca ccgggtgctg ggtgaagtga tcgttgcggg 31860caccgcgttg ctggagatcg ccttgcacgc gggggaacgt cttggttgtg aacgggtgga 31920agagctcacc ctggaagcac cgctggtcct gccggagcgc ggggcgatcc aggttcagct 31980gcgagtgggc gcgcccgaga attccggacg caggccgatg gcgctgtatt cacgccccga 32040aggggcggcg gagcatgact ggacgcggca cgccacgggc cggttggcgc caggccgcgg 32100cgaggcggct ggagacctgg ccgactggcc ggctcctggc gcgctgccgg tcgacctcga 32160cgaattctat cgggacctcg cagagcttgg gctggagtac ggcccgatct tccaagggct 32220caaggcggcc tggcggcaag gggacgaggt gtacgccgaa gccgcgctgc cgggaacgga 32280agattctggt ttcggggtgc atccggcact gctggacgcg gctctgcacg caacggctgt 32340ccgagacatg gatgacgcac gcttgccgtt ccagtgggaa ggtgtgtccc tgcacgccaa 32400ggccgcgccg gctttgcggg tccgcgtggt cccggctggt gacgatgcca agtccctgct 32460ggtttgtgat ggcaccggtc gaccggtgat ctcggtggac cgactcgtat tgcggtcggc 32520tgcggcccgg cggaccggtg cgcgccgaca ggcccatcaa gctcggttgt accggttgag 32580ctggccaacg gttcaactgc cgacatccgc tcagccaccg tcctgcgtgc ttctcggcac 32640ctcagaagtg tccgctgaca tacaggtgta tccggacctc cggtcgttga cggctgcgtt 32700ggatgccggt gccgaaccac ccggcgtcgt catcgcaccc acgccccccg gcggtggacg 32760aacagcggat gtccgggaga cgactcggca tgcactcgac ctggtacaag gctggctttc 32820cgatcagcga ctcaacgaat cccgattgct cctggtgaca cagggagcag tggccgtgga 32880gccgggcgaa cccgtgaccg atctggcgca ggccgcgctc tggggactgc tgcggtcgac 32940gcagaccgaa caccctgatc gcttcgtcct cgtcgatgtg cctgagcccg cgcaactcct 33000ccccgcgctg ccgggggcgc tggcctgcgg cgaacctcag cccgcgccgc gacgtggcgg 33060cgctcatgcg cccagactgg ctggactggg cagcgatgac gtcctgcccg tgccggacgg 33120caccgggtgg cgattggagg ccacgcgccc gggaagcctg gatgggttgg cattggtgga 33180cgaaccgacg gccacggcac cgctgggtga cggtgaggtc aggattgcga tgcgcgcggc 33240cggggtgaac ttccgggatg cgctcatcgc gctcggtatg tatcccggtg tggcatcgct 33300gggcagtgag ggcgccgggg tcgtggtgga gaccggcccc ggcgtcaccg gcctggcacc 33360cggcgaccgc gtgatgggaa tgatcccgaa ggcgttcggg ccgctcgcgg tcgccgacca 33420tcgcatggtg acgaggattc ccgctggttg gagcttcgcg cgggccgcat cggtgccgat 33480cgtctttctc accgcctact acgcgctggt tgatctcgcc gggttgagac caggggagtc 33540gttgctggtt cattcggccg ccggtggggt ggggatggcc gcgatccaac tcgccaggca 33600cctcggtgca gaggtgtacg ccaccgctag cgaggacaag tggcaagccg tggagctgag 33660ccgagaacac ctcgcttcgt cgcggacgtg cgatttcgag cagcagttcc tcggggcaac 33720cggcggacgc ggcgtcgacg tcgtgctcaa ctccctcgcc ggggagttcg ccgatgcgtc 33780tctgcgaatg ctgccgcgcg gtggccgttt cctggagttg gggaagacgg atgttcgtga 33840ccccgtcgag gtcgccgatg cgcatccggg cgtgtcttac caggctttcg ataccgtaga 33900ggcaggcccg cagcgaatcg gcgagatgct tcacgagctg gtggagttgt tcgagggacg 33960cgtgctggag cccctgcctg tcacggcttg ggacgttcgg caggcgcccg aggcgctacg 34020gcacctgagc caagcgcggc atgtgggaaa gctggtgctc accatgcctc cggtgtggga 34080cgccgcaggc acggttctgg ttaccggcgg aacgggagca cttggcgcag aggttgcccg 34140gcacctcgtg atcgagcgcg gggtgcgaaa cctggtcctc gtcagcaggc gcggtcccgc 34200agccagtggc gctgctgagc tcgtggcgca actgacggcc tacggtgccg aggtttcctt 34260gcaggcttgc gatgtcgccg atcgtgagac cttggcgaag gtgcttgcca gcatcccgga 34320cgagcatccg ttgaccgccg tggtgcacgc ggctggtgtt ctcgacgacg gagtgtccga 34380atcgctcacc gtggagcggc tggaccaggt tctgcgcccg aaggtcgatg gcgcgcggaa 34440tctgctcgag ctgatcgacc cggacgtggc cctcgtgttg ttctcgtcgg tgtcgggtgt 34500gctcggcagc ggtgggcagg gtaactacgc ggcggccaac tccttcctcg acgcattggc 34560gcagcaaagg cagtcgcgcg gcctaccgac gagatcattg gcctgggggc cctgggcgga 34620acatggcatg gccagcacct tgcgcgaagc cgagcaggat cgattggcgc gatctgggtt 34680gctgccgatc tcgaccgagg aggggttgtc ccagttcgac gccgcgtgcg gcggcgcgca 34740taccgtggtg gcgccggttc gattcagccg cttgtccgac gggaacgcga tcaagttctc 34800cgtcctgcaa ggtttggtcg ggccgcatcg cgtcaacaaa gcggcgactg cggatgatgc 34860cgagagcctc cggaaacggt tgggacgctt gccggatgca gaacaacatc ggattctgct 34920ggacctcgtc cgcatgcatg tggcggcagt gctcggattc gccggttctc aggagatcac 34980cgcggacggc acgttcaagg tgctgggctt cgactcgttg accgtggtcg agttgcgcaa 35040ccggatcaac ggggcgacgg ggctgcgact gcccgccacc ctggtgttca actacccgac 35100gccggatgcg ctcgccgcgc acctcgtcac cgcgctgtcc gcagaccgcc tggccgggac 35160attcgaggaa ctcgacaggt gggcggcgaa cctgcccacg ctggccaggg atgaggccac 35220gcgggcgcag atcaccaccc ggctacaggc gatcttgcag agcctggcgg acgtgtccgg 35280cggaaccggc ggcggctccg tgccggaccg gctcagatcg gccacggacg acgagctttt 35340ccaactcctc gacaacgatc tcgaacttcc ctgatgcctc agccggagcc ttcgcaactt 35400cctggaggga aacgccacat gtcgaatgaa gagaagctcc gggagtactt gcggcgtgcg 35460ctcgtggatc tgcaccaggc gcgcgagcgg ctgcacgagg cggagtcggg agagcgggaa 35520cccatcgcga tcgtggcgat gggctgccgg tacccgggtg gggtgcagga cccggaaggg 35580ctgtggaaac tggtcgcctc cggtggcgac gccatcggtg aattccccgc tgatcgtggt 35640tggcacctcg acgagctcta cgatcccgac ccggatcagc ccggaacctg ctacacccgg 35700cacggcggct tcctccacga cgccggcgag ttcgacgcgg gattcttcga catcagcccc 35760cgtgaggcgc tcgcgatgga cccgcagcag cggctgctgc tggaaatctc ctgggagacc 35820gtcgaacccg ctgggatgga cccgaggtcc ttgcggggga gccgcaccgg ggtgttcgcg 35880ggattgatgt acgagggcta tgacaccggc gcccaccggg caggagaagg tgtcgaaggc 35940tatctcggaa ccggcaatgc gggaagcgtc gcctctggtc gggttgcgta tgcgttcggg 36000ttcgagggcc cagcggtgac ggtagacacg gcgtgctcgt cgtcgttggt ggcgctgcat 36060ttggcgtgtc agtcgttgcg gcagggcgag tgtgatctgg cgctggccgg tggagtgacg 36120gtgatgtcga cgccggagag gttcgtggag ttctcccgtc agcgtggtct cgcaccggat 36180gggcggtgta agtcgttcgc ggcggctgcg gatggaaccg gttggggtga gggtgccggt 36240ttggtgttgc tggagcggct gtcagacgcc aggcggaacg ggcatcgggt actggcggtt 36300gttcgtggta gcgcggtgaa tcaggacggt gcgtcgaacg gattgacggc cccgaacggg 36360ctggcccagg agcgggtcat tcagcaggtg ctcacgagtg cggggctgtc ggcgtccgat 36420gtggacgctg tggaggcgca tggaacgggt acgcggcttg gtgatccgat cgaggcgcag 36480gctctgatag ccgcctatgg acaggatcgg gaccgggacc ggccgctgtg gttggggtcg 36540gtcaagtcca acatcggtca tacgcaggcg gctgcgggcg tcgctggtgt gatcaagatg 36600gtcatggcga tgcggcacgg ggagctgccg cgcacgttgc acgtggacga gccgaattcg 36660cacgtggact ggtcggctgg tgcggtccga gtcctgaccg agaacatccg ctggccaggg 36720acgggtacgc gccgcgctgg agtgtcgtcg ttcggggtaa gcggtaccaa cgcacacgtc 36780atcctcgaac acgacccgct cgccgtgacc gagaacgagg aagcagcgca gtccccagca 36840cctgggatcg tgccctgggc gttgtccggg cggtcgtcga cggcgctgcg ggcccaggcc 36900gaacggctgc gcgagctgtg cgagcagacc gatcccgacc ccgtcgatgt cggtttctca 36960ctggccgcca cgcgcacggc ttgggagcac cgagcggtgg tgcttggtcg ggacagcgct 37020acgttgcgct ccgggcttgg cgttgttgcc agcggtgaac cagcggtcga tgtcgttgag 37080gggagcgtcc tggacggcga ggtcgtcttc gtcttccccg gtcagggctg gcagtgggcc 37140ggtatggcag tcgacctgct ggacgcttcg ccgacgttcg cgcgccacat ggacgagtgc 37200gccaccgcgc tgcggaggta cgtggactgg tcgttggtcg acgtgctgcg cggagcggag 37260aactccccac cgctggaccg ggtggacgtg ctccagcccg cgtccttcgc ggtgatggtg 37320tcgctcgccg aggtgtggcg ttcctacggg gtgaggccgg cggccgtcgt cggccacagt 37380caaggcgaaa tcgccgcggc ctgcgcagcc ggggtgctgc cgctggagga tgcggccagg 37440cttgtcgcat tgcgcagcag agcgttgaag ggactttcgg ggcggggtgg catggcgtcg 37500ctggcctgcc ctgcggatga ggtcgcggca ttgttcgcgg gatcgggcgg ccgtctggaa 37560gttgcggcga tcaacggccc gcgatcggtc gtggtgtccg gcgatctgga agcggtggac 37620gaactgctgg cagagtgcgc tgaaaaggac atgcgtgcac gccgtatccc cgtcgactac 37680gcctcgcatt cagcgcacgt ggaggtggtt cggagcccgg tgctggcggc cgccgccggg 37740gtgcgacacc gggacggcca ggtgccgtgg tggtcgacgg tgatcggcga ctgggtggat 37800ccggccaggc tggacggcga gtattggtat cggaacctcc ggcagccggt ccggttcgaa 37860cacgccgtgc agggcctggt cgagcgggga ttcggcctgt tcatcgaaat gagtgcgcat 37920ccggtgctga ccacggcggt cgaggaaacc ggtgcggagt cggagaccgc cgtggccgcg 37980gtaggtacct tgcgacgtga ctcgggcggc ctccggaggt tgttgcattc gctggccgag 38040gcgtacgtgc gcggcgccac cgtggactgg gccgtggcgt tcgggggcgc gggccgacgg 38100ctggacctgc cgacctaccc gttccagcgc cagcggtact ggctggacaa gggagctgcc 38160tccgacgagg ctcgtgcggt ctcggacccg gcggcgggct ggttctggca agccgtggcg 38220cgccaagacc tgaaaagcgt gtccgatgcc ctcgatctcg acgccgacgc accgctgagc 38280gcaacacttc cagccctgtc cgtctggcac cgtcaggaac gagaaagggt cttggcagac 38340ggttggcggt accgagtcga ctgggtacgg gtggccccgc agccggtccg gagaacgcgg 38400gaaacctggc tcctggtcgt tcccccgggc ggcatcgagg aagcgctggt cgaacggctg 38460acggatgcgt tgaacacgcg agggatcagc accctgcgcc ccgacgtgcc accggcggcg 38520accagtggcg aactcgcaac cgaactccgc gccgcagccg acggtgaccc ggtgaaggca 38580atcctgtcgc tcaccgcgtt ggacgagcga ccccaccccg aatgcaagga cgtcccgagc 38640gggattgcct tgctgctgaa cctggtcaag gcgctcggtg aagccgacct cagaattcct 38700ctgtggacca tcacgcgtgg tgcggtcaag gcaggccccg cagatcggct gctgcgcccg 38760atgcaggcgc aagcatgggg tctggggcga gtagccgcac tcgaacaccc cgagcgctgg 38820ggtgggctga tcgacctgcc ggattcgctg gacggcgacg ccctcacgag gctgggcgaa 38880gcgctcacca acggcttggc ggaagaccaa ctggcgattc gccagtcggg cgtgctggcc 38940cggcgactgg tacccgcccc ggcgaatcag cccgctggac gtaagtggcg cccccgaggg 39000agcgcgctga tcacgggcgg actcggcgcg gtgggcgcac aggtggcgag gtggttggcc 39060gaaatcggag ccgagcgaat cgtgctcacc agtcgacggg gcaaccaagc agcaggcgcc 39120gccgagctgg aagccgaact ccgggccctt ggagcgcaag tgtccatcgt ggcttgcgac 39180gtgaccgatc gtgccgagat gtccgcacta ctggccgagt tcgacgtcac cgcggtgttc 39240cacgcggccg gagtcggtcg gctgctgccg ttggcggaga ccgaccagaa cggcctggcc 39300gaaatatgcg cggcgaaggt ccgcggcgct caggtgctgg acgaactgtg cgacagcacc 39360gatctcgatg ccttcgtcct gttctcctcg ggtgccgggg tatggggcgg gggcggtcag 39420ggcgcttacg gcgcggcgaa cgcattcttg gacacactcg ccgaacaacg ccgagcacgc 39480ggtctgccgg caacctcgat ctcctggggc agttgggccg gcggcggcat ggccgacggc 39540gcggcgggcg aacacctgcg gcgacgcggg atacgtccga tgccggcggc gtcggccatc 39600ctggctctgc aggaagtact tgaccaggat gagacgtgcg tgtcgatcgc tgatgtggac 39660tgggaccgat tcgttcccac gttcgccgcg actcgcgcca cccggttgtt cgacgaagtg 39720ccggcggcga gaaaggcgat gcccgcgaat gggccggcag aaccaggcgg ctcgccgttc 39780gcccgcaatc tcgcggagct gccggaagcc caacgacgcc acgaactggt ggatctggtg 39840tgcgcccagg tggcaaccgt gctcgggcac ggcagtcgcg aggaagtcca gcccgagcgg 39900gcgttccgcg cgctcgggtt cgactccctc atggcggtgg atctgcgcaa tcgtttgacc 39960accgccaccg ggttgcgcct gccgaccaca accgtcttcg 40000actacccgaa tccggccgcc ttggccgctc acctgctcga ggagctggtg ggtgatgtcg 40060cgtcggctgc ggtgaccgct gccagcgcgc ccgcgagtga cgaaccgatc gcgatcgtcg 40120cgatgagctg ccggtttccg ggtggcgcgc actcgccgga agacctgtgg cggctggtcg 40180ccgccggcac ggaggtgatc ggcgagttcc cctccgaccg gggctgggat gcggaaggcc 40240tttacgatcc ggatgcttcc aggcctggaa cgacgtatgc gcggatggcg ggattcctct 40300acgacgccgg tgagttcgat gccgacctgt tcggcatcag cccacgtgag gcgttggcga 40360tggatccgca gcagcggttg gtgctcgaaa tcgcctggga agccctcgaa cgggccggaa 40420tcgatccgtt gtccttgaag ggcagtgggg tcggcacgta catcggcgct ggaagccgtg 40480ggtacgcgac ggatgtgcgg cagtttcccg aggaggcgga gggctacctg ctgacgggta 40540cctcggccag tgtgctgtcg ggtcgggtcg cgtattcgtt tggtttcgag ggtcctgcgg 40600tgacggtgga tacggcttgt tcgtcgtcgt tggtggcgtt gcatctggcg tgccagtcgt 40660tgcgttcggg cgagtgtgat ctggcgttgg ccggtggtgt gaccgtgatg tcgacgccgg 40720agatgttcgt ggagttctcc cgtcagcgcg gtttggcgcc ggatgggcgg tgcaagtcgt 40780tcgcggagag cgcggacggc accggctggg gcgaaggcgc gggcctgttg ttgctggagc 40840ggttgtcgga cgcccaccgg aatgggcatc gggtgttggc ggtggttcgt gggtcagcgg 40900tgaatcagga cggcgcctcg aacggactgg cggcgccgaa cggtccgtcg cagcagcggg 40960tgatcaacca ggcactcgcg aatgcggctc tttcggcgtc cgatgtggat gcggtggagg 41020cacatggcac cgggaccagg ctgggtgatc cgatcgaggc gcaggcattg atcgcaacgt 41080atgggcaggc ccgggagcgg gatcggccct tgtggctggg gtcggtcaag tcgaacatcg 41140gtcatacgca ggccgcggcg ggtgttgccg gtgtgatcaa gatggtgatg gccatgcggc 41200acgggcagct gcccgcctcg ctgcacgcgg atgagcccac gtcggaggtc gattggtcgt 41260cgggggcggt ccggctcctc gccgaacagg taccttggcc ggagtctgac cgtgttcgtc 41320gggtgggggt ttcgtcgttc gggatcagcg gcaccaacgc acatgtgatc ctcgaacaag 41380ctacgaatgc gccagatagt acagcggaga cggacaaaac agaatccgga tctactgtcg 41440atattccggt cgttccctgg ttggtgtcgg gaaagacgac ggattccctg cggggacaag 41500ccgaacgagt cttgtctcag gtcgagtccc ggccggagca gcgttcgctg gatgttgcct 41560actcgcttgc ttctggccga gccgcgctgg atgaacgcgc tgtcgtgctg ggtgcggacc 41620gcggtgagct ggttgctgga ctggcggcgt tggccgccgg tcaggaggct tctggggtga 41680tcagcggaac tcgtgcttct gctcggttcg ggttcgtgtt ctcggggcag ggtggtcagt 41740ggttggggat gggcagagcg ctctactcga agtttccggt gttcgctgct gcgtttgatg 41800aggcttgcgc cgagttggag gcacatctgg gggaagaccg ccgggttcgg gatgtggtct 41860tcggttccga tgcgcagctg ctggatcaga cgctgtgggc gcagtcgggt ctgttcgcgc 41920tgcaagccgg cctcttgggg ctgctgggtt cgtggggcgt tcggccggat gtggtgatgg 41980ggcattcggt cggggagttg gccgccgcgt ttgcggctgg cgtgttgtcg ttgcgggatg 42040cggctcggtt ggtggccgcg cgcgcccggt tgatgcaagc cctgccctct gacggcgcga 42100tgttggcggt ggctgccggt gaagaccttg ttcggccatt gctggccggt cgggaggagt 42160ccgtgagcgt cgccgcgctc aatgcccccg gttcggtggt gttgtcgggc gatcgggagg 42220tgctggccag catcgtcggc cggctgaccg agctccgagt ccggacgcgg cgcttgcggg 42280tctcccatgc ttttcattcg caccggatgg acccgatgtt gggcgagttc gcccagatcg 42340ccgagtctgc ggagttcggt aagccaacga caccgcttgt gtcgacgttg acgggtgagc 42400tcgacagagc cgcggaaatg agcacaccag ggtattgggt gcgccaggcg cgtgaacccg 42460tccgtttcgc cgacggtgtc caggccctgg cagcgcaggg cataggcacg gtcgtcgagc 42520tcggcccgga cggaacgctg gcggcactgg ttcgggagtg tgcgaccgag tccgatcggg 42580ttgggcggat ttcgtcgatc ccactgatgc gcagggagcg ggacgagacc cgttcggtga 42640tgacagccct ggcgcatctc cacacccgtg gtggtgaggt ggactggcag gcgtttttcg 42700ccggtaccgg cgctaggcag ctcgagttgc caacgtatgc cttccaacga cagcactact 42760ggatcgagtc cagtgcgcgg ccagcacgcg accgcgcaga catcggcgag gtggcggaac 42820agttctggac cgcggttgac caaggcgatc tggcaacgtt ggtcgccgct ctggatcttg 42880gggcggacga cgacacatgc gcatcgttga gcgatgtatt gccggcgttg tcctcctggc 42940gaagcggact ccgcaaccgt tcgctcgtcg attcctgccg gtaccgaatc agttggcatt 43000cctctcggga ggtgccggcc ccgaagattt ccggtacctg gctgttggtc gtgcccggtg 43060ctgcggatga cggattggtc acggctttga cgagttcact ggtcggaggc ggcgccgagg 43120tcgtccggat cggcctgtcc gaagaggacc cgcaccgcga ggacgtcgca cagcggctgg 43180ccaatgcgct gacggatgcc ggtcaactcg gtggcgtgct ttcgctgttg gggctcgatg 43240aatcgcctgc tccgggattc tcctgcttgc caactggttt cgcgctgact gtgcagcttc 43300tgcgggcctt gcggaaggcc gacgtcgagg cgcctttttg ggcggtgacg cgcggcggcg 43360tcgcgttgga agatgtacgc gtgtctccgg agcaggccct ggtctggggg ctgctgcgtg 43420tcgcgggact ggagcacccg gagttctggg gtggcttgat cgacctgcca tcggactggg 43480acgaccgatt gggtgcccgg ttggcgggtg tgttggcgga tggtggcgag gatcaagtcg 43540ccattcgccg tggtggtgtg ttcgtgcggc ggttggaacg cgctggtgcg tcgggtgccg 43600ggtcggtgtg gcgtcctcgg gggacggtgt tggtgacggg tggtacgggc ggtttggggg 43660cgcatgttgc ccggtggttg gccggtgccg gggctgagca cgtggtgttg accagccgtc 43720gaggagcgga cgctccgggc gctggggaat tgcgggcgga gctggaggcg ctgggtgctc 43780gggtgtcgat tgtgccctgc gacgtggctg atcgtgacgc agtggctgga gtgttggcag 43840ggatcggtgg ggagtgtccg ctgactgcgg tggtacacgc cgccggggtc ggcgaggcgg 43900gcgacgtagt ggagatgggt ttggcggatt ttgcagcggt gttgtcggcg aaggtgcgtg 43960gtgcggcgaa tctggacgag ttgctggccg actcggagct ggatgcgttt gtgatgttct 44020cctcggtgtc gggggtgtgg ggagccggcg gacagggtgc gtatgcggct gcgaacgcct 44080acttggatgc gttggccgag cagcgtcggg cgaggggatt ggtcgggacc gcggttgcgt 44140ggggaccgtg ggccggtgac ggcatggccg ccggcgaaac cggcgcacag ctgcaccgga 44200tgggcctggc gtcgatggaa ccgagcgcgg cgctgctggc acttcagggt gcattggacc 44260gcgatgagac ctccctcgtc gtggccgatg tcgattgggc acggttcgcc ccagccttca 44320cctcggcacg tcgacgcccg ctgctggaca ccatcgacga ggcccgagcc gcattggaaa 44380ccaccggcga acaagcgggc acaggcaaac ccgttgagct gacgcaacgc ctggccggac 44440tgtcgcggaa ggaacgcgac gatgcggtat tggatctggt gcgggcggag acggcggctg 44500tgctgggacg cgacgatgcc acggccctgg cgccatcgcg gccgttccag gaactcggat 44560tcgactcctt gatggcggtg gagctgcgca accggctgaa caccgccacc gggatccagc 44620tgcccgccag cacgattttc gactacccca atgccgagtc gctgtcgcgt cacctctgcg 44680ccgagctttt cccaacggag actaccgtgg actcggccct tgccgagctc gatcgaatcg 44740agcagcagct ctcgatgctc accggcgaag cgcgggcacg ggaccgaatc gcgacacgac 44800tgcgagccct ccacgagaag tggaacagcg cagctgaagt accgaccgga gccgatgtcc 44860tgagcacgct cgattcggcg acgcacgacg agatattcga gttcatcgac aacgagctcg 44920acctgtcctg agtagttcct gcggaacttc aagcgccgaa atcgggtgga aatcacaatg 44980gccaatgaag aaaagctctt cggctatctg aagaaggtaa ctgcggacct gcatcagacc 45040cggcagcgcc tgctcgcggc cgagagccgg agtcaggagc cgatcgcgat cgtctcggcg 45100agctgccgac tgcccggcgg cgtcgactct cccgaagcgc tctggcaact cgtgcgcact 45160ggcaccgacg ccatctcgga gttccccgcc gaccggggct gggatctcgg ccggttgtac 45220gatcccgacc cgaaccacca gggaacgtcg tacacgcggg ccggcggttt cctcgcagga 45280gcgggcgatt tcgaccccgc catgttcggg atttcgccgc gtgaggcgtt ggcgatggac 45340ccgcagcaac ggttgttgct ggagctgtcc tgggaggccc tcgaacgggc gggcatagac 45400ccgacatccc tgcgcggcag caagaccggt gtcttcggtg gtgtcacgcc ccaggagtac 45460gggccgtcct tgcaggagat gagccgaaac gctgggggtt ttggactcac cgggcggatg 45520gtgagtgtgg cgtcgggtcg ggttgcgtat tcgtttggtt ttgagggtcc tgcggtgacg 45580gtggatacgg cgtgttcgtc gtcgttggtg gccctgcatt tggcgtgtca gtcgttgcgt 45640tccggcgaat gcgatctcgc gctggccggc ggtgtgacgg tgatggcgac accggcgacg 45700ttcgtggagt tctcccgtca gcgtggtttg gctccggacg ggcggtgcaa gtcgttcgcg 45760gctgccgcgg atggcaccgg gtggggtgag ggtgccggtc tggtgttgct ggagcggttg 45820tcggatgcgc ggcggaatgg gcacgaggtt ctggcggtgg tgcggggtag cgcggtgaac 45880caggacggcg cgtcgaatgg tttgactgcg ccgaatggtc cgtcgcagca gcgggtgatc 45940acccaggcgt tggcgagtgc ggggctgtcg gtttccgatg tggatgcggt cgaggcacat 46000gggaccggga ccacgttggg tgatccgatc gaggcacagg ccctgatcgc cacgtacggg 46060cagggccggg agaaggatcg gccgttgtgg ttggggtcgg tcaagtccaa catcggtcac 46120acgcaggcgg ccgctggcgt tgccggcgtc atcaagatgg tcttggcgat gcggcacggg 46180cagctgcccg ccacgttgca tgtggatgag cccacgtcgg cggtggactg gtcggcgggt 46240tcggtccggc ttctcacgga gaacacgccc tggccggaca gtggtcgtcc ttgccgggtg 46300ggggtgtcgt cgttcgggat cagcggcacc aacgcacatg tgattctcga acagtctcca 46360gtcgagcagg gcgaaccggc cgggccggtc gaaggcgagc gggaaccgga tgtagccgtc 46420cccgtggtgc cttgggtgct gtcgggtaag acaccggagg ctgcgcgggc gcaggccgaa 46480cgggtgcatt cgcatatcga ggaccggccg gggctgtcgc cggtggatgt ggcgtattcg 46540ctaggaatga cacgcgcggc gctggatgaa cgcgcagtgg tgttgggctc ggaccgtgcc 46600gcgctcctga ccgggttgag ggcattcgcc gacggctgcg atgcgcccga agtggtttcg 46660gggtctgtgg ggcttggtgg ccgcgtcggg ttcgtgttct cgggtcaggg tggtcagtgg 46720ccggggatgg gccgggggct ctactcggtg tttccggtgt tcgccgacgc gttcgacgag 46780gcttgcgcgg agttggatgc acacctgggc caggaactgc gggttcggga tgtggtgttc 46840ggttcgcaag cgtggttgct ggatcggacg gtgtgggcgc agtcgggttt gttcgcgttg 46900cagattggct tgctgcggct gctgggttcg tggggtgttc ggccggatgt ggtgttgggg 46960cactcggtgg gtgagctggc tgcggtgcat gcggctggtg tgttgtcgtt gtcggaggcc 47020gcgcggttgg tggcgggtcg cgcccggttg atgcaggcgt tgccttctgg tggtgccatg 47080ctcgcggtcg ctacgggtga gtttcaggtc gatcctctgc tggatggggt gcgggaccgg 47140atcggtatcg cggcggtgaa tggcccggaa tcggttgtgc tctctggtga ccgcgagctg 47200ctcaccgaga tcgctgatcg gttgcacgat caggggtgcc ggacccggtg gttgcgggtg 47260tcgcatgctt tccattcgcc ccatatggag ccgatgctgg aggagttcgc ccagatctcc 47320cgaggccgcg aatatcacgc accggaactg ccgatcatct cgaccctgat cggtgagctg 47380gacggtggtc gagtgatggg cactcccgag tactgggtgc gtcaggtgcg tgagcccgtc 47440cgtttcgccg agggtgtcca ggcgcttgtc ggtcagggtg tcggcacgat tgtcgaattg 47500ggtccggacg gggcgttgtc gacgttggtc gaggagtgtg tggcggaatc cgggcgggtg 47560gccgggatcc cgctgatgcg caaggaccgc gacgaggcgc gaaccgtgct ggcagctttg 47620gcgcagatcc acacccgtgg tggtgaggtg gactggcggt cgtttttcgc cggtaccggg 47680gcgaagcaag tcgacctgcc cacctacgcc ttccagcggc agcggtactg gctggcatcc 47740accgggcgtg cgggtgacgt gaccgccgcc ggattggccg aggcggacca tccgctgctc 47800ggtgcggtgg ttgcgttggc agacggcgaa ggtgtggtgc tgaccggtcg gttgacagcg 47860ggttcgcatc cgtggttgtc cgatcaccgg gtgctgggcg aaatcgtcgt ccccggcacc 47920gcgatcgtcg agctggtgtg gcacgtcggc gagcgcctcg gttgtggccg ggtggaagaa 47980ctggctttgg aagcgcccct gatcctgccg gatcatggag cggtccaggt tcaggtgctg 48040gtgggaccgc ccggggaatc cggagcccgg tcggtggcgc tctactcctg tcctggcgag 48100gcgatcgaac ccgagtggaa gaagcacgcg acgggcgtgc ttctcccacc cgtggccgcc 48160gagaaccatg agctgaccgc atggcccccg gagaatgcga ccgaaatcga tgcagacggg 48220gtctacgcat tccttgaagg gcacggtttc gcgtacggac cggcctttag atgtctgcgc 48280ggtgcctggc gacgaggcgg ggaggtgttc gccgaagtcg cattgccgga tgacatgcag 48340gcgggggtcg atcgattcgg cgtccacccc gcgttgctgg acgcggttct gcatgccgcc 48400gcagccgaga cgtcggtggt ccagagcgaa gcgcgggtgc cgttctcgtg gcgtggggtg 48460gaacttcgcg ccactgaaag cgcggtggtg cgggcgcgcc tctcgttgac ttcggatgac 48520gaactgtcgt tggtcgcagt ggacccggct ggccgattcg tggccacggt tgattcgctg 48580gtgacccgac cgatctcccg gcagcaggtg aggtctggcg cgatcggtga ttgcctgttc 48640gaggtggagt ggcaccggaa ggcgttgttg ggaacaaccg ccggcgacga ccttgccatc 48700gtcggtgacg gtcccagttg gccggaatcg gtgcgcgcaa ccgcacggtt cgcgaccctg 48760gatgagttcc gtgcggccgt ggactcggac gttcctgccc cgggttcggt gttggtcgca 48820gctatgtcgg ccgaagaggt cgagggtgga tccctgccgt cgcgcgccca agagtcgacc 48880tccgatctgc tggctctcgt gcagtcgtgg cttgcggacg agcggttcgc cgaatcccag 48940ctcgtggtcg tcacgcgtgc agcggtgtcg gccgactcgg attcggacgt cgcggacctg 49000gtgggtgcgt cgtcgtgggg gttgttgagt tcagcccagt cggagaaccc gggtcgcttc 49060gtgctggtgg acgtggacgg cacacctgag tcgtggcagg cgttgccggc cgccgtgcga 49120gcaggagaac cgcagctggc acttcggcgc ggcgtggcgc tggtgcctcg gttggcgcga 49180ctcacggtgc gcgaggaggg ctcctccccg caactcgaca cggacgggac cgtccccatc 49240acgggtggca ccggtgcgtt ggggggagtg gttgcccgtc acctggtgga ggagcacggg 49300attcggcgtt tggtgttggc aggccggcgt ggctggaatg cgcctggagt ccacgagttg 49360gtggatgagc tggcgcgcgc gggcgccgtg gttgaggtgg tggcttgcga tgtggctgac 49420cgcaccgatc tggagcacgt gctggccgcc attccggtcg actggccgct gcgggggatc 49480gtgcataccg ctggggtgct ggccgacgga gtgatcgggt ccttgtcggc ggcggatgtg 49540ggcacggtgt ttgccccgaa ggtgacgggg gcatggcatc tgcacgagtt gacccgcgat 49600ctggatctgt cgttcttcgt tcttttctct tccttctccg ggattgcggg tgccgcaggg 49660caggccaact acgcggcggc gaacacgttc ctggatgcat tggcgcgtta tcgccgggcg 49720cgtgggctgc ctgggttgtc gttggcgtgg ggactgtggg cgcaacccag cggtatgacg 49780agtggcttgg acgcggcgtc ggtggagcgg ttggcgcgga cgggcatcgc agaactttcc 49840acggaggatg gactccgcct gttcgatgcc gcgttcgcga aggaccgggc ttgcgtcgtt 49900gccgctcgat tggacagggc gctgctggtc gggaacggac gatcgcacgc gattccggcg 49960ctgttgagcg cgttggttcc tgttcgcggc ggtgtggcga ggaaaacagc caattctcag 50020gccgcggatg aggacgcact gttgggtttg gtgcgggagc acgtttcggc cgtgctgggt 50080tattcgggtg cggtcgaggt tgggggcgac cgtgctttcc gtgatctggg ttttgattcg 50140ttgtctggcg tggagttgcg gaaccgcctt gccggggtgc tgggggtgcg gttgccggcg 50200actgcggtgt tcgactatcc gacgccgcgg gcgctggcgc gtttcctgca tcaggaactg 50260gcaggcgagg tcgcgtccac gtcgacgccg gtgaccaggg cagcgagtgc cgaagaggat 50320cttgttgcga ttgtcgggat gggatgtcgt tttccgggtg gggtgtcgtc gccggaggag 50380ctttggcggc tggtggccgg cggcgtggat gcggtggctg ggttcccaga cgatcgcggc 50440tgggatctcg cggcgttgta cgatcctgat cccgatcgtc ccgggacctc gtatgtgtgt 50500gagggcgggt ttctgcggga cgcggcggag ttcgatgctg acatgttcgg catcagcccg 50560cgtgaggcgt tggcgatgga tccgcagcag cggttgctgc tggaggtcgc ctgggaaacc 50620ttggagcggg ctgggatcga tccgttctcg ttgcacggca gccggaccgg tgtgttcgcg 50680ggcttgatgt accacgacta tggggcccga ttcattacca gagcaccgga gggcttcgaa 50740gggcacctcg ggacgggcaa tgcggggagc gtgctgtcgg gtcgggttgc gtattcgttt 50800ggtttcgagg gtcctgcggt gacggtggat acggcgtgtt cgtcgtcgtt ggtggcgtta 50860cacctggcgg gtcaagcact gcgggccggt gagtgcgaat tcgcccttgc cggtggcgtc 50920acggtgatgt cgacgccgac gacgttcgtg gagttctccc gtcaacgggg tctggctccg 50980gatgggcggt gcaagtcgtt cgcggcggcc gcggatggca ccgggtgggg cgagggtgcc 51040ggtctggtgt tgctggagcg gttgtcggat gcccggcgca atgggcacga ggttctggcg 51100gtggtgcggg gtagcgcggt gaaccaggac ggcgcgtcga atggcttgac tgcgccaaat 51160ggtccgtcac agcaaagggt gatcacccag gcactcacga gtgccgggct gtccgtgtcc 51220gacgtggatg ctgtggaggc gcatgggacg ggcacgcggc ttggtgatcc gatcgaggcg 51280caggcgttga tcgctacgta cggccgggat cgtgatcccg gtcggccgtt gtggctgggg 51340tcggtgaagt cgaatattgg tcacacccag gcggcggcgg gtgtcgctgg tgtgatcaag 51400atggtgatgg cgatgcggca gggggagctg ccgcgcacgt tgcacgtgga cgagccctcc 51460gcgcaggtgg actggtctgc gggcacggtc caactcctca cggagaacac gccctggccc 51520gacagcggtc gtcttcgccg ggcgggcgtg tcatcgttcg ggatcagtgg caccaacgcg 51580cacctgatcc ttgaacaacc tccgcgagag tcgcagcgct caacagagcc ggattcgggt 51640tctgtccgcg attttccggt ggtgccgtgg atggtgtcgg gcaaaacacc cgaagcgcta 51700tccgcccagg cagatgcatt gatgtcctac ttgagcaatc gcgttgatgc ttccccgcga 51760gatatcggtt attcgcttgc ggtgacccgt ccggcgttgg accaccgcgc tgtcgtgctg 51820ggtgcggatc gtgccgcgtt gctgccgggc ttgaaagcgc tggccgttag taatgacgct 51880gccgaggtga tcaccggcac tcgtgccgct gggccggtcg gattcgtgtt ctccggtcaa 51940ggtggtcagt ggcccgggat gggaagcggg ctccactcgg cgtttccggt gttcgccgac 52000gcgtttgacg aagcctgctg cgagctggat gcgcatctcg ggcagatggc ccggctacga 52060gatgtgttgt ccggttcgga tacgcaactt ctggaccaga ccttgtgggc gcagccgggc 52120ctgttcgcgt tgcaagtcgg actctgggag ttgttgggtt cgtggggtgt ccggcccgct 52180gtggtgctgg gccactcggt cggtgagctg gcggcggcgt tcgcggctgg agtgttgtcg 52240ttgcgggatg cggctcggct ggtggcgggc cgtgcccggt tgatgcaagc cctgccaact 52300ggcggtgcca tgctcgctgc ggctgctgga gaggagcagc tgcgcccgtt gctggccgac 52360tgcggtgatc gtgtggggat cgccgcggtc aacgctcccg ggtcggtggt gctctccggt 52420gatcgggatg tgctcgatga cattgccggt cggctggacg ggcaagggat ccggtccagg 52480tggttgcggg tttcgcatgc gtttcattcg catcggatgg atccgatgct ggcggagttc 52540accgaaatcg cccggagcgt ggactaccgg tcgtcagggc tgccgatcgt gtcgacgttg 52600acgggtgagc tcgatgaggt cggcatgccg gctacgccgg agtattgggt gcgccaggtg 52660cgagaacccg tccgcttcgc cgacggtgtt gctgcgctcg cggctcacgg tgtgagcacc 52720gtcgtcgagg tcggtccgga tggggtgttg tcggcgctgg tgcaggagtg cgcggccgga 52780tccgatcagg gcggacgggt ggccgcggtt ccgctcatgc gcagcaatcg cgacgaggcg 52840cacacggtga caacggcatt ggcgcagatc catgtgcgtg gtgctgaggt ggactggcgg 52900tcgtttttcg ccggtaccgg ggcaaagcag gtcgagctgc ccacgtatgc cttccaacga 52960cagcggtact ggcttgactc accatccgaa ccggtcgggc aatccgccga tcccgcgcgc 53020cagtcgggct tctgggaact cgtcgagcag gaagatgtca gcgcgctcag cgccgctctg 53080cacattaccg gcgatcacga cgtgcaggcg tccctggaat cggtggttcc ggtcctctcc 53140tcctggcatc gccggatccg caacgaatcc ctggtgcacc agtggcggta ccggatttcc 53200tggcatgagc gggcagattt gccagacccc tcgttgtcgg ggacatggct cgtcgtcgtg 53260ccggaggggt ggtcggcgag tcggcaagtt ctgcgtttca acgagatgtt cgaggaacgg 53320ggttgcccgg cagttctgtt cgagctcgcc gggcacgacg aggaagccct ggcgcaacga 53380ttccgctcgt tgcctgttgc gtcaggggga ataagcggcg tgttgtcctt gctggcgctg 53440gatgaatcgc cgtcctcgcc gaacgctgct ttgccgaatg gcgcgctgaa ctcgttggta 53500ctgctgcgag ctctgcgggc cgcggatgtg tcggcgccat tgtggttggc gacgtgtggt 53560ggtgtcgcgg tcggggatgt gccggtgaac ccggggcagg cgctggtgtg gggactgggt 53620cgcgtcgtcg gtctggagca tccggcctgg tggggtggcc tggtcgacgt gccgtgcttg 53680ctcgatgagg acgctcgaga acgcttgtcg gtcgtgttgg caggtcttgg cgaggacgag 53740atcgcggtac gtcccggtgg tgtgttcgtg cggcggttgg aacgcgctgg tgcggcgtcg 53800ggtgccgggt cggtgtggcg tcctcggggg acggtgttgg tgacgggtgg tacgggcggt 53860ttgggggcgc atgttgcccg gtggttggcg ggtgccgggg ctgagcatgt ggtgttgacc 53920agccgtcgag gcgcggcggc tccgggcgct ggagatttgc gggcggagct ggaggcgctg 53980ggcgctcggg tttcgatcac ggcctgcgac gtggccgatc gtgacgcttt ggccgaagtg 54040ttggcgacca ttccggatga ttgcccgctg accgcggtga tgcatgcggc gggggtcgtt 54100gaagtcggcg acgtggcgtc gatgtgtttg accgacttcg ttggggtgct gtcggcgaag 54160gcaggtggtg cggcgaatct cgatgagttg ctcgccgatg tcgagctgga tgccttcgtg 54220ctgttctcat ccgtctcggg tgtgtggggt gctggcgggc agggcgctta tgcggcggcg 54280aatgcctact tggatgcgtt ggcgcagcag cgtcgggcaa gggggttggt ggggactgcg 54340gttgcgtggg gcccgtgggc cggtgacgga atggccgcag gtgaaggcgg tgcacagctg 54400cgccgggccg gcctggtgcc aatggctgcg gatcgggcgt tgctggcact tcagggcgca 54460ttggatcgtg acgagacatc cctggtcgtg gccgatatgg cgtgggagag gttcgccccg 54520gtgttcgcca tgtcccgtcg gcgtccgctg ctcgacgagc tgcccgaagc acagcaggcg 54580ttggcggatg cggagaacac cactgatgct gcggactcgg ccgtcccgct accgcggctc 54640gcgggcatgg cagccgccga acgccgccgc gcgatgctgg acctggtgct ggcggaggcc 54700tcgattgtgt tgggacacaa cgggtctgac ccagttggtc ccgaccgggc gttccaggag 54760ctcggatttg attcgctgat ggccgtcgaa ctgcgcaaca ggttgggcga ggcaacagga 54820ttgagtctgc cggccacgtt gatcttcgat tatccgagcc catccgcgct ggctgagcag 54880ctggtcggcg agctggtggg agcgcagccc gcgaccaccg tcgtggccgg ggccgatcca 54940gtggatgatc cggttgtcgt ggtcgcgatg ggatgccggt atccgggcga cgtctgctcg 55000cccgaggagc tgtggcagct ggtttctgcg ggacgtgatg cggtatcgac gttccccgtc 55060gatcggggtt gggactgcaa cacgttgttc gacccggatc cggatcgggc aggcagtacc 55120tatgtgcgag aaggtgcctt cctgaccggt gctgatcggt tcgacgccgg gttcttcggc 55180atcagccctc gcgaggcgcg cgcaatggat ccgcagcaga ggttgttgct cgaagtggcg 55240tgggaggttt tcgaacgagc aggaatcgct ccgctgtcgt tgcggggtag caggaccggt 55300gtgttcgcgg ggaccaatgg gcaggaccac ggtgcgaaag tggctgccgc gccggaggcg 55360gcgggtcacc tcctgaccgg aaacgccgcg agtgtcctgg ccggccggct ttcctacacg 55420ttcggccttg aggggcctgc ggtggcggtg gataccgcgt gttcgtcgtc gttggtggcg 55480ttgcatttgg cgtgccagtc gctgcgttcg ggtgagtgtg atatggcgtt ggcaggtggt 55540gtgacggtga tgtcgacacc cctggctttc ctcgagttct ctcgtcagcg cggtttggcg 55600ccagatggtc ggtgcaagtc gtttgcggcc gctgcggatg gcaccgggtg gggtgagggt 55660gccggcctgg tgttgctgga gcggttgtcg gatgctcgtc ggaatggtca ccgggtgttg 55720gccgtggttc gcgggtctgc ggtgaatcag gatggtgcgt cgaatggcct gactgcgccg 55780aatggtccgt cgcagcagcg ggtgattcgg caggccctcg cgaatgcggg gctgtcggcg 55840tccgatgtgg atgtcgtgga ggcgcacggg accggtaccg ggctcgggga tccgatcgag 55900gcgcaggcgc tgatcgcgac atatgggcag gagcgggatc ctgagcgggc cctgtggctg 55960gggtcgatca agtccaacat cggccacacg caggcggcgg ccggtgtggc gggggtcatc 56020aagatggtgc aggccatgcg gcacggggag ttgcctgcga cgttgcacgt ggacaagccc 56080actccacagg tggactggtc tgccggggcc gttcggctcc tcaccgggaa cacgccctgg 56140cccgagagcg gccgtcctcg tcgagcgggg gtgtcgtcgt tcgggatcag cggcaccaac 56200gcacacctca tcctcgaaca accaccgtcg gaaccagcgg agatcgacca atcggatcgg 56260cgggtcactg cgcatccagc ggtgatcccg tggatgttgt cggctaggag tctcgcagcg 56320ctgcaggccc aagcggctgc gctgcaggcc cggctggacc ggggtcctgg cgcttctccg 56380ctggatttgg ggtattcact cgcgaccact cgttctgcgc cggacgaacg cgccgtcgtg 56440tggggtgccg atcgggaggc actgctgtcc aggctggcag cgctcgccga tggccggacg 56500gcgccggggg tgataacggg ctctgcgaat tccggtggcc gcatcggatt cgttttttcc 56560ggtcagggca gtcagtggct ggggatggga aaggcgttgt gcgcggcttt cccggcgttc 56620gcggacgcct tcgaggaagc ctgcgacgcg ctaagcgcac acctgggcgc ggacgttcgg 56680ggtgtgctgt tcggtgctga tgagcagatg ctcgaccgga cgctgtgggc gcagtcgggg 56740atcttcgcgg ttcaagtcgg cctcctggga ttgctgaggt cgtggggcgt gcggccggcc 56800gcggtgctgg ggcactcggt cggcgagttg gctgcggcgc acgcggctgg tgtgttgtcc 56860ttgccggacg ctgcacggtt ggttgcggct cgggcccacc tgatgcaggc attgcccacc 56920ggcggcgcaa tgctcgcggt cgccaccagc gaggcggcgg tcggaccgct gctttccggg 56980gtgtgcgatc gggtcagcat cgctgcgatc aacggccccg agtcggtagt gctctccggc 57040gaccgcgatg tgctcgtgga gctcgcaggc gaattcgatg cccgagggct taggaccaaa 57100tggttgcggg tctcccatgc tttccactcg caccggatgg aaccgattct ggacgagtac 57160gcggaaaccg ccaggtgcgt cgagttcggt gaaccggtgg tgccgatcgt ctccgccgcg 57220accggtgcgc tggacaccac cggactgatg tgcgcggccg actactggac gcgccaagtg 57280cgtgatcctg tccgcttcgg agacggtgtc cgggcgctcg tcggccaagg cgtggacacg 57340atcgtcgagt tcggcccgga cggggcgttg tcggccctgg tcgagcagtg cttggccggg 57400tccgaccagg ctgggagggt ggcggcgatc ccgctgatgc gcagggaccg cgatgaggtc 57460gagaccgcgg tggcggccct ggcgcacgtg cacgtccgcg gtggtgcggt ggactggtcg 57520gcttgcttcg ccggcaccgg cgcccgcacc gtcgagttgc ccacctacgc cttccaacgc 57580cagcggtact ggctggccgg gcaagcggac gggcgcggcg gcgatgtggt tgccgacccg 57640gtcgacgcgc gcttctggga gttggtcgag cgcgccgatc cggaaccgtt ggtggatgaa 57700ctctgcatcg accgggacca gcccttccgg gaggtgctgc ccgttctggc ttcctggcgc 57760gagaaacaac gccaggaggc cctcgcggat tcctggcgct accaggtgcg ctggaggtcc 57820gtcgaggtgc cgtccgcagc cgccctccgg ggcgtgtggc tggtggtgct tccagctgac 57880gtgccccgag atcaaccggc ggtcgtcatc gacgcgctga tcgcgcgcgg cgccgaggtc 57940gcggtcctgg aattgaccga gcaggacctc caacgcagtg cgcttgtgga caaggtgcgc 58000gccgtcattg cggaccgcac cgaggtgacg ggtgtgttgt ctctgttggc gatggacggc 58060atgccctgcg cggcgcatcc gcacctgtcc cgtggtgtcg ccgctaccgt gatcctgacg 58120caggtgttgg gcgatgcggg tgtttccgcc ccgctgtggc tggccacgac cggtggcgtc 58180gaggccggga ccgaggacgg tccggccgat ccggaccacg gcttgatctg ggggctcggc 58240agggtcgtcg gccttgaaca tccgcagtgg tggggtggcc tgatcgacct tccggagaca 58300ctggacgaga cgtcccggaa cgggttggtg gccgcactcg ccgggacggc ggccgaagat 58360cagctcgccg tgcgttcatc cgggttgttc gttcgcagag tggtgcgcgc agcgcggaac 58420ccccggtcag agacatggcg tagccgggga acggtcctca tcacgggcgg aacaggcgcg 58480ctcggtgccg aggtcgcacg atggctggcc cggcggggag ctgagcacct ggtgttgatc 58540agtcgccgcg gcccggaagc tcccggcgca gcggacctag gggccgagct gactgaactc 58600ggcgtgaaag tcacagtctt ggcctgcgat gtgacggacc gcgacgagct ggcggcggtg 58660ctggcggccg ttcccacgga gtatccgctg tcggcggtcg tgcacaccgc cggcgtcggg 58720acgcctgcga acctggccga gacgaccttg gcgcagttcg ccgacgtgtt gtcggccaag 58780gtcgtcggcg cggcgaacct ggaccggctg cttggcgggc aaccgttgga cgccttcgtg 58840ctgttctcct cgatctcggg agtttgggga gccggcggcc aaggagccta ttcggccgcc 58900aatgcgtatc tcgatgccct tgccgagcgc cgacgggctt gcgggcggcc ggcgacgtgc 58960atcgcctggg gtccgtgggc gggtgcgggc atggccgttc aggaaggtaa cgaggcgcat 59020ctccgccgaa ggggcctggt accgatggaa ccgcagtcgg ccctcttcgc gctgcaacag 59080gccctgtccc aacgagaaac cgccatcacc gtcgcagatg tggactggga gcgattcgcc 59140gcctctttca ccgcggcccg cccgcgacca ctgttggaag agatcgtgga tctacggccc 59200gacaccgaga ccgaggagaa gcacggtgcc ggcgagctgg ggcagcagct ggccgcactg 59260ccgcccgctg agcgcggaca cctgctgctg gaggtggtgc tggcggaaac cgccagcacc 59320ctggggcacg attcggcgga ggctgtgcaa cccgatcgga ccttcgccga actgggcttc 59380gattcgctga ccgcggtaga gctgcgcaac aggttgaacg cggtgaccgg gcttcgcctg 59440ccgccgacgc tggttttcga ccacccgacg ccgctggcgt tgtccgaaca gttggttccg 59500gccctggtcg cggagccgga caacggcatc gaatcgctgc tcgccgagct cgacaggctg 59560gataccacgt tggcgcaagg gccttcgatc ccactggaag accaggccaa ggtggcggag 59620cgcttgcacg cactcctcgc caagtgggac ggggcgcgtg acggcacggc cagagcgacg 59680tcaccccaat cgctgacggc ggccacggac gacgaaatct tcgacctcat cgaccggaag 59740ttccggcgct gaccgccctt tcctcgcctc agctcccctg attactggaa cggtgtattt 59800cgatggccaa tgaagaaaag ctccgcgagt acctcaagcg tgtcgtcgtc gaactggaag 59860aggcgcacga acgcctgcac gagttggagc gccaggagca cgaccccatc gcgatcgtgt 59920cgatgggatg tcgttatccc ggtggcgtct ccactccgga ggagctgtgg cgactggtcg 59980tcgacggagg agacgcgatc gcgaacttcc ccgaagaccg tggctggaat ctggacgagc 60040tgttcgatcc tgatccgggc cgagccggga cctcctacgt ccgcgagggt ggtttcctgc 60100gcggggtcgc ggacttcgat gccgggctct tcgggatcag tccgcgcgag gcacaggcga 60160tggacccgca acagcggttg ctgctggaga tctcgtggga ggtgttcgag cgcgccggca 60220ttgacccgtt ttctttgcgg ggtaccaaga ccggtgtgtt cgcgggcctg atctaccacg 60280actacgcgtc gcggtttcgc aagacccccg cggagttcga gggttacttc gccaccggca 60340acgcgggcag cgtcgcatcc ggccgggtgg cttacacctt cgggttagag ggcccggcgg 60400tcaccgtgga caccgcctgc tcgtcgtccc tggtggcgct gcacctggcc tgccagtccc 60460tgcggctggg cgaatgcgac ctggccctgg ccggtggcat ttcggtgatg gccacgccgg 60520gagccttcgt cgagttcagc cggcaacgcg cactcgcctc ggatggccgg tgcaagccct 60580tcgcggatgc cgccgacggc accggctggg gcgagggcgc cggaatgctg ctgctggaac 60640ggctgtcgga cgcacgacga aacggccacc cggtgctggc ggcggtggtc ggttccgcga 60700tcaaccagga cgggacgtcc aacggcctga ccgcgcccag cggtcccgca cagcagcgag 60760tgatccgcca agccctggcg aacgccgggt tgtcgcccgc cgaggtcgat gtggtcgagg 60820cgcacggcac gggcacggcc ttgggcgacc cgatcgaggc gcaggccctg atcgccacct 60880acggggcgaa ccggtcggcg gatcatccgc tgctgctggg ttccctcaag tcgaacatcg 60940gccacaccca ggctgccgcc ggtgtggccg gggtgatcaa gtcggtcctg gccatcaggc 61000accgggagat gccccgcagc ctgcacatcg accagccatc gcagcacgtg gactggtcgg 61060cgggcgcggt gcggctgctc acggacagcg ttgactggcc ggatctcggc aggccgcgcc 61120gagcaggggt gtcctcgttc ggcatgagcg gtaccaacgc acacctgatc gtcgaggaag 61180tatccgacga gccggtctcg ggcagtaccg agccgaccgg ggcatttccc tggccgctgt 61240ccggcaagac ggagacggca ttgcgcgagc aggctgccga gttgctctcc gtagtgaccg 61300agcacccgga gccgggactg ggggacgtcg ggtactcgct ggccaccggt cgcgctgcga 61360tggagcaccg ggctgtcgtg gttgccgacg atcgggactc tttcgtcgcc ggactgacgg 61420cgttggctgc gggcgttccg gcagccaacg tggtgcaggg cgcggccgac tgcaagggaa 61480aggtcgcgtt cgtgttcccc ggccagggct cgcattggca ggggatggcg agggaactgt 61540ccgaatcctc gccggtgttc cggcggaagc tggcggaatg cgcggcggct acggcccctt 61600acgtggactg gtcgctgctc ggcgtccttc gcggtgatcc cgatgcaccc gcgctggatc 61660gcgacgacgt gattcagctc gcgctgttcg ccatgatggt gtcgctggcc gaactgtggc 61720gttcgtgcgg agtggagccc gccgcggtgg tcggtcattc ccagggcgag atcgccgccg 61780cccatgtggc aggcgctttg tccttgactg atgcggtgcg catcatcgct gcccgctgcg 61840atgcggtgtc ggcgctgacc gggaagggag gcatgctcgc gattgccttg ccggaaagcg 61900cggtggtgaa gcgaatcgca ggcctgccgg agctgaccgt tgcggcggtc aacggacccg 61960gctccactgt cgtttccggc gaaccgtcgg ctctggagcg tctgcagacc gaactgaccg 62020cggaaaacgt gcagacccgg cgggtgggaa ttgattacgc ctcgcattcg ccgcagatcg 62080cgcaggtcca gggccggctt ctggaccggc tgggcgaagt cgggtccgaa cctgctgaga 62140tcgctttcta ctcgacggtc accggcgagc ggacggacac cggccgactc gacgccgact 62200actggtacca gaaccttcgg cagcccgtcc gcttccagca gaccgtcgcc cggatggcag 62260atcagggcta tcggttcttc gtcgaggtga gcccgcaccc gctgctcacc gccggaatcc 62320aggaaacgct ggaagccgcg gacgcgggcg gggtggtggt cggttcgctg cggcgtggcg 62380agggcggctc ccggcgctgg ctgacttcgc tggccgagtg ccaggtgcgc ggactgccgg 62440tgaattggga acaggtattc ctcaacaccg gagcccgacg cgtgccgctg ccgacctacc 62500cgttccagcg gcagcggtac tggttggagt ccgccgagta cgacgcgggc gatctcggtt 62560cggtgggctt gctctccgcc gagcatcccc tgctcggggc tgcggtgacg ctggccgatg 62620WO99/46387 PCT/US99/03212cgggcgggtt cctgctgacc ggcaagctgt cggtcaagac ccagccctgg ttggccgacc 62680acgtggtcgg cggggcgatc ctgctgcccg gcaccgcgtt cgtggaaatg ctgatacgcg 62740ccgcggacca ggtcgggtgc gatctgatcg aggagttgtc cctgacgact ccgctggttt 62800tgcccgcgac cggtgcggtg caggtgcaga tcgcggttgg cggtccggac gaggccgggc 62860gccgctcggt ccgcgtgcat tcctgtcgag acgacgccgt gccgcaggac tcgtggacct 62920gccacgcgac cggcacgttg acctccagcg atcaccagga cgccggccag ggccccgatg 62980ggatttggcc gcccaacgat gctgtcgcgg ttccgctgga cagcttctac gcccgcgcag 63040ctgagcgggg cttcgatttc ggcccggcgt tccaggggtt gcaggcggct tggaagcgcg 63100gagacgagat cttcgccgag gtcggcctgc ccaccgcaca ccgcgaagac gccggcaggt 63160tcggaatcca ccctgctctg ctggatgcgg cactgcaggc gctgggcgca gccgaagagg 63220atccggacga gggatggctc ccgttcgcgt ggcaaggtgt gtccctcaaa gcgacgggcg 63280cactttccct tcgggtgcac ctcgttccgg cgggcgcgaa tgcggtgtcg gtgttcacga 63340ccgacacgac tggccaagcc gtgctctcca tcgattcgct ggtgctgcgc cagatttcgg 63400acaagcagtt ggcagcggcc cgtgcgatgg aacacgagtc cctgttccgg gtcgactgga 63460agcgaatctc gcccggcgct gccaagccgg tctcctgggc agtgatcggc aatgacgaac 63520tcgcccgagc ctgcggctcg gcacttggca cggaactcca ccccgacctg accgggttgg 63580ctgacccgcc cccggacgtc gtggtggtgc catgcggtgc gtctcgccag gacttggacg 63640ttgcttccga ggcacgtgcc gcgacacaac gcatgcttga cctgatccag gattggttgg 63700cggcggcgcg attcgccgga tctcgcctgg tggttgtgac gtgtggtgcg gcgtcgacag 63760gtcccgccga gggtgtttcc gacctggtgc atgctgcgtc gtggggtttg ttgcgttcgg 63820cgcagtcgga gaacccggac cgattcgtgt tggtcgatgt ggacggaacc gccgaatcat 63880ggcgtgcgct cgcggcggcc gtgcgttccg gagaaccgca gctggcgttg cgcgccggtg 63940aagtccgggt gcctcgcctg gcgcgatgtg ttgccgccga ggacagccgg atcccagtgc 64000ccggtgcgga tgggacggtg ttgatttccg gcggtacggg cctgctgggc gggttggttg 64060cccggcattt ggtggcggag cgcggtgtcc gccgcctggt gctcgcgggg cgacgcggct 64120ggagcgcccc cggggtcacc gacctggtgg atgagttggt gggcctggga gctgcggtcg 64180aggtggcgag ctgcgatgtc ggggatcggg cccagttgga ccggctgctg acgacgatct 64240cggcagagtt cccgctgcgc ggagtggtgc atgcggccgg ggcacttgcc gacggggtcg 64300tcgagtcgct gacaccagag cacgtggcaa aggtgttcgg cccgaaggcc gccggtgcgt 64360ggcacctgca cgagttgact cttgatctgg atctctcgtt cttcgtgctc ttctcctcgt 64420tctccggcgt ggcgggggct gcgggtcagg gaaactacgc ggcggcgaac gcgttcctgg 64480acggcctggc tcagcaccgg cggacggcgg ggctgcctgc ggtgtcgctg gcttggggct 64540tgtgggagca gcccagcggg atgaccggag cgctcgatgc ggcgggccgt agccgcattg 64600cgcgcaccaa tccgccgatg tccgcgccgg acgggttgcg gctgttcgag atggcgtttc 64660gcgttccggg cgaatcgctt ctggttccgg tccacgtcga cctgaacgcc ctgcgcgctg 64720atgcggccga cggcggtgtg cctgcgttgt tgcgcgacct ggtgccagcg cccgtgcggc 64780ggagcgcggt caacgagtcg gcggacgtca acggtctggt tggtcggctg cggaggctgc 64840cggacctgga tcaggaaacc cagctgttgg gtttggtgcg cgagcatgtt tcggcggtgc 64900tggggcattc gggtgcggtc gaggtcgggg ccgatcgtgc tttccgggat ttgggttttg 64960attcgttgtc cggtgtggag tttcggaacc ggcttggcgg ggtgctgggc gttcggttgc 65020cggctactgc ggtgttcgac tatccgacac cgcgggcgtt ggttcggttc ttgctcgaca 65080aactgattgg tggcgtggag gctccgactc ccgcaccggc ggctgtggcg gcggtgactg 65140ctgacgatcc cgttgtgatc gtggggatgg gctgtcgtta tccgggtggg gtgtcctcgc 65200cggaggagct ttggcgtttg gtggccgggg gcttggatgc ggtggcggag ttcccggacg 65260atcgtggctg ggatcaggcg gggttgttcg atccggatcc cgatcgtctt gggacctcgt 65320atgtgtgtga gggtggcttc ctgcgagatg cggcagagtt cgatgccggt ttcttcggga 65380tttccccgcg tgaggcgttg gcgatggatc cgcagcagcg gttgctgctg gaagtcgctt 65440gggaaaccgt ggagcgggcg gggattgatc cgctttcgtt gcgggggagc cggaccggcg 65500tgttcgcggg gctgatgcac cacgactacg gcgcgcggtt catcacgagg gcgccggagg 65560gtttcgaggg ttatctaggt aatggcagcg cgggaggcgt gttttcgggt cgggttgcgt 65620attcgtttgg tttcgagggt cctgcggtga cggtggatac ggcgtgttcg tcgtcgttgg 65680tggcgctgca cctggcgggt caagcactgc ggtctggtga gtgtgatctg gctcttgcgg 65740gtggtgtgac ggtgatggcc acgccgggga tgttcgtgga gttttcgcgt caacggggct 65800tggcggcgga tgggcggtgc aagtcgtttg cggcggctgc ggatggcacc ggttggggag 65860aaggcgcggg cttggtgttg ttggagcggc tgtcggatgc ccggcgcaac gggcacgcgg 65920ttctggcggt cgtgcggggt agcgcggtga atcaggatgg tgcgtcgaat ggtttgacgg 65980cgccgaatgg gccctcgcag cagcgggtga tcacgcaggc gttggcgagt gctggtttgt 66040cggtgtctga tgtggacgcc gtggaggcgc atgggactgg aaccaggctt ggtgatccga 66100ttgaggcgca ggctctgatt gccacttacg ggcaggggcg ggatagcgat cggccgttgt 66160ggttggggtc ggtgaagtcg aatattggtc atacgcaggc ggcggcgggt gtcgctggtg 66220tgatcaagat ggtgatggcg atgcggcacg ggcagctgcc cgcgacgttg catgtggatg 66280aacctacgtc ggaagtggat tggtcggcgg gggatgtcca gctcctcacg gagaacaccc 66340cctggcccgg caacagccat cctcggcggg tgggcgtgtc gtcgttcggg atcagcggca 66400ccaacgcaca cgtcatcctc gaacaagcct cgaaaacacc agacgagact gcggacaaga 66460gcggtcccga ttcggaatcg accgtggacc ttccagcggt cccgttgatc gtgtcgggga 66520gaacaccggc agcgctcagc gctcaggcga gcgcattgtt gtcctatttg ggtgagcgtg 66580gcgatatttc cacgctggat gcggcgtttt cgttggcttc ctcccgggcc gcgttggagg 66640agcgggcggt ggtgctggga gcggaccgcg aaacgttgtt gtccgggttg gaagcgctgg 66700cttccggtcg cgaggcttct ggggtggtgt cgggatcccc ggtctctggc ggggttgggt 66760tcgtgttcgc cggtcagggc ggacagtggt tggggatggg ccgggggctc tactcggttt 66820ttccggtgtt cgctgacgcg tttgacgaag catgtgccgg actggacgcg catctggggc 66880aggacgtggg ggtccgggat gtggtgtttg gttccgacgg gtccttgttg gatcggacgc 66940tgtgggccca gtcgggtttg ttcgcgttgc aggttggttt gctgagcctg ctgggttcgt 67000ggggtgtccg gccgggtgtg gtgctgggcc attcggtcgg cgagttcgcg gcggcggttg 67060cggcgggagt gttgtcgttg ccggatgcgg ctcggatggt ggcgggtcgt gcccggttga 67120tgcaggcgtt gccttctggc ggtgccatgt tggcggtggc tgctggtgag gagcagctgc 67180ggccgttgtt ggccgatcgg gttgatggtg cgggtatcgc cgcggtcaac gctcctgagt 67240cggtggtgct ctccggcgat cgggaggtgc ttgacgacat cgccggcgcg ctggatgggc 67300aagggattcg gtggcggcgg ttgcgggttt cgcatgcgtt tcattcgtat cggatggacc 67360cgatgttgca ggagttcgcc gaaatcgcac gcagcgtgga ctaccggcgt ggcgacctac 67420cggtcgtgtc gacgttgacg ggtgagctcg acaccgcagg tgtgatggct acgccggagt 67480attgggtgcg tcaggttcga gagcccgtcc gcttcgccga cggcgtccgg gtgctcgcgc 67540agcaaggggt cgccacgatc ttcgaactcg gccctgatgc gacgctgtcg gccctgattc 67600ccgattgtca ttcgtgggct gatcaggcca tgccgattcc gatgctgcgt aaagaccgta 67660cggaaaccga aactgtggtc gccgcggtgg cgcgggcgca cacgcgtggt gttccggtcg 67720aatggtcggc gtatttcgcc ggcaccgggg cacggcgggt cgagttgccg acgtatgcct 67780tccagcggca gcggtactgg ctggaaacat cggattacgg cgatgtgacg ggtatcggcc 67840tggctgcggc ggagcatccg ttgctggggg ccgtggttgc gctggccgat ggtgatggga 67900tggtgctgac cggccggttg tcggtgggga cgcatccgtg gctggcccag catcgcgtgc 67960tgggcgaggt cgtcgtcccc ggcaccgcca tcctggagat ggccctgcac gcaggggcgc 68020gtctcggctg tgaccgggtg gaagagctca ccctggaaac accgctggtg gtccccgaac 68080gcgcggcggg tgccggtagt cgtggccctg cgggagggac cacagtttca attgaaactg 68140cggaagaacg tgtgcggacg aacgacgcca tcgaaatcca gctgctggtg aacgcacccg 68200acgaaggcgg tcggcgaagg gtgtcgctgt attcccgccc ggccggtggg tcgagaggtg 68260ggggttggac gcgccacgcc accggcgaac tcgtcgtcgg caccaccggt ggtagggcgg 68320ttcctgattg gtcggctgag ggtgccgagt cgattgctct cgatgagttc tacgtcgctc 68380tggccggaaa cgggttcgag tacgggccgt tgttccaggg gcttcaggcg gcatggcgtc 68440gtggtgacga ggttctcgcc gaaatcgccc cgccggccga ggccgatgcg atggcgtcgg 68500gatacctgct cgacccagcg ttgctggatg ccgcgctgca ggcgtccgcg ctcggcgacc 68560gcccggagca aggcggcgcg tggctgccgt tctcattcac cggcgtcgaa ctttccgctc 68620cggcagggac gatcagcagg gtgcggctgg agaccaggcg acccgacgcg atatcggtgg 68680ccgtgatgga tgagagtggg cggttgctcg cctcgatcga ttctctcagg ctacgaagcg 68740tgtcgtcggg acagctggcg aatcgggacg ctgtccgcga cgcgctgttc gaggtgacct 68800gggagccggt ggcgacgcag tcgacggaac cgggtcgctg ggccctgctt ggtgatactg 68860cctgcggtaa agacgatctc atcaaactcg caacggattc cgccgaccgc tgcgcggatc 68920tggcggcgct agccgagaaa cttgattcca gcgcgctggt tcctgatgtc gtggtctact 68980gcgccggaga acaggcggat cccggcaccg gcgcagccgc acttgcggag acccagcaga 69040cgttggctct gctccaagcg tggttggctg agccgcggtt ggccgaggca cgtctggtgg 69100tggtgacgtg tgcagcggtg acgacggctc cgagtgacgg tgcatcagag ctggcacatg 69160cgccgttgtg ggggttgttg cgtgccgcgc aggtggagaa cccggggcag tttgtgctgg 69220cggacgtcga cggaaccgcc gaatcgtggc gtgcgttgcc gagtgcgttg ggctcgatgg 69280aaccgcagtt ggccctgcgg aagggcgcgg tgcgagcgcc ccgcttggct tcggtcgccg 69340ggcagatcga cgtgcccgcg gttgtggcgg atcccgaccg aaccgtgctg atttcgggcg 69400gcacgggcct gttggggggc gcggttgccc gccacctggt gaccgaacgc ggtgtccgcc 69460gattggtgtt gacgggccgt cgtggctggg atgctcctgg aatcaccgag ttggtgggtg 69520agctgaacgg cctcggtgcc gtggtcgacg tggtggcgtg cgacgtcgcg gatcgtgctg 69580atctggagtc gttgctggcg gcggtcccgg cggaatttcc gttgtgcggc gtggtgcatg 69640ccgcgggggc gctggccgac ggggtgatcg agtcgttgtc accggacgac gtgggagcgg 69700tgttcggccc gaaggcggcg ggggcgtgga atctgcacga gctgactcgt gatacggacc 69760tgtcgttctt cgcgttgttc tcctcgcttt ccggtgttgc cggcgctcct ggtcagggca 69820attatgcggc ggcgaacgcg ttcctggacg cattggcgca ttaccggcgg tcacagggac 69880tgcctgcggt gtcgctggcc tggggcctgt gggagcagcc gagcgggatg acggagacgc 69940tcagcgaggt cgaccggagc aggatcgcgc gcgccaaccc gccgttgtcc accaaggagg 70000gattgcggct gttcgatgcc gggctggcgc tggaccgggc agcggtagtt ccggcgaagt 70060tggacaggac tttcctggcc gagcaggcgc ggtcgggctc gctgcccgca ttgttgacgg 70120cactggtacc ccccatccgt cgtaataggc gggctagcgg aaccgagctc gcggacgagg 70180gcaccctgct cggggtggtg cgggagcatg ccgcggccgt gctggggtat tcgagcgcgg 70240ctgacgtcgg ggtcgagcgc gctttccggg atctgggttt tgattcgttg tctggtgtgg 70300agttgcggaa ccgccttgcc ggggtgctgg gggtgcggtt gccggcgact gcggtgttcg 70360actatccgac gccgagggcg ctggcccggt tcctgcacca ggaactggca gacgagatcg 70420ctacgacgcc agcgccggtg acgacgacca gggcaccggt cgccgaagac gatctcgtcg 70480cgatagtcgg gatgggatgc cgttttcccg gtcaggtgtc ctcgccggag gagctctggc 70540gtttggtggc cgggggcgtg gatgcggtcg cggacttccc agccgatcgc ggctgggatc 70600tggcaggctt gttcgatccg gacccggaac gggctgggaa gacctacgtg cgggaagggg 70660ccttcctcac cgacgccgat cggttcgatg cgggtttctt cgggatttcc ccgcgtgagg 70720cgttggcgat ggatccgcag caacggctgt tgctggagct gtcctgggag gccattgaac 70780gggcagggat cgatccgggt tcgctgaggg ggagtcggac cggtgtgttc gcggggctga 70840tgtaccacga ctatggcgcc cggttcgcca gccgagcccc ggaaggtttc gaggggtatc 70900tcggcaatgg cagtgctggg agtgtcgcgt cgggccggat tgcgtactcg tttggtttcg 70960agggtcctgc ggtgacggtg gatactgcgt gttcgtcgtc gttggtggcg ttgcatttgg 71020cgggtcagtc gttgcgttcc ggcgaatgcg atctcgccct tgccggtggt gtgacggtga 71080tgtcgacgcc cgggacgttt gtggaattct cccgtcagcg gggcctggca ccggacgggc 71140ggtgcaagtc gttcgcggag agcgcggacg gtaccggttg gggtgagggt gctggtttgg 71200tgttgttgga gcggttgtcg gatgctcggc ggaatgggca tcgggtgttg gcggtggttc 71260gtgggtcggc ggtgaatcag gatggtgcgt cgaatggctt gaccgcgccg aatggtccct 71320cgcagcagcg ggtcatccag caggcgttgg cgagtgcggg tctgtcggtg tccgatgtgg 71380atgccgtgga ggcgcatggg accgggacca ggttgggtga tccgattgag gcgcaggctc 71440tgattgctac gtatgggcgc gatcgtgatc ccggtcggcc gttgtggttg gggtcggtga 71500agtccaacat cggtcatacg caggcggcgg cgggtgttgc cggtgtgatc aagatggtga 71560tggcgatgcg gcacgggcaa cttccgcgca cgctgcacgt ggatgcaccc tcctcgcagg 71620tggattggtc ggcggggagg gtccagctcc tgacggagaa cacgccctgg cccgacagtg 71680gtcgcccctg tcgggtgggg gtgtcgtcgt tcgggatcag cggcaccaac gcgcacgtca 71740tcctggaaca gtccacgggg cagatggatc aggcagcgga gccggattcg agtcctgttc 71800tggatgttcc ggtggtgccg tgggtggtgt cgggcaaaac acccgaagcg ctatccgccc 71860aggcggcaac gttggcgacc tatttggacc aaaatgttga tgtctcccct ctggacgttg 71920ggatttcgct tgcggtgacc cgttcggcgc tggatgagcg ggcggtggtg ctggggtcgg 71980atcgtgacac gttgttgtct ggcctgaatg cgctggctgc cggtcatgag gctgctggcg 72040tggttacggg acctgtcggg attggtggcc ggaccgggtt tgtgttcgcc ggtcaaggcg 72100gtcagtggtt ggggatgggc cgccggttgt actcggagtt tccggcgttc gccggtgctt 72160tcgacgaagc atgcgccgag ctcgatgcga acctggggag ggaagtcggg gttcgggatg 72220tggtgttcgg ctccgacgag tccttgctgg atcggacttt gtgggcgcag tcgggtttgt 72280tcgcgttgca ggtcggtctc tgggaattgt tgggtacgtg gggtgttcgg cccagcgtag 72340tgctggggca ttcggtcggg gagctagccg cggcgttcgc cgcaggtgtg ctgtcgatgg 72400cggaggcggc tcggctggtg gcgggtcgtg cgcggttgat gcaggcgttg ccttctggcg 72460gtgccatgct ggcggtgtcc gcgaccgagg cccgagtcgg cccgctgctc gatggggtgc 72520gggatcgtgt tggtgtcgca gcggttaacg ctccggggtc ggtggtgctt tccggtgacc 72580gggatgtgct cgatggcatt gccggtcggc tggacgggca aggtatccgg tcgaggtggt 72640tgcgggtttc gcacgcgttt cattcgcatc ggatggatcc gatgctggcg gagttcgccg 72700agctcgcacg gagcgtggac taccggtctc cacggctgcc gattgtctcg acgctgaccg 72760gaaacctcga tgacgtgggc gtgatggcta cgccggagta ttgggtgcgc caggtgcgag 72820agcccgtccg cttcgccgac ggtgtccagg cgcttgtgga ccaaggcgtc gacacgattg 72880tggaactcgg tccggacggg gcgttgtcga gcttggttca agagtgtgtg gcggagtccg 72940ggcgggcgac ggggattccg ttggtgcgga gagaccgtga tgaggtccga acggtgctgg 73000acgctttggc gcagacccac actcgtggtg gcgcggtgga ctgggggtca tttttcgctg 73060gtacgagggc aacgcaagtc gaccttccca cgtatgcctt ccaacgacag cggtactggc 73120tggagccatc ggattccggt gatgtgaccg gtgttggcct gaccggggcg gagcatccgc 73180tgttgggtgc cgtggtgccg gtcgcgggcg gcgatgaggt gctgctgacc ggcaggctgt 73240cggtggggac gcatccgtgg ctggcggaac accgcgtgct gggcgaagtc gtcgtccccg 73300gcaccgcgtt gctggagatg gcgtggcggg ccggtagcca ggtcggttgt gaacgtgtgg 73360aggagctcac cttggaggca ccgctggtcc tgccggagcg gggcgctgcg gcggtgcagt 73420tggcggtggg ggctccggat gaggccggcc ggcgcagttt gcagctctat tcccgaggcg 73480ctgatgaaga cggcgactgg cggcggattg cctccgggct gttggcccag gccaatgcgg 73540tgccgccggc ggattcgacg gcatggccgc cggacggcgc cgggcaggtc gatctggcgg 73600agttctacga gcgcctcgcc gagcgcggct tgacctacgg cccggtattc caagggctcc 73660gcgccgcatg gcggcacggc gacgatatct tcgccgaatt ggccgggtca ccagacgcct 73720cgggtttcgg catccacccg gcgctgctgg acgctgcact gcacgcgatg gcgcttggtg 73780cttcgcccga ctcggaagcg cgtctgccgt tttcctggcg tggcgcccag ctgtaccgcg 73840ctgaaggagc agcgcttcgg gtacggctct cgccgctggg ctccggtgca gtctcattga 73900cgttggtgga tgccacaggg cgacgagtcg ctgcggtgga atcgctttcg acgcgaccgg 73960tctccaccga ccagatcggt gccggtcgcg gcgatcaaga gcggctgctg cacgtcgagt 74020gggtaaggtc ggctgaatct gcggggatgt ctctgacctc ctgcgcggtg gtcggtttgg 74080gcgaaccgga gtggcacgct gcgctgaaga ccactggtgt ccaagtcgag tcccatgcgg 74140accttgcttc gttggccacc gaggttgcca agcggggttc agctcctggt gcggtcatcg 74200tcccgtgccc gcgaccccga gcgatgcagg agctgccgac cgccgcgcga agggcgacgc 74260aacaggcgat ggcgatgctg cagcaatggc ttgccgatga ccggttcgtc agtacgcgcc 74320tgatcctgct gacgcatcgg gcggtctccg cagttgctgg agaagacgtg ctcgacctgg 74380tacacgcgcc gctgtggggc ttggtccgca gcgcgcaagc ggagcacccg gaccgattcg 74440ccttgatcga tatggacgac gagcgagcat cgcagacggc actcgccgaa gcgctgactg 74500cgggagaagc gcagctcgcg gtgcggtcgg gagttgtgcc ggcgccccgcctcggccagg 74560tgaaggtgag tggaggtgaa gcgttcaggt gggatgaagg caccgtgctg gtcaccggcg 74620gaaccggcgg gctcggggcc ctgctcgcac gccatctggt cagcgcccac ggtgtgcggc 74680acctgttgct cgcaagtcgc cgtggtctgg cggcgcccgg agcggatgag ctggtggccg 74740agctggagca ggccggcgcc gacgtcgcgg tcgtcgcgtg cgactcggca gatcgggact 74800cgcttgcgcg gctggtggcg tcggtgcctg cggaaaaccc gttgcgggtg gtggtgcacg 74860ccgccggtgt gctggatgac ggtgtgctga tgtcgatgtc gccggagcgc ttggacgcgg 74920tgttgcggcc caaagtggat gccgcgtggt acctgcacga gctgactcgg gaactcggtc 74980tgtcggcgtt cgtgttgttc tcctcggtcg cgggcctgtt cggcggtgcg gggcagagca 75040attacgctgc cggcaacgct ttcctggatg ccttggcgca ttgccggcag gcccaggggc 75100tgcccgcgct gtcgctggcc tccgggctgt gggcgagtat cgatggaatg gcgggcgacc 75160tcgctgcggc agatgtggag cggctgtcgc gggcaggcat tggcccgctt tcggcaccgg 75220gagggctggc cttgttcgac gctgccgttg gctcggacga accgttgctg gcaccggtgc 75280gactggatgt cgaagcactg cgtgtgcagg cccgatccgt gcagacccgg attccggaaa 75340tgctgcatgg catggcaatg gggccaagcc gccgcactcc gttcacttcc agggttgagc 75400cgttgcacga acggctggcc ggattgtcgg agggcgaacg tcggcagcaa gtgctccagc 75460gcgtccgcgc cgatatcgcg gtggtactgg ggcacggcag gtcgagcgat gtggacatcg 75520agaagccttt ggccgagctg ggtttcgact cgctgacggc catcgaactc cgcaaccgtc 75580tcgctaccgc caccggactg cggcttcccg cgacgctggc cttcgaccac ggcactgcgg 75640cggcactcgc ccagcacgtg tgcgcgcagc taggcaccgc gaccgcgccg gcaccgaggc 75700gaaccgacga caacgacgcc acggagcccg tgaggtcgct cttccaacag gcgtatgcgg 75760ctggccggat acttgacggg atggatttgg tgaaggtcgc tgcccagttg cgaccggtgt 75820tcggttcgcc tggcgagctg gaatccctgc cgaaacccgt ccagctttcc cgtggtcccg 75880aagagcttgc cttggtgtgc atgccggcgc tgatcgggat gccgcccgca cagcagtacg 75940cgcggatcgc cgccgggttc cgcgatgtgc gggacgtttc ggtgatcccg atgcctggat 76000tcattgcggg agaaccgctg ccgtccgcca tcgaggtggc ggttcggacg caggcggagg 76060cggtgctgca ggaattcgcc gggggctcgt tcgtactggt cgggcattcc tccgggggct 76120ggctggcgca cgaggtagcc ggtgagctgg agcgtcgcgg ggtcgtcccg gccggggtcg 76180tactgctgga cacctacatc cccggtgaga tcacgccgag gttctccgtg gcgatggccc 76240accggacgta tgagaagctc gcgactttca cggacatgca ggatgtcggt atcaccgcga 76300tgggcgggta cttccggatg ttcaccgagt ggactccgac gccgatcggt gctccgacgc 76360tgttcgtgcg gaccgaagat tgcgtcgcag accctgaagg gcggccgtgg acagatgact 76420cctggcggcc agggtggact ctcgcggatg ccacggtcca ggtgccgggc gaccacttct 76480cgatgatgga cgagcacgcc gggtccaccg cacaggcagt cgcgagttgg cttgacaaac 76540tcaaccagcg caccgctcgg caacgctgac gggcgtcctt ttaggacctt ctgggcggca 76600ccggccaccc cggcggtgcc gccttccgtg gtccaggctc gccgatcttg acggcgcacg 76660atgcgcggca cgcgcgctga tcgtgattcc gctgccgctc gtggccatcg gcctggcgaa 76720tcatgtcctt tcgggcaacg tcaaacgaat tcgtccgagc ccgcattccg aggtgagggg 76780cacccttggg tggctgagcc gctcaagggt gcccctcacc tcgaaattcg tccgatttgg 76840gcggtggacg caaccccggt gggcgtggtg cgtctttctt gttgacagag cggtgagaag 76900ccgctgacac acctgagagg aaaaggggag catgatgctc aagcgccacc gtttgacgac 76960cgccatcacc ggccttctgg ggggagtact gctggtcagc ggctgcggaa ccgccgccgc 77020acttcagtcc tcgccggcgc ccgggcatga cgcgcgcaat gttggtatgg cctcgggcgg 77080gggcggcggg gacatcggca cgtcgaactg ctcggaggcc gatttcctcg ccaccgcgac 77140accggtgaaa ggcgaccccg gcagtttcat cgtggcgtac gggaaccggt cggacaagac 77200ctgcacgatc aacggcggcg tgccgaacct caagggcgtg gacatgagca actcgccgat 77260cgaggacctg ccggtcgagg acgtgcggct tcccgacgcg cccaaggaat tcaccctcca 77320gcccggtcag agcgcgtacg ccggcattgg catggtcctg gccgacagcg gcgacccgaa 77380cgcccatgtc ctcaccgggt tccagtcctc gctgccggac atgtccgagg cccagccggt 77440caacgttctc ggcgacggca acgtgaagtt cgccgcgaag tacctgcgag tcagctcgct 77500ggtgtctacc gcagacgagc tgcgctaaaa cccatgtgag tcccgcagat tcgacctcgc 77560cgtgcggcgc ctccggcgaa gcgtccgtac gtttgtcgtt gtgaccagcg ttgttcacgt 77620ccgggcgcag cgctggtaca tactcaggcg tctcgggcgc ctccaacggg gcctggcatc 77680cggggccgtc gagtgcggcg gcgctgacgc gttctctgtc gggcgttgtc acgccgccgg 77740cctcgaaccg gtcccgcccc gtcggagccg gtggtccagc gcggtgtggc ggcggccgga 77800gccgacggtg cgcaccgcct gcccgagggc ctttttcgaa ccgacgagga ccacgacctt 77860cttggcccgg gtgaccgccg tgtagagcag gttgcgctgc agcatcatcc aggcgcttgt 77920ggtcaagggg atcaccacgc acgggtattc gcttccctgc gaacgatgga tggtcaccgc 77980gtaggcgtgg accagttcgt cgagttctgt gaagtcgtag tcgatgtcct cgtcctcgtc 78040ggttcgcacg gtcatggtct gtgcttcgtt gtcgagggcg gacacgacgc cctgcgtgcc 78100gttgaacacg ccgttggcgc ccttgtcgta gttgttgcgg atctgcgtga ccttgtcgcc 78160gacgcggaag atccgtccgc cgaaccgccg ctctggcagg ccctccctgg ccggggtgat 78220cgcttcctgc aacagctggt tcagcgcgcc tgcacctgcg gggcctcgat gcatcggggc 78280gaggacctgc acgtcggtgc gcgggttgaa ccggaacttc cgcggaatcc ggcgggcgac 78340gacgtcgacg gtgagctcgg cggtcggttc gctttcctct acgtggaaca ggaagaagtc 78400ggtcagcccg tgtgtcagcg gatagtcccc ggcgttgatt cggtgcgcgt tggtcaccac 78460cccggactcg gcggcctgcc ggaacacctc gttgagccgc acgtgtggaa tcggggtgcc 78520aggggcgagc agatcgcgca gtacctcacc ggctccgacc gacgggagct ggtcgacgtc 78580gccgaccagc agcaggtgcg cgccgggcgc gatcgccttg gccagtttgt tggctaacag 78640caggtcgagc atggacgcct cgtcgaccac gacgaggtcg gcgtccagcg ggttgtcccg 78700gtcgtaggcg gcgtccccgc ccggctggag ttggagcagg cggtgcacgg tcgccgcgtc 78760gtgtccggtg agctcggtca gccgcttcgc cgctcgtccc gtcggcgcgg cgaggatcac 78820cttggccttt ttcgcctgag ctaatgcgat gatcgaccgc acggtgaagc tcttgccgca 78880gcctggacct ccggtgagca cggcgacctt ctcggtcagg gccagcttga cggcgcgctc 78940ctgcgcctcg gcgagttcgg caccggtagc gcggcgcaac cagtcgaggg ccttgtgcca 79000atcgacgtcg gcgaagacgg gcatccggtc cgcgctggtg ttcagcagcc gggacagctg 79060gttggccagg gcgacttcgg cgcggtggaa gggcacgagg tagatcgcga ccgtcggcac 79120ctcgtcgtca tcggtgggga tctcctcgcg gaccacacct tcctcggtga cgagttcggc 79180gaggcattcg atcaccagcc cggtgtcgac ggcgaggatc ttcaccgcct cggcgatcag 79240ctcgttctcc ggcaggtagc agttgccgtc gccggtggac tccgacagcg tgaactgaag 79300gcccgccttt acccgctgcg gggagtcgtg cgggattccc accgctttgg cgatggtgtc 79360ggcggtcttg aaaccgattc cccacacgtc gcctgccagc cggtatggct cttccttgac 79420ggtccggatc gcgtcgtcgt ggtactgctt gtagatcttc accgccagcg aggtcgagac 79480gccgacgcct tgcaggaaga tcatcacctc cttgatcgcc ttctgctcct cccacgcgtc 79540ggcgatcagc ttcgtccgct tcgggccgag cttggggacc tcgatcagcc gcgcgggttc 79600ctgctcgatg acgtcgagcg cggcgacgcc gaagtggtcg acgatcttct cggcgagttt 79660ggggccgatg cccttgatca ggccagaccc caggtagcgg cggatacctt gcacggtcgc 79720aggcagcacg gtcgtgtagt cgtcgacgtg gaactgccgc ccgtactggg ggtgcgaccc 79780ccaccggccg cgcatgcgca acgcctcgcc gggctgcgcg cccagcagcg cgccgacgac 79840cgtcaccagg tcaccgcccc ggccggtgtc gatccgcgcg acggtgtagc cgctctcctc 79900gttggcgaac gtgatccgct ccagcgtgcc ctccagcacc gcagtccacg tggccgactc 79960ccgtcctttt tccaccgaca acacgtatca cgaacggctg tcaagcaaac cggcggtcac 80020cacatgcagc ggcatctccc gaacgcctcg ggctccggcg tcagcgggtg ggcgttcgcg 80080atgccttggt gcggccggtg ggagttgtag attttttcgt cctcgcgcag ggcctggagt 80140aggtgccgct ggctccagat c 80161<210>2<211>2595<212>PRT<213>刺糖多孢菌<400>2Met Ser Glu Ala Gly Asn Leu Ile Ala Val Ile Gly Leu Ser Cys Arg1 5 10 15Leu Pro Gln Ala Pro Asp Pro Ala Ser Phe Trp Arg Leu Leu Arg Thr
20 25 30Gly Thr Asp Ala Ile Thr Thr Val Pro Glu Gly Arg Trp Gly Asp Pro
35 40 45Leu Pro Gly Arg Asp Ala Pro Lys Gly Pro Glu Trp Gly Gly Phe Leu
50 55 60Ala Asp Val Asp Cys Phe Asp Pro Glu Phe Phe Gly IIe Ser Pro Arg65 70 75 80Glu Ala Ala Thr Val Asp Pro Gln Gln Arg Leu Ala Leu Glu Leu Ala
85 90 95Trp Glu Ala Leu Glu Asp Ala Gly Ile Pro Ala Gly Glu Leu Arg Gly
100 105 110Thr Ala Ala Gly Val Phe Met Gly Ala Ile Ser Asp Asp Tyr Ala Ala
115 120 125Leu Leu Arg Glu Ser Pro Pro Glu Val Ala Ala Gln Tyr Arg Leu Thr
130 135 140Gly Thr His Arg Ser Leu Ile Ala Asn Arg Val Ser Tyr Val Leu Gly145 150 155 160Leu Arg Gly Pro Ser Leu Thr Val Asp Ser Gly Gln Ser Ser Ser Leu
165 170 175Val Gly Val His Leu Ala Ser Glu Ser Leu Arg Arg Gly Glu Cys Thr
180 185 190Ile Ala Leu Ala Gly Gly Val Asn Leu Asn Leu Ala Ala Glu Ser Asn
195 200 205Ser Ala Leu Met Asp Phe Gly Ala Leu Ser Pro Asp Gly Arg Cys Phe
210 215 220Thr Phe Asp Val Arg Ala Asn Gly Tyr Val Arg Gly Glu Gly Gly Gly225 230 235 240Leu Val Val Leu Lys Lys Ala Asp Gln Ala His Ala Asp Gly Asp Arg
245 250 255Ile Tyr Cys Leu Ile Arg Gly Ser Ala Val Asn Asn Asp Gly Gly Gly
260 265 270Ala Gly Leu Thr Val Pro Ala Ala Asp Ala Gln Ala Glu Leu Leu Arg
275 280 285Gln Ala Tyr Arg Asn Ala Gly Val Asp Pro Ala Ala Val Gln Tyr Val
290 295 300Glu Leu His Gly Ser Ala Thr Arg Val Gly Asp Pro Val Glu Ala Ala305 310 315 320Ala Leu Gly Ala Val Leu Gly Ala Ala Arg Arg Pro Gly Asp Glu Leu
325 330 335Arg Val Gly Ser Ala Lys Thr Asn Val Gly His Leu Glu Ala Ala Ala
340 345 350Gly Val Thr Gly Leu Leu Lys Thr Ala Leu Ser Ile Trp His Arg Glu
355 360 365Leu Pro Pro Ser Leu His Phe Thr Ala Pro Asn Pro Glu Ile Pro Leu
370 375 380Asp Glu Leu Asn Leu Arg Val Gln Arg Asp Leu Arg Pro Trp Pro Glu385 390 395 400Ser Glu Gly Pro Leu Leu Ala Gly Val Ser Ala Phe G1y Met Gly Gly
405 410 415Thr Asn Cys His Leu Val Leu Ser Gly Thr Ser Arg Val Glu Arg Arg
420 425 430Arg Ser Gly Pro Ala Glu Ala Thr Met Pro Trp Val Leu Ser Ala Arg
435 440 445Thr Pro Val Ala Leu Arg Ala Gln Ala Ala Arg Leu His Thr His Leu
450 455 460Asn Thr Ala Gly Gln Ser Pro Leu Asp Val Ala Tyr Ser Leu Ala Thr465 470 475 480Thr Arg Ser Ala Leu Pro His Arg Ala Ala Leu Val Ala Asp Asp Glu
485 490 495Pro Lys Leu Leu Ala Gly Leu Lys Ala Leu Ala Asp Gly Asp Asp Ala
500 505 510Pro Thr Leu Cys His Gly Ala Thr Ser Gly Glu Arg Ala Ala Val Phe
515 520 525Val Phe Pro Gly Gln Gly Ser Gln Trp Ile Gly Met Gly Arg Gln Leu
530 535 540Leu Glu Thr Ser Glu Val Phe Ala Ala Set Met Ser Asp Cys Ala Asp54S 550 555 560Ala Leu Ala Pro His Leu Asp Trp Ser Leu Leu Asp Val Leu Arg Asn
565 570 575Ala Ala Gly Ala Ala His Leu Asp His Asp Asp Val Val Gln Pro Ala
580 585 590Leu Phe Ala Ila Met Val Ser Leu Ala Glu Leu Trp Arg Ser Trp Gly
595 600 605Val Arg Pro Val Ala Val Val Gly His Ser Gln Gly Glu Ile Ala Ala
610 615 620Ala Cys Val Ala Gly Ala Leu Ser Val Arg Asp Ala Ala Arg Val Val625 630 635 640Ala Val Arg Ser Arg Leu Leu Thr Ala Leu Ala Gly Ser Gly Ala Met
645 650 655Ala Ser Leu Gln His Pro Ala Glu Glu Val Arg Gln Ile Leu Leu Pro
660 665 670Trp Arg Asp Arg Ile Gly Val Ala Gly Val Asn Gly Pro Ser Ser Thr
675 680 685Leu Val Ser Gly Asp Arg Glu Ala Met Ala Glu Leu Leu Ala Glu Cys
690 695 700Ala Asp Arg Glu Leu Arg Met Arg Arg Ile Pro Val Glu Tyr Ala Ser705 710 715 720His Ser Pro His Ile Glu Val Val Arg Asp Glu Leu Leu Gly Leu Leu
725 730 735Ala Pro Val Glu Pro Arg Thr Gly Ser Ile Prc Ile Tyr Ser Thr Thr
740 745 750Thr Gly Asp Leu Leu Asp Arg Pro Met Asp Ala Asp Tyr Trp Tyr Arg
755 760 765Asn Leu Arg Gln Pro Val Leu Phe Glu Ala Ala Val Glu Ala Leu Leu
770 775 780Lys Arg Gly Tyr Asp Ala Phe Ile Glu Ile Ser Pro His Pro Val Leu785 790 795 800Thr Ala Ash Ile Gln Glu Thr Ala Val Arg Ala Gly Arg Glu Val Val
805 810 815Ala Leu Gly Thr Leu Arg Arg Gly Glu Gly Gly Met Arg Gln Ala Leu
820 825 830Thr Ser Leu Ala Arg Ala His Val His Gly Val Ala Ala Asp Trp His
835 840 845Ala Val Phe Ala Gly Thr Gly Ala Gln Arg Val Asp Leu Pro Thr Tyr
850 855 860Ala Phe Gln Arg Gln Arg Tyr Trp Leu Asp Ala Lys Leu Pro Asp Val865 870 875 880Ala Met Pro Glu Ser Asp Val Ser Thr Ala Leu Arg Glu Lys Leu Arg
885 890 895Ser Ser Pro Arg Ala Asp Val Asp Ser Thr Thr Leu Thr Met Ile Arg
900 905 910Ala Gln Ala Ala Val Val Leu Gly His Ser Asp Pro Lys Glu Val Asp
915 920 925Pro Asp Arg Thr Phe Lys Asp Leu Gly Phe Asp Ser Ser Met Val Val
930 935 940Glu Leu Cys Asp Arg Leu Ash Ala Ala Thr Gly Leu Arg Leu Ala Pro945 950 955 960Ser Val Val Phe Asp Cys Pro Thr Pro Asp Lys Leu Ala Arg Gln Val
965 970 975Arg Thr Leu Leu Leu Gly Glu Pro Ala Pro Met Thr Ser His Arg Pro
980 985 990Asp Ser Asp Ala Asp Glu Pro Ile Ala Val Ile Gly Met Gly Cys Arg
995 1000 1005Phe Pro Gly Gly Val Ser Ser Pro Glu Glu Leu Trp Gln Leu Val Ala1010 1015 1020Ala Gly Arg Asp Val Val Ser Glu Phe Pro Ala Asp Arg Gly Trp Asp1025 1030 1035 1040Leu Glu Arg Ala Gly Thr Ser His Val Arg Ala Gly Gly Phe Leu His
1045 1050 1055Gly Ala Pro Asp Phe Asp Pro Gly Phe Phe Arg Ile Ser Pro Arg Glu
1060 1065 1070Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu Ile Ala Trp
1075 1080 1085Glu Ala Val Glu Arg Gly Gly Ile Asn Pro Gln His Leu His Gly Sar1090 1095 1100Gln Thr Gly Val Phe Val Gly Ala Thr Ser Leu Asp Tyr Gly Pro Arg1105 1110 1115 1120Leu His Glu Ala Ser Glu Glu Ala Ala Gly Tyr Val Leu Thr Gly Ser
1125 1130 1135Thr Thr Ser Val Ala Ser Gly Arg Val Ala Tyr Ser Phe Gly Phe Glu
1140 1145 1150Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala
1155 1160 1165Leu His Leu Ala Cys Gln Ser Leu Arg Ser Gly Glu Cys Asp Leu Ala1170 1175 1180Leu Ala Gly Gly Val Thr Val Met Ala Thr Pro Gly Met Phe Val Glu1185 1190 1195 1200Phe Ser Arg Gln Arg Gly Leu Ala Pro Asp Gly Arg Cys Lys Ser Phe
1205 1210 1215Ala Glu Ala Ala Asp Gly Thr Gly Trp Ser Glu Gly Ala Gly Leu Val
1220 1225 1230Leu Leu Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly His Glu Val Leu
1235 1240 1245Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly1250 1255 1260Leu Thr Ala Pro Asn Gly Ser Ser Gln Gln Arg Val Ile Ala Gln Ala1265 1270 1275 1280Leu Ala Ser Ala Gly Leu Ser Val Ser Asp Val Asp Ala Val Glu Ala
1285 1290 1295His Gly Thr Gly Thr Arg Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu
1300 1305 1310Ile Ala Thr Tyr Gly Gln Gly Arg Leu Pro Glu Arg Pro Leu Trp Leu
1315 1320 1325Gly Ser Met Lys Ser Asn Ile Gly His Ala Gln Ala Ala Ala Gly Ile1330 1335 1340Ala Gly Val Met Lys Met Val Met Ala Met Arg His Gly Gln Leu Pro1345 1350 1355 1360Arg Thr Leu His Val Asp Glu Pro Thr Ser Gly Val Asp Trp Ser Ala
1365 1370 1375Gly Thr Val Gln Leu Leu Thr Glu Asn Thr Pro Trp Pro Gly Ser Gly
1380 1385 1390Arg Val Arg Arg Val Gly Val Ser Ser Phe Gly Ile Ser Gly Thr Asn
1395 1400 1405Ala His Val Ile Leu Glu Gln Pro Pro Gly Val Pro Ser Gln Ser Ala1410 1415 1420Gly Pro Gly Ser Gly Ser Val Val Asp Val Pro Val Val Pro Trp Met1425 1430 1435 1440Val Ser Gly Lys Thr Pro Glu Ala Leu Ser Ala Gln Ala Thr Ala Leu
1445 1450 1455Met Thr Tyr Leu Asp Glu Arg Pro Asp Val Ser Ser Leu Asp Val Gly
1460 1465 1470Tyr Ser Leu Ala Leu Thr Arg Ser Ala Leu Asp Glu Arg Ala Val Val
1475 1480 1485Leu Gly Ser Asp Arg Glu Thr Leu Leu Cys Gly Val Lys Ala Leu Ser1490 1495 1500Ala Gly His Glu Ala Ser Gly Leu Val Thr Gly Ser Val Gly Ala Gly1505 1510 1515 1520Gly Arg Ile Gly Phe Val Phe Ser Gly Gln Gly Gly Gln Trp Leu Gly
1525 1530 1535Met Gly Arg Gly Leu Tyr Arg Ala Phe Pro Val Phe Ala Ala Ala Phe
1540 1545 1550Asp Glu Ala Cys Ala Glu Leu Asp Ala His Leu Gly Gln Glu Ile Gly
1555 1560 1565Val Arg Glu Val Val Ser Gly Ser Asp Ala Gln Leu Leu Asp Arg Thr1570 1575 1580Leu Trp Ala Gln Ser Gly Leu Phe Ala Leu Gln Val Gly Leu Leu Lys1585 1590 1595 1600Leu Leu Asp Ser Trp Gly Val Arg Pro Ser Val Val Leu Gly His Ser
1605 1610 1615Val Gly Glu Leu Ala Ala Ala Phe Ala Ala Gly Val Val Ser Leu Ser
1620 1625 1630Gly Ala Ala Arg Leu Val Ala Gly Arg Ala Arg Leu Met Gln Ala Leu
1635 1640 1645Pro Ser Gly Gly Gly Met Leu Ala Val Pro Ala Gly Glu Glu Leu Leu1650 1655 1660Trp Sar Leu Leu Ala Asp Gln Gly Asp Arg Val Gly Ile Ala Ala Val1665 1670 1675 1680Asn Ala Ala Gly Ser Val Val Leu Ser Gly Asp Arg Asp Val Leu Asp
1685 1690 1695Asp Leu Ala Gly Arg Leu Asp Gly Gln Gly Ile Arg Ser Arg Trp Leu
1700 1705 1710Arg Val Ser His Ala Phe His Ser Tyr Arg Met Asp Pro Met Leu Ala
1715 1720 1725Glu Phe Ala Glu Leu Ala Arg Thr Val Asp Tyr Arg Arg Cys Glu Val1730 1735 1740Pro Ile Val Ser Thr Leu Thr Gly Asp Leu Asp Asp Ala Gly Arg Met1745 1750 1755 1760Ser Gly Pro Asp Tyr Trp Val Arg Gln Val Arg Glu Pro Val Arg Phe
1765 1770 1775Ala Asp Gly Val Gln Ala Leu Val Glu His Asp Val Ala Thr Val Val
1780 1785 1790Glu Leu Gly Pro Asp Gly Ala Leu Ser Ala Leu Ile Gln Glu Cys Val
1795 1800 1805Ala Ala Ser Asp His Ala Gly Arg Leu Ser Ala Val Pro Ala Met Arg1810 1815 1820Arg Ash Gln Asp Glu Ala Gln Lys Val Met Thr Ala Leu Ala His Val1825 1830 1835 1840His Val Arg Gly Gly Ala Val Asp Trp Arg Ser Phe Phe Ala Gly Thr
1845 1850 1855Arg Ala Lys Gln Ile Glu Leu Pro Thr Tyr Ala Phe Gln Arg Gln Arg
1860 1865 1870Tyr Trp Leu Asn Ala Leu Arg Glu Ser Ser Ala Gly Asp Met Gly Arg
1875 1880 1885Arg Val Glu Ala Lys Phe Trp Gly Ala Val Glu His Glu Asp Val Glu1890 1895 1900Ser Leu Ala Arg Val Leu Gly Ile Val Asp Asp Gly Ala Ala Val Asp1905 1910 1915 1920Ser Leu Arg Ser Ala Leu Pro Val Leu Ala Gly Trp Gln Arg Thr Arg
1925 1930 1935Thr Thr Glu Ser Ile Met Asp Pro Arg Cys Tyr Arg Ile Gly Trp Arg
1940 1945 1950Gln Val Ala Gly Leu Pro Pro Met Gly Thr Val Phe Gly Thr Trp Leu
1955 1960 1965Val Phe Ala Pro His Gly Trp Ser Ser Glu Pro Glu Val Val Asp Cys1970 1975 1980Val Thr Ala Leu Arg Ala Arg Gly Ala Ser Val Val Leu Val Glu Ala1985 1990 1995 2000Asp Pro Asp Pro Thr Ser Phe Gly Asp Arg Val Arg Thr Leu Cys Ser
2005 2010 2015Gly Leu Pro Asp Leu Val Gly Val Leu Ser Met Leu Cys Leu Glu Glu
2020 2025 2030Ser Val Leu Pro Gly Phe Ser Ala Val Ser Arg Gly Phe Ala Leu Thr
2035 2040 2045Val Glu Leu Val Arg Val Leu Arg Ala Ala Gly Ala Thr Ala Arg Leu2050 2055 2060Trp Leu Leu Thr Cys Gly Gly Val Ser Val Gly Asp Val Pro Val Arg2065 2070 2075 2080Pro Ala Gln Ala Leu Ala Trp Gly Leu Gly Arg Val Val Gly Leu Glu
2085 2090 2095His Pro Asp Trp Trp Gly Gly Leu Ile Asp Ile Pro Val Leu Phe Asp
2100 2105 2110Glu Asp Ala Gln Glu Arg Leu Ser Ile Val Leu Ala Gly Leu Asp Glu
2115 2120 2125Asp Glu Val Ala Ile Arg Pro Asp Gly Met Phe Ala Arg Arg Leu Val2130 2135 2140Arg His Thr Val Ser Ala Asp Val Lys Lys Ala Trp Arg Pro Arg Gly2145 2150 2155 2160Ser Val Leu Val Thr Gly Gly Thr Gly Gly Leu Gly Ala His Val Ala
2165 2170 2175Arg Trp Leu Ala Asp Ala Gly Ala Glu His Val Ala Met Val Ser Arg
2180 2185 2190Arg Gly Glu Gln Ala Pro Ser Ala Glu Lys Leu Arg Thr Glu Leu Glu
2195 2200 2205Asp Leu Gly Thr Arg Val Ser Ile Val Ser Cys Asp Val Thr Asp Arg 2210 2215 2220Glu Ala Leu Ala Glu Val Leu Lys Ala Leu Pro Ala Glu Asn Pro Leu2225 2230 2235 2240Thr Ala Val Val His Ala Ala Gly Val Ile Glu Thr Gly Asp Ala Ala
2245 2250 2255Ala Met Ser Leu Ala Asp Phe Asp His Val Leu Ser Ala Lys Val Ala
2260 2265 2270Gly Ala Ala Asn Leu Asp Ala Leu Leu Ala Asp Val Glu Leu Asp Ala
2275 2280 2285Phe Val Leu Phe Ser Ser Val Ser Gly Val Trp Gly Ala Gly Gly His2290 2295 2300Gly Ala Tyr Ala Ala Ala Asn Ala Tyr Leu Asp Ala Leu Ala Glu Gln2305 2310 2315 2320Arg Arg Ser Arg Gly Leu Val Ala Thr Ala Val Ala Trp Gly Pro Trp
2325 2330 2335Ala Gly Glu Gly Met Ala Ser Gly Glu Thr Gly Asp Gln Leu Arg Arg
2340 2345 2350Tyr Gly Leu Ser Pro Met Ala Pro Gln His Ala Ile Ala Gly Ile Arg
2355 2360 2365Gln Ala Val Glu Gln Asp Glu Ile Ser Leu Val Val Ala Asp Val Asp2370 2375 2380Trp Ala Arg Phe Ser Ala Gly Leu Leu Ala Ala Arg Pro Arg Pro Leu2385 2390 2395 2400Leu Asn Glu Leu Ala Glu Val Lys Glu Leu Leu Val Asp Ala Gln Pro
2405 2410 2415Glu Ala Gly Val Leu Ala Asp Ala Ser Leu Glu Trp Arg Gln Arg Leu
2420 2425 2430Ser Ala Ala Pro Arg Pro Thr Gln Glu Gln Leu Ile Leu Glu Leu Val
2435 2440 2445Arg Gly Glu Thr Ala Leu Val Leu Gly His Pro Gly Ala Ala Ala Val2450 2455 2460Ala Ser Glu Arg Ala Phe Lys Asp Ser Gly Phe Asp Ser Gln Ala Ala2465 2470 2475 2480Val Glu Leu Arg Val Arg Leu Asn Arg Ala Thr Gly Leu Gln Leu Pro
2485 2490 2495Ser Thr Ile Ile Phe Ser His Pro Thr Pro Ala Glu Leu Ala Ala Glu
2500 2505 2510Leu Arg Ala Arg Leu Leu Pro Glu Ser Ala Gly Ala Gly Ile Pro Glu
2515 2520 2525Glu Asp Glu Ala Arg Ile Arg Ala Ala Leu Thr Ser Ile Pro Phe Pro2530 2535 2540Ala Leu Arg Glu Ala Gly Leu Val Ser Pro Leu Leu Ala Leu Ala Gly2545 2550 2555 2560His Pro Val Asp Ser Gly Ile Ser Ser Asp Asp Ala Ala Ala Thr Ser
2565 2570 2575Ile Asp Ala Met Asp Val Ala Gly Leu Val Glu Ala Ala Leu Gly Glu
2580 2585 2590Arg Glu Ser
2595<210>3<211>2152<212>PRT<213>刺糖多孢菌<400>3Met Thr Val Thr Thr Ser Tyr Glu Glu Val Val Glu Ala Leu Arg Ala1 5 10 15Ser Leu Lys Glu Asn Glu Arg Leu Arg Arg Gly Arg Asp Arg Phe Ser
20 25 30Ala Glu Lys Asp Asp Pro Ile Ala Ile Val Ala Met Ser Cys Arg Tyr
35 40 45Pro Gly Gln Val Ser Ser Pro Glu Asp Leu Trp Gln Leu Ala Ala Gly
50 55 60Gly Val Asp Ala Ile Ser Glu Val Pro Gly Asp Arg Gly Trp Asp Leu65 70 75 80Asp Gly Val Phe Val Pro Asp Ser Asp Arg Pro Gly Thr Ser Tyr Ala
85 90 95Cys Ala Gly Gly Phe Leu Gln Gly Val Ser Glu Phe Asp Ala Gly Phe
100 105 110Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg
115 120 125Leu Leu Leu Glu Val Ala Trp Glu Val Phe Glu Arg Ala Gly Leu Glu
130 135 140Gln Arg Ser Thr Arg Gly Ser Arg Val Gly Val Phe Val Gly Thr Asn145 150 155 160Gly Gln Asp Tyr Ala Ser Trp Leu Arg Thr Pro Pro Pro Ala Val Ala
165 170 175Gly His Val Leu Thr Gly Gly Ala Ala Ala Val Leu Ser Gly Arg Val
180 185 190Ala Tyr Ser Phe Gly Phe Glu Gly Pro Ala Val Thr Val Asp Thr Ala
195 200 205Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Gly Gln Ala Leu Arg
210 215 220Ala Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly Val Thr Val Met Ser225 230 235 240Thr Pro Lys Val Phe Leu Glu Phe Ser Arg Gln Arg Gly Leu Ala Pro
245 250 255Asp Gly Arg Cys Lys Ser Phe Ala Ala Gly Ala Asp Gly Thr Gly Trp
260 265 270Gly Glu Gly Ala Gly Leu Leu Leu Leu Glu Arg Leu Ser Asp Ala Arg
275 280 285Arg Asn Gly His Glu Val Leu Ala Val Val Arg Gly Ser Aia Val Asn
290 295 300Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro ASn Gly Ser Ser Gln305 310 315 320Gln Arg Val Ile Thr Gln Ala Leu Ala Ser Ala Gly Leu Ser Val Ser
325 330 335Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Arg Leu Gly Asp
340 345 350Pro Ile Glu Ala Gln Ala Leu Ile Ala Thr Tyr Gly Arg Asp Arg Asp
355 360 365Pro Gly Arg Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His
370 375 380Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met Ala385 390 395 400Met Arg His Gly Gln Leu Pro Arg Thr Leu His Val Glu Ser Pro Ser
405 410 415Pro Glu Val Asp Trp Ser Ala Gly Thr Val Gln Leu Leu Thr Glu Asn
420 425 430Thr Pro Trp Pro Arg Ser Gly Arg Val Arg Arg Val Gly Val Ser Ser
435 440 445Phe Gly Ile Ser Gly Thr Asn Ala His Val Ile Leu Glu Gln Pro Pro
450 455 460Gly Val Pro Ser Gln Ser Ala Gly Pro Gly Ser Gly Ser Val Val Asp465 470 475 480Val Pro Val Val Pro Trp Met Val Ser Gly Lys Thr Pro Glu Ala Leu
485 490 495Ser Ala Gln Ala Thr Ala Leu Met Thr Tyr Leu Asp Glu Arg Pro Asp
500 505 510Val Ser Ser Leu Asp Val Gly Tyr Ser Leu Ala Leu Thr Arg Ser Ala
515 520 525Leu Asp Glu Arg Ala Val Val Leu Gly Ser Asp Arg Glu Thr Leu Leu
530 535 540Cys Gly Val Lys Ala Leu Ser Ala Gly His Glu Ala Ser Gly Leu Val545 550 555 560Thr Gly Ser Val Gly Ala Gly Gly Arg Ile Gly Phe Val Phe Ser Gly
565 570 575Gln Gly Gly Gln Trp Leu Gly Met Gly Arg Gly Leu Tyr Arg Ala Phe
580 585 590Pro Val Phe Ala Ala Ala Phe Asp Glu Ala Cys Ala Glu Leu Asp Ala
595 600 605His Leu Gly Gln Glu Ile Gly Val Arg Glu Val Val Ser Gly Ser Asp
610 615 620Ala Gln Leu Leu Asp Arg Thr Leu Trp Ala Gln Ser Gly Leu Phe Ala625 630 635 640Leu Gln Val Gly Leu Leu Lys Leu Leu Asp Ser Trp Gly Val Arg Pro
645 650 655Ser Val Val Leu Gly His Ser Val Gly Glu Leu Ala Ala Ala Phe Ala
660 665 670Ala Gly Val Val Ser Leu Ser Gly Ala Ala Arg Leu Val Ala Gly Arg
675 680 685Ala Arg Leu Met Gln Ala Leu Pro Ser Gly Gly Gly Met Leu Ala Val
690 695 700Pro Ala Gly Glu Glu Leu Leu Trp Ser Leu Leu Ala Asp Gln Gly Asp705 710 715 720Arg Val Gly Ile Ala Ala Val Asn Ala Ala Gly Ser Val Val Leu Ser
725 730 735Gly Asp Arg Asp Val Leu Asp Asp Leu Ala Gly Arg Leu Asp Gly Gln
740 745 750Gly Ile Arg Ser Arg Trp Leu Arg Val Ser His Ala Phe His Ser Tyr
755 760 765Arg Met Asp Pro Met Leu Ala Glu Phe Ala Glu Leu Ala Arg Thr Val
770 775 780Asp Tyr Arg Arg Cys Glu Val Pro Ile Val Ser Thr Leu Thr Gly Asp785 790 795 800Leu Asp Asp Ala Gly Arg Met Ser Giy Pro Asp Tyr Trp Val Arg Gln
805 810 815Val Arg Glu Pro Val Arg phe Ala Asp Gly Val Gln Ala Leu Val Glu
820 825 830His Asp Val Ala Thr Val Val Glu Leu Gly Pro Asp Gly Ala Leu Ser
835 840 845Ala Leu Ile Gln Glu Cys Val Ala Ala Ser Asp His Ala Gly Arg Leu
850 855 860Ser Ala Val Pro Ala Met Arg Arg Ash Gln Asp Glu Ala Gln Lys Val865 870 875 880Met Thr Ala Leu Ala His Val His Val Arg Gly Gly Ala Val Asp Trp
885 890 895Arg Ser Phe Phe Ala Gly Thr Gly Ala Lys Gln Ile Glu Leu Pro Thr
900 905 910Tyr Ala Phe Gln Arg Gln Arg Tyr Trp Leu Val Pro Ser Asp Ser Gly
915 920 925Asp Val Thr Gly Ala Gly Leu Ala Gly Ala Glu His Pro Leu Leu Gly
930 935 940Ala Val Val Pro Val Ala Gly Gly Asp Glu Val Leu Leu Thr Gly Arg945 950 955 960Ile Ser Val Arg Thr His Pro Trp Leu Ala Glu His Arg Val Leu Gly
965 970 975Glu Val Ile Val Ala Gly Thr Ala Leu Leu Glu Ile Ala Leu His Ala
980 985 990Gly Glu Arg Leu Gly Cys Glu Arg Val Glu Glu Leu Thr Leu Glu Ala
995 1000 1005Pro Leu Val Leu Pro Glu Arg Gly Ala Ile Gln Val Gln Leu Arg Val1010 1015 1020Gly Ala Pro Glu Asn Ser Gly Arg Arg Pro Met Ala Leu Tyr Ser Arg1025 1030 1035 1040Pro Glu Gly Ala Ala Glu His Asp Trp Thr Arg His Ala Thr Gly Arg
1045 1050 1055Leu Ala Pro Gly Arg Gly Glu Ala Ala Gly Asp Leu Ala Asp Trp Pro
1060 1065 1070Ala Pro Gly Ala Leu Pro Val Asp Leu Asp Glu Phe Tyr Arg Asp Leu
1075 1080 1085Ala Glu Leu Gly Leu Glu Tyr Gly Pro Ile Phe Gln Gly Leu Lys Ala1090 1095 1100Ala Trp Arg Gln Gly Asp Glu Val Tyr Ala Glu Ala Ala Leu Pro Gly1105 1110 1115 1120Thr Glu Asp Ser Gly Phe Gly Val His Pro Ala Leu Leu Asp Ala Ala
1125 1130 1135Leu His Ala Thr Ala Val Arg Asp Met Asp Asp Ala Arg Leu Pro Phe
1140 114 1150Gln Trp Glu Gly Val Ser Leu His Ala Lys Ala Ala Pro Ala Leu Arg
1155 1160 1165Val Arg Val Val Pro Ala Gly Asp Asp Ala Lys Ser Leu Leu Val Cys1170 1175 1180Asp Gly Thr Gly Arg Pro Val Ile Ser Val Asp Arg Leu Val Leu Arg1185 1190 l195 1200Ser Ala Ala Ala Arg Arg Thr Gly Ala Arg Arg Gln Ala His Gln Ala
1205 1210 1215Arg Leu Tyr Arg Leu Ser Trp Pro Thr Val Gln Leu Pro Thr Ser Ala
1220 1225 1230Gln Pro Pro Ser Cys Val Leu Leu Gly Thr Ser Glu Val Sar Ala Asp
1235 1240 1245Ile Gln Val Tyr Pro Asp Leu Arg Ser Leu Thr Ala Ala Leu Asp Ala1250 1255 1260Gly Ala Glu Pro Pro Gly Val Val Ile Ala Pro Thr Pro Pro Gly Gly1265 1270 1275 1280Gly Arg Thr Ala Asp Val Arg Glu Thr Thr Arg His Ala Leu Asp Leu
1285 1290 1295Val Gln Gly Trp Leu Ser Asp Gln Arg Leu Asn Glu Ser Arg Leu Leu
1300 1305 1310Leu Val Thr Gln Gly Ala Val Ala Val Glu Pro Gly Glu Pro Val Thr
1315 1320 1325Asp Leu Ala Gln Ala Ala Leu Trp Gly Leu Leu Arg Ser Thr Gln Thr1330 1335 1340Glu His Pro Asp Arg Phe Val Leu Val Asp Val Pro Glu Pro Ala Gln1345 1350 1355 1360Leu Leu Pro Ala Leu Pro Gly Val Leu Ala Cys Gly Glu Pro Gln Leu
1365 1370 1375Ala Leu Arg Arg Gly Gly Ala His Ala Pro Arg Leu Ala Gly Leu Gly
1380 1385 1390Ser Asp Asp Val Leu Pro Val Pro Asp Gly Thr Gly Trp Arg Leu Glu
1395 1400 1405Ala Thr Arg Pro Gly Ser Leu Asp Gly Leu Ala Leu Val Asp Glu Pro1410 1415 1420Thr Ala Thr Ala Pro Leu Gly Asp Gly Glu Val Arg Ile Ala Met Arg1425 1430 1435 1440Ala Ala Gly Val Asn Phe Arg Asp Ala Leu Ile Ala Leu Gly Met Tyr
1445 1450 1455Pro Gly Val Ala Ser Leu Gly Ser Glu Gly Ala Gly Val Val Val Glu
1460 1465 1470Thr Gly Pro Gly Val Thr Gly Leu Ala Pro Gly Asp Arg Val Met Gly
1475 1480 1485Met Ile Pro Lys Ala Phe Gly Pro Leu Ala Val Ala Asp His Arg Met1490 1495 1500Val Thr Arg Ile Pro Ala Gly Trp Ser Phe Ala Arg Ala Ala Ser Val1505 1510 1515 1520Pro Ile Val Phe Leu Thr Ala Tyr Tyr Ala Leu Val Asp Leu Ala Gly
1525 1530 1535Leu Arg Pro Gly Glu Ser Leu Leu Val His Ser Ala Ala Gly Gly Val
1540 1545 1550Gly Met Ala Ala Ile Gln Leu Ala Arg His Leu Gly Ala Glu Val Tyr
1555 1560 1565Ala Thr Ala Ser Glu Asp Lys Trp Gln Ala Val Glu Leu Ser Arg Glu1570 1575 1580His Leu Ala Ser Ser Arg Thr Cys Asp Phe Glu Gln Gln Phe Leu Gly1585 1590 1595 1600Ala Thr Gly Gly Arg Gly Val Asp Val Val Leu Asn Ser Leu Ala Gly
1605 1610 1615Glu Phe Ala Asp Ala Ser Leu Arg Met Leu Pro Arg Gly Gly Arg Phe
1620 1625 1630Leu Glu Leu Gly Lys Thr Asp Val Arg Asp Pro Val Glu Val Ala Asp
1635 1640 1645Ala His Pro Gly Val Ser Tyr Gln Ala Phe Asp Thr Val Glu Ala Gly1650 1655 1660Pro Gln Arg Ile Gly Glu Met Leu His Glu Leu Val Glu Leu Phe Glu1665 1670 1675 1680Gly Arg Val Leu Glu Pro Leu Pro Val Thr Ala Trp Asp Val Arg Gln
1685 1690 1695Ala Pro Glu Ala Leu Arg His Leu Ser Gln Ala Arg His Val Gly Lys
1700 1705 1710Leu Val Leu Thr Met Pro Pro Val Trp Asp Ala Ala Gly Thr Val Leu
1715 1720 1725Val Thr Gly Gly Thr Gly Ala Leu Gly Ala Glu Val Ala Arg His Leu 1730 1735 1740Val Ile Glu Arg Gly Val Arg Asn Leu Val Leu Val Ser Arg Arg Gly1745 1750 1755 1760Pro Ala Ala Ser Gly Ala Ala Glu Leu Val Ala Gln Leu Thr Ala Tyr
1765 1770 1775Gly Ala Glu Val Ser Leu Gln Ala Cys Asp Val Ala Asp Arg Glu Thr
1780 1785 1790Leu Ala Lys Val Leu Ala Ser Ile Pro Asp Glu His Pro Leu Thr Ala
1795 1800 1805Val Val His Ala Ala Gly Val Leu Asp Asp Gly Val Ser Glu Ser Leu1810 1815 1820Thr Val Glu Arg Leu Asp Gln Val Leu Arg Pro Lys Val Asp Gly Ala1825 1830 1835 1840Arg Asn Leu Leu Glu Leu Ile Asp Pro Asp Val Ala Leu Val Leu Phe
1845 1850 1855Ser Ser Val Ser Gly Val Leu Gly Ser Gly Gly Gln Gly Asn Tyr Ala
1860 1865 1870Ala Ala Asn Ser Phe Leu Asp Ala Leu Ala Gln Gln Arg Gln Ser Arg
1875 1880 1885Gly Leu Pro Thr Arg Ser Leu Ala Trp Gly Pro Trp Ala Glu His Gly1890 1895 1900Met Ala Ser Thr Leu Arg Glu Ala Glu Gln Asp Arg Leu Ala Arg Ser1905 1910 1915 1920Gly Leu Leu Pro Ile Ser Thr Glu Glu Gly Leu Ser Gln Phe Asp Ala
1925 1930 1935Ala Cys Gly Gly Ala His Thr Val Val Ala Pro Val Arg Phe Ser Arg
1940 1945 1950Leu Ser Asp Gly Asn Ala Ile Lys Phe Ser Val Leu Gln Gly Leu Val
1955 1960 1965Gly Pro His Arg Val Asn Lys Ala Ala Thr Ala Asp Asp Ala Glu Ser1970 1975 1980Leu Arg Lys Arg Leu Gly Arg Leu Pro Asp Ala Glu Gln His Arg Ile1985 1990 1995 2000Leu Leu Asp Leu Val Arg Met His Val Ala Ala Val Leu Gly Phe Ala
2005 2010 2015Gly Ser Gln Glu Ile Thr Ala Asp Gly Thr Phe Lys Val Leu Gly Phe
2020 2025 2030Asp Ser Leu Thr Val Val Glu Leu Arg Asn Arg Ile Asn Gly Ala Thr
2035 2040 2045Gly Leu Arg Leu Pro Ala Thr Leu Val Phe Asn Tyr Pro Thr Pro Asp2050 2055 2060Ala Leu Ala Ala His Leu Val Thr Ala Leu Ser Ala Asp Arg Leu Ala2065 2070 2075 2080Gly Thr Phe Glu Glu Leu Asp Arg Trp Ala Ala Asn Leu Pro Thr Leu
2085 2090 2095Ala Arg Asp Glu Ala Thr Arg Ala Gln Ile Thr Thr Arg Leu Gln Ala
2100 2105 2110Ile Leu Gln Ser Leu Ala Asp Val Ser Gly Gly Thr Gly Gly Gly Ser
2115 2120 2125Val Pro Asp Arg Leu Arg Ser Ala Thr Asp Asp Glu Leu Phe Gln Leu2130 2135 2140Leu Asp Asn Asp Leu Glu Leu Pro2145 2150<210>4<211>3170<212>PRT<213>刺糖多孢菌<400>4Met Ser Asn Glu Glu Lys Leu Arg Glu Tyr Leu Arg Arg Ala Leu Val1 5 10 15Asp Leu His Gln Ala Arg Glu Arg Leu His Glu Ala Glu Ser Gly Glu
20 25 30Arg Glu Pro Ile Ala Ile Val Ala Met Gly Cys Arg Tyr Pro Gly Gly
35 40 45Val Gln Asp Pro Glu Gly Leu Trp Lys Leu Val Ala Ser Gly Gly Asp
50 55 60Ala Ile Gly Glu Phe Pro Ala Asp Arg Gly Trp His Leu Asp Glu Leu65 70 75 80Tyr Asp Pro Asp Pro Asp Gln Pro Gly Thr Cys Tyr Thr Arg His Gly
85 90 95Gly Phe Leu His Asp Ala Gly Glu Phe Asp Ala Gly Phe Phe Asp Ile
100 105 110Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu
115 120 125Glu Ile Ser Trp Glu Thr Val Glu Ser Ala Gly Met Asp Pro Arg Ser
130 135 140Leu Arg Gly Ser Arg Thr Gly Val Phe Ala Gly Leu Met Tyr Glu Gly145 150 155 160Tyr Asp Thr Gly Ala His Arg Ala Gly Glu Gly Val Glu Gly Tyr Leu
165 170 175Gly Thr Gly Asn Ala Gly Ser Val Ala Ser Gly Arg Val Ala Tyr Ala
180 185 190Phe Gly Phe Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser
195 200 205Ser Leu Val Ala Leu His Leu Ala Cys Gln Ser Leu Arg Gln Gly Glu
210 215 220Cys Asp Leu Ala Leu Ala Gly Gly Val Thr Val Met Ser Thr Pro Glu225 230 235 240Arg Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala Pro Asp Gly Arg
245 250 255Cys Lys Ser Phe Ala Ala Ala Ala Asp Gly Thr Gly Trp Gly Glu Gly
260 265 270Ala Gly Leu Val Leu Leu Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly
275 280 285His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly
290 295 300Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Leu Ala Gln Glu Arg Val305 310 315 320Ile Gln Gln Val Leu Thr Ser Ala Gly Leu Ser Ala Ser Asp Val Asp
325 330 335Ala Val Glu Ala His Gly Thr Gly Thr Arg Leu Gly Asp Pro Ile Glu
340 345 350Ala Gln Ala Leu Ile Ala Ala Tyr Gly Gln Asp Arg Asp Arg Asp Arg
355 360 365Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile Gly His Thr Gln Ala
370 375 380Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met Ala Met Arg His385 390 395 400Gly Glu Leu Pro Arg Thr Leu His Val Asp Glu Pro Asn Ser His Val
405 410 415Asp Trp Ser Ala Gly Ala Val Arg Leu Leu Thr Glu Asn Ile Arg Trp
420 425 430Pro Gly Thr Gly Thr Arg Arg Ala Gly Val Ser Ser Phe Gly Val Ser
435 440 445Gly Thr Asn Ala His Val Ile Leu Glu His Asp Pro Leu Ala Val Thr
450 455 460Glu Asn Glu Glu Ala Ala Gln Ser Pro Ala Pro Gly Ile Val Pro Trp465 470 475 480Ala Leu Ser Gly Arg Ser Ser Thr Ala Leu Arg Ala Gln Ala Glu Arg
485 490 495Leu Arg Glu Leu Cys Glu Gln Thr Asp Pro Asp Pro Val Asp Val Gly
500 505 510Phe Ser Leu Ala Ala Thr Arg Thr Ala Trp Glu His Arg Ala Val Val
515 520 525Leu Gly Arg Asp Ser Ala Thr Leu Arg Ser Gly Leu Gly Val Val Ala
530 535 540Ser Gly Glu Pro Ala Val Asp Val Val Glu Gly Ser Val Leu Asp Gly545 550 555 560Glu Val Val Phe Val Phe Pro Gly Gln Gly Trp Gln Trp Ala Gly Met
565 570 575Ala Val Asp Leu Leu Asp Ala Ser Pro Thr Phe Ala Arg His Met Asp
580 585 590Glu Cys Ala Thr Ala Leu Arg Arg Tyr Val Asp Trp Ser Leu Val Asp
595 600 605Val Leu Arg Gly Ala Glu Asn Ser Pro Pro Leu Asp Arg Val Asp Val
610 615 620Leu Gln Pro Ala Ser Phe Ala Val Met Val Ser Leu Ala Glu Val Trp625 630 635 640Arg Ser Tyr Gly Val Arg Pro Ala Ala Val Val Gly His Ser Gln Gly
645 650 655Glu Ile Ala Ala Ala Cys Ala Ala Gly Val Leu Pro Leu Glu Asp Ala
660 665 670Ala Arg Leu Val Ala Leu Arg Ser Arg Ala Leu Lys Gly Leu Ser Gly
675 680 685Arg Gly Gly Met Ala Ser Leu Ala Cys Pro Ala Asp Glu Val Ala Ala
690 695 700Leu Phe Ala Gly Ser Gly Gly Arg Leu Glu Val Ala Ala Ile Asn Gly705 710 715 720Pro Arg Ser Val Val Val Ser Gly Asp Leu Glu Ala Val Asp Glu Leu
725 730 735Leu Ala Glu Cys Ala Glu Lys Asp Met Arg Ala Arg Arg Ile Pro Val
740 745 750Asp Tyr Ala Ser His Ser Ala His Val Glu Val Val Arg Ser Pro Val
755 760 765Leu Ala Ala Ala Ala Gly Val Arg His Arg Asp Gly Gln Val Pro Trp
770 775 780Trp Ser Thr Val Ile Gly Asp Trp Val Asp Pro Ala Arg Leu Asp Gly785 790 795 800Glu Tyr Trp Tyr Arg Asn Leu Arg Gln Pro Val Arg Phe Glu His Ala
805 810 815Val Gln Gly Leu Val Glu Arg Gly Phe Gly Leu Phe Ile Glu Met Ser
820 825 830Ala His Pro Val Leu Thr Thr Ala Val Glu Glu Thr Gly Ala Glu Ser
835 840 845Glu Thr Ala Val Ala Ala Val Gly Thr Leu Arg Arg Asp Ser Gly Gly
850 855 860Leu Arg Arg Leu Leu His Ser Leu Ala Glu Ala Tyr Val Arg Gly Ala865 870 875 880Thr Val Asp Trp Ala Val Ala Phe Gly Gly Ala Gly Arg Arg Leu Asp
885 890 895Leu Pro Thr Tyr Pro Phe Gln Arg Gln Arg Tyr Trp Leu Asp Lys Gly
900 905 910Ala Ala Ser Asp Glu Ala Arg Ala Val Ser Asp Pro Ala Ala Gly Trp
915 920 925Phe Trp Gln Ala Val Ala Arg Gln Asp Leu Lys Ser Val Ser Asp Ala
930 935 940Leu Asp Leu Asp Ala Asp Ala Pro Leu Ser Ala Thr Leu Pro Ala Leu945 950 955 960Ser Val Trp His Arg Gln Glu Arg Glu Arg Val Leu Ala Asp Gly Trp
965 970 975Arg Tyr Arg Val Asp Trp Val Arg Val Ala Pro Gln Pro Val Arg Arg
980 985 990Thr Arg Glu Thr Trp Leu Leu Val Val Pro Pro Gly Gly Ile Glu Glu
995 1000 1005Ala Leu Val Glu Arg Leu Thr Asp Ala Leu Asn Thr Arg Gly Ile Ser1010 1015 1020Thr Leu Arg Leu Asp Val Pro Pro Ala Ala Thr Ser Gly Glu Leu Ala1025 1030 1035 1040Thr Glu Leu Arg Ala Ala Ala Asp Gly Asp Pro Val Lys Ala Ile Leu
1045 1050 1055Ser Leu Thr Ala Leu Asp Glu Arg Pro His Pro Glu Cys Lys Asp Val
1060 1065 1070Pro Ser Gly Ile Ala Leu Leu Leu Asn Leu Val Lys Ala Leu Gly Glu
1075 1080 1085Ala Asp Leu Arg Ile Pro Leu Trp Thr Ile Thr Arg Gly Ala Val Lys1090 1095 1100Ala Gly Pro Ala Asp Arg Leu Leu Arg Pro Met Gln Ala Gln Ala Trp1105 1110 1115 1120Gly Leu Gly Arg Val Ala Ala Leu Glu His Pro Glu Arg Trp Gly Gly
1125 1130 1135Leu Ile Asp Leu Pro Asp Ser Leu Asp Gly Asp Val Leu Thr Arg Leu
1140 1145 1150Gly Glu Ala Leu Thr Asn Gly Leu Ala Glu Asp Gln Leu Ala Ile Arg
1155 1160 1165Gln Ser Gly Val Leu Ala Arg Arg Leu Val Pro Ala Pro Ala Asn Gln1170 1175 1180Pro Ala Gly Arg Lys Trp Arg Pro Arg Gly Ser Ala Leu Ile Thr Gly1185 1190 1195 1200Gly Lau Gly Ala Val Gly Ala Gln Val Ala Arg Trp Leu Ala Glu Ile
1205 1210 1215Gly Ala Glu Arg Ile Val Leu Thr Ser Arg Arg Gly Asn Gln Ala Ala
1220 1225 1230Gly Ala Ala Glu Leu Glu Ala Glu Leu Arg Ala Leu Gly Ala Gln Val
1235 1240 1245Ser Ile Val Ala Cys Asp Val Thr Asp Arg Ala Glu Met Ser Ala Leu1250 1255 1260Leu Ala Glu Phe Asp Val Thr Ala Val Phe His Ala Ala Gly Val Gly1265 1270 1275 1280Arg Leu Leu Pro Leu Ala Glu Thr Asp Gln Asn Gly Leu Ala Glu Ile
1285 1290 1295Cys Ala Ala Lys Val Arg Gly Ala Gln Val Leu Asp Glu Leu Cys Asp
1300 1305 1310Ser Thr Asp Leu Asp Ala Phe Val Leu Phe Ser Ser Gly Ala Gly Val
1315 1320 1325Trp Gly Gly Gly Gly Gln Gly Ala Tyr Gly Ala Ala Asn Ala Phe Leu1330 1335 1340Asp Thr Leu Ala Glu Gln Arg Arg Ala Arg Gly Leu Pro Ala Thr Ser1345 1350 1355 1360Ile Ser Trp Gly Ser Trp Ala Gly Gly Gly Met Ala Asp Gly Ala Ala
1365 1370 1375Gly Glu His Leu Arg Arg Arg Gly Ile Arg Pro Met Pro Ala Ala Sar
1380 1385 1390Ala Ile Leu Ala Leu Gln Glu Val Leu Asp Gln Asp Glu Thr Cys Val
1395 1400 1405Ser Ile Ala Asp Val Asp Trp Asp Arg Phe Val Pro Thr Phe Ala Ala1410 1415 1420Thr Arg Ala Thr Arg Leu Phe Asp Glu Val Pro Ala Ala Arg Lys Ala1425 1430 1435 1440Met Pro Ala Asn Gly Pro Ala Glu Pro Gly Gly Ser Pro Phe Ala Arg
1445 1450 1455Asn Leu Ala Glu Leu Pro Glu Ala Gln Arg Arg His Glu Leu Val Asp
1460 1465 1470Leu Val Cys Ala Gln Val Ala Thr Val Leu Gly His Gly Ser Arg Glu
1475 1480 1485Glu Val Gln Pro Glu Arg Ala Phe Arg Ala Leu Gly ghe Asp Ser Leu1490 1495 1500Met Ala Val Asp Leu Arg Asn Arg Leu Thr Thr Ala Thr Gly Leu Arg1505 1510 1515 1520Leu Pro Thr Thr Thr Val Phe Asp Tyr Pro Asn Pro Ala Ala Leu Ala
1525 1530 1535Ala His Leu Leu Glu Glu Leu Val Gly Asp Val Ala Ser Ala Ala Val
1540 1545 1550Thr Ala Ala Ser Ala Pro Ala Ser Asp Glu Pro Ile Ala Ile Val Ala
1555 1560 1565Met Ser Cys Arg Phe Pro Gly Gly Ala His Ser Pro Glu Asp Leu Trp1570 1575 1580Arg Leu Val Ala Ala Gly Thr Glu Val Ile Gly Glu Phe Pro Ser Asp1585 1590 1595 1600Arg Gly Trp Asp Ala Glu Gly Leu Tyr Asp Pro Asp Ala Ser Arg Pro
1605 1610 1615Gly Thr Thr Tyr Ala Arg Met Ala Gly Phe Leu Tyr Asp Ala Gly Glu
1620 1625 1630Phe Asp Ala Asp Leu Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met
1635 1640 1645Asp Pro Gln Gln Arg Leu Val Leu Glu Ile Ala Trp Glu Ala Leu Glu1650 1655 1660Arg Ala Gly Ile Asp Pro Leu Ser Leu Lys Gly Ser Gly Val Gly Thr1665 1670 1675 1680Tyr Ile Gly Ala Gly Ser Arg Gly Tyr Ala Thr Asp Val Arg Gln Phe
1685 1690 1695Pro Glu Glu Ala Glu Gly Tyr Leu Leu Thr Gly Thr Ser Ala Ser Val
1700 1705 1710Leu Ser Gly Arg Val Ala Tyr Ser Phe Gly Phe Glu Gly Pro Ala Val
1715 1720 1725Thr Val Asp Thr Ala Cys Sar Ser Ser Leu Val Ala Leu His Leu Ala1730 1735 1740Cys Gln Ser Leu Arg Ser Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly1745 1750 1755 1760Val Thr Val Met Ser Thr Pro Glu Met Phe Val Glu Phe Ser Arg Gln
1765 1770 1775Arg Gly Leu Ala Pro Asp Gly Arg Cys Lys Ser Phe Ala Glu Ser Ala
1780 1785 1790Asp Gly Thr Gly Trp Gly Glu Gly Ala Gly Leu Leu Leu Leu Glu Arg
1795 1800 1805Leu Ser Asp Ala His Arg Asn Gly His Arg Val Leu Ala Val Val Arg1810 1815 1820Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Ala Ala Pro1825 1830 1835 1840Asn Gly Pro Ser Gln Gln Arg Val Ile Asn Gln Ala Leu Ala Asn Ala
1845 1850 1855Ala Leu Ser Ala Ser Asp Val Asp Ala Val Glu Ala His Gly Thr Gly
1860 1865 1870Thr Arg Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Ile Ala Thr Tyr
1875 1880 1885Gly Gln Ala Arg Glu Arg Asp Arg Pro Leu Trp Leu Gly Ser Val Lys1890 1895 1900Ser Asn Ile Gly His Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile1905 1910 1915 1920Lys Met Val Met Ala Met Arg His Gly Gln Leu Pro Ala Ser Leu His
1925 1930 1935Ala Asp Glu Pro Thr Ser Glu Val Asp Trp Ser Ser Gly Ala Val Arg
1940 1945 1950Leu Leu Ala Glu Gln Val Pro Trp Pro Glu Ser Asp Arg Val Arg Arg
1955 1960 1965Val Gly Val Ser Ser Phe Gly Ile Ser Gly Thr Asn Ala His Val Ile1970 1975 1980Leu Glu Gln Ala Thr Asn Ala Pro Asp Ser Thr Ala Glu Thr Asp Lys1985 1990 1995 2000Thr Glu Ser Gly Ser Thr Val Asp Ile Pro Val Val Pro Trp Leu Val
2005 2010 2015Ser Gly Lys Thr Thr Asp Ser Leu Arg Gly Gln Ala Glu Arg Val Leu
2020 2025 2030Ser Gln Val Glu Ser Arg Pro Glu Gln Arg Ser Leu Asp Val Ala Tyr
2035 2040 2045Ser Leu Ala Ser Gly Arg Ala Ala Leu Asp Glu Arg Ala Val Val Leu2050 2055 2060Gly Ala Asp Arg Gly Glu Leu Val Ala Gly Leu Ala Ala Leu Ala Ala2065 2070 2075 2080Gly Gln Glu Ala Ser Gly Val Ile Ser Gly Thr Arg Ala Ser Ala Arg
2085 2090 2095Phe Gly Phe Val Phe Ser Gly Gln Gly Gly Gln Trp Leu Gly Met Gly
2100 2105 2110Arg Ala Leu Tyr Ser Lys Phe Pro Val Phe Ala Ala Ala Phe Asp Glu
2115 2120 2125Ala Cys Ala Glu Leu Glu Ala His Leu Gly Glu Asp Arg Arg Val Arg2130 2135 2140Asp Val Val Phe Gly Ser Asp Ala Gln Leu Leu Asp Gln Thr Leu Trp2145 2150 2155 2160Ala Gln Ser Gly Leu Phe Ala Leu Gln Ala Gly Leu Leu Gly Leu Leu
2165 2170 2175Gly Ser Trp Gly Val Arg Pro Asp Val Val Met Gly His Ser Val Gly
2180 2185 2190Glu Leu Ala Ala Ala Phe Ala Ala Gly Val Leu Ser Leu Arg Asp Ala
2195 2200 2205Ala Arg Leu Val Ala Ala Arg Ala Arg Leu Met Gln Ala Leu Pro Ser2210 2215 2220Asp Gly Ala Met Leu Ala Val Ala Ala Gly Glu Asp Leu Val Arg Pro2225 2230 2235 2240Leu Leu Ala Gly Arg Glu Glu Ser Val Ser Val Ala Ala Leu Asn Ala
2245 2250 2255Pro Gly Ser Val Val Leu Ser Gly Asp Arg Glu Val Leu Ala Ser Ile
2260 2265 2270Val Gly Arg Leu Thr Glu Leu Arg Val Arg Thr Arg Arg Leu Arg Val
2275 2280 2285Ser His Ala Phe His Ser His Arg Met Asp Pro Met Leu Gly Glu Phe2290 2295 2300Ala Gln Ile Ala Glu Ser Ala Glu Phe Gly Lys Pro Thr Thr Pro Leu2305 2310 2315 2320Val Ser Thr Leu Thr Gly Glu Leu Asp Arg Ala Ala Glu Met Ser Thr
2325 2330 2335Pro Gly Tyr Trp Val Arg Gln Ala Arg Glu Pro Val Arg Phe Ala Asp
2340 2345 2350Gly Val Gln Ala Leu Ala Ala Gln Gly Ile Gly Thr Val Val Glu Leu
2355 2360 2365Gly Pro Asp Gly Thr Leu Ala Ala Leu Val Arg Glu Cys Ala Thr Glu2370 2375 2380Ser Asp Arg Val Gly Arg Ile Ser Ser Ile Pro Leu Met Arg Arg Glu2385 2390 2395 2400
Arg Asp Glu Thr Arg Ser Val Met Thr Ala Leu Ala His Leu His Thr
2405 2410 2415Arg Gly Gly Glu Val Asp Trp Gln Ala Phe Phe Ala Gly Thr Gly Ala
2420 2425 2430Arg Gln Leu Glu Leu Pro Thr Ala Phe Gln Arg Gln His Tyr Trp
2435 2440 2445Ile Glu Ser Ser Ala Arg Pro Ala Arg Asp Arg Ala Asp Ile Gly Glu2450 2455 2460Val Ala Glu Gln Phe Trp Thr Ala Val Asp Gln Gly Asp Leu Ala Thr2465 2470 2475 2480Leu Val Ala Ala Leu Asp Leu Gly Ala Asp Asp Asp Thr Cys Ala Ser
2485 2490 2495Leu Ser Asp Val Leu Pro Ala Leu Ser Ser Trp Arg Ser Gly Leu Arg
2500 2505 2510Asn Arg Ser Leu Val Asp Ser Cys Arg Tyr Arg Ile Ser Trp His Ser
2515 2520 2525Ser Arg Glu Val Pro Ala Pro Lys Ile Ser Gly Thr Trp Leu Leu Val2530 2535 2540Val Pro Gly Ala Ala Asp Asp Gly Leu Val Thr Ala Leu Thr Ser Ser2545 2550 2555 2560Leu Val Gly Gly Gly Ala Glu Val Val Arg Ile Gly Leu Ser Glu Glu
2565 2570 2575Asp Pro His Arg Glu Asp Val Ala Gln Arg Leu Ala Asn Ala Leu Thr
2580 2585 2590Asp Ala Gly Gln Leu Gly Gly Val Leu Ser Leu Leu Gly Leu Asp Glu
2595 2600 2605Ser Pro Ala Pro Gly Phe Ser Cys Leu Pro Thr Gly Phe Ala Leu Thr2610 2615 2620Val Gln Leu Leu Arg Ala Leu Arg Lys Ala Asp Val Glu Ala Pro Phe2625 2630 2635 2640Trp Ala Val Thr Arg Gly Gly Val Ala Leu Glu Asp Val Arg Val Ser
2645 2650 2655Pro Glu Gln Ala Leu Val Trp Gly Leu Leu Arg Val Ala Gly Leu Glu
2660 2665 2670His Pro Glu Phe Trp Gly Gly Leu Ile Asp Leu Pro Ser Asp Trp Asp
2675 2680 2685Asp Arg Leu Gly Ala Arg Leu Ala Gly Val Leu Ala Asp Gly Gly Glu2690 2695 2700Asp Gln Val Ala Ile Arg Arg Gly Gly Val Phe Val Arg Arg Leu Glu2705 2710 2715 2720Arg Ala Gly Ala Ser Gly Ala Gly Ser Val Trp Arg Pro Arg Gly Thr
2725 2730 2735Val Leu Val Thr Gly Gly Thr Gly Gly Leu Gly Ala His Val Ala Arg
2740 2745 2750Trp Leu Ala Giy Ala Gly Ala Glu His Val Val Leu Thr Ser Arg Arg
2755 2760 2765Gly Ala Asp Ala Pro Gly Ala Gly Glu Leu Arg Ala Glu Leu Glu Ala2770 2775 2780Leu Gly Ala Arg Val Ser Ile Val Pro Cys Asp Val Ala Asp Arg Asp2785 2790 2795 2800Ala Val Ala Gly Val Leu Ala Gly Ile Gly Gly Glu Cys Pro Leu Thr
2805 2810 2815Ala Val Val His Ala Ala Gly Val Gly Glu Ala Gly Asp Val Val Glu
2820 2825 2830Met Gly Leu Ala Asp Pha Ala Ala Val Leu Ser Ala Lys Val Arg Gly
2835 2840 2845Ala Ala Asn Leu Asp Glu Leu Leu Ala Asp Ser Glu Leu Asp Ala Phe2850 2855 2860Val Met Phe Ser Ser Val Ser Gly Val Trp Gly Ala Gly Gly Gln Gly2865 2870 2875 2880Ala Tyr Ala Ala Ala Asn Ala Tyr Leu Asp Ala Leu Ala Glu Gln Arg
2885 2890 2895Arg Ala Arg Gly Leu Val Gly Thr Ala Val Ala Trp Gly Pro Trp Ala
2900 2905 2910Gly Asp Gly Met Ala Ala Gly Glu Thr Gly Ala Gln Leu His Arg Met
2915 2920 2925Gly Leu Ala Ser Met Glu Pro Ser Ala Ala Leu Leu Ala Leu Gln Gly2930 2935 2940Ala Leu Asp Arg Asp Glu Thr Ser Leu Val Val Ala Asp Val Asp Trp2945 2950 2955 2960Ala Arg Phe Ala Pro Ala Phe Thr Ser Ala Arg Arg Arg Pro Leu Leu
2965 2970 2975Asg Thr Ile Asp Glu Ala Arg Ala Ala Leu Glu Thr Thr Gly Glu Gln
2980 2985 2990Ala Gly Thr Gly Lys Pro Val Glu Leu Thr Gln Arg Leu Ala Gly Leu
2995 3000 3005Ser Arg Lys Glu Arg Asp Asp Ala Val Leu Asp Leu Val Arg Ala Glu3010 3015 3020Thr Ala Ala Val Leu Gly Arg Asp Asp Ala Thr Ala Leu Ala Pro Ser3025 3030 3035 3040Arg Pro Phe Gln Glu Leu Gly Phe Asp Ser Leu Met Ala Val Glu Leu
3045 3050 3055Arg Asn Arg Leu Asn Thr Ala Thr Gly Ile Gln Leu Pro Ala Ser Thr
3060 3065 3070Ile Phe Asp Tyr Pro Asn Ala Glu Ser Leu Ser Arg His Leu Cys Ala
3075 3080 3085Glu Leu Phe Pro Thr Glu Thr Thr Val Asp Ser Ala Leu Ala Glu Leu3090 3095 3100Asp Arg Ile Glu Gln Gln Leu Ser Met Leu Thr Giy Glu Ala Arg Ala3105 3110 3115 3120Arg Asp Arg Ile Ala Thr Arg Leu Arg Ala Leu His Glu Lys Trp Asn
3125 3130 3135Ser Ala Ala Glu Val Pro Thr Gly Ala Asp Val Leu Ser Thr Leu Asp
3140 3145 3150Ser Ala Thr His Asp Glu Ile Phe Glu Phe Ile Asp Asn Glu Leu Asp
3155 3160 3165Leu Ser3170<210>5<211>4928<212>PRT<213>刺糖多孢菌<400>5Val Glu Ile Thr Met Ala Asn Glu Glu Lys Leu Phe Gly Tyr Leu Lys1 5 10 15Lys Val Thr Ala Asp Leu His Gln Thr Arg Gln Arg Leu Leu Ala Ala
20 25 30Glu Ser Arg Ser Gln Glu Pro Ile Ala Ile Val Ser Ala Ser Cys Arg
35 40 45Leu Pro Gly Gly Val Asp Ser Pro Glu Ala Leu Trp Gln Leu Val Arg
50 55 60Thr Gly Thr Asp Ala Ile Ser Glu Phe Pro Ala Asp Arg Gly Trp Asp65 70 75 80Leu Gly Arg Leu Tyr Asp Pro Asp Pro Asn His Gln Gly Thr Ser Tyr
85 90 95Thr Arg Ala Gly Gly Phe Leu Ala Gly Ala G1y Asp Phe Asp Pro Ala
100 105 110Met Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln
115 120 125Arg Leu Leu Leu Glu Leu Ser Trp Glu Ala Leu Glu Arg Ala Gly Ile
130 135 140Asp Pro Thr Ser Leu Arg Gly Ser Lys Thr Gly Val Phe Gly Gly Val145 150 155 160Thr Pro Gln Glu Tyr Gly Pro Ser Leu Gln Glu Met Ser Arg Asn Ala
165 170 175Gly Gly Phe Gly Leu Thr Gly Arg Met Val Ser Val Ala Ser Gly Arg
180 185 190Val Ala Tyr Ser Phe Gly Phe Glu Gly Pro Ala Val Thr Val Asp Thr
195 200 205Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Cys Gln Ser Leu
210 215 220Arg Ser Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly Val Thr Val Met225 230 235 240Ala Thr Pro Ala Thr Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala
245 250 255Pro Asp Gly Arg Cys Lys Ser Phe Ala Ala Ala Ala Asp Gly Thr Gly
260 265 270Trp Gly Glu Gly Ala Gly Leu Val Leu Leu Glu Arg Leu Ser Asp Ala
275 280 285Arg Arg Asn Gly His Glu Val Leu Ala Val Val Arg Gly Ser Ala Val
290 295 300Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro Ser305 310 315 320Gln Gln Arg Val Ile Thr Gln Ala Leu Ala Ser Ala Gly Leu Ser Val
325 330 335Ser Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Thr Leu Gly
340 345 350Asp Pro Ile Glu Ala Gln Ala Leu Ile Ala Thr Tyr Gly Gln Gly Arg
355 360 365Glu Lys Asp Arg Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile Gly
370 375 380His Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Leu385 390 395 400Ala Met Arg His Gly Gln Leu Pro Ala Thr Leu His Val Asp Glu Pro
405 410 415Thr Ser Ala Val Asp Trp Ser Ala Gly Ser Val Arg Leu Leu Thr Glu
420 425 430Asn Thr Pro Trp Pro Asp Ser Gly Arg Pro Cys Arg Val Gly Val Ser
435 440 445Ser Phe Gly Ile Ser Gly Thr Asn Ala His Val Ile Leu Glu Gln Ser
450 455 460Pro Val Glu Gln Gly Glu Pro Ala Gly Pro Val Glu Gly Glu Arg Glu465 470 475 480Pro Asp Val Ala Val Pro Val Val Pro Trp Val Leu Ser Gly Lys Thr
485 490 495Pro Glu Ala Ala Arg Ala Gln Ala Glu Arg Val His Ser His Ile Glu
500 505 510Asp Arg Pro Gly Leu Ser Pro Val Asp Val Ala Tyr Ser Leu Gly Met
515 520 525Thr Arg Ala Ala Leu Asp Glu Arg Ala Val Val Leu Gly Ser Asp Arg
530 535 540Ala Ala Leu Leu Thr Gly Leu Arg Ala Phe Ala Asp Gly Cys Asp Ala545 550 555 560Pro Glu Val Val Ser Gly Ser Val Gly Leu Gly Gly Arg Val Gly Phe
565 570 575Val Phe Ser Gly Gln Gly Gly Gln Trp Pro Gly Met Gly Arg Gly Leu
580 585 590Tyr Ser Val Phe Pro Val Phe Ala Asp Ala Phe Asp Glu Ala Cys Ala
595 600 605Glu Leu Asp Ala His Leu Gly Gln Glu Leu Arg Val Arg Asp Val Val
610 615 620Phe Gly Ser Gln Ala Trp Leu Leu Asp Arg Thr Val Trp Ala Gln Ser625 630 635 640Gly Leu Phe Ala Leu Gln Ile Gly Leu Leu Arg Leu Leu Gly Ser Trp
645 650 655Gly Val Arg Pro Asp Val Val Leu Gly His Ser Val Gly Glu Leu Ala
660 665 670Ala Val His Ala Ala Gly Val Leu Ser Leu Ser Glu Ala Ala Arg Leu
675 680 685Val Ala Gly Arg Ala Arg Leu Met Gln Ala Leu Pro Ser Gly Gly Ala
690 695 700Met Leu Ala Val Ala Thr Gly Glu Phe Gln Val Asp Pro Leu Leu Asp705 710 715 720Gly Val Arg Asp Arg Ile Gly Ile Ala Ala Val Asn Gly Pro Glu Ser
725 730 735Val Val Leu Ser Gly Asp Arg Glu Leu Leu Thr Glu Ile Ala Asp Arg
740 745 750Leu His Asp Gln Gly Cys Arg Thr Arg Trp Leu Arg Val Ser His Ala
755 760 765Phe His Ser Pro His Met Glu Pro Met Leu Glu Glu Phe Ala Gln Ile
770 775 780Ser Arg Gly Arg Glu Tyr His Ala Pro Glu Leu Pro Ile Ile Ser Thr785 790 795 800Leu Ile Gly Glu Leu Asp Gly Gly Arg Val Met Gly Thr Pro Glu Tlr
805 810 815Trp Val Arg Gln Val Arg Glu Pro Val Arg Phe Ala Glu Gly Val Gln
820 825 830Ala Leu Val Gly Gln Gly Val Gly Thr Ile Val Glu Leu Gly Pro Asp
835 840 845Gly Ala Leu Ser Thr Leu Val Glu Glu Cys Val Ala Glu Ser Gly Arg
850 855 860Val Ala Gly Ile Pro Leu Met Arg Lys Asp Arg Asp Glu Ala Arg Thr865 870 875 880Val Leu Ala Ala Leu Ala Gln Ile His Thr Arg Gly Gly Glu Val Asp
885 890 895Trp Arg Ser Phe Phe Ala Gly Thr Gly Ala Lys Gln Val Asp Leu Pro
900 905 910Thr Tyr Ala Phe Gln Arg Gln Arg Tyr Trp Leu Ala Ser Thr Gly Arg
915 920 925Ala Gly Asp Val Thr Ala Ala Gly Leu Ala Glu Ala Asp His Pro Leu
930 935 940Leu Gly Ala Val Val Ala Leu Ala Asp Gly Glu Gly Val Val Leu Thr945 950 955 960Gly Arg Leu Thr Ala Gly Ser His Pro Trp Leu Ser Asp His Arg Val
965 970 975Leu Gly Glu Ile Val Val Pro Gly Thr Ala Ile Val Glu Leu Val Trp
980 985 990His Val Gly Glu Arg Leu Gly Cys Gly Arg Val Glu Glu Leu Ala Leu
995 1000 1005Glu Ala Pro Leu Ile Leu Pro Asp His Gly Ala Val Gln Val Gln Val1010 1015 1020Leu Val Gly Pro Pro Gly Glu Ser Gly Ala Arg Ser Val Ala Leu Tyr1025 1030 1035 1040Ser Cys Pro Gly Glu Ala Ile Glu Pro Glu Trp Lys Lys His Ala Thr
1045 1050 1055Gly Val Leu Leu Pro Pro Val Ala Ala Glu Asn His Glu Leu Thr Ala
1060 1065 1070Trp Pro Pro Glu Asn Ala Thr Glu Ile Asp Ala Asp Gly Val Tyr Ala
1075 1080 1085Phe Leu Glu Gly His Gly Phe Ala Tyr Gly Pro Ala Phe Arg Cys Leu1090 1095 1100Arg Gly Ala Trp Arg Arg Gly Gly Glu Val Phe Ala Glu Val Ala Leu1105 1110 1115 1120Pro Asp Asp Met Gln Ala Gly Val Asp Arg Phe Gly Val His Pro Ala
1125 1130 1135Leu Leu Asp Ala Val Leu His Ala Ala Ala Ala Glu Thr Ser Val Val
1140 1145 1150Gln Ser Glu Ala Arg Val Pro Phe Ser Trp Arg Gly Val Glu Leu Arg
1155 1160 1165Ala Thr Glu Ser Ala Val Val Arg Ala Arg Leu Ser Leu Thr Ser Asp1170 1175 1180Asp Glu Leu Ser Leu Val Ala Val Asp Pro Ala Gly Arg Phe Val Ala1185 1190 1195 1200Thr Val Asp Ser Leu Val Thr Arg Pro Ile Ser Arg Gln Gln Val Arg
1205 1210 1215Ser Gly Ala Ile Gly Asp Cys Leu Phe Glu Val Glu Trp His Arg Lys
1220 1225 1230Ala Leu Leu Gly Thr Thr Ala Gly Asp Asp Leu Ala Ile Val Gly Asp
1235 1240 1245Gly Pro Ser Trp Pro Glu Ser Val Arg Ala Thr Ala Arg Phe Ala Thr1250 1255 1260Leu Asp Glu Phe Arg Ala Ala Val Asp Ser Asp Val Pro Ala Pro Gly1265 1270 1275 1280Ser Val Leu Val Ala Ala Met Ser Ala Glu Glu Val Glu Gly Gly Ser
1285 1290 1295Leu Pro Ser Arg Ala Gln Glu Ser Thr Ser Asp Leu Leu Ala Leu Val
1300 1305 1310Gln Ser Trp Leu Ala Asp Glu Arg Phe Ala Glu Ser Gln Leu Val Val
1315 1320 1325Val Thr Arg Ala Ala Val Ser Ala Asp Ser Asp Ser Asp Val Ala Asp1330 1335 1340Leu Val Gly Ala Ser Ser Trp Gly Leu Leu Ser Ser Ala Gln Ser Glu1345 1350 1355 1360Asn Pro Gly Arg Phe Val Leu Val Asp Val Asp Gly Thr Pro Glu Ser
1365 1370 1375Trp Gln Ala Leu Pro Ala Ala Val Arg Ala Gly Glu Pro Gln Leu Ala
1380 1385 1390Leu Arg Arg Gly Val Ala Leu Val Pro Arg Leu Ala Arg Leu Thr Val
1395 1400 1405Arg Glu Glu Gly Ser Ser Pro Gln Leu Asp Thr Asp Gly Thr Val Leu1410 1415 1420Ile Thr Gly Gly Thr Gly Ala Leu Gly Gly Val Val Ala Arg His Leu1425 1430 1435 1440Val Glu Glu His Gly Ile Arg Arg Leu Val Leu Ala Gly Arg Arg Gly
1445 1450 1455Trp Asn Ala Pro Gly Val His Glu Leu Val Asp Glu Leu Ala Arg Ala
1460 1465 1470Gly Ala Val Val Glu Val Val Ala Cys Asp Val Ala Asp Arg Thr Asp
1475 1480 1485Leu Glu His Val Leu Ala Ala Ile Pro Val Asp Trp Pro Leu Arg Gly1490 1495 1500Ile Val His Thr Ala Gly Val Leu Ala Asp Gly Val Ile Gly Sar Leu1505 1510 1515 1520Ser Ala Ala Asp Val Gly Thr Val Phe Ala Pro Lys Val Thr Gly Ala
1525 1530 1535Trp His Leu His Glu Leu Thr Arg Asp Leu Asp Leu Ser Phe Phe Val
1540 1545 1550Leu Phe Ser Ser Phe Ser Gly Ile Ala Gly Ala Ala Gly Gln Ala Asn
1555 1560 1565Tyr Ala Ala Ala Asn Thr Phe Leu Asp Ala Leu Ala Arg Tyr Arg ArgWO99/46387 PCT/US99/03212
1570 1575 1580Ala Arg Gly Leu Pro Gly Leu Ser Leu Ala Trp Gly Leu Trp Ala Gln1585 1590 1595 1600Pro Ser Gly Met Thr Ser Gly Leu Asp Ala Ala Ser Val Glu Arg Leu
1605 1610 1615Ala Arg Thr Gly Ile Ala Glu Leu Ser Thr Glu Asp Gly Leu Arg Leu
1620 1625 1630Phe Asp Ala Ala Phe Ala Lys Asp Arg Ala Cys Val Val Ala Ala Arg
1635 1640 1645Leu Asp Arg Ala Leu Leu Val Gly Asn Gly Arg Ser His Ala Ile Pro
1650 1655 1660Ala Leu Leu Ser Ala Leu Val Pro Val Arg Gly Gly Val Ala Arg Lys1665 1670 1675 1680Thr Ala Asn Ser Gln Ala Ala Asp Glu Asp Ala Leu Leu Gly Leu Val
1685 1690 1695Arg Glu His Val Ser Ala Val Leu Gly Tyr Ser Gly Ala Val Glu Val
1700 1705 1710Gly Gly Asp Arg Ala Phe Arg Asp Leu Gly Phe Asp Sar Leu Ser Gly
1715 1720 1725Val Glu Leu Arg Asn Arg Leu Ala Gly Val Leu Gly Val Arg Leu Pro
1730 1735 1740Ala Thr Ala Val Phe Asp Tyr Pro Thr Pro Arg Ala Leu Ala Arg Phe1745 1750 1755 1760Leu His Gln Glu Leu Ala Gly Glu Val Ala Ser Thr Ser Thr Pro Val
1765 1770 1775Thr Arg Ala Ala Ser Ala Glu Glu Asp Leu Val Ala Ile Val Gly Met
1780 1785 1790Gly Cys Arg Phe Pro Gly Gly Val Ser Ser Pro Glu Glu Leu Trp Arg
1795 1800 1805Leu Val Ala Gly Gly Val Asp Ala Val Ala Gly Phe Pro Asp Asp Arg
1810 1815 1820Gly Trp Asp Leu Ala Ala Leu Tyr Asp Pro Asp Pro Asp Arg Leu Gly1825 1830 1835 1840Thr Ser Tyr Val Cys Glu Gly Gly Phe Leu Arg Asp Ala Ala Glu Phe
1845 1850 1855Asp Ala Asp Met Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp
1860 1865 1870Pro Gln Gln Arg Leu Leu Leu Glu Val Ala Trp Glu Thr Leu Glu Arg
1875 1880 1885Ala Gly Ile Asp Pro Phe Ser Leu His Gly Ser Arg Thr Gly Val Phe1890 1895 1900Ala Gly Leu Met Tyr His Asp Tyr Gly Ala Arg Phe Ile Thr Arg Ala1905 1910 1915 1920Pro Glu Gly Phe Glu Gly His Leu Gly Thr Gly Asn Ala Gly Ser Val
1925 1930 1935Leu Ser Gly Arg Val Ala Tyr Ser Phe Gly Phe Glu Gly Pro Ala Val
1940 1945 1950Thr Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala
1955 1960 1965Gly Gln Ala Leu Arg Ala Gly Glu Cys Glu Phe Ala Leu Ala Gly Gly1970 1975 1980Val Thr Val Met Ser Thr Pro Thr Thr Phe Val Glu Phe Ser Arg Gln1985 1990 1995 2000Arg Gly Leu Ala Pro Asp Gly Arg Cys Lys Ser Phe Ala Ala Ala Ala
2005 2010 2015Asp Gly Thr Gly Trp Gly Glu Gly Ala Gly Leu Val Leu Leu Glu Arg
2020 2025 2030Leu Ser Asp Ala Arg Arg Asn Gly His Glu Val Leu Ala Val Val Arg
2035 2040 2045Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro2050 2055 2060Asn Gly Pro Ser Gln Gln Arg Val Ile Thr Gln Ala Leu Thr Ser Ala2065 2070 2075 2080Gly Leu Ser Val Ser Asp Val Asp Ala Val Glu Ala His Gly Thr Gly
2085 2090 2095Thr Arg Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Ile Ala Thr Tyr
2100 2105 2110Gly Arg Asp Arg Asp Pro Gly Arg Pro Leu Trp Leu Gly Ser Val Lys
2115 2120 2125Ser Asn Ile Gly His Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile2130 2135 2140Lys Met Val Met Ala Met Arg Gln Gly Glu Leu Pro Arg Thr Leu His2145 2150 2155 2160Val Asp Glu Pro Ser Ala Gln Val Asp Trp Ser Ala Gly Thr Val Gln
2165 2170 2175Leu Leu Thr Glu Asn Thr Pro Trp Pro Asp Ser Gly Arg Leu Arg Arg
2180 2185 2190Ala Gly Val Ser Ser Phe Gly Ile Ser Gly Thr Asn Ala His Leu Ile
2195 2200 2205Leu Glu Gln Pro Pro Arg Glu Ser Gln Arg Ser Thr Glu Pro Asp Ser2210 2215 2220Gly Ser Val Arg Asp Phe Pro Val Val Pro Trp Met Val Ser Gly Lys2225 2230 2235 2240Thr Pro Glu Ala Leu Ser Ala Gln Ala Asp Ala Leu Met Ser Tyr Leu
2245 2250 2255Ser Asn Arg Val Asp Ala Ser Pro Arg Asp Ile Gly Tyr Ser Leu Ala
2260 2265 2270Val Thr Arg Pro Ala Leu Asp His Arg Ala Val Val Leu Gly Ala Asp
2275 2280 2285Arg Ala Ala Leu Leu Pro Gly Leu Lys Ala Leu Ala Val Ser Asn Asp2290 2295 2300Ala Ala Glu Val Ile Thr Gly Thr Arg Ala Ala Gly Pro Val Gly Phe2305 2310 2315 2320Val Phe Ser Gly Gln Gly Gly Gln Trp Pro Gly MeT Gly Ser Gly Leu
2325 2330 2335His Ser Ala Phe Pro Val Phe Ala Asp Ala Phe Asp Glu Ala Cys Cys
2340 2345 2350Glu Leu Asp Ala His Leu Gly Gln Met Ala Arg Leu Arg Asp Val Leu
2355 2360 2365Ser Gly Ser Asp Thr Gln Leu Leu Asp Gln Thr Leu Trp Ala Gln Pro2370 2375 2380Gly Leu Phe Ala Leu Gln Val Gly Leu Trp Glu Leu Leu Gly Ser Trp2385 2390 2395 2400Gly Val Arg Pro Ala Val Val Leu Gly His Ser Val Gly Glu Leu Ala
2405 2410 2415Ala Ala Phe Ala Ala Gly Val Leu Ser Leu Arg Asp Ala Ala Arg Leu
2420 2425 2430Val Ala Gly Arg Ala Arg Leu Met Gln Ala Leu Pro Thr Gly Gly Ala
2435 2440 2445Met Leu Ala Ala Ala Ala Gly Glu Glu Gln Leu Arg Pro Leu Leu Ala2450 2455 2460Asp Cys Gly Asp Arg Val Gly Ile Ala Ala Val Asn Ala Pro Gly Ser2465 2470 2475 2480Val Val Leu Ser Gly Asp Arg Asp Val Leu Asp Asp Ile Ala Gly Arg
2485 2490 2495Leu Asp Gly Gln Gly Ile Arg Ser Arg Trp Leu Arg Val Ser His Ala
2500 2505 2510Phe His Ser His Arg Met Asp Pro Met Leu Ala Glu Phe Thr Glu Ile
2515 2520 2525Ala Arg Ser Val Asp Tyr Arg Ser Ser Gly Leu Pro Ile Val Ser Thr2530 2535 2540Leu Thr Gly Glu Leu Asp Glu Val Gly Met Pro Ala Thr Pro Glu Tyr2545 2550 2555 2560Trp Val Arg Gln Val Arg Glu Pro Val Arg Phe Ala Asp Gly Val Ala
2565 2570 2575Ala Leu Ala Ala His Gly Val 5er Thr Val Val Glu Val Gly Pro Asp
2580 2585 2590Gly Val Leu Ser Ala Leu Val Gln Glu Cys Ala Ala Gly Ser Asp Gln
2595 2600 2605Gly Gly Arg Val Ala Ala Val Pro Leu Met Arg Ser Asn Arg Asp Glu2610 2615 2620Ala His Thr Val Thr Thr Ala Leu Ala Gln Ile His Val Arg Gly Ala2625 2630 2635 2640Glu Val Asp Trp Arg Ser Phe Phe Ala Gly Thr Gly Ala Lys Gln Val
2645 2650 2655Glu Leu Pro Thr Tyr Ala Phe Gln Arg Gln Arg Tyr Trp Leu Asp Ser
2660 2665 2670Pro Ser Glu Pro Val Gly Gln Ser Ala Asp Pro Ala Arg Gln 5er Gly
2675 2680 2685Phe Trp Glu Leu Val Glu Gln Glu Asp Val Ser Ala Leu Ser Ala Ala2690 2695 2700Leu His Ile Thr Gly Asp His Asp Val Gln Ala Ser Leu Glu Ser Val2705 2710 2715 2720Val Pro Val Leu Ser Ser Trp His Arg Arg Ile Arg Asn Glu Ser Leu
2725 2730 2735Val His Gln Trp Arg Tyr Arg Ile Ser Trp His Glu Arg Ala Asp Leu
2740 2745 2750Pro Asp Pro Ser Leu Ser Gly Thr Trp Leu Val Val Val Pro Glu Gly
2755 2760 2765Trp Ser Ala Ser Arg Gln Val Leu Arg Phe Asn Glu Met Phe Glu Glu2770 2775 2780Arg Gly Cys Pro Ala Val Leu Phe Glu Leu Ala Gly His Asp Glu Glu2785 2790 2795 2800Ala Leu Ala Gln Arg Phe Arg Ser Leu Pro Val Ala Ser Gly Gly Ile
2805 2810 2815Ser Gly Val Leu Ser Leu Leu Ala Leu Asp Glu Ser Pro Ser Ser Pro
2820 2825 2830Asn Ala Ala Leu Pro Asn Gly Ala Leu Asn Ser Leu Val Leu Leu Arg
2835 2840 2845Ala Leu Arg Ala Ala Asp Val Ser Ala Pro Leu Trp Leu Ala Thr Cys2850 2855 2860Gly Gly Val Ala Val Gly Asp Val Pro Val Asn Pro Gly Gln Ala Leu2865 2870 2875 2880Val Trp Gly Leu Gly Arg Val Val Gly Leu Glu His Pro Ala Trp Trp
2885 2890 2895Gly Gly Leu Val Asp Val Pro Cys Leu Leu Asp Glu Asp Ala Arg Glu
2900 2905 2910Arg Leu Ser Val Val Leu Ala Gly Leu Gly Glu Asp Glu Ile Ala Val
2915 2920 2925Arg Pro Gly Gly Val Phe Val Arg Arg Leu Glu Arg Ala Gly Ala Ala2930 2935 2940Ser Gly Ala Gly Ser Val Trp Arg Pro Arg Gly Thr Val Leu Val Thr2945 2950 2955 2960Gly Gly Thr Gly Gly Leu Gly Ala His Val Ala Arg Trp Leu Ala Gly
2965 2970 2975Ala Gly Ala Glu His Val Val Leu Thr Ser Arg Arg Gly Ala Ala Ala
2980 2985 2990Pro Gly Ala Gly Asp Leu Arg Ala Glu Leu Glu Ala Leu Gly Ala Arg
2995 3000 3005Val Ser Ile Thr Ala Cys Asp Val Ala Asp Arg Asp Ala Leu Ala Glu3010 3015 3020Val Leu Ala Thr Ile Pro Asp Asp Cys Pro Leu Thr Ala Val Met His3025 3030 3035 3040Ala Ala Gly Val Val Glu Val Gly Asp Val Ala Ser Met Cys Leu Thr
3045 3050 3055Asp Phe Val Gly Val Leu Ser Ala Lys Ala Gly Gly Ala Ala Asn Leu
3060 3065 3070Asp Glu Leu Leu Ala Asp Val Glu Leu Asp Ala Phe Val Leu Phe Ser
3075 3080 3085Ser Val Ser Gly Val Trp Gly Ala Gly Gly Gln Gly Ala Tyr Ala Ala3090 3095 3100Ala Asn Ala Tyr Leu Asp Ala Leu Ala Gln Gln Arg Arg Ala Arg Gly3105 3110 3115 3120Leu Val Gly Thr Ala Val Ala Trp Gly Pro Trp Ala Gly Asp Gly Met
3125 3130 3135Ala Ala Gly Glu Gly Gly Ala Gln Leu Arg Arg Ala Gly Leu Val Pro
3140 3145 3150Met Ala Ala Asp Arg Ala Leu Leu Ala Leu Gln Gly Ala Leu Asp Arg
3155 3160 3165Asp Glu Thr Ser Leu Val Val Ala Asp Met Ala Trp Glu Arg Phe Ala3170 3175 3180Pro Val Phe Ala Met Ser Arg Arg Arg Pro Leu Leu Asp Glu Leu Pro3185 3190 3195 3200Glu Ala Gln Gln Ala Leu Ala Asp Ala Glu Asn Thr Thr Asp Ala Ala
3205 3210 3215Asp Ser Ala Val Pro Leu Pro Arg Leu Ala Gly Met Ala Ala Ala Glu
3220 3225 3230Arg Arg Arg Ala Met Leu Asp Leu Val Leu Ala Glu Ala Ser Ile Val
3235 3240 3245Leu Gly His Asn Gly Ser Asp Pro Val Gly Pro Asp Arg Ala Phe Gln3250 3255 3260Glu Leu Gly Phe Asp Ser Leu Met Ala Val Glu Leu Arg Asn Arg Leu3265 3270 3275 3280Gly Glu Ala Thr Gly Leu Ser Leu Pro Ala Thr Leu Ile Phe Asp Tyr
3285 3290 3295Pro Ser Pro Ser Ala Leu Ala Glu Gln Leu Val Gly Glu Leu Val Gly
3300 3305 3310Ala Gln Pro Ala Thr Thr Val Val Ala Gly Ala Asp Pro Val Asp Asp
3315 3320 3325Pro Val Val Val Val Ala Met Gly Cys Arg Tyr Pro Gly Asp Val Cys3330 3335 3340Ser Pro Glu Glu Leu Trp Gln Leu Val Ser Ala Gly Arg Asp Ala Val3345 3350 3355 3360Ser Thr Phe Pro Val Asp Arg Gly Trp Asp Cys Asn Thr Leu Phe Asp
3365 3370 3375Pro Asp Pro Asp Arg Ala Gly Ser Thr Tyr Val Arg Glu Gly Ala Phe
3380 3385 3390Leu Thr Gly Ala Asp Arg Phe Asp Ala Gly Phe Phe Gly Ile Ser Pro
3395 3400 3405Arg Glu Ala Arg Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu Val3410 3415 3420Ala Trp Glu Val Phe Glu Arg Ala Gly Ile Ala Pro Leu Ser Leu Arg3425 3430 3435 3440Gly Ser Arg Thr Gly Val Phe Ala Gly Thr Asn Gly Gln Asp His Gly
3445 3450 3455Ala Lys Val Ala Ala Ala Pro Glu Ala Ala Gly His Leu Leu Thr Gly
3460 3465 3470Asn Ala Ala Ser Val Leu Ala Gly Arg Leu Ser Tyr Thr Phe Gly Leu
3475 3480 3485Glu Gly Pro Ala Val Ala Val Asp Thr Ala Cys Ser Ser Ser Leu Val3490 3495 3500Ala Leu His Leu Ala Cys Gln Ser Leu Arg Ser Gly Glu Cys Asp Met3505 3510 3515 3520Ala Leu Ala Gly Gly Val Thr Val Met Ser Thr Pro Leu Ala Phe Leu
3525 3530 3535Glu Phe Ser Arg Gln Arg Gly Leu Ala Pro Asp Gly Arg Cys Lys Ser
3540 3545 3550Phe Ala Ala Ala Ala Asp Gly Thr Gly Trp Gly Glu Gly Ala Gly Leu
3555 3560 3565Val Leu Leu Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly His Arg Val3570 3575 3580Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn3585 3590 3595 3600Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val Ile Arg Gln
3605 3610 3615Ala Leu Ala Asn Ala Gly Leu Ser Ala Ser Asp Val Asp Val Val Glu
3620 3625 3630Ala His Gly Thr Gly Thr Gly Leu Gly Asp Pro Ile Glu Ala Gln Ala
3635 3640 3645Leu Ile Ala Thr Tyr Gly Gln Glu Arg Asp Pro Glu Arg Ala Leu Trp3650 3655 3660Leu Gly Ser Ile Lys Ser Asn Ile Gly His Thr Gln Ala Ala Ala Gly3665 3670 3675 3680Val Ala Gly Val Ile Lys Met Val Gln Ala Met Arg His Gly Glu Leu
3685 3690 3695Pro Ala Thr Leu His Val Asp Lys Pro Thr Pro Gln Val Asp Trp Ser
3700 3705 3710Ala Gly Ala Val Arg Leu Leu Thr Gly Asn Thr Pro Trp Pro Glu Ser
3715 3720 3725Gly Arg Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Ile Ser Gly Thr3730 3735 3740Asn Ala His Leu Ile Leu Glu Gln Pro Pro Ser Glu Pro Ala Glu Ile3745 3750 3755 3760Asp Gln Ser Asp Arg Arg Val Thr Ala His Pro Ala Val Ile Pro Trp
3765 3770 3775Met Leu Ser Ala Arg Ser Leu Ala Ala Leu Gln Ala Gln Ala Ala Ala
3780 3785 3790Leu Gln Ala Arg Leu Asp Arg Gly Pro Gly Ala Ser Pro Leu Asp Leu
3795 3800 3805Gly Tyr Ser Leu Ala Thr Thr Arg Ser Val Leu Asp Glu Arg Ala Val
3810 3815 3820Val Trp Gly Ala Asp Arg Glu Ala Leu Leu Ser Arg Leu Ala Ala Leu3825 3830 3835 3840Ala Asp Gly Arg Thr Ala Pro Gly Val Ile Thr Gly Ser Ala Asn Ser
3845 3850 3855Gly Gly Arg Ile Gly Phe Val Phe Ser Gly Gln Gly Ser Gln Trp Leu
3860 3865 3870Gly Met Gly Lys Ala Leu Cys Ala Ala Phe Pro Ala Phe Ala Asp Ala
3875 3880 3885Phe Glu Glu Ala Cys Asp Ala Leu Ser Ala His Leu Gly Ala Asp Val3890 3895 3900Arg Gly Val Leu Phe Gly Ala Asp Glu Gln Met Leu Asp Arg Thr Leu3905 3910 3915 3920Trp Ala Gln Ser Gly Ile Phe Ala Val Gln Val Gly Leu Leu Gly Leu
3925 3930 3935Leu Arg Ser Trp Gly Val Arg Pro Ala Ala Val Leu Gly His Ser Val
3940 3945 3950Gly Glu Leu Ala Ala Ala His Ala Ala Gly Val Leu Ser Leu Pro Asp
3955 3960 3965Ala Ala Arg Leu Val Ala Ala Arg Ala His Leu Met Gln Ala Leu Pro3970 3975 3980Thr Gly Gly Ala Met Leu Ala Val Ala Thr Ser Glu Ala Ala Val Gly3985 3990 3995 4000Pro Leu Leu Ser Gly Val Cys Asp Arg Val Ser Ile Ala Ala Ile Asn
4005 4010 4015Gly Pro Glu Ser Val Val Leu Ser Gly Asp Arg Asp Val Leu Val Glu
4020 4025 4030Leu Ala Gly Glu Phe Asp Ala Arg Gly Leu Arg Thr Lys Trp Leu Arg
4035 4040 4045Val Ser His Ala Phe His Ser His Arg Met Glu Pro Ile Leu Asp Glu4050 4055 4060Tyr Ala Glu Thr Ala Arg Cys Val Glu Phe Gly Glu Pro Val Val Pro4065 4070 4075 4080Ile Val Ser Ala Ala Thr Gly Ala Leu Asp Thr Thr Gly Leu Met Cys
4085 4090 4095Ala Ala Asp Tyr Trp Thr Arg Gln Val Arg Asp Pro Val Arg Phe Gly
4100 4105 4110Asp Gly Val Arg Ala Leu Val Gly Gln Gly Val Asp Thr Ile Val Glu
4115 4120 4125Phe Gly Pro Asp Gly Ala Leu Ser Ala Leu Val Glu Gln Cys Leu Ala4130 4135 4140Gly Ser Asp Gln Ala Gly Arg Val Ala Ala Ile Pro Leu Met Arg Arg4145 4150 4155 4160Asp Arg Asp Glu Val Glu Thr Ala Val Ala Ala Leu Ala His Val His
4165 4170 4175Val Arg Gly Gly Ala Val Asp Trp Ser Ala Cys Phe Ala Gly Thr Gly
4180 4185 4190Ala Arg Thr Val Glu Leu Pro Thr Tyr Ala Phe Gln Arg Gln Arg Tyr
4195 4200 4205Trp Leu Ala Gly Gln Ala Asp Gly Arg Gly Gly Asp Val Val Ala Asp4210 4215 4220Pro Val Asp Ala Arg Phe Trp Glu Leu Val Glu Arg Ala Asp Pro Glu4225 4230 4235 4240Pro Leu Val Asp Glu Leu Cys Ile Asp Arg Asp Gln Pro Phe Arg Glu
4245 4250 4255Val Leu Pro Val Leu Ala Ser Trp Arg Glu Lys Gln Arg Gln Glu Ala
4260 4265 4270Leu Ala Asp Ser Trp Arg Tyr Gln Val Arg Trp Arg Ser Val Glu Val
4275 4280 4285Pro Ser Ala Ala Ala Leu Arg Gly Val Trp Leu Val Val Leu Pro Ala4290 4295 4300Asp Val Pro Arg Asp Gln Pro Ala Val Val Ile Asp Ala Leu Ile Ala4305 4310 4315 4320Arg Gly Ala Glu Val Ala Val Leu Glu Leu Thr Glu Gln Asp Leu Gln
4325 4330 4335Arg Ser Ala Leu Val Asp Lys Val Arg Ala Val Ile Ala Asp Arg Thr
4340 4345 4350Glu Val Thr Gly Val Leu Ser Leu Leu Ala Met Asp Gly Met Pro Cys
4355 4360 4365Ala Ala His Pro His Leu Ser Arg Gly Val Ala Ala Thr Val Ile Leu4370 4375 4380Thr Gln Val Leu Gly Asp Ala Gly Val Ser Ala Pro Leu Trp Leu Ala4385 4390 4395 4400Thr Thr Gly Gly Val Glu Ala Gly Thr Glu Asp Gly Pro Ala Asp Pro
4405 4410 4415Asp His Gly Leu Ile Trp Gly Leu Gly Arg Val Val Gly Leu Glu His
4420 4425 4430Pro Gln Trp Trp Gly Gly Leu Ile Asp Leu Pro Glu Thr Leu Asp Glu
4435 4440 4445Thr Ser Arg Asn Gly Leu Val Ala Ala Leu Ala Gly Thr Ala Ala Glu4450 4455 4460Asp Gln Leu Ala Val Arg Ser Ser Gly Leu ghe Val Arg Arg Val Val4465 4470 4475 4480Arg Ala Ala Arg Asn Pro Arg Ser Glu Thr Trp Arg Ser Arg Gly Thr
4485 4490 4495Val Leu Ile Thr Gly Gly Thr Gly Ala Leu Gly Ala Glu Val Ala Arg
4500 4505 4510Trp Leu Ala Arg Arg Gly Ala Glu His Leu Val Leu Ile Ser Arg Arg
4515 4520 4525Gly Pro Glu Ala Pro Gly Ala Ala Asp Leu Gly Ala Glu Leu Thr Glu4530 4535 4540Leu Gly Val Lys Val Thr Val Leu Ala Cys Asp Val Thr Asp Arg Asp4545 4550 4555 4560Glu Leu Ala Ala Val Leu Ala Ala Val Pro Thr Glu Tyr Pro Leu Ser
4565 4570 4575Ala Val Val His Thr Ala Gly Val Gly Thr Pro Ala Asn Leu Ala Glu
4580 4585 4590Thr Thr Leu Ala Gln Phe Ala Asp Val Leu Ser Ala Lys Val Val Gly
4595 4600 4605Ala Ala Asn Leu Asp Arg Leu Leu Gly Gly Gln Pro Leu Asp Ala Phe4610 4615 4620Val Leu Phe Ser Ser Ile Ser Gly Val Trp Gly Ala Gly Gly Gln Gly4625 4630 4635 4640Ala Tyr Ser Ala Ala Asn Ala Tyr Leu Asp Ala Leu Ala Glu Arg Arg
4645 4650 4655Arg Ala Cys Gly Arg Pro Ala Thr Cys Ile Ala Trp Gly Pro Trp Ala
4660 4665 4670Gly Ala Gly Met Ala Val Gln Glu Gly Asn Glu Ala His Leu Arg Arg
4675 4680 4685Arg Gly Leu Val Pro Met GIu Pro Gln Ser Ala Leu PheAla Leu Gln4690 4695 4700Gln Ala Leu Ser Gln Arg Glu Thr Ala Ile Thr Val Ala Asp Val Asp4705 4710 4715 4720Trp Glu Arg Phe Ala Ala Ser Phe Thr Ala Ala Arg Pro Arg Pro Leu
4725 4730 4735Leu Glu Glu Ile Val Asp Leu Arg Pro Asp Thr Glu Thr Glu Glu Lys
4740 4745 4750His Gly Ala Gly Glu Leu Gly Gln Gln Leu Ala Ala Leu Pro Pro Ala
4755 4760 4765Glu Arg Gly His Leu Leu Leu Glu Val Val Leu Ala Glu Thr Ala Ser4770 4775 4780Thr Leu Gly His Asp Ser Ala Glu Ala Val Gln Pro Asp Arg Thr Phe4785 4790 4795 4800Ala Glu Leu Gly Phe Asp Ser Leu Thr Ala Val Glu Leu Arg Asn Arg
4805 4810 4815Leu Asn Ala Val Thr Gly Leu Arg Leu Pro Pro Thr Leu Val Phe Asp
4820 4825 4830His Pro Thr Pro Leu Ala Leu Ser Glu Gln Leu Val Pro Ala Leu Val
4835 4840 4845Ala Glu Pro Asp Asn Gly Ile Glu Ser Leu Leu Ala Glu Leu Asp Arg4850 4855 4860Leu Asp Thr Thr Leu Ala Gln Gly Pro Ser Ile Pro Leu Glu Asp Gln4865 4870 4875 4880Ala Lys Val Ala Glu Arg Leu His Ala Leu Leu Ala Lys Trp Asp Gly
4885 4890 4895Ala Arg Asp Gly Thr Ala Arg Ala Thr Ser Pro Gln Ser Leu Thr Ala
4900 4905 4910Ala Thr Asp Asp Glu Ile Phe Asp Leu Ile Asp Arg Lys Phe Arg Arg
4915 4920 4925<210>6<211>5588<212>PRT<213>刺糖多孢菌<400>6Met Ala Asn Glu Glu Lys Leu Arg Glu Tyr Leu Lys Arg Val Val Val1 5 10 15Glu Leu Glu Glu Ala His Glu Arg Leu His Glu Leu Glu Arg Gln Glu
20 25 30His Asp Pro Ile Ala Ile Val Ser Met Gly Cys Arg Tyr Pro Gly Gly
35 40 45Val Ser Thr Pro Glu Glu Leu Trp Arg Leu Val Val Asp Gly Gly Asp
50 55 60Ala Ile Ala Asn Phe Pro Glu Asp Arg Gly Trp Asn Leu Asp Glu Leu65 70 75 80Phe Asp Pro Asp Pro Gly Arg Ala Gly Thr Ser Tyr Val Arg Glu Gly
85 90 95Gly Phe Leu Arg Gly Val Ala Asp Phe Asp Ala Gly Leu Phe Gly Ile
100 105 110Ser Pro Arg Glu Ala Gln Ala Met Asp Pro Gln Gln Arg Leu Leu Leu
115 120 125Glu Ile Ser Trp Glu Val Phe Glu Arg Ala Gly Ile Asp Pro Phe Ser
130 135 140Leu Arg Gly Thr Lys Thr Gly Val Phe Ala Gly Leu Ile Tyr His Asp145 150 155 160Tyr Ala Ser Arg Phe Arg Lys Thr Pro Ala Glu Phe Glu Gly Tyr Phe
165 170 175Ala Thr Gly Ash Ala Gly Ser Val Ala Ser Gly Arg Val Ala Tyr Thr
180 185 190Phe Gly Leu Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser
195 200 205Ser Leu Val Ala Leu His Leu Ala Cys Gln Ser Leu Arg Leu Gly Glu
210 215 220Cys Asp Leu Ala Leu Ala Gly Gly Ile Ser Val Met Ala Thr Pro Gly225 230 235 240Ala Phe Val Glu Phe Ser Arg Gln Arg Ala Leu Ala Ser Asp Gly Arg
245 250 255Cys Lys Pro Phe Ala Asp Ala Ala Asp Gly Thr Gly Trp Gly Glu Gly
260 265 270Ala Gly Met Leu Leu Leu Glu Arg Leu Ser Asp Ala Arg Arg Asn Gly
275 280 285His Pro Val Leu Ala Ala Val Val Gly Ser Ala Ile Asn Gln Asp Gly
290 295 300Thr Ser Asn Gly Leu Thr Ala Pro Ser Gly Pro Ala Gln Gln Arg Val305 310 315 320Ile Arg Gln Ala Leu Ala Asn Ala Gly Leu Ser Pro Ala Glu Val Asp
325 330 335Val Val Glu Ala His Gly Thr Gly Thr Ala Leu Gly Asp Pro Ile Glu
340 345 350Ala Gln Ala Leu Ile Ala Thr Tyr Gly Ala Asn Arg Sar Ala Asp His
355 360 365Pro Leu Leu Leu Gly Ser Leu Lys Ser Asn Ile Gly His Thr Gln Ala
370 375 380Ala Ala Gly Val Ala Gly Val Ile Lys Ser Val Leu Ala Ile Arg His385 390 395 400Arg Glu Met Pro Arg Ser Leu His Ile Asp Gln Pro Ser Gln His Val
405 410 415Asp Trp Ser Ala Gly Ala Val Arg Leu Leu Thr Asp Ser Val Asp Trp
420 425 430Pro Asp Leu Gly Arg Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Met
435 440 445Ser Gly Thr Asn Ala His Leu Ile Val Glu Glu Val Ser Asp Glu Pro
450 455 460Val Ser Gly Ser Thr Glu Pro Thr Gly Ala Phe Pro Trp Pro Leu Ser465 470 475 480Gly Lys Thr Glu Thr Ala Leu Arg Glu Gln Ala Ala Glu Leu Leu Ser
485 490 495Val Val Thr Glu His Pro Glu Pro Gly Leu Gly Asp Val Gly Tyr Ser
500 505 510Leu Ala Thr Gly Arg Ala Ala Met Glu His Arg Ala Val Val Val Ala
515 520 525Asp Asp Arg Asp Ser Phe Val Ala Gly Leu Thr Ala Leu Ala Ala Gly
530 535 540Val Pro Ala Ala Asn Val Val Gln Gly Ala Ala Asp Cys Lys Gly Lys545 550 555 560Val Ala Phe Val Phe Pro Gly Gln Gly Ser His Trp Gln Gly Met Ala
565 570 575Arg Glu Leu Ser Glu Ser Ser Pro Val Phe Arg Arg Lys Leu Ala Glu
580 585 590Cys Ala Ala Ala Thr Ala Pro Tyr Val Asp Trp Ser Leu Leu Gly Val
595 600 605Leu Arg Gly Asp Pro Asp Ala Pro Ala Leu Asp Arg Asp Asp Val Ile
610 615 620Gln Leu Ala Leu Phe Ala Met Met Val Ser Leu Ala Glu Leu Trp Arg625 630 635 640Ser Cys Gly Val Glu Pro Ala Ala Val Val Gly His Ser Gln Gly Glu
645 650 655Ile Ala Ala Ala His Val Ala Gly Ala Leu Ser Leu Thr Asp Ala Val
660 665 670Arg Ile Ile Ala Ala Arg Cys Asp Ala Val Ser Ala Leu Thr Gly Lys
675 680 685Gly Gly Met Leu Ala Ile Ala Leu Pro Glu Ser Ala Val Val Lys Arg
690 695 700Ile Ala Gly Leu Pro Glu Leu Thr Val Ala Ala Val Asn Gly Pro Gly705 710 715 720Ser Thr Val Val Ser Gly Glu Pro Ser Ala Leu Glu Arg Leu Gln Thr
725 730 735Glu Leu Thr Ala Glu Asn Val Gln Thr Arg Arg Val Gly Ile Asp Tyr
740 745 750Ala Ser His Ser Pro Gln Ile Ala Gln Val Gln Gly Arg Leu Leu Asp
755 760 765Arg Leu Gly Glu Val Gly Ser Glu Pro Ala Glu Ile Ala Phe Tyr Ser
770 775 780Thr Val Thr Gly Glu Arg Thr Asp Thr Gly Arg Leu Asp Ala Asp Tyr785 790 795 800Trp Tyr Gln Asn Leu Arg Gln Pro Val Arg Phe Gln Gln Thr Val Ala
805 810 815Arg Met Ala Asp Gln Gly Tyr Arg Phe Phe Val Glu Val Ser Pro His
820 825 830Pro Leu Leu Thr Ala Gly Ile Gln Glu Thr Leu Glu Ala Ala Asp Ala
835 840 845Gly Gly Val Val Val Gly Ser Leu Arg Arg Gly Glu Gly Gly Ser Arg
850 855 860Arg Trp Leu Thr Ser Leu Ala Glu Cys Gln Val Arg Gly Leu Pro Val865 870 875 880Asn Trp Glu Gln Val Phe Leu Asn Thr Gly Ala Arg Arg Val Pro Leu
885 890 895Pro Thr Tyr Pro Phe Gln Arg Gln Arg Tyr Trp Leu Glu Ser Ala Glu
900 905 910Tyr Asp Ala Gly Asp Leu Gly Ser Val Gly Leu Leu Ser Ala Glu His
915 920 925Pro Leu Leu Gly Ala Ala Val Thr Leu Ala Asp Ala Gly Gly Phe Leu
930 935 940Leu Thr Gly Lys Leu Ser Val Lys Thr Gln Pro Trp Leu Ala Asp His945 950 955 960Val Val Gly Gly Ala Ile Leu Leu Pro Gly Thr Ala Phe Val Glu Met
965 970 975Leu Ile Arg Ala Ala Asp Gln Val Gly Cys Asp Leu Ile Glu Glu Leu
980 985 990Ser Leu Thr Thr Pro Leu Val Leu Pro Ala Thr Gly Ala Val Gln Val
995 1000 1005Gln Ile Ala Val Gly Gly Pro Asp Glu Ala Gly Arg Arg Ser Val Arg1010 1015 1020Val His Ser Cys Arg Asp Asp Ala Val Pro Gln Asp Ser Trp Thr Cys1025 1030 1035 1040His Ala Thr Gly Thr Leu Thr Ser Ser Asp His Gln Asp Ala Gly Gln
1045 1050 1055Gly Pro Asp Gly Ile Trp Pro Pro Asn Asp Ala Val Ala Val Pro Leu
1060 1065 1070Asp Ser Phe Tyr Ala Arg Ala Ala Glu Arg Gly Phe Asp Phe Gly Pro
1075 1080 1085Ala Phe Gln Gly Leu Gln Ala Ala Trp Lys Arg Gly Asp Glu Ile Phe1090 1095 1100Ala Glu Val Gly Leu Pro Thr Ala His Arg Glu Asp Ala Gly Arg Phe1105 1110 1115 1120Gly Ile His Pro Ala Leu Leu Asp Ala Ala Leu Gln Ala Leu Gly Ala
1125 1130 1135Ala Glu Glu Asp Pro Asp Glu Gly Trp Leu Pro Phe Ala Trp Gln Gly
1140 1145 1150Val Ser Leu Lys Ala Thr Gly Ala Leu Ser Leu Arg Val His Leu Val
1155 1160 1165Pro Ala Gly Ala Asn Ala Val Ser Val Phe Thr Thr Asp Thr Thr Gly1170 1175 1180Gln Ala Val Leu Ser Ile Asp Ser Leu Val Leu Arg Gln Ile Ser Asp1185 1190 1195 1200Lys Gln Leu Ala Ala Ala Arg Ala Met Glu His Glu Ser Leu Phe Arg
1205 1210 1215Val Asp Trp Lys Arg Ile Ser Pro Gly Ala Ala Lys Pro Val Ser Trp
1220 1225 1230Ala Val Ile Gly Asn Asp Glu Leu Ala Arg Ala Cys Gly Ser Ala Leu
1235 1240 1245Gly Thr Glu Leu His Pro Asp Leu Thr Gly Leu Ala Asp Pro Pro Pro1250 1255 1260Asp Val Val Val Val Pro Cys Gly Ala Ser Arg Gln Asp Leu Asp Val1265 1270 1275 1280Ala Ser Glu Ala Arg Ala Ala Thr Gln Arg Met Leu Asp Leu Ile Gln
1285 1290 1295Asp Trp Leu Ala Ala Ala Arg Phe Ala Gly Ser Arg Leu Val Val Val
1300 1305 1310Thr Cys Gly Ala Ala Ser Thr Gly Pro Ala Glu Gly Val Ser Asp Leu
1315 1320 1325Val His Ala Ala Ser Trp Gly Leu Leu Arg Ser Ala Gln Ser Glu Asn1330 1335 1340Pro Asp Arg Phe Val Leu Val Asp Val Asp Gly Thr Ala Glu Ser Trp1345 1350 1355 1360Arg Ala Leu Ala Ala Ala Val Arg Ser Gly Glu Pro Gln Leu Ala Leu
1365 1370 1375Arg Ala Gly Glu Val Arg Val Pro Arg Leu Ala Arg Cys Val Ala Ala
1380 1385 1390Glu Asp Ser Arg Ile Pro Val Pro Gly Ala Asp Gly Thr Val Leu Ile
1395 1400 1405Ser Gly Gly Thr Gly Leu Leu Gly Gly Leu Val Ala Arg His Leu Val1410 1415 1420Ala Glu Arg Gly Val Arg Arg Leu Val Leu Ala Gly Arg Arg Gly Trp1425 1430 1435 1440Ser Ala Pro Gly Val Thr Asp Leu Val Asp Glu Leu Val Gly Leu Gly
1445 1450 1455Ala Ala Val Glu Val Ala Ser Cys Asp Val Gly Asp Arg Ala Gln Leu
1460 1465 1470Asp Arg Leu Lau Thr Thr Ile Ser Ala Glu Phe Pro Leu Arg Gly Val
1475 1480 1485Val His Ala Ala Gly Ala Leu Ala Asp Gly Val Val Glu Ser Leu Thr1490 1495 1500Pro Glu His Val Ala Lys Val Phe Gly Pro Lys Ala Ala Gly Ala Trp1505 1510 1515 1520His Leu His Glu Leu Thr Leu Asp Leu Asp Leu Ser Phe Phe Val Leu
1525 1530 1535Phe Ser Ser Phe Ser Gly Val Ala Gly Ala Ala Gly Gln Gly Asn Tyr
1540 1545 1550Ala Ala Ala Asn Ala Phe Leu Asp Gly Leu Ala Gln His Arg Arg Thr
1555 1560 1565Ala Gly Leu Pro Ala Val Ser Leu Ala Trp Gly Leu Trp Glu Gln Pro1570 1575 1580Ser Gly Met Thr Gly Ala Leu Asp Ala Ala Gly Arg Ser Arg Ile Ala1585 1590 1595 1600Arg Thr Asn Pro Pro Met Ser Ala Pro Asp Gly Leu Arg Leu Phe Glu
1605 1610 1615Met Ala Phe Arg Val Pro Gly Glu Ser Leu Leu Val Pro Val His Val
1620 1625 1630Asp Leu Asn Ala Leu Arg Ala Asp Ala Ala Asp Gly Gly Val Pro Ala
1635 1640 1645Leu Leu Arg Asp Leu Val Pro Ala Pro Val Arg Arg Ser Ala Val Asn1650 1655 1660Glu Ser Ala Asp Val Asn Gly Leu Val Gly Arg Leu Arg Arg Leu Pro1665 1670 1675 1680Asp Leu Asp Gln Glu Thr Gln Leu Leu Gly Leu Val Arg Glu His Val
1685 1690 1695Ser Ala Val Leu Gly His Ser Gly Ala Val Glu Val Gly Ala Asp Arg
1700 1705 1710Ala Phe Arg Asp Leu Gly Phe Asp Ser Leu Ser Gly Val Glu Phe Arg
1715 1720 1725Asn Arg Leu Gly Gly Val Leu Gly Val Arg Leu Pro Ala Thr Ala Val1730 1735 1740Phe Asp Tyr Pro Thr Pro Arg Ala Leu Val Arg Phe Leu Leu Asp Lys1745 1750 1755 1760Leu Ile Gly Gly Val Glu Ala Pro Thr Pro Ala Pro Ala Ala Val Ala
1765 1770 1775Ala Val Thr Ala Asp Asp Pro Val Val Ile Val Gly Met Gly Cys Arg
1780 1785 1790Tyr Pro Gly Gly Val Ser Ser Pro Glu Glu Leu Trp Arg Leu Val Ala
1795 1800 1805Gly Gly Leu Asp Ala Val Ala Glu Phe Pro Asp Asp Arg Gly Trp Asp1810 1815 1820Gln Ala Gly Leu Phe Asp Pro Asp Pro Asp Arg Leu Gly Thr Ser Tyr1825 1830 1835 1840Val Cys Glu Gly Gly Phe Leu Arg Asp Ala Ala Glu Phe Asp Ala Gly
1845 1850 1855Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln
1860 1865 1870Arg Leu Leu Leu Glu Val Ala Trp Glu Thr Val Glu Arg Ala Gly Ile
1875 1880 1885Asp Pro Leu Ser Leu Arg Gly Ser Arg Thr Gly Val Phe Ala Gly Leu1890 1895 1900Met His His Asp Tyr Gly Ala Arg Phe Ile Thr Arg Ala Pro Glu Gly1905 1910 1915 1920Phe Glu Gly Tyr Leu Gly Asn Gly Ser Ala Gly Gly Val Phe Ser Gly
1925 1930 1935Arg Val Ala Tyr Ser Phe Gly Phe Glu Gly Pro Ala Val Thr Val Asp
1940 1945 1950Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Gly Gln Ala
1955 1960 1965Leu Arg Ser Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly Val Thr Val1970 1975 1980Met Ala Thr Pro Gly Met Phe Val Glu Phe Ser Arg Gln Arg Gly Leu1985 1990 1995 2000Ala Ala Asp Gly Arg Cys Lys Ser Phe Ala Ala Ala Ala Asp Gly Thr
2005 2010 2015Gly Trp Gly Glu Gly Ala Gly Leu Val Leu Leu Glu Arg Leu Ser Asp
2020 2025 2030Ala Arg Arg Asn Gly His Ala Val Leu Ala Val Val Arg Gly Ser Ala
2035 2040 2045Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Pro2050 2055 2060Ser Gln Gln Arg Val Ile Thr Gln Ala Leu Ala Ser Ala Gly Leu Ser2065 2070 2075 2080Val Ser Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Arg Leu
2085 2090 2095Gly Asp Pro Ile Glu Ala Gln Ala Leu Ile Ala Thr Tyr Gly Gln Gly
2100 2105 2110Arg Asp Ser Asp Arg Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile
2115 2120 2125Gly His Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val2130 2135 2140Met Ala Met Arg His Gly Gln Leu Pro Ala Thr Leu His Val Asp Glu2145 2150 2155 2160Pro Thr Ser Glu Val Asp Trp Ser Ala Gly Asp Val Gln Leu Leu Thr
2165 2170 2175Glu Asn Thr Pro Trp Pro Gly Asn Ser His Pro Arg Arg Val Gly Val
2180 2185 2190Ser Ser Phe Gly Ile Ser Gly Thr Asn Ala His Val Ile Leu Glu Gln
2195 2200 2205Ala Ser Lys Thr Pro Asp Glu Thr Ala Asp Lys Ser Gly Pro Asp 5er2210 2215 2220Glu Ser Thr Val Asp Leu Pro Ala Val Pro Leu Ile Val Ser Gly Arg2225 2230 2235 2240Thr Pro Ala Ala Leu Ser Ala Gln Ala Ser Ala Leu Leu Ser Tyr Leu
2245 2250 2255Gly Glu Arg Gly Asp Ile Ser Thr Leu Asp Ala Ala Phe Ser Leu Ala
2260 2265 2270Ser Ser Arg Ala Ala Leu Glu Glu Arg Ala Val Val Leu Gly Ala Asp
2275 2280 2285Arg Glu Thr Leu Leu Ser Gly Leu Glu Ala Leu Ala Ser Gly Arg Glu2290 2295 2300Ala Ser Gly Val Val Ser Gly Ser Pro Val Ser Gly Gly Val Gly Phe2305 2310 2315 2320Val Phe Ala Gly Gln Gly Gly Gln Trp Leu Gly Met Gly Arg Gly Leu
2325 2330 2335Tyr Ser Val Phe Pro Val Phe Ala Asp Ala Phe Asp Glu Ala Cys Ala
2340 2345 2350Gly Leu Asp Ala His Leu Gly Gln Asp Val Gly Val Arg Asp Val Val
2355 2360 2365Phe Gly Ser Asp Gly Ser Leu Leu Asp Arg Thr Leu Trp Ala Gln Ser2370 2375 2380Gly Leu Phe Ala Leu Gln Val Gly Leu Leu Ser Leu Leu Gly Ser Trp2385 2390 2395 2400Gly Val Arg Pro Gly Val Val Leu Gly His Ser Val Gly Glu Phe Ala
2405 2410 2415Ala Ala Val Ala Ala Gly Val Leu Ser Leu Pro Asp Ala Ala Arg Met
2420 2425 2430Val Ala Gly Arg Ala Arg Leu Met Gln Ala Leu Pro Ser Gly Gly Ala
2435 2440 2445Met Leu Ala Val Ala Ala Gly Glu Glu Gln Leu Arg Pro Leu Leu Ala2450 2455 2460Asp Arg Val Asp Gly Ala Gly Ile Ala Ala Val Asn Ala Pro Glu Ser2465 2470 2475 2480Val Val Leu Ser Gly Asp Arg Glu Val Leu Asp Asp Ile Ala Gly Ala
2485 2490 2495Leu Asp Gly Gln Gly Ile Arg Trp Arg Arg Leu Arg Val Ser His Ala
2500 2505 2510Phe His Ser Tyr Arg Met Asp Pro Met Leu Gln Glu Phe Ala Glu Ile
2515 2520 2525Ala Arg Ser Val Asp Tyr Arg Arg Gly Asp Leu Pro Val Val Ser Thr2530 2535 2540Leu Thr Gly Glu Leu Asp Thr Ala Gly Val Met Ala Thr Pro Glu Tyr2545 2550 2555 2560Trp Val Arg Gln Val Arg Glu Pro Val Arg Phe Ala Asp Gly Val Arg
2565 2570 2575Val Leu Ala Gln Gln Gly Val Ala Thr Ile Phe Glu Leu Gly Pro Asp
2580 2585 2590Ala Thr Leu Ser Ala Leu Ile Pro Asp Cys His Ser Trp Ala Asp Gln
2595 2600 2605Ala Met Pro Ile Pro Met Leu Arg Lys Asp Arg Thr Glu Thr Glu Thr2610 2615 2620Val Val Ala Ala Val Ala Arg Ala His Thr Arg Gly Val Pro Val Glu2625 2630 2635 2640Trp Ser Ala Tyr Phe Ala Gly Thr Gly Ala Arg Arg Val Glu Leu Pro
2645 2650 2655Thr Tyr Ala Phe Gln Arg Gln Arg Tyr Trp Leu Glu Thr Ser Asp Tyr
2660 2665 2670Gly Asp Val Thr Gly Ile Gly Leu Ala Ala Ala Glu His Pro Leu Leu
2675 2680 2685Gly Ala Val Val Ala Leu Ala Asp Gly Asp Gly Met Val Leu Thr Gly2690 2695 2700Arg Leu Ser Val Gly Thr His Pro Trp Leu Ala Gln His Arg Val Leu2705 2710 2715 2720Gly Glu Val Val Val Pro Gly Thr Ala Ile Leu Glu Met Ala Leu His
2725 2730 2735Ala Gly Ala Arg Leu Gly Cys Asp Arg Val Glu Glu Leu Thr Leu Glu
2740 2745 2750Thr Pro Leu Val Val Pro Glu Arg Ala Ala Gly Ala Gly Ser Arg Gly
2755 2760 2765Pro Ala Gly Gly Thr Thr Val Ser Ile Glu Thr Ala Glu Glu Arg Val2770 2775 2780Arg Thr Asn Asp Ala Ile Glu Ile Gln Leu Leu Val Asn Ala Pro Asp2785 2790 2795 2800Glu Gly Gly Arg Arg Arg Val Ser Leu Tyr Ser Arg Pro Ala Gly Gly
2805 2810 2815Ser Arg Gly Gly Gly Trp Thr Arg His Ala Thr Gly Glu Leu Val Val
2820 2825 2830Gly Thr Thr Gly Gly Arg Ala Val Pro Asp Trp Ser Ala Glu Gly Ala
2835 2840 2845Glu Ser Ile Ala Leu Asp Glu Phe Tyr Val Ala Leu Ala Gly Asn Gly2850 2855 2860Phe Glu Tyr Gly Pro Leu Phe Gln Gly Leu Gln Ala Ala Trp Arg Arg2865 2870 2875 2880Gly Asp Glu Val Leu Ala Glu Ile Ala Pro Pro Ala Glu Ala Asp Ala
2885 2890 2895Met Ala Ser Gly Tyr Leu Leu Asp Pro Ala Leu Leu Asp Ala Ala Leu
2900 2905 2910Gln Ala Ser Ala Leu Gly Asp Arg Pro Glu Gln Gly Gly Ala Trp Leu
2915 2920 2925Pro Phe Ser Phe Thr Gly Val Glu Leu Ser Ala Pro Ala Gly Thr Ile2930 2935 2940Ser Arg Val Arg Leu Glu Thr Arg Arg Pro Asp Ala Ile Ser Val Ala2945 2950 2955 2960Val Met Asp Glu Ser Gly Arg Leu Leu Ala Ser Ile Asp Ser Leu Arg
2965 2970 2975Leu Arg Ser Val Ser Ser Gly Gln Leu Ala Ash Arg Asp Ala Val Arg
2980 2985 2990Asp Ala Leu Phe Glu Val Thr Trp Glu Pro Val Ala Thr Gln Ser Thr
2995 3000 3005Glu Pro Gly Arg Trp Ala Leu Leu Gly Asp Thr Ala Cys Gly Lys Asp3010 3015 3020Asp Leu Ile Lys Leu Ala Thr Asp Ser Ala Asp Arg Cys Ala Asp Leu3025 3030 3035 3040Ala Ala Leu Ala Glu Lys Leu Asp Ser Ser Ala Leu Val Pro Asp Val
3045 3050 3055Val Val Tyr Cys Ala Gly Glu Gln Ala Asp Pro Gly Thr Gly Ala Ala
3060 3065 3070Ala Leu Ala Glu Thr Gln Gln Thr Leu Ala Leu Leu Gln Ala Trp Leu
3075 3080 3085Ala Glu Pro Arg Leu Ala Glu Ala Arg Leu Val Val Val Thr Cys Ala3090 3095 3100Ala Val Thr Thr Ala Pro Ser Asp Gly Ala Ser Glu Leu Ala His Ala3105 3110 3115 3120Pro Leu Trp Gly Leu Leu Arg Ala Ala Gln Val Glu Asn Pro Gly Gln
3125 3130 3135Phe Val Leu Ala Asp Val Asp Gly Thr Ala Glu Ser Trp Arg Ala Leu
3140 3145 3150Pro Ser Ala Leu Gly Ser Met Glu Pro Gln Leu Ala Leu Arg Lys Gly
3155 3160 3165Ala Val Arg Ala Pro Arg Leu Ala Ser Val Ala Gly Gln Ile Asp Val3170 3175 3180Pro Ala Val Val Ala Asp Pro Asp Arg Thr Val Leu Ile Ser Gly Gly3185 3190 3195 3200Thr Gly Leu Leu Gly Gly Ala Val Ala Arg His Leu Val Thr Glu Arg
3205 3210 3215Gly Val Arg Arg Leu Val Leu Thr Gly Arg Arg Gly Trp Asp Ala Pro
3220 3225 3230Gly Ile Thr Glu Leu Val Gly Glu Leu Asn Gly Leu Gly Ala Val Val
3235 3240 3245Asp Val Val Ala Cys Asp Val Ala Asp Arg Ala Asp Leu Glu Ser Leu3250 3255 3260Leu Ala Ala Val Pro Ala Glu Phe Pro Leu Cys Gly Val Val His Ala3265 3270 3275 3280Ala Gly Ala Leu Ala Asp Gly Val Ile Glu Ser Leu Ser Pro Asp Asp
3285 3290 3295Val Gly Ala Val Phe Gly Pro Lys Ala Ala Gly Ala Trp Asn Leu His
3300 3305 3310Glu Leu Thr Arg Asp Thr Asp Leu Ser Phe Phe Ala Leu Phe Ser Ser
3315 3320 3325Leu Ser Gly Val Ala Gly Ala Pro Gly Gln Gly Asn Tyr Ala Ala Ala3330 3335 3340Asn Ala Phe Leu Asp Ala Leu Ala His Tyr Arg Arg Ser Gln Gly Leu3345 3350 3355 3360Pro Ala Val Ser Leu Ala Trp Gly Leu Trp Glu Gln Pro Ser Gly Met
3365 3370 3375Thr Glu Thr Leu Ser Glu Val Asp Arg Ser Arg Ile Ala Arg Ala Asn
3380 3385 3390Pro Pro Leu Ser Thr Lys Glu Gly Leu Arg Leu Phe Asp Ala Gly Leu
3395 3400 3405Ala Leu Asp Arg Ala Ala Val Val Pro Ala Lys Leu Asp Arg Thr Phe3410 3415 3420Leu Ala Glu Gln Ala Arg Ser Gly Ser Leu Pro Ala Leu Leu Thr Ala3425 3430 3435 3440Leu Val Pro Pro Ile Arg Arg Asn Arg Arg Ala Ser Gly Thr Glu Leu
3445 3450 3455Ala Asp Glu Gly Thr Leu Leu Gly Val Val Arg Glu His Ala Ala Ala
3460 3465 3470Val Leu Gly Tyr Ser Ser Ala Ala Asp Val Gly Val Glu Arg Ala Phe
3475 3480 3485Arg Asp Leu Gly Phe Asp Ser Leu Ser Gly Val Glu Leu Arg Asn Arg3490 3495 3500Leu Ala Gly Val Leu Gly Val Arg Leu Pro Ala Thr Ala Val Phe Asp3505 3510 3515 3520Tyr Pro Thr Pro Arg Ala Leu Ala Arg Phe Leu His Gln Glu Leu Ala
3525 3530 3535Asp Glu Ile Ala Thr Thr Pro Ala Pro Val Thr Thr Thr Arg Ala Pro
3540 3545 3550Val Ala Glu Asp Asp Leu Val Ala Ile Val Gly Met Gly Cys Arg Phe
3555 3560 3565Pro Gly Gln Val Ser Ser Pro Glu Glu Leu Trp Arg Leu Val Ala Gly3570 3575 3580Gly Val Asp Ala Val Ala Asp Phe Pro Ala Asp Arg Gly Trp Asp Leu3585 3590 3595 3600Ala Gly Leu Phe Asp Pro Asp Pro Glu Arg Ala Gly Lys Thr Tyr Val
3605 3610 3615Arg Glu Gly Ala Phe Leu Thr Asp Ala Asp Arg Phe Asp Ala Gly Phe
3620 3625 3630Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg
3635 3640 3645Leu Leu Leu Glu Leu Ser Trp Glu Ala Ile Glu Arg Ala Gly Ile Asp3650 3655 3660Pro Gly Ser Leu Arg Gly Ser Arg Thr Gly Val Phe Ala Gly Leu Met3665 3670 3675 3680Tyr His Asp Tyr Gly Ala Arg Phe Ala Ser Arg Ala Pro Glu Gly Phe
3685 3690 3695Glu Gly Tyr Leu Gly Asn Gly Ser Ala Gly Ser Val Ala Ser Gly Arg
3700 3705 3710Ile Ala Tyr Ser Phe Gly Phe Glu Gly Pro Ala Val Thr Val Asp Thr
3715 3720 3725Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Gly Gln Ser Leu3730 3735 3740Arg Ser Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly Val Thr Val Met3745 3750 3755 3760Ser Thr Pro Gly Thr Phe Val Glu Phe Ser Arg Gln Arg Gly Leu Ala
3765 3770 3775Pro Asp Gly Arg Cys Lys Ser Phe Ala Glu Ser Ala Asp Gly Thr Gly
3780 3785 3790Trp Gly Glu Gly Ala Gly Leu Val Leu Leu Glu Arg Leu Ser Asp Ala
3795 3800 3805Arg Arg Asn Gly His Arg Val Leu Ala Val Val Arg Gly Ser Ala Val3810 3815 3820Ash Gln Asp Gly Ala Ser Ash Gly Leu Thr Ala Pro Asn Gly Pro Ser3825 3830 3835 3840Gln Gln Arg Val Ile Gln Gln Ala Leu Ala Ser Ala Gly Leu Ser Val
3845 3850 3855Ser Asp Val Asp Ala Val Glu Ala His Gly Thr Gly Thr Arg Leu Gly
3860 3865 3870Asp Pro Ile Glu Ala Gln Ala Leu Ile Ala Thr Tyr Gly Arg Asp Arg
3875 3880 3885Asp Pro Gly Arg Pro Leu Trp Leu Gly Ser Val Lys Ser Asn Ile Gly3890 3895 3900His Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met3905 3910 3915 3920Ala Met Arg His Gly Gln Leu Pro Arg Thr Leu His Val Asp Ala Pro
3925 3930 3935Ser Ser Gln Val Asp Trp Ser Ala Gly Arg Val Gln Leu Leu Thr Glu
3940 3945 3950Asn Thr Pro Trp Pro Asp Ser Gly Arg Pro Cys Arg Val Gly Val Ser
3955 3960 3965Ser Phe Gly Ile Ser Gly Thr Asn Ala His Val Ile Leu Glu Gln Ser3970 3975 3980Thr Gly Gln Met Asp Gln Ala Ala Glu Pro Asp Ser Ser Pro Val Leu3985 3990 3995 4000Asp Val Pro Val Val Pro Trp Val Val Ser Gly Lys Thr Pro Glu Ala
4005 4010 4015Leu Ser Ala Gln Ala Ala Thr Leu Ala Thr Tyr Leu Asp Gln Asn Val
4020 4025 4030Asp Val Ser Pro Leu Asp Val Gly Ile Ser Leu Ala Val Thr Arg Ser
4035 4040 4045Ala Leu Asp Glu Arg Ala Val Val Leu Gly Ser Asp Arg Asp Thr Leu4050 4055 4060Leu Ser Gly Leu Asn Ala Leu Ala Ala Gly His Glu Ala Ala Gly Val4065 4070 4075 4080Val Thr Gly Pro Val Gly Ile Gly Gly Arg Thr Gly Phe Val Phe Ala
4085 4090 4095Gly Gln Gly Gly Gln Trp Leu Gly Met Gly Arg Arg Leu Tyr Ser Glu
4100 4105 4110Phe Pro Ala Phe Ala Gly Ala Phe Asp Glu Ala Cys Ala Glu Leu Asp
4115 4120 4125Ala Asn Leu Gly Arg Glu Val Gly Val Arg Asp Val Val Phe Gly Ser4130 4135 4140Asp Glu Ser Leu Leu Asp Arg Thr Leu Trp Ala Gln Ser Gly Leu Phe4145 4150 4155 4160Ala Leu Gln Val Gly Leu Trp Glu Leu Leu Gly Thr Trp Gly Val Arg
4165 4170 4175Pro Ser Val Val Leu Gly His Ser Val Gly Glu Leu Ala Ala Ala Phe
4180 4185 4190Ala Ala Gly Val Leu Ser Met Ala Glu Ala Ala Arg Leu Val Ala Gly
4195 4200 4205Arg Ala Arg Leu Met Gln Ala Leu Pro Ser Gly Gly Ala Met Leu Ala4210 4215 4220Val Ser Ala Thr Glu Ala Arg Val Gly Pro Leu Leu Asp Gly Val Arg4225 4230 4235 4240Asp Arg Val Gly Val Ala Ala Val Asn Ala Pro Gly Ser Val Val Leu
4245 4250 4255Ser Gly Asp Arg Asp Val Leu Asp Gly Ile Ala Gly Arg Leu Asp Gly
4260 4265 4270Gln Gly Ile Arg Ser Arg Trp Leu Arg Val Ser His Ala Phe His Ser
4275 4280 4285His Arg Met Asp Pro Met Leu Ala Glu Phe Ala Glu Leu Ala Arg Ser4290 4295 4300Val Asp Tyr Arg Ser Pro Arg Leu Pro Ile Val Ser Thr Leu Thr Gly4305 4310 4315 4320Asn Leu Asp Asp Val Gly Val Met Ala Thr Pro Glu Tyr Trp Val Arg
4325 4330 4335Gln Val Arg Glu Pro Val Arg Phe Ala Asp Gly Val Gln Ala Leu Val
4340 4345 4350Asp Gln Gly Val Asp Thr Ile Val Glu Leu Gly Pro Asp Gly Ala Leu
4355 4360 4365Ser Ser Leu Val Gln Glu Cys Val Ala Glu Ser Gly Arg Ala Thr Gly4370 4375 4380Ile Pro Leu Val Arg Arg Asp Arg Asp Glu Val Arg Thr Val Leu Asp4385 4390 4395 4400Ala Leu Ala Gln Thr His Thr Arg Gly Gly Ala Val Asp Trp Gly Ser
4405 4410 4415Phe Phe Ala Gly Thr Arg Ala Thr Gln Val Asp Leu Pro Thr Tyr Ala
4420 4425 4430Phe Gln Arg Gln Arg Tyr Trp Leu Glu Pro Ser Asp Ser Gly Asp Val
4435 4440 4445Thr Gly Val Gly Leu Thr Gly Ala Glu His Pro Leu Leu Gly Ala Val4450 4455 4460Val Pro Val Ala Gly Gly Asp Glu Val Leu Leu Thr Gly Arg Leu Ser4465 4470 4475 4480Val Gly Thr His Pro Trp Leu Ala Glu His Arg Val Leu Gly Glu Val
4485 4490 4495Val Val Pro Gly Thr Ala Leu Leu Glu Met Ala Trp Arg Ala Gly Ser
4500 4505 4510Gln Val Gly Cys Glu Arg Val Glu Glu Leu Thr Leu Glu Ala Pro Leu
4515 4520 4525Val Leu Pro Glu Arg Gly Ala Ala Ala Val Gln Leu Ala Val Gly Ala4530 4535 4540Pro Asp Glu Ala Gly Arg Arg Ser Leu Gln Leu Tyr Ser Arg Gly Ala4545 4550 4555 4560Asp Glu Asp Gly Asp Trp Arg Arg Ile Ala Ser Gly Leu Leu Ala Gln
4565 4570 4575Ala Asn Ala Val Pro Pro Ala Asp Ser Thr Ala Trp Pro Pro Asp Gly
4580 4585 4590Ala Gly Gln Val Asp Leu Ala Glu Phe Tyr Glu Arg Leu Ala Glu Arg
4595 4600 4605Gly Leu Thr Tyr Gly Pro Val Phe Gln Gly Leu Arg Ala Ala Trp Arg4610 4615 4620His Gly Asp Asp Ile Phe Ala Glu Leu Ala Gly Ser Pro Asp Ala Ser4625 4630 4635 4640Gly Phe Gly Ile His Pro Ala Leu Leu Asp Ala Ala Leu His Ala Met
4645 4650 4655Ala Leu Gly Ala Ser Pro Asp Ser Glu Ala Arg Leu Pro Phe Ser Trp
4660 4665 4670Arg Gly Ala Gln Leu Tyr Arg Ala Glu Gly Ala Ala Leu Arg Val Arg
4675 4680 4685Leu Ser Pro Leu Gly Ser Gly Ala Val Ser Leu Thr Leu Val Asp Ala4690 4695 4700Thr Gly Arg Arg Val Ala Ala Val Glu Ser Leu Ser Thr Arg Pro Val4705 4710 4715 4720Ser Thr Asp Gln Ile Gly Ala Gly Arg Gly Asp Gln Glu Arg Leu Leu
4725 4730 4735His Val Glu Trp Val Arg Ser Ala Glu Ser Ala Gly Met Ser Leu Thr
4740 4745 4750Ser Cys Ala Val Val Gly Leu Gly Glu Pro Glu Trp His Ala Ala Leu
4755 4760 4765Lys Thr Thr Gly Val Gln Val Glu Ser His Ala Asp Leu Ala Ser Leu4770 4775 4780Ala Thr Glu Val Ala Lys Arg Gly Ser Ala Pro Gly Ala Val Ile Val4785 4790 4795 4800Pro Cys Pro Arg Pro Arg Ala Met Gln Glu Leu Pro Thr Ala Ala Arg
4805 4810 4815Arg Ala Thr Gln Gln Ala Met Ala Met Leu Gln Gln Trp Leu Ala Asp
4820 4825 4830Asp Arg Phe Val Ser Thr Arg Leu Ile Leu Leu Thr His Arg Ala Val
4835 4840 4845Ser Ala Val Ala Gly Glu Asp Val Leu Asp Leu Val His Ala Pro Leu4850 4855 4860Trp Gly Leu Val Arg Ser Ala Gln Ala Glu His Pro Asp Arg Phe Ala4865 4870 4875 4880Leu Ile Asp Met Asp Asp Glu Arg Ala Ser Gln Thr Ala Leu Ala Glu
4885 4890 4895Ala Leu Thr Ala Gly Glu Ala Gln Leu Ala Val Arg Ser Gly Val Val
4900 4905 4910Leu Ala Pro Arg Leu Gly Gln Val Lys Val Ser Gly Gly Glu Ala Phe
4915 4920 4925Arg Trp Asp Glu Gly Thr Val Leu Val Thr Gly Gly Thr Gly Gly Leu4930 4935 4940Gly Ala Leu Leu Ala Arg His Leu Val Ser Ala His Gly Val Arg His4945 4950 4955 4960Leu Leu Leu Ala Ser Arg Arg Gly Leu Ala Ala Pro Gly Ala Asp Glu
4965 4970 4975Leu Val Ala Glu Leu Glu Gln Ala Gly Ala Asp Val Ala Val Val Ala
4980 4985 4990Cys Asp Ser Ala Asp Arg Asp Ser Leu Ala Arg Leu Val Ala Ser Val
4995 5000 5005Pro Ala Glu Asn Pro Leu Arg Val Val Val His Ala Ala Gly Val Leu5010 5015 5020Asp Asp Gly Val Leu Met Ser Met Ser Pro Glu Arg Leu Asp Ala Val5025 5030 5035 5040Leu Arg Pro Lys Val Asp Ala Ala Trp Tyr Leu His Glu Leu Thr Arg
5045 5050 5055Glu Leu Gly Leu Ser Ala Phe Val Leu Phe Ser Ser Val Ala Gly Leu
5060 5065 5070Phe Gly Gly Ala Gly Gln Ser Asn Tyr Ala Ala Gly Asn Ala Phe Leu
5075 5080 5085Asp Ala Leu Ala His Cys Arg Gln Ala Gln Gly Leu Pro Ala Leu Ser5090 5095 5100Leu Ala Ser Gly Leu Trp Ala Ser Ile Asp Gly Met Ala Gly Asp Leu5105 5110 5115 5120Ala Ala Ala Asp Val Glu Arg Leu Ser Arg Ala Gly Ile Gly Pro Leu
5125 5130 5135Sar Ala Pro Gly Gly Leu Ala Leu Phe Asp Ala Ala Val Gly Ser Asp
5140 5145 5150Glu Pro Leu Leu Ala Pro Val Arg Leu Asp Val Glu Ala Leu Arg Val
5155 5160 5165Gln Ala Arg Ser Val Gln Thr Arg Ile Pro Glu Met Leu His Gly Met5170 5175 5180Ala Met Gly Pro Ser Arg Arg Thr Pro Phe Thr Ser Arg Val Glu Pro5185 5190 5195 5200Leu His Glu Arg Leu Ala Gly Leu Ser Glu Gly Glu Arg Arg Gln Gln
5205 5210 5215Val Leu Gln Arg Val Arg Ala Asp Ile Ala Val Val Leu Gly His Gly
5220 5225 5230Arg Ser Ser Asp Val Asp Ile Glu Lys Pro Leu Ala Glu Leu Gly Phe
5235 5240 5245Asp Ser Leu Thr Ala Ile Glu Leu Arg Asn Arg Leu Ala Thr Ala Thr 5250 5255 5260Gly Leu Arg Leu Pro Ala Thr Leu Ala Phe Asp His Gly Thr Ala Ala5265 5270 5275 5280Ala Leu Ala Gln His Val Cys Ala Gln Leu Gly Thr Ala Thr Ala Pro
5285 5290 5295Ala Pro Arg Arg Thr Asp Asp Asn Asp Ala Thr Glu Pro Val Arg Sar
5300 5305 5310Leu Phe Gln Gln Ala Tyr Ala Ala Gly Arg Ile Leu Asp Gly Met Asp
5315 5320 5325Leu Val Lys Val Ala Ala Gln Leu Arg Pro Val Phe Gly Ser Pro Gly5330 5335 5340Glu Leu Glu Ser Leu Pro Lys Pro Val Gln Leu Ser Arg Gly Pro Glu5345 5350 5355 5360Glu Leu Ala Leu Val Cys Met Pro Ala Leu Ile Gly Met Pro Pro Ala
5365 5370 5375Gln Gln Tyr Ala Arg Ile Ala Ala Gly Phe Arg Asp Val Arg Asp Val
5380 5385 5390Ser Val Ile Pro Met Pro Gly Phe Ile Ala Gly Glu Pro Leu Pro Ser
5395 5400 5405Ala Ile Glu Val Ala Val Arg Thr Gln Ala Glu Ala Val Leu Gln Glu5410 5415 5420Phe Ala Gly Gly Ser Phe Val Leu Val Gly His Ser Ser Gly Gly Trp5425 5430 5435 5440Leu Ala His Glu Val Ala Gly Glu Leu Glu Arg Arg Gly Val Val Pro
5445 5450 5455Ala Gly Val Val Leu Leu Asp Thr Tyr Ile Pro Gly Glu Ile Thr Pro
5460 5465 5470Arg Phe Ser Val Ala Met Ala His Arg Thr Tyr Glu Lys Leu Ala Thr
5475 5480 5485Phe Thr Asp Met Gln Asp Val Gly Ile Thr Ala Met Gly Gly Tyr Phe5490 5495 5500Arg Met Phe Thr Glu Trp Thr Pro Thr Pro Ile Gly Ala Pro Thr Leu5505 5510 5515 5520Phe Val Arg Thr Glu Asp Cys Val Ala Asp Pro Glu Gly Arg Pro Trp
5525 5530 5535Thr Asp Asp Ser Trp Arg Pro Gly Trp Thr Leu Ala Asp Ala Thr Val
5540 5545 5550Gln Val Pro Gly Asp His Phe Ser Met Met Asp Glu His Ala Gly Ser
5555 5560 5565Thr Ala Gln Ala Val Ala Ser Trp Leu Asp Lys Leu Asn Gln Arg Thr5570 5575 5580Ala Arg Gln Arg5585<210>7<211>275<212>PRr<213>刺糖多孢菌<400>7Val Leu Pro Gly Gly Ala Pro Thr Ser Gln Gln Val Gly Gln Met Tyr1 5 10 15Asp Leu Val Thr Pro Leu Leu Asn Ser Val Ala Gly Gly Pro Cys Ala
20 25 30Ile His His Gly Tyr Trp Glu Asn Asp Gly Arg Ala Ser Trp Gln Gln
35 40 45Ala Ala Asp Arg Leu Thr Asp Leu Val Ala Glu Arg Thr Val Leu Asp
50 55 60Gly Gly Val Arg Leu Leu Asp Val Gly Cys Gly Thr Gly Gln Pro Ala65 70 75 80Leu Arg Val Ala Arg Asp Asn Ala Ile Gln Ile Thr Gly Ile Thr Val
85 90 95Ser Gln Val Gln Val Ala Ile Ala Ala Asp Cys Ala Arg Glu Arg Gly
100 105 110Leu Ser His Arg Val Asp Phe Ser Cys Val Asp Ala Met Ser Leu Pro
115 120 125Tyr Pro Asp Asn Ala Phe Asp Ala Ala Trp Ala Met Gln Ser Leu Leu
130 135 140Glu Met Ser Glu Pro Asp Arg Ala Ile Arg Glu Ile Leu Arg Val Leu145 150 155 160Lys Pro Gly Gly Ile Leu Gly Val Thr Glu Val Val Lys Arg Glu Ala
165 170 175Gly Gly Gly Met Pro Val Ser Gly Asp Arg Trp Pro Thr Gly Leu Arg
180 185 190Ile Cys Leu Ala Glu Gln Leu Leu Glu Ser Leu Arg Ala Ala Gly Phe
195 200 205Glu Ile Leu Asp Trp Glu Asp Val Ser Ser Arg Thr Arg Tyr Phe Met
210 215 220Pro Gln Phe Ala Glu Glu Leu Ala Ala His Gln His Gly Ile Ala Asp225 230 235 240Arg Tyr Gly Pro Ala Val Ala Gly Trp Ala Ala Ala Val Cys Asp Tyr
245 250 255Glu Lys Tyr Ala His Asp Met Gly Tyr Ala Ile Leu Thr Ala Arg Lys
260 265 270Pro Val Gly
275<210>8<211>390<212>PRT<213>刺糖多孢菌<400>8Met Arg Val Leu Val Val Pro Leu Pro Tyr Pro Thr His Leu Met Ala1 5 10 15Met Val Pro Leu Cys Trp Ala Leu Gln Ala Ser Gly His Glu Val Leu
20 25 30Ile Ala Ala Pro Pro Glu Leu Gln Ala Thr Ala His Gly Ala Gly Leu
35 40 45Thr Thr Ala Gly Ile Arg Gly Asn Asp Arg Thr Gly Asp Thr Gly Gly
50 55 60Thr Thr Gln Leu Arg Phe Pro Asn Pro Ala Phe Gly Gln Arg Asp Thr65 70 75 80Glu Ala Gly Arg Gln Leu Trp Glu Gln Thr Ala Ser Asn Val Ala Gln
85 90 95Ser Ser Leu Asp Gln Leu Pro Glu Tyr Leu Arg Leu Ala Glu Ala Trp
100 105 110Arg Pro Ser Val Leu Leu Val Asp Val Cys Ala Leu Ile Gly Arg Val
115 120 125Leu Gly Gly Leu Leu Asp Leu Pro Val Val Leu His Arg Trp Gly Val
130 135 140Asp Pro Thr Ala Gly Pro Phe Ser Asp Arg Ala His Glu Leu Leu Asp145 150 155 160Pro Val Cys Arg His His Gly Leu Thr Gly Leu Pro Thr Pro Glu Leu
165 170 175Ile Leu Asp Pro Cys Pro Pro Ser Leu Gln Ala Ser Asp Ala Pro Gln
180 185 190Gly Ala Pro Val Gln Tyr Val Pro Tyr Asn Gly Ser Gly Ala Phe Pro
195 200 205Ala Trp Gly Ala Ala Arg Thr Ser Ala Arg Arg Val Cys Ile Cys Met
210 215 220Gly Arg Met Val Leu Asn Ala Thr Gly Pro Ala Pro Leu Leu Arg Ala225 230 235 240Val Ala Ala Ala Thr Glu Leu Pro Gly Val Glu Ala Val Ile Ala Val
245 250 255Pro Pro Glu His Arg Ala Leu Leu Thr Asp Leu Pro Asp Asn Ala Arg
260 265 270Ile Ala Glu Ser Val Pro Leu Asn Leu Phe Leu Arg Thr Cys Glu Leu
275 280 285Val Ile Cys Ala Gly Gly Ser Gly Thr Ala Phe Thr Ala Thr Arg Leu
290 295 300Gly Ile Pro Gln Leu Val Leu Pro Gln Tyr Phe Asp Gln Phe Asp Tyr305 310 315 320Ala Arg Asn Leu Ala Ala Ala Gly Ala Gly Ile Cys Leu Pro Asp Glu
325 330 335Gln Ala Gln Ser Asp His Glu Gln Phe Thr Asp Ser Ile Ala Thr Val
340 345 350Leu Gly Asp Thr Gly Phe Ala Ser Ala Ala Ile Lys Leu Ser Asp Glu
355 360 365Ile Thr Ala Met Pro His Pro Ala Ala Leu Val Arg Thr Leu Glu Asn
370 375 380Thr Ala Ala Ile Arg Ala385 390<210>9<211>250<212>PRT<213>刺糖多孢菌<400>9Met Pro Ser Gln Asn Ala Leu Tyr Leu Asp Leu Leu Lys Lys Val Leu1 5 10 15Thr Asn Thr Ile Tyr Ser Asp Arg Pro His Pro Asn Ala Trp Gln Asp
20 25 30Asn Thr Asp Tyr Arg Gln Ala Ala Arg Ala Lys Gly Thr Asp Trp Pro
35 40 45Thr Val Ala His Thr Met Ile Gly Leu Glu Arg Leu Asp Asn Leu Gln
50 55 60His Cys Val Glu Ala Val Leu Ala Asp Gly Val Pro Gly Asp Phe Ala65 70 75 80Glu Thr Gly Val Trp Arg Gly Gly Ala Cys Ile Phe Met Arg Ala Val
85 90 95Leu Gln Ala Phe Gly Asp Thr Gly Arg Thr Val Trp Val Val Asp Ser
100 105 110Phe Gln Gly Met Pro Glu Ser Ser Ala Gln Asp His Gln Ala Asp Gln
115 120 125Ala Met Ala Leu His Glu Tyr Asn Asp Val Leu Gly Val Ser Leu Glu
130 135 140Thr Val Arg Gln Asn Phe Ala Arg Tyr Gly Leu Leu Asp Glu Gln Val145 150 155 160Arg Phe Leu Pro Gly Trp Phe Arg Asp Thr Leu Pro Thr Ala Pro Ile
165 170 175Gln Glu Leu Ala Val Leu Arg Leu Asp Gly Asp Leu Tyr Glu Ser Thr
180 185 190Met Asp Ser Leu Arg Asn Leu Tyr Pro Lys Leu Ser Pro Gly Gly Phe
195 200 205Val Ile Ile Asp Asp Tyr Phe Leu Pro Ser Cys Gln Asp Ala Val Lys
210 215 220Gly Phe Arg Ala Glu Leu Gly Ile Thr Glu Pro Ile His Asp Ile Asp225 230 235 240Gly Thr Gly Ala Tyr Trp Arg Arg Ser Trp
245 250<210>10<211>395<212>PRT<213>刺糖多孢菌<400>10Met Ser Glu Ile Ala Val Ala Pro Trp Ser Val Val Glu Arg Leu Leu1 5 10 15Leu Ala Ala Gly Ala Gly Pro Ala Lys Leu Gln Glu Ala Val Gln Val
20 25 30Ala Gly Leu Asp Ala Val Ala Asp Ala Ile Val Asp Glu Leu Val Val
35 40 45Arg Cys Asp Pro Leu Ser Leu Asp Glu Ser Val Arg Ile Gly Leu Glu
50 55 60Ile Thr Ser Gly Ala Gln Leu Val Arg Arg Thr Val Glu Leu Asp His65 70 75 80Ala Gly Leu Arg Leu Ala Ala Val Ala Glu Ala Ala Ala Val Leu Arg
85 90 95Phe Asp Ala Val Asp Leu Leu Glu Gly Leu Phe Gly Pro Val Asp Gly
100 105 110Arg Arg His Asn Ser Arg Glu Val Arg Trp Ser Asp Ser Met Thr Gln
115 120 125Phe Ser Pro Asp Gln Gly Leu Ala Gly Ala Gln Arg Leu Leu Ala Phe
130 135 140Arg Asn Arg Val Ser Thr Ala Val His Ala Val Leu Ala Ala Ala Ala145 150 155 160Thr Arg Arg Ala Asp Leu Gly Ala Leu Ala Val Arg Tyr Gly Ser Asp
165 170 175Lys Trp Ala Asp Leu His Trp Tyr Thr Glu His Tyr Glu His His Phe
180 185 190Ser Arg Phe Gln Asp Ala Pro Val Arg Val Leu Glu Ile Gly Ile Gly
195 200 205Gly Tyr His Ala Pro Glu Leu Gly Gly Ala Ser Leu Arg Met Trp Gln
210 215 220Arg Tyr Phe Arg Arg Gly Leu Val Tyr Gly Leu Asp Ile Phe Glu Lys225 230 235 240Ala Gly Asn Glu Gly His Arg Val Arg Lys Leu Arg Gly Asp Gln Ser
245 250 255Asp Ala Glu Phe Leu Glu Asp Met Val Ala Lys Ile Gly Pro Phe Asp
260 265 270Ile Val Ile Asp Asp Gly Ser His Val Asn Asp His Val Lys Lys Ser
275 280 285Phe Gln Ser Leu Phe Pro His Val Arg Pro Gly Gly Leu Tyr Val Ile
290 295 300Glu Asp Leu Gln Thr Ala Tyr Trp Pro Gly Tyr Gly Gly Arg Asp Gly305 310 315 320Glu Pro Ala Ala Gln Arg Thr Ser Ile Asp Met Leu Lys Glu Leu Ile
325 330 335Asp Gly Leu His Tyr Gln Glu Arg Glu Ser Arg Cys Gly Thr Glu Pro
340 345 350Ser Tyr Thr Glu Arg Asn Val Ala Ala Leu His Phe Tyr His Asn Leu
355 360 365Val Phe Val Glu Lys Gly Leu Asn Ala Glu Thr Ala Ala Pro Gly Phe
370 375 380Val Pro Arg Gln Ala Leu Gly Val Glu Gly Gly385 390 395<210>11<211>539<212>PRT<213>刺糖多孢菌<400>11Met Ile Ser Ala Ala Gly Glu Gln Ser Gly Pro Val Arg Lys Gly Gly1 5 10 15Ala Val Pro Glu Phe His Asp Pro Ala Pro Met ASn Arg Arg Thr Pro
20 25 30Gly Thr Glu Ile Thr Val Glu Pro Asp Asp Pro Arg Tyr Pro Asp Leu
35 40 45Val Val Gly His Asn Pro Arg Phe Thr Gly Lys Pro Glu Arg Ile His
50 55 60Ile Ala Ser Ser Ala Glu Asp Val Val His Ala Val Ala Asp Ala Val65 70 75 80Arg Thr Gly Arg Arg Val Gly Val Arg Ser Gly Gly His Cys Phe Glu
85 90 95Asn Leu Val Ala Asp Pro Ala Ile Arg Val Leu Val Asp Leu Ser Glu
100 105 110Leu Asn Arg Val Tyr Tyr Asp Ser Thr Arg Gly Ala Phe Ala Ile Glu
115 120 125Ala Gly Ala Ala Leu Gly Gln Val Tyr Arg Thr Leu Phe Lys Asn Trp
130 135 140Gly Val Thr Ile Pro Thr Gly Ala Cys Pro Gly Val Gly Ala Gly Gly145 150 155 160His Ile Leu Gly Gly Gly Tyr Gly Pro Leu Ser Arg Arg Phe Gly Ser
165 170 175Val Val Asp Tyr Leu Gln Gly Val Glu Val Val Val Val Asp Gln Ala
l80 185 190Gly Glu Val His Ile Val Glu Ala Asp Arg Asn Ser Thr Gly Ala Gly
195 200 205His Asp Leu Trp Trp Ala His Thr Gly Gly Gly Gly Gly Asn Phe Gly
210 215 220Ile Val Thr Arg Phe Trp Leu Arg Thr Pro Asp Val Val Ser Thr Asp225 230 235 240Ala Ala Glu Leu Leu Pro Arg Pro Pro Ala Thr Val Leu Leu Arg Ser
245 250 255Phe His Trp Pro Trp His Glu Leu Thr Glu Gln Ser Phe Ala Val Leu
260 265 270Leu Gln Asn Phe Gly Asn Trp Tyr Glu Gln His Ser Ala Pro Glu Ser
275 280 285Thr Gln Leu Gly Leu Phe Ser Thr Leu Val Cys Ala His Arg Gln Ala
290 295 300Gly Tyr Val Thr Lau Asn Val His Leu Asp Gly Thr Asp Pro Asn Ala305 310 315 320Glu Arg Thr Leu Ala Glu His Leu Ser Ala Ile Asn Ala Gln Val Gly
325 330 335Val Thr Pro Ala Glu Gly Leu Arg Glu Thr Leu Pro Trp Leu Arg Ser
340 345 350Thr Gln Val Ala Gly Ala Ile Ala Glu Gly Gly Glu Pro Gly Met Gln
355 360 365Arg Thr Lys Val Lys Ala Ala Tyr Leu Arg Thr Gly Leu Ser Glu Ala
570 375 380Gln Leu Ala Thr Val Tyr Arg Arg Leu Thr Val Tyr Gly Tyr Asp Asn385 390 395 400Pro Ala Ala Ala Leu Leu Leu Leu Gly Tyr Gly Gly Met Ala Asn Ala
405 410 415Val Ala Pro Ser Ala Thr Ala Leu Ala Gln Arg Asp Ser Val Leu Lys
420 425 430Ala Leu Phe Val Thr Asn Trp Ser Glu Pro Ala Glu Asp Glu Arg His
435 440 445Leu Thr Trp Ile Arg Gly Phe Tyr Arg Glu Met Tyr Ala Glu Thr Gly
450 455 460Gly Val Pro Val Pro Gly Thr Arg Val Asp Gly Ser Tyr Ile Asn Tyr465 470 475 480Pro Asp Thr Asp Leu Ala Asp Pro Leu Trp Asn Thr Ser Gly Val Ala
485 490 495Trp His Asp Leu Tyr Tyr Lys Asp Asn Tyr Pro Arg Leu Gln Arg Ala
500 505 510Lys Ala Arg Trp Asp Pro Gln Asn Ile Phe Gln His Gly Leu Ser Ile
515 520 525Lys Pro Pro Ala Arg Leu Ser Pro Gly Gln Pro
530 535<210>12<211>397<212>PRT<213>刺糖多孢菌<400>12Met Ser Thr Thr His Glu Ile Glu Thr Val Glu Arg Ile Ile Leu Ala1 5 10 15Ala Gly Ser Ser Ala Ala Ser Leu Ala Asp Leu Thr Thr Glu Leu Gly
20 25 30Leu Ala Arg Ile Ala Pro Val Leu Ile Asp Glu Ile Leu Phe Arg Ala
35 40 45Glu Pro Ala Pro Asp Ile Glu Arg Thr Glu Val Ala Val Gln Ile Thr
50 55 60His Arg Gly Glu Thr Val Asp Phe Val Leu Thr Leu Gln Ser Gly Glu65 70 75 80Leu Ile Lys Ala Glu Gln Arg Pro Val Gly Asp Val Pro Leu Arg Ile
85 90 95Gly Tyr Glu Leu Thr Asp Leu Ile Ala Glu Leu Phe Gly Pro Gly Ala
100 105 110Pro Arg Ala Val Gly Ala Arg Ser Thr Asn Phe Leu Arg Thr Thr Thr
115 120 125Ser Gly Ser Ile Pro Gly Pro Ser Glu Leu Sar Asp Gly Phe Gln Ala
130 135 140Ile Ser Ala Val Val Ala Gly Cys Gly His Arg Arg Pro Asp Leu Asn145 150 155 160Leu Leu Ala Ser His Tyr Arg Thr Asp Lys Trp Gly Gly Leu His Trp
165 170 175Phe Thr Pro Leu Tyr Glu Arg His Leu Gly Glu Phe Arg Asp Arg Pro
180 185 190Val Arg Ile Leu Glu Ile Gly Val Gly Gly Tyr Asn Phe Asp Gly Gly
195 200 205Gly Gly Glu Ser Leu Lys Met Trp Lys Arg Tyr Phe His Arg Gly Leu
210 215 220Val Phe Gly Met Asp Val Phe Asp Lys Ser Phe Leu Asp Gln Gln Arg225 230 235 240Leu Cys Thr Val Arg Ala Asp Gln Ser Lys Pro Glu Glu Leu Ala Ala
245 250 255Val Asp Asp Lys Tyr Gly Pro Phe Asp Ile Ile Ile Asp Asp Gly Ser
260 265 270His Ile Ash Gly His Val Arg Thr Ser Leu Glu Thr Leu Phe Pro Arg
275 280 285Leu Arg Ser Gly Gly Val Tyr Val Ile Glu Asp Leu Trp Thr Thr Tyr
290 295 300Ala Pro Gly Phe Gly Gly Gln Ala Gln Cys Pro Ala Ala Pro Gly Thr305 310 315 320Thr Val Ser Leu Leu Lys Asn Leu Leu Glu Gly Val Gln His Glu Glu
325 330 335Gln Pro His Ala Gly Ser Tyr Glu Pro Ser Tyr Leu Glu Arg Asn Leu
340 345 350Val Gly Leu His Thr Tyr His Asn Ile Ala Phe Leu Glu Lys Gly Val
355 360 365Asn Ala Glu Gly Gly Val Pro Ala Trp Val Pro Arg Ser Leu Asp Asp
370 375 380Ile Leu His Leu Ala Asp Val Asn Ser Ala Glu Asp Glu385 39 395<210>13<211>283<212>PRT<213>刺糖多孢菌<400>13Val Glu Ser Ile Phe Asp Ala Leu Ala His Gly Arg Pro Leu His His1 5 10 15Gly Tyr Trp Ala Gly Gly Tyr Arg Glu Asp Ala Gly Ala Thr Pro Trp
20 25 30Ser Asp Ala Ala Asp Gln Leu Thr Asp Leu Phe Ile Asp Lys Ala Ala
35 40 45Leu Arg Pro Gly Ala His Leu Phe Asp Leu Gly Cys Gly Asn Gly Gln
50 55 60Pro Val Val Arg Ala Ala Cys Ala Ser Gly Val Arg Val Thr Gly Ile65 70 75 80Thr Val Asn Ala Gln His Leu Ala Ala Ala Thr Arg Leu Ala Asn Glu
85 90 95Thr Gly Leu Ala Gly Ser Leu Glu Phe Asp Leu Val Asp Gly Ala Gln
100 105 110Leu Pro Tyr Pro Asp Gly Phe Phe Gln Ala Ala Trp Ala Met Gln Ser
115 120 125Val Val Gln Ile Val Asp Gln Ala Ala Ala Ile Arg Glu Val His Arg
130 135 140Ile Leu Glu Pro Gly Gly Arg Phe Val Leu Gly Asp Ile Ile Thr Arg145 150 155 160Val Arg Leu Pro Glu Glu Tyr Ala Ala Val Trp Thr Gly Thr Thr Ala
165 170 175His Thr Leu Asn Ser Phe Thr Ala Leu Val Ser Glu Ala Gly Phe Glu
180 185 190Ile Leu Glu Val Thr Asp Leu Thr Ala Gln Thr Arg Cys Met Val Ser
195 200 205Trp Tyr Val Asp Glu Leu Leu Arg Lys Leu Asp Glu Leu Ala Gly Val
210 215 220Glu Pro Ala Ala Val Gly Thr Tyr Gln Gln Arg Tyr Leu Gly Asp Ile225 230 235 240Ala Ala Lys His Gly Pro Gly Pro Ala Gln Leu Ile Ala Ala Val Ala
245 250 255Glu Tyr Arg Lys His Pro Asp Tyr Ala Arg Asn Glu Glu Ser Met Gly
260 265 270Phe Met Leu Leu Gln Ala Arg Lys Lys Gln Ser
275 280<210>14<211>320<212>PRT<213>刺糖多孢菌<400>14Met Pro Asn Ala Val Ser Gly Thr Val Leu Val Pro Asn Ile Pro Trp1 5 10 15Pro Arg Glu Asp Arg Pro Ile Ile Thr Phe Ala Val Gly Thr His Gly
20 25 30Leu Gly Ser Gln Val Ala Pro Ser Tyr Leu Leu Arg Thr Gly Thr Glu
35 40 45Pro Glu Thr Glu Leu Ile Ala Val Ala Leu Asp Arg Gly Trp Ala Val
50 55 60Val Ile Thr Asp Tyr Glu Gly Leu Gly Thr Pro Gly Thr His Thr Tyr65 70 75 80Thr Val Gly Arg Ala Gln Gly His Ala Met Leu Asp Ala Ala Arg Ala
85 90 95Ala Gln Arg Leu Pro Gly Ser Gly Leu Thr Thr Asp Cys Pro Val Gly
100 105 110Ile Trp Gly Tyr Ala Gln Gly Gly Gln Ala Ser Ala Phe Ala Gly Glu
115 120 125Leu His Pro Thr Tyr Ala Pro Glu Leu Arg Ile Arg Ala Ala Ala Ala
130 135 140Gly Ala Val Pro Ile Asp Leu Leu Asp Ile Ile His Arg Asn Asp Gly145 150 155 160Val Phe Thr Gly Pro Val Leu Ala Gly Leu Val Gly His Ala Ala Ala
165 170 175Tyr Pro Asp Leu Pro Phe Asp Glu Leu Leu Thr Glu Ala Gly Arg Thr
180 185 190Ala Val Asp Gln Val Arg Glu Leu Gly Ala Pro Glu Leu Val Thr Arg
195 200 205Phe Leu Gly Arg Glu Leu Ser Asp Phe Leu Asp Thr Ser Gly Leu Phe
210 215 220Glu Gln Pro Arg Trp Arg Ala Arg Leu Ala Glu Ser Val Ala Gly Arg225 230 225 240Asn Gly Gly Pro Val Val Pro Thr Leu Val Tyr His Ser Thr Asp Asp
245 250 255Glu Ile Val Pro Phe Ala Phe Gly Glu Arg Leu Arg Asp Ser Tyr Arg
260 265 270Ala Ala Gly Thr Pro Val Arg Trp His Pro Leu Ser Gly Leu Ala His
275 280 285Phe Pro Ala Ala Leu Ala Ser Ser Arg Val Val Val Ser Trp Phe Asp
290 295 300Glu His Phe Ser Glu Pro Ser Ala Ile Ser Gly Pro Arg Asp Ala Arg305 310 315 320<210>15<211>332<212>PRT<213>刺糖多孢菌<400>15Met Arg Lys Pro Val Arg Ile Gly Val Leu Gly Cys Ala Ser Phe Ala1 5 10 15Trp Arg Arg Met Leu Pro Ala Met Cys Asp Val Ala Glu Thr Glu Val
20 25 30Val Ala Val Ala Ser Arg Asp Pro Ala Lys Ala Glu Arg Phe Ala Ala
35 40 45Arg Phe Glu Cys Glu Ala Val Leu Gly Tyr Gln Arg Leu Leu Glu Arg
50 55 60Pro Asp Ile Asp Ala Val Tyr Val Pro Leu Pro Pro Gly Met His Ala65 70 75 80Glu Trp Ile Gly Lys Ala Leu Glu Ala Asp Lys His Val Leu Ala Glu
85 90 95Lys Pro Leu Thr Thr Thr Ala Ser Asp Thr Ala Arg Leu Val Gly Leu
100 105 110Ala Arg Arg Lys Asn Leu Leu Leu Arg Glu Asn Tyr Leu Phe Leu His
115 120 125His Gly Arg His Asp Val Val Arg Asp Leu Leu Gln Ser Gly Glu Ile
130 135 140Gly Glu Leu Arg Glu Phe Thr Ala Val Phe Gly Ile Pro Pro Leu Pro145 150 155 160Asp Thr Asp Ile Arg Tyr Arg Thr Glu Leu Gly Gly Gly Ala Leu Leu
165 170 175Asp Ile Gly Val Tyr Pro Ala Arg Ala Ala Arg His Phe Leu Leu Gly
180 185 190Pro Leu Thr Val Leu Gly Ala Ser Ser His Glu Ala Gln Glu Ser Gly
195 200 205Val Asp Leu Ser Gly Ser Val Leu Leu Gln Ser Glu Gly Gly Thr Val
210 215 220Ala His Leu Gly Tyr Gly Phe Val His His Tyr Arg Ser Ala Tyr Glu225 230 235 240Leu Trp Gly Ser Arg Gly Arg Ile Val Val Asp Arg Ala Phe Thr Pro
245 250 255Pro Ala Glu Trp Gln Ala Val Ile Arg Ile Glu Arg Lys Gly Val Val
260 265 270Asp Glu Leu Ser Leu Pro Ala Glu Asp Gln Val Arg Lys Ala Val Thr
275 280 285Ala Phe Ala Arg Asp Ile Arg Ala Gly Thr Gly Val Asp Asp Pro Ala
290 295 300Val Ala Gly Asp Ser Gly Glu Ser Met Ile Gln Gln Ala Ala Leu Val305 310 315 320Glu Ala Ile Gly Gln Ala Arg Arg Cys Gly Ser Thr
325 330<210>16<211>486<212>PRT<213>刺糖多孢菌<400>16Met Ser Ser Ser Val Glu Ala Glu Ala Ser Ala Ala Ala Pro Leu Gly1 5 10 15Ser Asn Asn Thr Arg Arg Phe Val Asp Ser Ala Leu Ser Ala Cys Asn
20 25 30Gly Met Ile Pro Thr Thr Glu Phe His Cys Trp Leu Ala Asp Arg Leu
35 40 45Gly Glu Asn Ser Phe Glu Thr Asn Arg Ile Pro Phe Asp Arg Leu Ser
50 55 60Lys Trp Lys Phe Asp Ala Ser Thr Glu Asn Leu Val His Ala Asp Gly65 70 75 80Arg Phe Phe Thr Val Glu Gly Leu Gln Val Glu Thr Asn Tyr Gly Ala
85 90 95Ala Pro Ser Trp His Gln Pro Ile Ile Asn Gln Ala Glu Val Gly Ile
100 105 110Leu Gly Ile Leu Val Lys Glu Ile Asp Gly Val Leu His Cys Leu Met
115 120 125Ser Ala Lys Met Glu Pro Gly Asn Val Asn Val Leu Gln Leu Ser Pro
130 135 140Thr Val Gln Ala Thr Arg Ser Asn Tyr Thr Gln Ala His Arg Gly Ser145 150 155 160Val Pro Pro Tyr Val Asp Tyr Phe Leu Gly Arg Gly Arg Gly Arg Val
165 170 175Leu Val Asp Val Leu Gln Ser Glu Gln Gly Ser Trp Phe Tyr Arg Lys
180 185 190Arg Asn Arg Asn Met Val Val Glu Val Gln Glu Glu Val Pro Val Leu
195 200 205Pro Asp Phe Cys Trp Leu Thr Leu Gly Gln Val Leu Ala Leu Leu Arg
210 215 220Gln Asp Asn Ile Val Asn Met Asp Thr Arg Thr Val Leu Ser Cys Ile225 230 235 240Pro Phe His Asp Ser Ala Thr Gly Pro Glu Leu Ala Ala Ser Glu Glu
245 250 255Pro Phe Arg Gln Ala Val Ala Arg Ser Leu Ser His Gly Ile Asp Ser
260 265 270Ser Ser Ile Ser Glu Ala Val Gly Trp Phe Glu Glu Ala Lys Ala Arg
275 280 285Tyr Arg Leu Arg Ala Thr Arg Val Pro Leu Ser Arg Val Asp Lys Trp
290 295 300Tyr Arg Thr Asp Thr Glu Ile Ala His Gln Asp Gly Lys Tyr Phe Ala305 310 315 320Val Ile Ala Val Ser Val Ser Ala Thr Asn Arg Glu Val Ala Ser Trp
325 330 335Thr Gln Pro Met Ile Glu Pro Arg Glu Gln Gly Glu Ile Ala Leu Leu
340 345 350Val Lys Arg Ile Gly Gly Val Leu His Gly Leu Val His Ala Arg Val
355 360 365Glu Ala Gly Tyr Lys Trp Thr Ala Glu Ile Ala Pro Thr Val Gln Cys
370 375 380Ser Val Ala Asn Tyr Gln Ser Thr Pro Ser Asn Asp Trp Pro Pro Phe385 390 395 400Leu Asp Asp Val Leu Thr Ala Asp Pro Glu Thr Val Arg Tyr Glu Ser
405 410 415Ile Leu Ser Glu Glu Gly Gly Arg Phe Tyr Gln Ala Gln Asn Arg Tyr
420 425 430Arg Ile Ile Glu Val His Glu Asp Phe Ala Ala Arg Pro Pro Ser Asp
435 440 445Phe Arg Trp Met Thr Leu Gly Gln Leu Gly Glu Leu Leu Arg Ser Thr
450 455 460His Phe Leu Asn Ile Gln Ala Arg Ser Leu Val Ala Ser Leu His Ser465 470 475 480Leu Trp Ala Leu Gly Arg
485<210>17<211>455<212>PRT<213>刺糖多孢菌<400>17Val Ile Leu Gly Met Leu Pro Gly Cys Ser Ile AlaIle Gly Glu Phe1 5 10 15Met Arg Val Leu Phe Thr Pro Leu Pro Ala Ser Ser His Phe Phe Asn
20 25 30Leu Val Pro Leu Ala Trp Ala Leu Arg Ala Ala Gly His Glu Val Arg
35 40 45Val Ala Ile Cys Pro Asn Met Val Ser Met Val Thr Gly Ala Gly Leu
50 55 60Thr Ala Val Pro Val Gly Asp Glu Leu Asp Leu Ile Ser Leu Ala Ala65 70 75 80Lys Asn Glu Leu Val Leu Gly Ser Gly Val Ser Phe Asp Glu Lys Gly
85 90 95Arg His Pro Glu Leu Phe Asp Glu Leu Leu Ser Ile Asn Ser Gly Arg
100 105 110Asp Thr Asp Ala Val Glu Gln Leu His Leu Val Asp Asp Arg Ser Leu
115 120 125Asp Asp Leu Met Gly Phe Ala Glu Lys Trp Gln Pro Asp Leu Val Val
130 135 140Trp Asp Ala Met Val Cys Ser Gly Pro Val Val Ala Arg Ala Leu Gly145 150 155 160Ala Arg His Val Arg Met Leu Val Ala Leu Asp Val Ser Gly Trp Leu
165 170 175Arg Ser Gly Phe Leu Glu Tyr Gln Glu Ser Lys Pro Pro Glu Gln Arg
180 185 190Val Asp Pro Leu Gly Thr Trp Leu Gly Ala Lys Leu Ala Lys Phe Gly
195 200 205Ala Thr Phe Asp Glu Glu Ile Val Thr Gly Gln Ala Thr Ile Asp Pro
210 215 220Ile Pro Ser Trp Met Arg Leu Pro Val Asp Leu Asp Tyr Ile Ser Met225 230 235 240Arg Phe Val Pro Tyr Asn Gly Pro Ala Val Leu Pro Glu Trp Leu Arg
245 250 255Glu Arg Pro Thr Lys Pro Arg Val Cys Ile Thr Arg Gly Leu Thr Lys
260 265 270Arg Arg Leu Ser Arg Val Thr Glu Gln Tyr Gly Glu Gln Ser Asp Gln
275 280 285Glu Gln Ala Met Val Glu Arg Leu Leu Arg Gly Ala Ala Arg Leu Asp
290 295 300Val Glu Val Ile Ala Thr Leu Ser Asp Asp Glu Val Arg Glu Met Gly305 310 315 320Glu Leu Pro Ser Asn Val Arg Val His Glu Tyr Val Pro Leu Asn Glu
325 330 335Leu Leu Glu Ser Cys Ser Val Ile Ile His His Gly Ser Thr Thr Thr
340 345 350Gln Glu Thr Ala Thr Val Asn Gly Val Pro Gln Leu Ile Leu Pro Gly
355 360 365Thr Phe Trp Asp Glu Ser Arg Arg Ala Glu Leu Leu Ala Asp Arg Gly
370 375 380Ala Gly Leu Val Leu Asp Pro Ala Thr Phe Thr Glu Asp Asp Val Arg385 390 395 400GIy Gln Leu Ala Arg Leu Leu Asp Glu Pro Ser Phe Ala Ala Asn Ala
405 410 415Ala Leu Ile Arg Arg Glu Ile Glu Glu Ser Pro Ser Pro His Asp Ile
420 425 430Val Pro Arg Leu Glu Lys Leu Val Ala Glu Arg Glu Asn Arg Arg Thr
435 440 445Gly Gln Ser Asp Gly His Pro
450 455<210>18<211>462<212>PRT<213>刺糖多孢菌<400>18Met Gln Ser Arg Lys Thr Arg Ala Leu Gly Lys Gly Arg Ala Arg Val1 5 10 15Thr Ser Cys Asp Asp Thr Cys Ala Thr Ala Thr Glu Met Val Pro Asp
20 25 30Ala Lys Asp Arg Ile Leu Ala Ser Val Arg Asp Tyr His Arg Glu Gln
35 40 45Glu Ser Pro Thr Phe Val Ala Gly Ser Thr Pro Ile Arg Pro Ser Gly
50 55 60Ala Val Leu Asp Glu Asp Asp Arg Val Ala Leu Val Glu Ala Ala Leu65 70 75 80Glu Leu Arg Ile Ala Ala Gly Gly Asn Ala Arg Arg Phe Glu Ser Glu
85 90 95Phe Ala Arg Phe Phe Gly Leu Arg Lys Ala His Leu Val Asn Ser Gly
100 105 110Ser Ser Ala Asn Leu Leu Ala Leu Ser Ser Leu Thr Ser Pro Lys Leu
115 120 125Gly Glu Ala Arg Leu Arg Pro Gly AsP Glu Val Ile Thr Ala Ala Val
130 135 140Gly Phe Pro Thr Thr Ile Asn Pro Ala Val Gln Asn Gly Leu Val Pro145 150 155 160Val Phe Val Asp Val Glu Leu Gly Thr Tyr Asn Ala Thr Pro Asp Arg
165 170 175Ile Lys Ala Ala Val Thr Glu Arg Thr Arg Ala Ile Met Leu Ala His
180 185 190Thr Leu Gly Asn Pro Phe Ala Ala Asp Glu Ile Ala Glu Ile Ala Lys
195 200 205Glu His Glu Leu Phe Leu Val Glu Asp Asn Cys Asp Ala Val Gly Ser
210 215 220Thr Tyr Arg Gly Arg Leu Thr Gly Thr Phe Gly Asp Leu Thr Thr Val225 230 235 240Ser Phe Tyr Pro Ala His His Ile Thr Ser Gly Glu Gly Gly Cys Val
245 250 255Leu Thr Gly Ser Leu Glu Leu Ala Arg Ile Ile Glu Ser Leu Arg Asp
260 265 270Trp Gly Arg Asp Cys Trp Cys Glu Pro Gly Val Asp Asn Thr Cys Arg
275 280 285Lys Arg Phe Asp Tyr His Leu Gly Thr Leu Pro Pro Gly Tyr Asp His
290 295 300Lys Tyr Thr Phe Ser His Val Gly Tyr Asn Leu Lys Thr Thr Asp Leu305 310 315 320Gln Ala Ala Leu Ala Leu Ser Gln Leu Ser Lys Ile Ser Ala Phe Gly
325 330 335Ser Ala Arg Arg Arg Asn Trp Arg Arg Leu Arg Glu Gly Leu Ser Gly
340 345 350Leu Pro Gly Leu Leu Leu Pro Val Ala Thr Pro His Ser Asp Pro Ser
355 360 365Trp Phe Gly Phe Ala Ile Thr Ile Ser Ala Asp Ala Gly Phe Thr Arg
370 375 380Ala Ala Leu Val Asn Phe Leu Glu Ser Arg Asn Ile Gly Thr Arg Leu385 390 395 400Leu Phe Gly Gly Asn Ile Thr Arg His Pro Ala Phe Glu Gln Val Arg
405 410 415Tyr Arg Ile Ala Asp Ala Leu Thr Asn Ser Asp Ile Val Thr Asp Arg
420 425 430Thr Phe Trp Val Gly Val Tyr Pro Gly Ile Thr Asp Gln Met Ile Asp
435 440 445Tyr Val Val Glu Ser Ile Ala Glu Phe Val Ala Lys Ser Ser
450 455 460<210>19<211>385<212>PRT<213>刺糖多孢菌<400>19Val Ile Asn Leu His Gln Pro Ile Leu Gly Thr Glu Glu Leu Asp Ala1 5 10 15Ile Ala Glu Val Phe Ala Ser Ash Trp Ile Gly Leu Gly Pro Arg Thr
20 25 30Arg Thr Phe Glu Ala Glu Phe Ala His His Leu Gly Val Asp Pro Glu
35 40 45Gln Val Val Phe Leu Asn Ser Gly Thr Ala Ala Leu Phe Leu Thr Val
50 55 60Gln Val Leu Asp Leu Gly Pro Gly Asp Asp Val Val Leu Pro Ser Ile65 70 75 80Ser Phe Val Ala Ala Ala Asn Ala Ile Ala Ser Ser Gly Ala Arg Pro
85 90 95Val Phe Cys Asp Val Asp Pro Arg Thr Leu Asn Pro Thr Leu Asp Asp
100 105 110Val Ala Arg Ala Ile Thr Pro Ala Thr Lys Ala Val Leu Leu Leu His
115 120 125Tyr Gly Gly Ser Pro Gly Glu Val Thr Ala Ile Ala Asp Phe Cys Arg
130 135 140Glu Lys Gly Leu Met Leu Ile Glu Asp Ser Ala Cys Ala Val Ala Ser145 150 155 160Ser Val His Gly Thr Ala Cys Gly Thr Phe G1y Asp Leu Ala Thr Trp
165 170 175Ser Phe Asp Ala Met Lys Ile Leu Val Thr Gly Asp Gly Gly Met Phe
180 185 190Tyr Ala Ala Asp Pro Glu Leu Ala His Arg Ala Arg Arg Leu Ala Tyr
195 200 205His Gly Leu Glu Gln Met Ser Gly Phe Asp Ser Ala Lys Ser Ser Asn
210 215 220Arg Trp Trp Asp Ile Arg Val Glu Asp Ile Gly Gln Arg Leu Ile Gly225 230 235 240Asn Asp Met Thr Ala Ala Leu Gly Ser Val Gln Leu Arg Lys Leu Pro
245 250 255Glu Phe Ila Asn Arg Arg Arg Glu Ile Ala Thr Gln Tyr Asp Arg Leu
260 265 270Leu Ser Asp Val Pro Gly Val Leu Leu Pro Pro Thr Leu Pro Asp Gly
275 280 285His Val Ser Ser His Tyr Phe Tyr Trp Val Gln Leu Ala Pro Glu Ile
290 295 300Arg Asp Gln Val Ala Gln Gln Met Leu Glu Arg Gly Ile Tyr Thr Ser305 310 315 320Tyr Arg Tyr Pro Pro Leu His Lys Val Pro Ile Tyr Arg Ala Asp Cys
325 330 335Lys Leu Pro Ser Ala Glu Asp Ala Cys Arg Arg Thr Leu Leu Leu Pro
340 345 350Leu His Pro Ser Leu Asp Asp Ala Glu Val Arg Thr Val Ala Asp Glu
355 360 365Phe Gln Lys Ala Val Glu His His Ile Ser Gln Arg Ser Pro Leu Arg
370 375 380Lys385<210>20<211>249<212>PRT<213>糖多孢菌<400>20Met Ser Arg Val Ser Asp Thr Phe Ala Glu Thr Ser Ser Val Tyr Ser1 5 10 15Pro Asp His Ala Asp Ile Tyr Asp Ala Ile His Ser Ala Arg Gly Arg
20 25 30Asp Trp Ala Ala Glu Ala Gly Glu Val Val Gln Leu Val Arg Thr Arg
35 40 45Leu Pro Glu Ala Gln Ser Leu Leu Asp Val Ala Cys Gly Thr Gly Ala
50 55 60His Leu Glu Arg Phe Arg Ala Glu Tyr Ala Lys Val Ala Gly Leu Glu65 70 75 80Leu Ser Asp Ala Met Arg Glu Ile Ala Ile Arg Arg Val Pro Glu Val
85 90 95Pro Ile His Ile Gly Asp Ile Arg Asp Phe Asp Leu Gly Glu Pro Phe
100 105 110Asp Val Ile Thr Cys Leu Cys Phe Thr Ala Ala Tyr Met Arg Thr Val
115 120 125Asp Asp Leu Arg Arg Val Thr Arg Asn Met Ala Arg His Leu Ala Pro
130 135 140Gly Gly Val Ala Val Ile Glu Pro Trp Trp Phe Pro Asp Lys Phe Ile145 150 155 160Asp Gly Phe Val Thr Gly Ala Val Ala His His Gly Glu Arg Val Ile
165 170 175Ser Arg Leu Ser His Ser Val Leu Glu Gly Arg Thr Ser Arg Met Thr
180 185 190Val Arg Tyr Thr Val Ala Glu Pro Thr Gly Ile Arg Asp Phe Thr Glu
195 200 205Phe Glu Ile Leu Ser Leu Phe Thr Glu Asp Glu Tyr Thr Ala Ala Leu
210 215 220Glu Asp Ala Gly Ile Arg Ala Glu Tyr Leu Pro Gly Ala Pro Asn Gly225 230 235 240Arg Gly Leu Phe Val Gly Ile Arg Asn
245<210>21<211>255<212>PRT<213>刺糖多孢菌<400>21Met Val Leu Val Pro Arg Arg Phe Arg Ala Thr Leu Glu Ser Met Ser1 5 10 15Glu Gln Thr Ile Ala Leu Val Thr Gly Ala Asn Lys Gly Ile Gly Tyr
20 25 30Glu Ile Ala Ala Gly Leu Gly Ala Leu Gly Trp Ser Val Gly Ile Gly
35 40 45Ala Arg Asp His Gln Arg Gly Glu Asp Ala Val Ala Lys Leu Arg Ala
50 55 60Asp Gly Val Asp Ala Phe Ala Val Ser Leu Asp Val Thr Asp Asp Ala65 70 75 80Ser Val Ala Ala Ala Ala Ala Leu Leu Glu Glu Arg Ala Gly Arg Leu
85 90 95Asp Val Leu Val Asn Asn Ala Gly Ile Ala Gly Ala Trp Pro Glu Glu
100 105 110Pro Ser Thr Val Thr Pro Ala Ser Leu Arg Ala Val Val Glu Thr Asn
115 120 125Val Ile Gly Val Val Arg Val Thr Asn Ala Met Leu Pro Leu Leu Arg
130 135 140Arg Ser Glu Arg Pro Arg Ile Val Asn Gln Ser Ser His Val Ala Ser145 150 155 160Leu Thr Leu Gln Thr Thr Pro Gly Val Asp Leu Gly Gly Ile Ser Gly
165 170 175Ala Tyr Ser Pro Ser Lys Thr Phe Leu Asn Ala Ile Thr Ile Gln Tyr
180 185 190Ala Lys Glu Leu Ser Asp Thr Asn Ile Lys Ile Asn Asn Ala Cys Pro
195 200 205Gly Tyr Val Ala Thr Asp Leu Asn Gly Phe Eis Gly Thr Ser Thr Pro
210 215 220Ala Asp Gly Ala Arg Ile Ala Ile Arg Leu Ala Thr Leu Pro Asp Asp225 230 235 240Gly Pro Thr Gly Gly Met Phe Asp Asp Ala Gly Asn Val Pro Trp
245 250 255<210>22<211>278<212>PRT<213>刺糖多孢菌<400>22Met Glu Thr Arg Glu Leu Arg Tyr Phe Val Ala Val Ala Glu Glu Leu1 5 10 15His Phe Gly Arg Ala Ala Gln Arg Leu Gly Ile Ala Gln Pro Pro Leu
20 25 30Ser Arg Thr Ile Ala Gln Leu Glu Gln Arg Leu Gly Val Val Leu Leu
35 40 45Gln Arg Thr Ser Arg Lys Val Ser Leu Thr Glu Ala Gly Ala Met Leu
50 55 60Leu Thr Glu Gly Arg Ala Ile Leu Gly Ala Leu Ala Ala Ala Glu Arg65 70 75 80Arg Thr Gln Arg Ala Ala Thr Ser Gln Pro Ser Leu Val Leu Ala Ala
85 90 95Lys Ala Gly Ala Ser Gly Glu Leu Leu Ala Lys Leu Leu Asp Ala Tyr
100 105 110Ala Ala Glu Pro Gly Ala Val Ala Val Asp Leu Leu Leu Cys Glu Ser
115 120 125Gln Pro Gln Lys Thr Leu His Asp Gly Arg Ala Asp Val Ala Leu Leu
130 135 140His Gln Pro Phe Asp Pro Thr Ala Glu Leu Asp Ile Glu Ile Leu Asn145 150 155 160Thr Glu Gln Gln Val Ala Ile Leu Pro Thr Sar His Pro Leu Ala Ser
165 170 175Glu Pro His Val Arg Met Ala Asp Val Ser Ser Leu Pro Asp Leu Pro
180 185 190Leu Ala Arg Trp Pro Gly Pro Asp Gly Val Tyr Pro Asp Gly Pro Gly
195 200 205Val Glu Val Arg Asn Gln Thr Gln Leu Phe Gln Met Ile Ala Leu Gly
210 215 220Arg Thr Thr Val Val Met Pro Glu Ser Ser Arg Val Asn Leu Leu Glu225 230 235 240Gly Leu Ala Ala Val Pro Val Leu Asp Ala Pro Asp Val Thr Thr Val
245 250 255Ile Ala Trp Pro Pro His Ser Arg Ser Arg Ala Leu Ala Gly Leu Val
260 265 270Arg Val Ala Thr Leu Leu
275<210>23<211>198<212>PRT<213>刺糖多孢菌<400>23Met Met Leu Lys Arg His Arg Leu Thr Thr Ala Ile Thr Gly Leu Leu1 5 10 15Gly Gly Val Leu Leu Val Ser Gly Cys Gly Thr Ala Ala Ala Leu Gln
20 25 30Ser Ser Pro Ala Pro Gly His Asp Ala Arg Asn Val Gly Met Ala Ser
35 40 45Gly Gly Gly Gly Gly Asp Ile Gly Thr Ser Asn Cys Ser Glu Ala Asp
50 55 60Phe Leu Ala Thr Ala Thr Pro Val Lys Gly Asp Pro Gly Ser Phe Ile65 70 75 80Val Ala Tyr Gly Asn Arg Ser Asp Lys Thr Cys Thr Ile Asn Gly Gly
85 90 95Val Pro Asn Leu Lys Gly Val Asp Met Ser Asn Ser Pro Ile Glu Asp
100 105 110Leu Pro Val Glu Asp Val Arg Leu Pro Asp Ala Pro Lys Glu Phe Thr
115 120 125Leu Gln Pro Gly Gln Ser Ala Tyr Ala Gly Ile Gly Met Val Leu Ala
130 135 140Asp Ser Gly Asp Pro Asn Ala His Val Leu Thr Gly Phe Gln Ser Ser145 150 155 160Leu Pro Asp Met Ser Glu Ala Gln Pro Val Asn Val Leu Gly Asp Gly
165 170 175Asn Val Lys Phe Ala Ala Lys Tyr Leu Arg Val Ser Ser Leu Val Ser
180 185 190Thr Ala Asp Glu Leu Atg
195<210>24<211>751<212>PRT<213>刺糖多孢菌<400>24Val Leu Ser Val Glu Lys Gly Arg GIu Ser Ala Thr Trp Thr Ala Val1 5 10 15Leu Glu Gly Thr Leu Glu Arg Ile Thr Phe Ala ASn Glu Glu Ser Gly
20 25 30Tyr Thr Val Ala Arg Ile Asp Thr Gly Arg Gly Gly Asp Leu Val Thr
35 40 45Val Val Gly Ala Leu Leu Gly Ala Gln Pro Gly Glu Ala Leu Arg Met
50 55 60Arg Gly Arg Trp Gly Ser His Pro Gln Tyr Gly Arg Gln Phe His Val65 70 75 80Asp Asp Tyr Thr Thr Val Leu Pro Ala Thr Val Gln Gly Ile Arg Arg
85 90 95Tyr Leu Gly Ser Gly Leu Ile Lys Gly Ile Gly Pro Lys Leu Ala Glu
100 105 110Lys Ile Val Asp His Phe Gly Val Ala Ala Leu Asp Val Ile Glu Gln
115 120 125Glu Pro Ala Arg Leu Ile Glu Val Pro Lys Leu Gly Pro Lys Arg Thr
130 135 140Lys Leu Ile Ala Asp Ala Trp Glu Glu Gln Lys Ala Ile Lys Glu Val145 150 155 160Met Ile Phe Leu Gln Gly Val Gly Val Ser Thr Ser Leu Ala Val Lys
165 170 175Ile Tyr Lys Gln Tyr His Asp Asp Ala Ile Arg Thr Val Lys Glu Glu
180 185 190Pro Tyr Arg Leu Ala Gly Asp Val Trp Gly Ile Gly Phe Lys Thr Ala
195 200 205Asp Thr Ile Ala Lys Ala Val Gly Ile Pro His Asp Ser Pro Gln Arg
210 215 220Val Lys Ala Gly Leu Gln Phe Thr Leu Ser Glu Ser Thr Gly Asp Gly225 230 235 240Asn Cys Tyr Leu Pro Glu Asn Glu Leu Ile Ala Glu Ala Val Lys Ile
245 250 255Leu Ala Val Asp Thr Gly Leu Val Ile Glu Cys Leu Ala Glu Leu Val
260 265 270Thr Glu Glu Gly Val Val Arg Glu Glu Ile Pro Thr Asp Asp Asp Glu
275 280 285Val Pro Thr Val Ala Ile Tyr Leu Val Pro Phe His Arg Ala Glu Val290 295 300Ala Leu Ala Asn Gln Leu Ser Arg Leu Leu Asn Thr Ser Ala Asp Arg305 310 315 320Met Pro Val Phe Ala Asp Val Asp Trp His Lys Ala Leu Asp Trp Leu
325 330 335Arg Arg Ala Thr Gly Ala Glu Leu Ala Glu Ala Gln Glu Arg Ala Val
340 345 350Lys Leu Ala Leu Thr Glu Lys Val Ala Val Leu Thr Gly Gly Pro Gly
355 360 365Cys Gly Lys Ser Phe Thr Val Arg Ser Ile Ile Ala Leu Ala Gln Ala
370 375 380Lys Lys Ala Lys Val Ile Leu Ala Ala Pro Thr Gly Arg Ala Ala Lys385 390 395 400Arg Leu Thr Glu Leu Thr Gly His Asp Ala Ala Thr Val His Arg Leu
405 410 415Leu Gln Leu Gln Pro Gly Gly Asp Ala Ala Tyr Asp Arg Asp Asn Pro
420 425 430Leu Asp Ala Asp Leu Val Val Val Asp Glu Ala Ser Met Leu Asp Leu
435 440 445Leu Leu Ala Asn Lys Leu Ala Lys Ala Ile Ala Pro Gly Ala His Leu
450 455 460Leu Leu Val Gly Asp Val Asp Gln Leu Pro Ser Val Gly Ala Gly Glu465 470 475 480Val Leu Arg Asp Leu Leu Ala Pro Gly Thr Pro Ile Pro His Val Arg
485 490 495Leu Asn Glu Val Phe Arg Gln Ala Ala Glu Ser Gly Val Val Thr Asn
500 505 510Ala His Arg Ile Asn Ala Gly Asp Tyr Pro Leu Thr His Gly Leu Thr
515 520 525Asp Phe Phe Leu Phe His Val Glu Glu Ser Glu Pro Thr Ala Glu Leu
530 535 540Thr Val Asp Val Val Ala Arg Arg Ile Pro Arg Lys Phe Arg Phe Asn545 550 555 560Pro Arg Thr Asp Val Gln Val Leu Ala Pro Met His Arg Gly Pro Ala
565 570 575Gly Ala Gly Ala Leu Asn Gln Leu Leu Gln Glu Ala Ile Thr Pro Ala
580 585 590Arg Glu Gly Leu Pro Glu Arg Arg Phe Gly Gly Arg Ile Phe Arg Val
595 600 605Gly Asp Lys Val Thr Gln Ile Arg Asn Asn Tyr Asp Lys Gly Ala Asn
610 615 620Gly Val Phe Asn Gly Thr Gln Gly Val Val Ser Ala Leu Asp Asn Glu625 630 635 640Ala Gln Thr Met Thr Val Arg Thr Asp Glu Asp Glu Asp Ile Asp Tyr
645 650 655Asp Phe Thr Glu Leu Asp Glu Leu Val His Ala Tyr Ala Val Thr Ile
660 665 670His Arg Ser Gln Gly Ser Glu Tyr Pro Cys Val Val Ile Pro Leu Thr
675 680 685Thr Ser Ala Trp Met Met Leu Gln Arg Asn Leu Leu Tyr Thr Ala Val
690 695 700Thr Arg Ala Lys Lys Val Val Val Leu Val Gly Ser Lys Lys Ala Leu705 710 715 720Gly Gln Ala Val Arg Thr Val Gly Ser Gly Arg Arg His Thr Ala Leu
725 730 735Asp His Arg Leu Arg Arg Gly Gly Thr Gly Ser Arg Pro Ala Ala
740 745 750<210>25<211>2310<212>DNA<213>刺糖多孢菌<220><221>CDS<222>(88)..(1077)<220><221>CDS<222>(1165)..(1992)<400>25ggatcctgct tcgtagctcg gtgtgtcatg ccagactgcg cacgcggacc tgcagcgggc 60cgcgaaatcc cggcgaggaa gggcgcg atg cgg att ctg gtc acc ggc gga gcc 114
Met Arg Ile Leu Val Thr Gly Gly Ala
1 5ggt ttc atc ggc tcg cac tac gtt cgg cag ttg ctc ggt ggt gcg tac 162Gly Phe Ile Gly Ser His Tyr Val Arg Gln Leu Leu Gly Gly Ala Tyr10 15 20 25ccc gca ttc gcc gac gcc gac gtg gtc gtg ctc gac aag ctc acc tac 210Pro Ala Phe Ala Asp Ala Asp Val Val Val Leu Asp Lys Leu Thr Tyr
30 35 40gcc ggc aac gag gcg aac ctg gcg ccg gtc gcg gac aac ccc cgg ctg 258Ala Gly Asn Glu Ala Asn Leu Ala Pro Val Ala Asp Asn Pro Arg Leu
45 50 55aag ttc gtc tgc ggc gac atc tgc gac cgc gaa ctg gtt ggc ggc ctg 306Lys Phe Val Cys Gly Asp Ile Cys Asp Arg Glu Leu Val Gly Gly Leu
60 65 70atg tcc ggc gtg gac gtg gtg gtg cac ttc gcc gcc gaa acc cac gtc 354Met Ser Gly Val Asp Val Val Val His Phe Ala Ala Glu Thr His Val
75 80 85gac cgc tcg atc acc ggc tcg gac gcc ttc gtg atc acc aac gtg gtc 402Asp Arg Ser Ile Thr Gly Ser Asp Ala Phe Val Ile Thr Asn Val Val90 95 100 105ggc acc aac gtg ctg ctg cag gcc gcg ctc gac gcc gag atc ggc aag 450Gly Thr Asn Val Leu Leu Gln Ala Ala Leu Asp Ala Glu Ile Gly Lys
110 115 120ttc gtg cac gtt tcc acc gac gag gtc tac ggc tcc atc gag gac ggc 498Phe Val His Val Ser Thr Asp Glu Val Tyr Gly Ser Ile Glu Asp Gly
125 130 135tcg tgg ccc gaa gac cac gcg ctg gag ccg aat tcc ccg tac tcg gcg 546Ser Trp Pro Glu Asp His Ala Leu Glu Pro Asn Ser Pro Tyr Ser Ala
140 145 150gcg aaa gcg ggc tcg gac ctg ctg gcc cgc gcc tac cac cgc acc cac 594Ala Lys Ala Gly Ser Asp Leu Leu Ala Arg Ala Tyr His Arg Thr His
155 160 165gga ctg ccg gtg tgc atc acc cgc tgc tcc aac aac tac ggg ccc tac 642Gly Leu Pro Val Cys Ile Thr Arg Cys Ser Asn Asn Tyr Gly Pro Tyr170 175 180 185cag ttc ccg gag aag gtg ctg ccg ctg ttc atc acg aac ctg atg gac 690Gln Phe Pro Glu Lys Val Leu Pro Leu Phe Ile Thr Asn Leu Met Asp
190 195 200ggc agc cag gtg ccg ctc tac ggc gac ggg ctc aac gtg cgg gac tgg 738Gly Ser Gln Val Pro Leu Tyr Gly Asp Gly Leu Asn Val Arg Asp Trp
205 210 215ctg cac gtc agc gac cac tgc cgg ggc atc cag ctg gtg gcc gac tcc 786Leu His Val Ser Asp His Cys Arg Gly Ile Gln Leu Val Ala Asp Ser
220 225 230ggg cgc gcg ggc gag atc tac aac atc ggc ggc ggc acc gag ctg acc 834Gly Arg Ala Gly Glu Ile Tyr Asn Ile Gly Gly Gly Thr Glu Leu Thr
235 240 245aac aac gag ctg acc gag cgg ctg ctg gca gag ctg ggc ctc gac tgg 882Asn Asn Glu Leu Thr Glu Arg Leu Leu Ala Glu Leu Gly Leu Asp Trp250 255 260 265tcg gtg gtg cgg ccg gtc acc gac cgc aag ggc cac gac cgc cgc tac 930Ser Val Val Arg Pro Val Thr Asp Arg Lys Gly His Asp Arg Arg Tyr
270 275 280tcg gtg gac cac agc aag atc gtc gag gaa ctg ggg tac gcg ccg cag 978Ser Val Asp His Ser Lys Ile Val Glu Glu Leu Gly Tyr Ala Pro Gln
285 290 295gtc gac ttc gag acc ggg ctg cgc gag aca atc cgc tgg tac cag gac 1026Val Asp Phe Glu Thr Gly Leu Arg Glu Thr Ile Arg Trp Tyr Gln Asp
300 305 310aac cgg gac tgg tgg gag ccg ctg aag gcc cga tcg gcg gtg gct cga 1074Asn Arg Asp Trp Trp Glu Pro Leu Lys Ala Arg Ser Ala Val Ala Arg
315 320 325tga gtcgcctcgc cgtgctggtt gcccggcggc cgcggccagc tgggctcgga 1127330gctggcccgg atcctcgccg cgcggacggg ggcgctg gtg cac cgg ccg ggt tcc 1182
Val His Arg Pro Gly Set
335ggg gaa ctg gac gtc acc gac gcc gag gag gtc gcc gac gcg ttg ggt 1230Gly Glu Leu Asp Val Thr Asp Ala Glu Glu Val Ala Asp Ala Leu Gly
340 345 350tcc ttc gcg gag acg gcg aag gac gcg gag ctg cga ccg gtg gtg atc 1278Ser Phe Ala Glu Thr Ala Lys Asp Ala Glu Leu Arg Pto Val Val Ile
355 360 365aac gcc gcg gcg tac acg gcg gtg gac gcg gcc gag tcc gac ccg gac 1326Asn Ala Ala Ala Tyr Thr Ala Val Asp Ala Ala Glu Ser Asp Pro Asp
370 375 380cgc gcg gcc cgg atc aac gcc gaa ggc gcg gcc tcg ctg gcg aaa gcg 1374Arg Ala Ala Arg Ile Asn Ala Glu Gly Ala Ala Ser Leu Ala Lys Ala385 390 395 400tgc cgg agc agc ggt ctg ccc ctg gtg cac gtg tcg acg gat tac gtg 1422Cys Arg Ser Ser Gly Leu Pro Leu Val His Val Ser Thr Asp Tyr Val
405 410 415ttc ccc cgt gat ggg gcc cgg ccg tac gag ccg acg gac ccg acc ggg 1470Phe Pro Arg Asp Gly Ala Arg Pro Tyr Glu Pro Thr Asp Pro Thr Gly
420 425 430ccg cga tcg gtc tac ggg cgc acc aag ctc gaa ggc gaa cgg gcc gtg 1518Pro Arg Ser Val Tyr Gly Arg Thr Lys Leu Glu Gly Glu Arg Ala Val
435 440 445ctg gag tcc ggc gcg cgg gcc tgg gtg gtg cgc acg gca tgg gtg tac 1566Leu Glu Ser Gly Ala Arg Ala Trp Val Val Arg Thr Ala Trp Val Tyr
450 455 460ggc gcg agc ggc aag aac ttc ctg aaa acg atg atc cgc ctc tcg ggg 1614Gly Ala Ser Gly Lys Asn Phe Leu Lys Thr Met Ile Arg Leu Ser Gly465 470 475 480gag cgc gac acg ctg tcc gtt gtg gac aat cag atc ggc tcg ccg act 1662Glu Arg Asp Thr Leu Ser Val Val Asp Asn Gln Ile Gly Ser Pro Thr
485 490 495tgg gcg gcg gac ctg gcg agc ggc ctg ctg gag ctg gcc gaa cgg gtc 1710Trp Ala Ala Asp Leu Ala Ser Gly Leu Leu Glu Leu Ala Glu Arg Val
500 505 510gcc gaa cgc cgt gga ccg gag cag aag gtg ctg cac tgc acc aat tcc 1758Ala Glu Arg Arg Gly Pro Glu Gln Lys Val Leu His Cys Thr Asn Ser
515 520 525ggc cag gtg acc tgg tac gag ttc gcg cgg gcg atc ttc gcg gaa ttc 1806Gly Gln Val Thr Trp Tyr Glu Phe Ala Arg Ala Ile Phe Ala Glu Phe
530 535 540ggc ctg gac gag aac cgc gtc cac ccg tgc acg acg gcg gac ttc ccc 1854Gly Leu Asp Glu Asn Arg Val His Pro Cys Thr Thr Ala Asp Phe Pro545 550 555 560ctc ccg gcg cac cgc ccg gcc tac tcg gtc ctg tcc gac gtg gcg tgg 1902Leu Pro Ala His Arg Pro Ala Tyr Ser Val Leu Ser Asp Val Ala Trp
565 570 575cga gag gcg ggc ctg acc ccg atg cgc acc tgg cgg gaa gcc ctg gcg 1950Arg Glu Ala Gly Leu Thr Pro Met Arg Thr Trp Arg Glu Ala Leu Ala
580 585 590gcg gcc ttc gag aaa gac ggc gaa acc ctc cga acc cgc tga 1992Ala Ala Phe Glu Lys Asp Gly Glu Thr Leu Arg Thr Arg
595 600 605ccagtcaccc ggagggcgcg agtagccccg gcagggccgt ttcgacgcga tatcggctgg 2052cgcggtgcgc acaatgggtg tcgccggggc gaggaaggaa ggccaggtgc cccgggggca 2112tgactgggag cctggcctga tgcctgtccg gggcgttcag cctgcggcga ggcggtatgc 2172gttcagggtt gcttcggcgc aggttcgcca ggtgaaggct ttagcttggg cacggccctt 2232ttccgcgtct gggggactgg tcagggcttg gtgcagggct tcgttgaggg ccgtcgggtc 2292gccgtggggg aagcggat 2310<210>26<211>329<212>PRT<213>刺糖多孢菌<400>26Met Arg Ile Leu Val Thr Gly Gly Ala Gly Phe Ile Gly Ser His Tyr1 5 10 15Val Arg Gln Leu Leu Gly Gly Ala Tyr Pro Ala Phe Ala Asp Ala Asp
20 25 30Val Val Val Leu Asp Lys Leu Thr Tyr Ala Gly Asn Glu Ala Asn Leu
35 40 45Ala Pro Val Ala Asp Asn Pro Arg Leu Lys Phe Val Cys Gly Asp Ile
50 55 60Cys Asp Arg Glu Leu Val Gly Gly Leu Met Ser Gly Val Asp Val Val65 70 75 80Val His Phe Ala Ala Glu Thr His Val Asp Arg Ser Ile Thr Gly Ser
85 90 95Asp Ala Phe Val Ile Thr Asn Val Val Gly Thr Asn Val Leu Leu Gln
100 105 110Ala Ala Leu Asp Ala Glu Ile Gly Lys Phe Val His Val Ser Thr Asp
115 120 125Glu Val Tyr Gly Ser Ile Glu Asp Gly Ser Trp Pro Glu Asp His Ala
130 135 140Leu Glu Pro Asn Ser Pro Tyr Ser Ala Ala Lys Ala Gly Ser Asp Leu145 150 155 160Leu Ala Arg Ala Tyr His Arg Thr His Gly Leu Pro Val Cys Ile Thr
165 170 175Arg Cys Ser Asn Asn Tyr Gly Pro Tyr Gln Phe Pro Glu Lys Val Leu
180 185 190Pro Leu Phe Ile Thr Asn Leu Met Asp Gly Ser Gln Val Pro Leu Tyr
195 200 205Gly Asp Gly Leu Asn Val Arg Asp Trp Leu His Val Ser Asp His Cys
210 215 220Arg Gly Ile Gln Leu Val Ala Asp Ser Gly Arg Ala Gly Glu Ile Tyr225 230 235 240Asn Ile Gly Gly Gly Thr Glu Leu Thr Asn Asn Glu Leu Thr Glu Arg
245 250 255Leu Leu Ala Glu Leu Gly Leu Asp Trp Ser Val Val Arg Pro Val Thr
260 265 270Asp Arg Lys Gly His Asp Arg Arg Tyr Ser Val Asp His Ser Lys Ile
275 280 285Val Glu Glu Leu Gly Tyr Ala Pro Gln Val Asp Phe Glu Thr Gly Leu
290 295 300Arg Glu Thr Ile Arg Trp Tyr Gln Asp Asn Arg Asp Trp Trp Glu Pro305 310 315 320Leu Lys Ala Arg Ser Ala Val Ala Arg
325<210>27<211>275<212>PRT<213>刺糖多孢菌<400>27Val His Arg Pro Gly Ser Gly Glu Leu Asp Val Thr Asp Ala Glu Glu1 5 10 15Val Ala Asp Ala Leu Gly Ser Phe Ala Glu Thr Ala Lys Asp Ala Glu
20 25 30Leu Arg Pro Val Val Ile Asn Ala Ala Ala Tyr Thr Ala Val Asp Ala
35 40 45Ala Glu Ser Asp Pro Asp Arg Ala Ala Arg Ile Asn Ala Glu Gly Ala
50 55 60Ala Ser Leu Ala Lys Ala Cys Arg Ser Ser Gly Leu Pro Leu Val His65 70 75 80Val Ser Thr Asp Tyr Val Phe Pro Arg Asp Gly Ala Arg Pro Tyr Glu
85 90 95Pro Thr Asp Pro Thr Gly Pro Arg Ser Val Tyr Gly Arg Thr Lys Leu
100 105 110Glu Gly Glu Arg Ala Val Leu Glu Ser Gly Ala Arg Ala Trp Val Val
115 120 125Arg Thr Ala Trp Val Tyr Gly Ala Ser Gly Lys Asn Phe Leu Lys Thr
130 135 140Met Ile Arg Leu Ser Gly Glu Arg Asp Thr Leu Ser Val Val Asp Asn145 150 155 160Gln Ile Gly Ser Pro Thr Trp Ala Ala Asp Leu Ala Ser Gly Leu Leu
165 170 175Glu Leu Ala Glu Arg Val Ala Glu Arg Arg Gly Pro Glu Gln Lys Val
180 185 190Leu His Cys Thr Asn Ser Gly Gln Val Thr Trp Tyr Glu Phe Ala Arg
195 200 205Ala Ile Phe Ala Glu Phe Gly Leu Asp Glu Asn Arg Val His Pro Cys
210 215 220Thr Thr Ala Asp Phe Pro Leu Pro Ala His Arg Pro Ala Tyr Ser Val225 230 235 240Leu Ser Asp Val Ala Trp Arg Glu Ala Gly Leu Thr Pro Met Arg Thr
245 250 255Trp Arg Glu Ala Leu Ala Ala Ala Phe Glu Lys Asp Gly Glu Thr Leu
260 265 270Arg Thr Arg
275<210>28<211>1272<212>DNA<213>刺糖多孢菌<220><221>CDS<222>(334)..(1119)<400>28aaggccaccg gcaaggtcgt gcagggcatc tcgcaggacg tcgcgaagaa gatctccaag 60aagatccgcg acgagggccc gaagggcgtt caggcccaga tccagggcga gcagctgcgg 120gtgtccggca agaagaagga cgacctgcag gccgtgatcc agttgctgaa gtcgagcgac 180ttcgacgtcg cgctccagtt cgagaatttc cggtaatcca ccgctggagg tatccgggtg 240aaggggatcg tgctggcggg tggcaacggg acccggctgc atccgctgac gcaggccgtg 300tccaaacagc tacttccggt gtacgacaag ccg atg atc tac tac ccg ctg tcg 354
Met Ile Tyr Tyr Pro Leu Ser
1 5gtg ctg atg ctg gcc ggc atc cgg gac gtg ctg ctg atc tcg acc ccg 402Val Leu Met Leu Ala Gly Ile Arg Asp Val Leu Leu Ile Ser Thr Pro
10 15 20gcc gac atg ccg ttg ttc cag cgg ctg ctc ggg aac ggg tcg cag ttc 450Ala Asp Met Pro Leu Phe Gln Arg Leu Leu Gly Asn Gly Ser Gln Phe
25 30 35ggc att cgg atc gag tac gcc gag cag tcc cag ccc aac ggg cta gcc 498Gly Ile Arg Ile Glu Tyr Ala Glu Gln Ser Gln Pro Asn Gly Leu Ala40 45 50 55gag gcg ttc gtg atc ggt gcc gac ttc gtc ggc gac gac tcg gtg gcg 546Glu Ala Phe Val Ile Gly Ala Asp Phe Val Gly Asp Asp Ser Val Ala
60 65 70ttg gtg ctc ggc gac aac atc ttt tac ggg cag ggc ttt tcc ggg atc 594Leu Val Leu Gly Asp Asn Ile Phe Tyr Gly Gln Gly Phe Ser Gly Ile
75 80 85ctc cag cag tgc gtc cgg gag ctc gac ggc tgc acg ctg ttc ggc tac 642Leu Gln Gln Cys Val Arg Glu Leu Asp Gly Cys Thr Leu Phe Gly Tyr
90 95 100ccg gtc cgc gac ccg cag cgc tac ggc gtc ggt gag gtg gac gac gac 690Pro Val Arg Asp Pro Gln Arg Tyr Gly Val Gly Glu Val Asp Asp Asp
105 110 115ggt cgg ctg ttg tcc atc gtg gag aag ccg gag cgg ccg aag tcc aac 738Gly Arg Leu Leu Ser Ile Val Glu Lys Pro Glu Arg Pro Lys Ser Asn120 125 130 135atg gcc atc acc ggc ctg tac ttc tac gac aac gac gtg gtg cgc atc 786Met Ala Ile Thr Gly Leu Tyr Phe Tyr Asp Asn Asp Val Val Arg Ile
140 145 150gcc aag ggg ctc acg ccg tcg gcc cgc ggc gag ctg gag atc acc gac 834Ala Lys Gly Leu Thr Pro Ser Ala Arg Gly Glu Leu Glu Ile Thr Asp
155 160 165gtc aac ctg gcc tac ctg cag gag ggc cgg gcg cac ctg acc aag ctc 882Val Asn Leu Ala Tyr Leu Gln Glu Gly Arg Ala His Leu Thr Lys Leu
170 175 180ggc cgc ggg ttc gcc tgg ctg gac acc ggg acc cac gac tcg cta gtg 930Gly Arg Gly Phe Ala Trp Leu Asp Thr Gly Thr His Asp Ser Leu Val
185 190 195gag gcc tcg cag ttc gtg cag gtg ctg gag cac cgg cag ggc gtg cgg 978Glu Ala Ser Gln Phe Val Gln Val Leu Glu His Arg Gln Gly Val Arg200 205 210 215atc gcc tgc ctg gag gag atc ncc ctg cgc atg ggc tac atc tcg gcc 1026Ile Ala Cys Leu Glu Glu Ile Xaa Leu Arg Met Gly Tyr Ile Ser Ala
220 225 230gac gac tgt ttc gcg ctg ggc gtg aag ctg gcc aag tcg ggc tac agc 1074Asp Asp Cys Phe Ala Leu Gly Val Lys Leu Ala Lys Ser Gly Tyr Ser
235 240 245gag tac gtc atg gac gtc gcc cgc aac tcc ggc gcg cgg ggc tga 1119Glu Tyr Val Met Asp Val Ala Arg Asn Ser G1y Ala Arg Gly
250 255 260cccgagctcg tccgatttcc attgaaatcg cggaccgtcg gcgtgtcgta gtccggtgcg 1179ccgatattcc gggcggcgtc accaggccgg gggtagttgg tggccggcca tgccctccag 1239gcggcgaaat gcggtcggcc atcggcgggt tgc 1272<210>29<211>261<212>PRT<213>刺糖多孢菌<400>29Met Ile Tyr Tyr Pro Leu Ser Val Leu Met Leu Ala Gly Ile Arg Asp1 5 10 15Val Leu Leu Ile Ser Thr Prc Ala Asp Met Pro Leu Phe Gln Arg Leu
20 25 30Leu Gly Asn Gly Ser Gln Phe Gly Ile Arg Ile Glu Tyr Ala Glu Gln
35 40 45Ser Gln Pro Asn Gly Leu Ala Glu Ala Phe Val Ile Gly Ala Asp Phe
50 55 60Val Gly Asp Asp Ser Val Ala Leu Val Leu Gly Asp Asn Ile Phe Tyr65 70 75 80Gly Gln Gly Phe Ser Gly Ile Leu Gln Gln Cys Val Arg Glu Leu Asp
85 90 95Gly Cys Thr Leu Phe Gly Tyr Pro Val Arg Asp Pro Gln Arg Tyr Gly
100 105 110Val Gly Glu Val Asp Asp Asp Gly Arg Leu Leu Ser Ile Val Glu Lys
115 120 125Pro Glu Arg Pro Lys Ser Asn Met Ala Ile Thr Gly Leu Tyr Phe Tyr
130 135 140Asp Asn Asp Val Val Arg Ile Ala Lys Gly Leu Thr Pro Ser Ala Arg145 150 155 160Gly Glu Leu Glu Ile Thr Asp Val Asn Leu Ala Tyr Leu Gln Glu Gly
165 170 175Arg Ala His Leu Thr Lys Leu Gly Arg Gly Phe Ala Trp Leu Asp Thr
180 185 190Gly Thr His Asp Ser Leu Val Glu Ala Ser Gln Phe Val Gln Val Leu
195 200 205Glu His Arg Gln Gly Val Arg Ile Ala Cys Leu Glu Glu Ile Xaa Leu
210 215 220Arg Met Gly Tyr Ile Ser Ala Asp Asp Cys Phe Ala Leu Gly Val Lys225 230 235 240Leu Ala Lys Ser Gly Tyr Ser Glu Tyr Val Met Asp Val Ala Arg Asn
245 250 255Ser Gly Ala Arg Gly
260<210>30<211>23<212>DNA<213>人工序列<220><223>人工序列描述:引物<220><221>不确定<222>(1)<223>n为a,t,c或g<220><221>不确定<222>(10)<223>n为a,t,c或g<400>30ngsgtsggsn ssccaccttc cgg 23<210>31<211>33<212>DNA<213>人工序列<220><223>人工序列描述:引物<220><221>不确定<222>(6)<223>n为a,t,c或g<220><221>不确定<222>(18)<223>n为a,t,c或g<400>31catsangtcg tcytcsansg csacgaacgc gtg 33<210>32<211>1165<212>DNA<213>人工序列<220><221>CDS<222>(226)..(834)<220><223>人工序列描述:Pdab1622<400> 32gggatcaaca acaacttcac cagcaggttc aacaatttgt caatcccact tggcagtacg 60cgcgtccttt ttggatcggg attgcggcag tacgtgcacc cggtttcagt gccccatttc 120gcagtacgta cgtccgtttt gaatatggcg atcaatggct cgcatgaccc atatcaactc 180cgccccaccg aaccgcattc caaccaacgt cataggcttt cggcc gtg cag gta cgt 237
Val Gln Val Arg
1cga ctt gac atc acg ggt gca tac gag ttc acc ccg aag gcc ttc ccc 285Arg Leu Asp Ile Thr Gly Ala Tyr Glu Phe Thr Pro Lys Ala Phe Pro5 10 15 20gac cac cgg ggc ctg ttc gtg gcc ccg ttc cag gag gcg gcg ttc arc 333Asp His Arg Gly Leu Phe Val Ala Pro Phe Gln Glu Ala Ala Phe Ile
25 30 35gac gcc acg ggg cac ccg ctg cga gtc gcg cag acc aac cac agc gtc 381Asp Ala Thr Gly His Pro Leu Arg Val Ala Gln Thr Asn His Ser Val
40 45 50tcg gcg cgc aac gtc atc cgc ggc gtg cac ttc tcg gac gtg ccg ccg 429Ser Ala Arg Asn Val Ile Arg Gly Val His Phe Ser Asp Val Pro Pro
55 60 65ggc caa gcg aag tac gtg tac tgc ccg cag ggc gcg ctg ctc gac gtg 477Gly Gln Ala Lys Tyr Val Tyr Cys Pro Gln Gly Ala Leu Leu Asp Val
70 75 80gtc atc gac atc cgg gtc ggt tcc ccg acc ttc ggc cgc tgg gag gcg 525Val Ile Asp Ile Arg Val Gly Ser Pro Thr Phe Gly Arg Trp Glu Ala85 90 95 100gtc cgg ctc gac gac acc gag tac cgg gcc gtc tac cta gcc gaa gga 573Val Arg Leu Asp Asp Thr Glu Tyr Arg Ala Val Tyr Leu Ala Glu Gly
105 110 115ctc ggg cac gcg ttc gcc gcg ctg acc gac gac acc gtg atg acc tac 621Leu Gly His Ala Phe Ala Ala Leu Thr Asp Asp Thr Val Met Thr Tyr
120 125 130ctc tgc tcg acg ccc tac acc ccg ggc gcc gag cac ggc atc gac ccg 669Leu Cys Ser Thr Pro Tyr Thr Pro Gly Ala Glu His Gly Ile Asp Pro
135 140 145ttc gac ccg gaa ctc gcg ttg ccg tgg tcc gac ctc gac ggt gaa ccg 717Phe Asp Pro Glu Leu Ala Leu Pro Trp Ser Asp Leu Asp Gly Glu Pro
150 155 160gtc ctg tcc gaa aag gac cgg acc gcc ccg agc ctc gcg gaa gcc gcc 765Val Leu Ser Glu Lys Asp Arg Thr Ala Pro Ser Leu Ala Glu Ala Ala165 170 175 180gac aac ggc ctg ctt ccg gac tac gaa aca tgc ctc gcc cac tac gaa 813Asp Asn Gly Leu Leu Pro Asp Tyr Glu Thr Cys Leu Ala His Tyr Glu
185 190 195ggc ctg cgc agc ccc ggc tga acggtcaccg caagcggccc ggcttcggcc 864Gly Leu Arg Ser Pro Gly
200agaggcgcca ccggataatg ccgagcacct cggccgggcc gagctcccgc gagtccgtcg 924agccgaagtt gttgtcgccc tcgacgtacc agccatcgcc ctcgcggcgc agcgcgcgct 984tcaccgacaa ctgccccggg cgctgggccc aacgcaccag cacgacgttt ccccggccgg 1044
gcggaacccc gaagccgcag cagcaccact tcgcgatccc gcagggtggg aaccataaac 1104ggcccgcgca ccaccaaccg ccgccagggc cagcgcccga gggatttcac atccacctcc 1164a 1165<210>33<211>202<212>PRT<213>人工序列<400>33Val Gln Val Arg Arg Leu Asp Ile Thr Gly Ala Tyr Glu Phe Thr Pro1 5 10 15Lys Ala Phe Pro Asp His Arg Gly Leu Phe Val Ala Pro Phe Gln Glu
20 25 30Ala Ala Phe Ile Asp Ala Thr Gly His Pro Leu Arg Val Ala Gln Thr
35 40 45Asn His Ser Val Ser Ala Arg Asn Val Ile Arg Gly Val His Phe Ser
50 55 60Asp Val Pro Pro Gly Gln Ala Lys Tyr Val Tyr Cys Pro Gln Gly Ala65 70 75 80
Leu Leu Asp Val Val Ile Asp Ile Arg Val Gly Ser Pro Thr Phe Gly
85 90 95Arg Trp Glu Ala Val Arg Leu Asp Asp Thr Glu Tyr Arg Ala Val Tyr
100 105 110Leu Ala Glu Gly Leu Gly His Ala Phe Ala Ala Leu Thr Asp Asp Thr
115 120 125Val Met Thr Tyr Leu Cys Ser Thr Pro Tyr Thr Pro Gly Ala Glu His
130 135 140Gly Ile Asp Pro Phe Asp Pro Glu Leu Ala Leu Pro Trp Ser Asp Leu145 150 155 160Asp Gly Glu Pro Val Leu Ser Glu Lys Asp Arg Thr Ala Pro Ser Leu
165 170 175Ala Glu Ala Ala Asp Asn Gly Leu Leu Pro Asp Tyr Glu Thr Cys Leu
180 185 190Ala His Tyr Glu Gly Leu Arg Ser Pro Gly
195 200<210>34<211>28<212>DNA<213>人工序列<220><223>人工序列描述:引物<400>34cccgaattcg agctgctgtc aatcaact 28<210>35<211>29<212>DNA<213>人工序列<220><223>人工序列描述:引物<400>35gggaagcttg ttgaccgtgg cggtttcct 29<210>36<211>42<212>DNA<213>人工序列<220><223>人工序列描述:诱变引物<400>36ctggttcatt cggccgcctc accggtgggg atggccgcga tc 42<210>37<211>42<212>DNA<213>人工序列<220><223>人工序列描述:诱变引物<400>37gatcgcggcc atccccaccg gtgaggcggc cgaatgaacc ag 42<210>38<211>20<212>DNA<213>人工序列<220><223>人工序列描述:侧翼引物<400>38gctgctcgaa atcgcacgtc 20<210>39<211>19<212>DNA<213>人工序列<220><223>人工序列描述:侧翼引物<400>39gcatcgctgg gcagtgagg 19
Claims (30)
1.分离的DNA分子,其含有编码刺糖噻生物合成酶的DNA序列,其中所述酶由选自SEQ ID NO:2-5,7-24,26,27,29和33的氨基酸序列限定,或者所述酶由选自SEQ ID NO:2-5,7-24,26,27,29和33的氨基酸序列限定,但该氨基酸序列中进行了一个或多个不会影响到酶的功能特性的氨基酸取代。
2.权利要求1的分离的DNA分子,其中所述DNA序列选自基因spnA,spnB, spnC,spnD,spnE,spnF,spn G,spnH,spnI,spnJ,spnK,spnL,spnM,spnN,spnO,spnP,spnQ,spnR,spnS,ORFL15,ORFL16,ORFR1,ORFR2,刺糖多孢菌gtt,刺糖多孢菌gdh,刺糖多孢菌epi和刺糖多孢菌kre,所述基因分别描述于SEQ ID NO:1的碱基21111-28898,28916-35374,35419-44931,44966-59752,59803-76569,20168-20995,18541-19713,17749-18501,16556-17743,14799-16418,13592-14785,12696-13547,11530-12492,10436-11434,8967-10427,7083-8450,5363-6751,4168-5325,3416-4165,2024-2791,1135-1971,76932-77528和77729-79984,SEQ ID NO:27的碱基334-1119,SEQ ID NO:24的碱基88-1077,SEQ ID NO:31的碱基226-834,和SEQ ID NO:24的碱基1165-1992。
3.分离的DNA分子,其含有编码选自KSi,ATi,ACPi,KS1,AT1,KR1和ACP1的刺糖噻PKS结构域的DNA序列,所述结构域分别对应于SEQ ID NO:2的氨基酸6-423,528-853,895-977,998-1413,1525-1858,2158-2337和2432-2513,或者所述结构域是进行了一个或多个不会影响到结构域的功能特性的氨基酸取代的所述氨基酸序列之一。
4.权利要求3的分离的DNA分子,其中所述DNA序列选自SEQ IDNO:1的碱基21126-22379,22692-23669,23793-24041,24102-25349,25683-26684,27582-28121和28404-28649。
5.分离的DNA分子,其含有编码选自KS2,AT2,DH2,ER2,KR2和ACP2的刺糖噻PKS结构域的DNA序列,所述结构域分别对应于SEQ IDNO:3的氨基酸1-424,536-866,892-1077,1338-1683,1687-1866和1955-2034,或者所述结构域是具有一个或多个不会影响到结构域的功能特性的氨基酸取代的所述氨基酸序列之一。
6.权利要求5的分离的DNA分子,其中所述DNA序列选自SEQ IDNO:1的碱基29024-30295,30629-31621,31697-32254,33035-34072,34082-34621,34886-35125。
7.分离的DNA分子,其含有编码选自KS3,AT3,KR3,ACP3,KS4,AT4,KR4和ACP4的刺糖噻PKS结构域的DNA序列,所述结构域分别对应于SEQ ID NO:4的氨基酸1-423,531-280,1159-1337,1425-1506,1529-1952,2066-2396,2700-2880和2972-3053,或者所述结构域是进行了一个或多个不会影响到结构域的功能特性的氨基酸取代的所述氨基酸序列之一。
8.权利要求7的分离的DNA分子,其中所述DNA序列选自SEQ IDNO:1的碱基35518-36786,37108-38097,38992-39528,39790-40035,40102-41373,41713-42705,43615-44157和44431-44676。
9.分离的DNA分子,其含有编码选自KS5,AT5,DH5,KR5,ACP5,KS6,AT6,KR6,ACP6,KS7,AT7,KR7和ACP7的刺糖噻PKS结构域的DNA序列,所述结构域分别对应于SEQ ID NO:5的氨基酸1-424,539-866,893-1078,1384-1565,1645-1726,1748-2172,2283-2613,2916-3095,3188-3269,3291-3713,3825-4153,4344-4638和4725-4806,或者所述结构域是进行了一个或多个不会影响到结构域的功能特性的氨基酸取代的所述氨基酸序列之一。
10.权利要求9的分离的DNA分子,其中所述DNA序列选自SEQ IDNO:1的碱基45077-46348,46691-47674,47753-48310,49226-49771,50009-50254,50318-51592,51923-52915,53822-54361,54638-54883,54947-56215,56549-57535,58106-58990和59249-59494。
11.分离的DNA分子,其含有编码选自KS8,AT8,DH8,KR8,ACP8,KS9,AT9,DH9,KR9,ACP9,KS10,AT10,DH10,KR10,ACP10和TE10的刺糖噻PKS结构域的DNA序列,所述结构域分别对应于SEQ ID NO:6的氨基酸1-424,530-848,883-1070,1369-1552,1648-1726,1749-2173,2287-2614,2640-2800,3157-3341,3422-3500,3534-3948,4060-4390,4413-4597,4900-5078,5172-5253和5302-5555,或者所述结构域是进行了一个或多个不会影响到结构域的功能特性的氨基酸取代的所述氨基酸序列之一。
12.权利要求11的分离的DNA分子,其中所述DNA序列选自SEQ IDNO:1的碱基59902-61173,61489-62445,62548-63111,64006-64557,64843-65079,65146-66420,66760-67743,67819-68301,69370-69924,70165-70401,70471-71745,72079-73071,73138-73692,74599-75135,75415-75660和75805-76566。
13.分离的DNA分子,其含有编码刺糖噻PKS组件的DNA序列,所述组件选自SEQ ID NO:2的氨基酸6-1413,SEQ ID NO:2的1525-2513,SEQ ID NO:3的1-2034,SEQ ID NO:4的1-1506,SEQ ID NO:4的1529-3053,SEQ ID NO:5的1-1726,SEQ ID NO:5的1748-3269,SEQ ID NO:5的3291-4806,SEQ ID NO:5的1-1726,SEQ ID NO:6的1-1726,SEQ IDNO:6的1749-3500和SEQ ID NO:6的35434-5555,或者所述组件是进行了一个或多个不会影响到结构域的功能特性的氨基酸取代的所述氨基酸序列之一。
14.权利要求13的分离的DNA分子,其中所述DNA序列选自SEQ IDNO:1的碱基21126-24041,24102-28649,29024-35125,35518-40035,40102-44676,45077-50254,50318-54883,54947-59494,59902-65079,65146-70401和70471-76566。
15.重组DNA载体,其含有如权利要求1所述的DNA序列。
16.被权利要求15所述的重组载体转化的宿主细胞。
17.提高刺糖噻之产量的方法,所述方法包括下列步骤:
1)用重组DNA载体或其部分转化利用生物合成途径生产刺糖噻或刺糖噻前体的微生物,所述载体或其部分含有权利要求1所述的DNA序列,所述DNA序列编码所述途径中限速活性的表达,和
2)在适于细胞生长和分裂、表达所述DNA序列和生产刺糖噻的条件下培养被所述载体转化的所述微生物。
18.权利要求17的方法,其中步骤1)包括用含有编码刺糖多孢菌gtt和刺糖多孢菌gdh的DNA序列的载体或其部分转化所述微生物。
19.经转化的生产刺糖噻的微生物,其基因组中含有刺糖噻生物合成基因,其中至少一个选自spnA,spnB,spnC,spnD,spnE,sppnF,spnG,spnH,spnI,spnJ, spnK,spnL,spnM,spnN,spnO,spnP,spnQ,spnR,spnS,刺糖多孢菌gtt,刺糖多孢菌gdh,刺糖多孢菌epi或刺糖多孢菌kre的刺糖噻生物合成基因已被复制。
20.权利要求19的经转化的生产刺糖噻的微生物,其中刺糖多孢菌gtt和刺糖多孢菌gdh被复制。
21.生产刺糖噻化合物的方法,所述方法包括培养权利要求20的经转化的生产刺糖噻的微生物。
22.权利要求19的经转化的生产刺糖噻的微生物,其中刺糖多孢菌gtt,刺糖多孢菌gdh和刺糖多孢菌kre被复制。
23.生产刺糖噻化合物的方法,所述方法包括培养权利要求22的经转化的生产刺糖噻的微生物。
24.生产刺糖噻化合物的方法,所述方法包括培养权利要求19的经转化的生产刺糖噻的微生物。
25.经转化的生产刺糖噻的微生物,其基因组中含有刺糖噻生物合成基因,其中所述基因中的至少一个基因已通过与该基因的内部片段重组而被破坏,其余所述基因可有效产生刺糖噻,而不是被破坏的基因有效时产生的产物。
26.生产刺糖噻化合物的方法,所述方法包括培养权利要求25的经转化的生产刺糖噻的微生物。
27.经转化的生产刺糖噻的微生物,所述微生物的基因组中含有可操作的包括多个PKS组件的刺糖噻生物合成基因,其中所述基因a)包括至少一个可操作的PKS组件,所述组件比SEQ ID NO:1中所述组件少一个以上或至少少一个;或b)包括通过缺失,失活或添加KR,DH或ER结构域,或通过取代针对不同羧酸的AT结构域而与SEQ IDNO:1所述的相应组件有所不同的PKS组件。
28.生产刺糖噻化合物的方法,所述方法包括培养权利要求27的经转化的生产刺糖噻的微生物。
29.分离大环内酯生物合成基因的方法,所述方法包括制备大环内酯生产微生物的基因组文库,并将长度至少为20个碱基的经标记的SEQ ID NO:1,SEQ ID NO:25,SEQ ID NO:28或SEQ ID NO:32片段用作杂交探针。
30.权利要求29的方法,其中微生物是生产刺糖噻的微生物。
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CN102816783A (zh) * | 2011-05-03 | 2012-12-12 | 陶氏益农公司 | 刺糖多孢菌染色体的基因整合 |
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US6521406B1 (en) | 2003-02-18 |
EP1062345A1 (en) | 2000-12-27 |
AU2680099A (en) | 1999-09-27 |
NZ506624A (en) | 2003-08-29 |
KR20010041750A (ko) | 2001-05-25 |
ZA991837B (en) | 2000-09-08 |
BR9909257A (pt) | 2000-11-28 |
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WO1999046387A9 (en) | 2001-10-04 |
BR9909257B1 (pt) | 2014-01-14 |
EP1062345B1 (en) | 2007-12-12 |
US7015001B2 (en) | 2006-03-21 |
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DE69937732T2 (de) | 2008-12-04 |
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ID26862A (id) | 2001-02-15 |
CN1227362C (zh) | 2005-11-16 |
IL138241A0 (en) | 2001-10-31 |
AU764737B2 (en) | 2003-08-28 |
US6274350B1 (en) | 2001-08-14 |
US6143526A (en) | 2000-11-07 |
ATE380872T1 (de) | 2007-12-15 |
ES2299240T3 (es) | 2008-05-16 |
CA2322449A1 (en) | 1999-09-16 |
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