CN114502720A - 包含myo-肌醇至丙酸途径的细菌 - Google Patents

包含myo-肌醇至丙酸途径的细菌 Download PDF

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CN114502720A
CN114502720A CN202080057480.9A CN202080057480A CN114502720A CN 114502720 A CN114502720 A CN 114502720A CN 202080057480 A CN202080057480 A CN 202080057480A CN 114502720 A CN114502720 A CN 114502720A
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gly
glu
val
lys
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W·M·德沃斯
T·P·N·布
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Wageningen Universiteit
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Abstract

本发明涉及一种包含肌醇至丙酸途径基因集的细菌，该基因集允许所述细菌将肌醇转化成丙酸或其盐或酯。该细菌可用作益生菌或补充剂以促进胃肠道内丙酸的产生，从而预防和/或治疗受益于丙酸产生的病症或疾病，例如代谢疾病、代谢综合征、胰岛素抵抗或胰岛素抵抗相关病症，特别是血脂异常、2型糖尿病和内分泌疾病的胰岛素抵抗。

Description

包含myo-肌醇至丙酸途径的细菌
技术领域
本发明涉及预防和/或治疗代谢疾病的领域，如代谢综合征和胰岛素抵抗或胰岛素抵抗相关病症，包括血脂异常和2型糖尿病以及内分泌疾病(例如，患有1型糖尿病、库欣病或脂肪代谢障碍综合症(lipodystrophy syndrome)的肥胖对象)中的胰岛素抵抗。
背景技术
胰岛素抵抗是一种医学症状，其中细胞对胰岛素产生抵抗，导致高血糖水平。2型糖尿病患者通常已经经历了胰岛素抵抗的早期阶段，尽管这个早期阶段往往没有被诊断出来。
已经发现膳食补充myo-肌醇能有效降低几个糖尿病或胰岛素抵抗的动物模型中的餐后血浆葡萄糖(Ortmeyer等1993 Endocrinology 132：646-651；Ortmeyer等1995Obesity Research 3：605S-608S；Croze和Soulage 2013 Biochimie 95：1811-1827)。
已证明，与健康对照组相比，患有2型糖尿病的对象的肌肉活检物中显示肌醇磷酸聚糖水平下降，myo-肌醇被认为是推定的胰岛素信号转导通路的下游第二信使(Kennington等1990 New England Journal of Medicine 323：373-378)。
膳食中的myo-肌醇可以来自磷脂或植酸(一种存在于豆类、种子和坚果中的植物成分)，从中其通过植酸酶被释放出来。此外，人体可以从葡萄糖中产生myo-肌醇。
然而，尽管已知膳食补充肌醇可以减少胰岛素抵抗，但该现象的发生机制尚不清楚。
本公开的目的是提供一种新的或改进的策略，用于预防和/或治疗代谢疾病，特别是代谢综合征和胰岛素抵抗或胰岛素抵抗相关病症，包括血脂异常和2型糖尿病以及内分泌疾病(例如，患有1型糖尿病、库欣病或脂肪代谢障碍综合症的肥胖对象)中的胰岛素抵抗。
发明内容
本发明人发现，myo-肌醇可以作为一种从健康婴儿的粪便中分离出来的产丁酸细菌(butyrogenic bacterium)鼠李厌氧菌(Anaerostipes rhamnosivorans)的碳和能量来源(Bui等2014 International Journal of Systematic and EvolutionaryMicrobiology 64：787-793)。这种细菌能够高效地将myo-肌醇发酵成丙酸，并且在其封闭基因组(closed genome)中发现了完整的肌醇发酵途径，其可选地能被引入任何其他细菌中。参见图2A和图2B。
众所周知，膳食补充myo-肌醇可以减少胰岛素抵抗。然而，在本发明之前，其发生的机制是未知的。
本发明人认为，myo-肌醇可能具有间接的有益作用，有益于对象的是myo-肌醇的代谢转化，而不是myo-肌醇本身。因此，值得注意的是，鼠李厌氧菌(A.rhamnosivorans)生产丁酸或其盐/酯(butyrate)和(特别是)丙酸或其盐/酯(propionate)确定是有益于对象的(参见，例如，Hamer等2008 Pharmacology&Therapeutics 27：104-119；Hosseini等2011Nutrition Reviews 69：245-258)。
本发明人设想给对象补充根据本公开所述的细菌，或替代性地补充根据本公开所述的myo-肌醇和细菌二者，以提供直接或协同效应，通过原位丙酸和可选的丁酸生产导致改善的胰岛素抵抗。
具体实施方式
本公开涉及一种包含编码肌醇至丙酸途径的基因集的细菌，其允许所述细菌将肌醇转化为丙酸或其盐或酯，用于预防和/或治疗代谢综合征、胰岛素抵抗和/或胰岛素抵抗相关病症。
具体地，该细菌能够通过肌醇代谢和丙酸合成而将肌醇转化为丙酸或其衍生物。肌醇可以是chiro-肌醇或myo-肌醇，优选myo-肌醇。在一个优选的实施方式中，该细菌还是生产丁酸和/或丁酸(盐/酯)的(产丁酸的(butyrogenic))细菌(即还包含丁酸/丁酸盐/酯合成途径基因集)。
不希望受理论束缚，据信根据本公开的细菌(或由其衍生的菌株)，当被给予人或被人足量摄取时，能够存活并至少在所述人的胃肠道中短暂定殖。这种定殖能够使丙酸/丙酸盐/酯(和/或丁酸/丁酸盐/酯)的原位生产增加。丙酸原位生产的增加被认为是如本文所教导的有益作用的基础，例如预防和/或治疗病症或疾病，例如代谢疾病，如代谢综合征和胰岛素抵抗或胰岛素抵抗相关的并发症，如血脂异常和2型糖尿病，以及内分泌疾病(如患有1型糖尿病、库欣病或脂肪代谢障碍综合征的肥胖对象)中的胰岛素抵抗。
细菌
一方面，本公开涉及一种包含编码肌醇至丙酸途径的基因集的细菌，其允许所述细菌将肌醇转化为丙酸或其盐或酯，具体地(但不一定)，在厌氧条件下，例如其中该细菌和/或其培养基不与包含多于1、2、3、4、5、10体积％氧气的气体接触。细菌菌种优选，但不一定，是分离菌种，例如，人肠道分离菌种。
肌醇至丙酸途径基因集可以包含一个或多个(至少两个或三个，或全部)编码以下蛋白质的基因：myo-肌醇2-脱氢酶、肌糖脱水酶、表肌醇水解酶、5-脱氧-葡萄糖醛酸异构酶、5-酮基-2-脱氧葡萄糖酸激酶、5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶、甘油醛-3-磷酸酮基-异构酶、甘油醛-3-磷酸脱氢酶、磷酸甘油酸激酶、磷酸甘油酸变位酶、烯醇酶、丙酮酸激酶、丙酮酸-黄素氧还蛋白氧化还原酶、3-含氧酸CoA转移酶、酰基-CoA脱氢酶、烯酰-CoA水合酶和丙烯酰基-CoA脱氢酶/Etf。此外，肌醇至丙酸途径基因集可以包含编码蛋白质肌糖异构酶和/或myo-肌醇2-脱氢酶的另一拷贝的基因，因为它允许将D-chiro-肌醇转化为鲨肌糖(scyllo-inosose)。
附加或替代性地，根据本公开的细菌可以包含编码乳酸脱氢酶的基因、编码乙醛脱氢酶的基因和/或编码乙醇脱氢酶的基因。
在优选的实施方式中，与当细菌在不存在(myo)肌醇的情况下生长时相比，当细菌在存在(myo)肌醇的情况下生长时，以下蛋白质中的至少一种(或至少两种或三种或全部)可被过度产生(或其编码基因被过度表达)：肌醇2-脱氢酶、肌糖脱水酶、表肌醇水解酶、5-脱氧-葡萄糖醛酸异构酶、5-酮基-2-脱氧葡萄糖酸激酶、5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶和甘油醛-3-磷酸酮基-异构酶、甘油醛-3-磷酸脱氢酶、磷酸甘油酸激酶、磷酸甘油酸变位酶、烯醇酶、丙酮酸激酶、丙酮酸-黄素氧还蛋白氧化还原酶、3-含氧酸CoA转移酶、酰基-CoA脱氢酶、烯酰-CoA水合酶、丙烯酰基-CoA脱氢酶/Eft和肌糖异构酶。
在本公开的上下文中，与当所述细菌在不存在(myo)肌醇的情况下生长时相比，用于确定细菌中基因是否被上调或蛋白质是否过表达的(myo)肌醇的量可以在以下范围内：约5mM至约100mM，优选约10mM至约50mM，更优选约15mM至约25mM，最优选约20mM。
在一个实施方式中，根据本公开的细菌可以是分离的肠道细菌菌株，或衍生自其的菌株，和/或可以是从人中分离的肠道细菌，其天然地包含本文所教导的肌醇至丙酸途径基因集并且其能够将(myo和/或chiro)肌醇转化为丙酸或其衍生物。
在另一方面，根据本公开的细菌可以是由瓦赫宁恩大学(WageningenUniversity)于2015年6月26日保藏在位于荷兰乌德勒支3584CT乌普萨拉8号(Uppsalalaan8，3584CT Utrecht)的真菌菌种保藏中心(the Centraalbureau voor Schimmelcultures)(现称为韦斯特迪克真菌生物多样性研究所(Westerdijk Fungal BiodiversityInstitute))的细菌鼠李厌氧菌(Anaerostipes rhamnosivorans)1y2，分配保藏号CBS140182。本公开也涵盖衍生自保藏细菌的任何细菌菌株。
替代性地，根据本公开的细菌可以是已经用本文所教导的肌醇至丙酸途径基因集转染的细菌，且其能够将(myo和/或chiro)肌醇转化为丙酸或其衍生物。本领域技术人员熟知用所需遗传构建体(即途径基因集)转化细菌的方法。
在一个实施方式中，根据本公开的细菌属于厚壁菌门(phylum Firmicutes)，优选属于梭菌纲(class Clostridia)(和/或梭菌目(order Clostridiales))，更优选属于毛螺菌科(family Lachnospiraceae)，更优选属于厌氧菌属(genus Anaerostipes)，甚至更优选属于种鼠李厌氧菌(Anaerostipes rhamnosivorans)种。
在一个实施方式中，根据本公开的细菌不是庞大厌氧杆菌(Anaerostipeshadrus)。替代性地，在根据本公开的细菌是庞大厌氧杆菌(Anaerostipes hadrus)的情况下，该用途是用于预防和/或治疗如本文教导的胰岛素抵抗或胰岛素抵抗相关并发症。优选地，庞大厌氧杆菌(Anaerostipes hadrus)涉及模式菌株DSM3319或108065。或者，根据本公开的细菌是丁酸厌氧杆菌(Anaerostipes butyraticus)，优选模式菌株DSM22094。
如本文前文所述，肌醇至丙酸途径基因集可以包含编码以下蛋白质的一个或多个基因：myo-肌醇2-脱氢酶、肌糖脱水酶、表肌醇水解酶、5-脱氧-葡萄糖醛酸异构酶、5-酮基-2-脱氧葡萄糖酸激酶、5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶、甘油醛-3-磷酸酮基-异构酶、甘油醛-3-磷酸脱氢酶、磷酸甘油酸激酶、磷酸甘油酸变位酶、烯醇酶、丙酮酸激酶、丙酮酸-黄素氧还蛋白氧化还原酶、3-含氧酸CoA转移酶、酰基-CoA脱氢酶、烯酰-CoA水合酶和丙烯酰基-CoA脱氢酶/Etf。此外，肌醇至丙酸途径基因集可以包含编码蛋白质肌糖异构酶和/或myo-肌醇2-脱氢酶的另一拷贝的基因，因为其各自将允许将D-chiro-肌醇转化为鲨肌糖。
编码myo-肌醇2-脱氢酶的基因可以与SEQ ID NO：1具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码myo-肌醇2-脱氢酶的基因可以涉及与SEQ ID NO：2具有至少70、80、90、95、99、100％的序列等同性的myo-肌醇2-脱氢酶。myo-肌醇2-脱氢酶基因的功能可见于将myo-肌醇转化为鲨肌糖。
编码myo-肌醇2-脱氢酶的基因的其他或替代性拷贝可以与SEQ ID NO：3具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码myo-肌醇2-脱氢酶的基因的其他或替代性拷贝可以涉及与SEQ ID NO：4具有至少70、80、90、95、99、100％序列等同性的myo-肌醇4-脱氢酶。该基因的功能可见于将D-chiro-肌醇转化为1-酮基-D-chiro-肌醇。
编码肌糖脱水酶的基因可以与SEQ ID NO：5具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码肌糖脱水酶的基因可以涉及具有至少70、80、90、95、99、100％与SEQ ID NO：6等同的序列的肌糖脱水酶。肌糖脱水酶基因的功能可见于将鲨肌糖转化为3，5/4-三羟基环己-1，2-二酮。
编码表肌醇水解酶的基因可以与SEQ ID NO：7具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码表肌醇水解酶的基因可以涉及与SEQ ID NO：8具有至少70、80、90、95、99、100％的序列等同性的表肌醇水解酶。表肌醇水解酶基因的功能可见于将3，5/4-三羟基环己-1，2-二酮转化为5-脱氧-D-葡萄糖醛酸(盐/酯)。
编码5-脱氧-葡萄糖醛酸异构酶的基因可以与SEQ ID NO：9具有至少70、80、90、95、99、100％序列等同性。附加或替代地，编码5-脱氧-葡萄糖醛酸异构酶的基因可以涉及与SEQ ID NO：10具有至少70、80、90、95、99、100％序列等同性的5-脱氧-葡萄糖醛酸异构酶。5-脱氧-葡萄糖醛酸异构酶基因的功能可见于将5-脱氧-D-葡萄糖醛酸(盐/酯)转化为2-脱氧-5-酮基-D-葡糖酸(盐/酯)。
编码5-酮基-2-脱氧葡萄糖酸激酶的基因可以与SEQ ID NO：11具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码5-酮基-2-脱氧葡萄糖酸激酶的基因可以涉及与SEQ ID NO：12具有至少70、80、90、95、99、100％序列等同性的5-酮基-2-脱氧葡萄糖酸激酶。5-酮基-2-脱氧葡萄糖酸激酶基因的功能可见于将2-脱氧-5-酮基-D-葡糖酸(盐/酯)转化为2-脱氧-5-酮基-D-葡糖酸-6P。
编码5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶的基因可以与SEQ ID NO：13具有至少70、80、90、95、99、100％序列等同性的序列。附加或替代地，编码5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶的基因可以涉及与SEQ ID NO：14具有至少70、80、90、95、99、100％序列等同性的5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶。5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶基因的功能可见于将2-脱氧-5-酮基-D-葡糖酸-6P转化为3-氧代丙酸(盐/酯)(oxopropionate)和磷酸甘油酮(glycerone phosphate)。
编码甘油醛-3-磷酸酮基-异构酶的基因可以与SEQ ID NO：15具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码甘油醛-3-磷酸酮基-异构酶的基因可以涉及与SEQ ID NO：16具有至少70、80、90、95、99、100％序列等同性的甘油醛-3-磷酸酮基-异构酶。甘油醛-3-磷酸酮基-异构酶基因的功能可见于将磷酸甘油酮转化为甘油醛-3P。
编码甘油醛-3-磷酸脱氢酶的基因可以与SEQ ID NO：17具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码甘油醛-3-磷酸脱氢酶的基因可以涉及与SEQID NO：18具有至少70、80、90、95、99、100％的序列等同性的甘油醛-3-磷酸脱氢酶。甘油醛-3-磷酸脱氢酶基因的功能可见于将甘油醛-3P转化为1，3-二磷酸甘油酸。
编码磷酸甘油酸激酶的基因可以与SEQ ID NO：19具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码磷酸甘油酸激酶的基因可以涉及与SEQ ID NO：20具有至少70、80、90、95、99、100％的序列等同性的序列的磷酸甘油酸激酶。磷酸甘油酸激酶基因的功能可见于将1，3-二磷酸甘油酸(盐/酯)转化为3-磷酸甘油酸(盐/酯)。
编码磷酸甘油酸变位酶的基因可以与SEQ ID NO：21具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码磷酸甘油酸变位酶的基因可以涉及与SEQ ID NO：22具有至少70、80、90、95、99、100％的序列等同性的磷酸甘油酸变位酶。磷酸甘油酸变位酶基因的功能可见于将3-磷酸甘油酸(盐/酯)转化为2-磷酸烯醇式丙酮酸(盐/酯)。
编码烯醇酶的基因可以与SEQ ID NO：23具有至少70、80、90、95、99、100％的序列等同性的序列。附加或替代地，编码烯醇酶的基因可以涉及与SEQ ID NO：24具有至少70、80、90、95、99、100％的序列等同性的序列的烯醇酶。烯醇酶基因的功能可见于将3-磷酸甘油酸(盐/酯)转化为2-磷酸烯醇式丙酮酸(盐/酯)。
编码丙酮酸激酶的基因可以与SEQ ID NO：47具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码丙酮酸激酶的基因可以涉及与SEQ ID NO：48具有至少70、80、90、95、99、100％的序列等同性的丙酮酸激酶。丙酮酸激酶基因的功能可见于将2-磷酸烯醇式丙酮酸(盐/酯)转化为丙酮酸(盐/酯)。
编码丙酮酸-黄素氧还蛋白氧化还原酶的基因可以与SEQ ID NO：25具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码丙酮酸-黄素氧还蛋白氧化还原酶的基因可以涉及与SEQ ID NO：26具有至少70、80、90、95、99、100％的序列等同性的丙酮酸-黄素氧还蛋白氧化还原酶。丙酮酸-黄素氧还蛋白氧化还原酶基因的功能可见于将丙酮酸转化为乙酰-CoA和CO2/甲酸。
编码3-含氧酸CoA转移酶的基因可以与SEQ ID NO：27具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码3-含氧酸CoA转移酶的基因可以涉及与SEQ IDNO：28具有至少70、80、90、95、99、100％的序列等同性的3-含氧酸CoA转移酶。3-含氧酸CoA转移酶基因的功能可见于将3-氧代丙酸(盐/酯)转化为3-氧代丙酰基-CoA和/或见于将丙酰基-CoA转化为丙酸(盐/酯)。
编码酰基-CoA脱氢酶的基因可以与SEQ ID NO：29具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码酰基-CoA脱氢酶的基因可以涉及与SEQ ID NO：30具有至少70、80、90、95、99、100％的序列等同性的酰基-CoA脱氢酶。酰基-CoA脱氢酶基因的功能可见于将3-氧代丙酰基-CoA转化为3-羟基丙酰基-CoA。
编码烯酰-CoA水合酶的基因可以与SEQ ID NO：31具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码烯酰-CoA水合酶的基因可以涉及与SEQ ID NO：32具有至少70、80、90、95、99、100％的序列等同性的烯酰-CoA水合酶。烯酰-CoA水合酶基因的功能可见于将3-羟基丙酰基-CoA转化为丙烯酰基-CoA。
编码丙烯酰基-CoA脱氢酶/Eft的基因可以与SEQ ID NO：33具有至少70、80、90、95、99、100％的序列等同性。编码丙烯酰基-CoA脱氢酶/Eft的基因的其他(第二)或替代性拷贝可以与SEQ ID NO：35具有至少70、80、90、95、99、100％的序列等同性。编码丙烯酰基-CoA脱氢酶/Eft的基因的其他(第三)或替代性拷贝可以与SEQ ID NO：37具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码丙烯酰基-CoA脱氢酶/Eft的基因可以涉及与SEQ ID NO：34具有至少70、80、90、95、99、100％的序列等同性的丙烯酰基-CoA脱氢酶/Eft。编码丙烯酰基-CoA脱氢酶/Etf的基因的其他(第二)或替代性拷贝可以涉及与SEQID NO：36具有至少70、80、90、95、99、100％的序列等同性的丙烯酰基-CoA脱氢酶/Eft。编码丙烯酰基-CoA脱氢酶/Eft的基因的其他(第三)或替代性拷贝可以涉及与SEQ ID NO：38具有至少70、80、90、95、99、100％的序列等同性的丙烯酰基-CoA脱氢酶/Etf。丙烯酰基-CoA脱氢酶/Etf可以是复合物，其中AR1Y2_1051和AR1Y2_1052是作为丙烯酰基-CoA脱氢酶(AR1Y2_1050)的电子受体的复合物的α和β亚基。丙烯酰基-CoA脱氢酶/Etf基因的功能可见于将丙烯酰基-CoA转化为丙酰基-CoA。
编码肌糖异构酶的基因可以与SEQ ID NO：39具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码肌糖异构酶的基因可以涉及与SEQ ID NO：40具有至少70、80、90、95、99、100％的序列等同性的肌糖异构酶。该基因的功能可见于将1-酮基-D-chiro-肌醇转化为鲨肌糖。
编码乳酸脱氢酶的基因可以与SEQ ID NO：41具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码乳酸脱氢酶的基因可以涉及与SEQ ID NO：42具有至少70、80、90、95、99、100％的序列等同性的乳酸脱氢酶。乳酸脱氢酶基因的功能可见于将丙酮酸(盐/酯)转化为乳酸(盐/酯)。
编码乙醛脱氢酶的基因可以与SEQ ID NO：43具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码乙醛脱氢酶的基因可以涉及与SEQ ID NO：44具有至少70、80、90、95、99、100％的序列等同性的乙醛脱氢酶。乙醛脱氢酶基因的功能可见于将乙酰-CoA转化为乙醛。
编码乙醇脱氢酶的基因可以与SEQ ID NO：45具有至少70、80、90、95、99、100％的序列等同性。附加或替代地，编码乙醇脱氢酶的基因可以涉及与SEQ ID NO：46具有至少70、80、90、95、99、100％的序列等同性的乙醇脱氢酶。乙醇脱氢酶基因的功能可见于将乙醛转化为乙醇。
在某些实施方式中，根据本公开的细菌不包含编码丙二酸-半醛脱氢酶的基因(参与丙二酸半-醛至乙酰-CoA的转化)。
组合物
本公开进一步提供了一种组合物，其包含根据本公开的细菌和可选地包含生理学上可接受的运载体。生理学上可接受的运载体可以是任何适合于保持本文教导的细菌诱惑力直到被对象(例如人或动物)摄入的运载体。例如，适用于该目的的可接受运载体的非限制性实例包括任何众所周知的生理学或药学运载体、缓冲剂和赋形剂。应理解，合适的生理学或药学运载体的选择将取决于本文所教导的组合物的预期给药方式(如口服)和组合物的预期形式(如饮料、酸奶、粉末、胶囊等)。技术人员知道如何选择适用于本文所教导的组合物的生理学或药学运载体。
在一个实施方式中，本文所教导的组合物可以是以食品组合物、饲料组合物、饲料补充剂组合物、食品补充剂组合物或药物组合物的形式。组合物优选适于被人摄取。
在一个实施方式中，组合物是食品或食品补充剂组合物。该食品或食品补充剂组合物可以选自下组：液体、液体饮料(包括乳饮料和发酵饮料)、酸奶、奶酪、凝胶、明胶、明胶胶囊、粉末、糊剂、压片和胶囊锭(gel cap)。在一个合适的实施方式中，组合物是液体，优选液体饮料(如乳饮料)。食品或食品补充剂组合物可以是乳制品，优选发酵的乳制品，优选酸奶或酸奶饮料。
在一个实施方式中，本文所教导的组合物可以是益生菌组合物。这种益生菌组合物可包括本文所教导的(分离的)细菌，或由其衍生的菌株。在一个实施方式中，如本文所教导的组合物进一步包含一个或多个额外的有益的分离的肠道细菌菌株。
在一个实施方式中，一个或多个额外的有益的分离的肠道细菌菌株可以是任何选自乳酸菌(Lactobacillus)属和/或双歧杆菌(Bifidobacterium)属的乳酸菌株和/或任何通过乙酰-CoA途径生产丁酸(盐/酯)的产丁酸(盐/酯)(butyrate-producing)细菌。
在一个实施方式中，本文所教导的组合物可以是共生组合物。将一种或多种益生元组分添加到本文所教导的组合物中可能是有利的，例如，以补充本文所教导的细菌的作用(例如，生产丙酸/丙酸盐/酯和/或丁酸/丁酸盐/酯或其衍生物)。
在一个实施方式中，一种或多种益生元组分可以是任何益生元组分，其适合于增强本文所教导的细菌或其衍生菌株的活性和/或刺激其生长。适合的益生元组分的非限制性例子包括纤维(例如菊粉、果胶和抗性淀粉)，以及纤维二糖，麦芽糖，甘露糖，水杨苷，海藻糖，苦杏仁苷，阿拉伯糖，蜜二糖，山梨糖醇，鼠李糖和/或木糖。
在一个实施方式中，本文所教导的组合物包含富含(myo)肌醇的源和/或(myo)肌醇。例如，将富含(myo)肌醇的源和/或(myo)肌醇添加到本文所教导的组合物中可能是有利的，以进一步促进丙酸/丙酸盐/酯和/或丁酸/丁酸盐/酯或其衍生物在哺乳动物(例如人)的胃肠道中的生产。
在一个实施方式中，本文所教导的组合物可以包含一种或多种组分，其适用于促进本文所教导的细菌或其衍生菌株在储存和/或暴露于胆汁和/或通过哺乳动物(例如人)的胃肠道期间的生存和/或活力。这种组分的非限制性例子包括肠溶包衣和允许通过胃的控释剂。技术人员知道如何选择合适的组分来维持本文所教导的细菌的活力和功能，即能够执行预期的一种或多种功能。
在一个实施方式中，本文所教导的组合物可进一步包含一种或多种组分，其进一步增强本文所教导的组合物的营养价值和/或治疗性价值。例如，添加一种或多种组分(例如营养组分、兽药或药物等)可能是有利的，其选自蛋白质、氨基酸、酶、矿物盐、维生素(如盐酸硫胺素、核黄素、盐酸吡哆醇、烟酸、肌醇、氯化胆碱、泛酸钙、生物素、叶酸、抗坏血酸、维生素B12、对氨基苯甲酸、醋酸维生素A、维生素K、维生素D、维生素E等)、糖和复合碳水化合物(如水溶性和水不溶性单糖、双糖和多糖)、药用化合物(如抗生素)、抗氧化剂、微量元素成分(如钴、铜、锰、铁、锌、锡、镍、铬、钼、碘、氯、硅、钒、硒、钙、镁、钠和钾等的化合物)。技术人员熟悉适于增强本文所教导的组合物的营养和/或治疗性/药用价值的方法和组分。
如本文所教导的细菌可以被纳入冻干形式、微囊化形式的组合物中(由，例如，Solanki等BioMed Res.Int.2013，文章编号620719进行了综述)，或任何其它保存细菌菌株活性和/或活力的形式。
本文所教导的组合物可以是药物组合物。该药物组合物可以用作补充剂。药物组合物通常包含药物运载体，以及本文所教导的细菌。运载体优选是惰性运载体。优选形式取决于预期的给药方式和(治疗性)应用。药物运载体可以是任何相容性的、无毒的物质，适合于将本文所教导的细菌递送至对象的胃肠道中。例如，可使用无菌水或惰性固体作为运载体，通常辅以药学上可接受的佐剂、缓冲剂、分散剂等。本文所教导的药物组合物可以是液体形式，例如本文所教导的细菌的细菌稳定悬浮液，或固体形式，例如本文所教导的冻干细菌的粉末。如果本文所教导的细菌是冻干的，可以采用冷冻保护剂(cryoprotectant)，如乳糖、海藻糖或糖原。例如，对于口服给药，本文所教导的细菌可以以固体剂型给予，如胶囊、片剂和粉剂，包括冻干的细菌，或以液体剂型，如酏剂、糖浆和悬浮液。本文所教导的细菌，例如以冻干形式，可以与非活性组分和粉末状运载体一起封装在胶囊(例如明胶胶囊)中，例如葡萄糖、乳糖、蔗糖、甘露醇、淀粉、纤维素或纤维素衍生物、硬脂酸镁、硬脂酸、糖精钠、滑石粉、碳酸镁等。
在一个实施方式中，本文所教导的细菌可以以约106至约1015个菌落形成单位(CFU)的量被包含在本文所教导的组合物中。例如，肠道细菌可以以约107CFU至约1014CFU，优选约108CFU至约1013CFU，优选约109CFU至约1012CFU，更优选约1010CFU至约1012CFU的量被包含于该组合物。
本公开的方法和用途
本公开涉及本文所教导的细菌或本文所教导的组合物，用于作为药物、作为食品或食品补充剂、或作为益生菌和/或共生体。
在一个优选的实施方式中，用于根据本公开用途的细菌可以与(myo)肌醇，或与(myo)肌醇源(或磷脂或植酸源)分别、顺序或同时给予，其可以与细菌存在于同一组合物中，或存在于分开的组合物中，例如包含约5mM至约100mM，优选约10mM至约50mM，更优选约15mM至约25mM且最优选约20mM(myo)肌醇，或例如包含约1mg至约1000mg，优选约10mg至约500mg，更优选约15mg至约50mg。或者，肌醇和的量和/或给予频率被选择为每天消耗0.1至100克，或0.5至10、或0.5至10、或0.1至5，都是以每天的克数计。
本公开特别涉及本文所教导的细菌或本文所教导的组合物，用于维持、恢复和/或改善总体胃肠道健康，和/或预防和/或治疗病症或疾病，例如肥胖、代谢疾病，例如代谢综合征和胰岛素抵抗或胰岛素抵抗相关的并发症，例如血脂异常和2型糖尿病，以及内分泌疾病(例如，患有1型糖尿病、库欣病或脂肪代谢障碍综合征的肥胖对象)中的胰岛素抵抗。
本公开还涉及一种方法，用于在有需要的对象中维持、恢复和/或改善总体胃肠道健康，和/或预防和/或治疗病症或疾病，例如肥胖、代谢疾病，例如代谢综合征和胰岛素抵抗或胰岛素抵抗相关的并发症，例如血脂异常和2型糖尿病，以及内分泌疾病(例如，患有1型糖尿病、库欣病或脂肪代谢障碍综合征的肥胖对象)中的胰岛素抵抗，所述方法包括在所述对象中增加如本文所教导的细菌的水平的步骤。
通过向所述对象给予有效量的所述细菌，和/或通过给予有效量的能够增加所述对象(胃肠道)中所述细菌水平的化合物，可以增加所述对象中如本文所教导的细菌的水平。
在一个实施方式中，本文所教导的细菌可以与(myo)肌醇或(myo)肌醇源(或磷脂或植酸源)，如果实、豆类、谷物和坚果相伴给予。本领域技术人员可以(没有过度负担)容易地确定富含(myo)肌醇的来源。
在一个优选的实施方式中，通过向所述对象给予有效量的本文所教导的细菌，但优选鼠李厌氧菌(Anaerostipes rhamnosivorans)1y2，和/或如本文所教导的含有鼠李厌氧菌(Anaerostipes rhamnosivorana)1y2的组合物，可以增加对象的胃肠道中如本文所教导的细菌的水平。
在一个实施方式中，对象可以选自下组：人、非人灵长类、小鼠、大鼠、狗、牛和猪。在一个优选的实施方式中，对象是人。
本公开还涉及一种生产丙酸的方法，所述方法包括在允许本文所教导的细菌将能量源转化为丙酸的条件下，使本文所教导的细菌与合适的能量源(例如(myo)肌醇和/或葡萄糖/乙酸盐)接触的步骤。
本文所教导的方法可以是体外方法。
条款
1.一种细菌，其包含允许所述细菌将肌醇转化为丙酸或其盐或酯的基因集，用于预防和/或治疗代谢综合征、胰岛素抵抗或胰岛素抵抗相关病症。
2.用于如条款1所述用途的细菌，其中所述基因集包含基因其编码一个多个以下蛋白质：myo-肌醇2-脱氢酶、肌糖脱水酶、表肌醇水解酶、5-脱氧-葡萄糖醛酸异构酶、5-酮基-2-脱氧葡萄糖酸激酶、5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶、甘油醛-3-磷酸酮醇-异构酶和肌糖异构酶。
3.用于如前述条款中任一项所述用途的细菌，其中，当与所述细菌在不存在肌醇的情况下生长时相比，当所述细菌在存在肌醇的情况下生长时，以下蛋白质的编码基因中的至少一种过表达：myo-肌醇2-脱氢酶、肌糖脱水酶、表肌醇水解酶、5-脱氧-葡萄糖醛酸异构酶、5-酮基-2-脱氧葡萄糖酸激酶、5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶、甘油醛-3-磷酸酮醇-异构酶和肌糖异构酶的至少一个基因。
4.用于如前述条款中任一项所述用途的细菌，其中所述用途是在预防和/或治疗胰岛素抵抗或胰岛素抵抗相关病症中。
5.用于如前述条款中任一项所述用途的细菌，其中所述胰岛素抵抗相关病症选自血脂异常、2型糖尿病和内分泌疾病中的胰岛素抵抗。
6.用于如前述条款中任一项所述用途的细菌，其中所述细菌是人肠道分离细菌。
7.用于如前述条款中任一项所述用途的细菌，其中所述细菌保藏为CBS 140182。
8.用于如前述条款中任一项所述用途的细菌，其中所述细菌被包含在进一步包含生理学上可接受的运载体的组合物中。
9.用于如条款8所述用途的细菌，其中所述组合物是食品组合物，优选乳制品，更优选发酵的乳制品，优选酸奶或酸奶饮料。
10.用于如条款8所述用途的细菌，其中所述组合物是药物组合物，优选以固体剂型，优选胶囊、片剂或粉末。
11.用于如条款8-10中任一项所述用途的细菌，其中在所述组合物中所述细菌以冻干或微囊化形式存在。
12.用于如前述条款中任一项所述用途的细菌，其中所述细菌以106至1015菌落形成单位(CFU)范围内的量存在。
13.用于如前述条款中任一项所述用途的细菌，其中所述细菌与肌醇分别给予、顺序给予或同时给予。
14.用于如前述条款中任一项所述用途的细菌，其用作益生菌。
通用定义
本文所使用的术语‘益生菌’或‘益生菌产品’是指微生物，如肠道细菌，其-当以有效量给予或摄取时-会给宿主(如人或哺乳动物)带来健康益处。优选地，在给予对象时益生菌应当是活的或有活力的，以便允许益生菌在宿主的大肠中定殖。然而，在某些条件下，如果益生菌产生的物质仍然对宿主产生有益的益生作用，那么益生菌给予时也可以是死亡的。大多数益生菌或益生菌产品由乳酸菌如乳酸杆菌(Lactobacilli)或双歧杆菌(Bifidobacteria)构成。技术人员熟知益生菌领域，知道如何选择具有益生菌活性的乳酸菌。
本文所用的术语‘益生元’或‘益生元产品’通常是指促进胃肠道微生物生长和/或活性的化合物，其有助于其宿主的健康。益生元或益生元产品主要由可发酵纤维或不可消化的碳水化合物组成。益生菌对这些纤维的发酵促进了有益的终产物(如SCFA，特别是丁酸盐/酯)的生产。技术人员熟知益生元领域，知道如何选择具有益生元活性的组分。
如本文所用的术语‘共生体’或‘共生体产品’通常是指结合益生菌和一种或多种促进胃肠道微生物的生长和/或活性的化合物(如益生元)的组合物和/或营养补充剂。共生体通过改进益生菌在胃肠道中的存活和定殖，通过选择性地刺激益生菌的生长和/或激活其代谢，对宿主产生有益影响，从而改善宿主的健康。技术人员熟知共生体，知道如何选择可以组合成共生体的成分。
本文所用的术语‘丙酸’是指化学式为CH3CH2CO2H的羧酸。该术语可包括其衍生物，即从丙酸衍生的化合物，特别是丙酸的盐和酯，其被称为丙酸盐/酯(propionate)或丙酸酯(propanoate)。丙酸盐的非限制性例子为丙酸铵、丙酸钙、丙酸镁、丙酸钾和丙酸钠。丙酸酯的非限制性例子为丙酸乙酯。
本文所用的术语‘丁酸(butyric acid)’(也以系统命名称为丁酸(butanoicacid))是指结构式为CH3CH2CH2COOH的羧酸。该术语可包括其衍生物，即从丁酸衍生的化合物，且包括丁酸的盐和酯，其被称为丁酸盐/酯(butyrate)或丁酸酯(butanoate)。丁酸盐的非限制性例子包括丁酸钠、丁酸钙、丁酸镁、丁酸锰、丁酸钴、丁酸钡、丁酸锂、丁酸锌、丁酸钾、丁酸亚铁等。丁酸酯(即丁酸的酯)的非限制性例子包括乙酸丁酸纤维素、丁酸甲酯、丁酸乙酯、丁酸丁酯、丁酸戊酯等。
术语‘生产丁酸(盐/酯)的细菌(butyrate-producing bacterium)’或‘生产丁酸的细菌(butyric acid-producing bacterium)’或‘产丁酸细菌(butyrogenicbacterium)’在本文中可互换使用，指的是能够生产丁酸和/或丁酸盐/酯和/或其一种或多种衍生物的细菌。可在哺乳动物肠道内(或在体外培养中)原位生产丁酸和/或丁酸盐/酯及其衍生物的主要途径，即丁酸/丁酸盐/酯合成途径基因集，是所谓的‘乙酰-CoA途径’。乙酰-CoA途径已被人们所熟知，并且已知在属于(例如)肠道毛螺菌(Lachnospiraceae)和瘤胃菌(Ruminococcaceae)属(它们共同构成了总肠道微生物群的高达20％)的肠道细菌中特别普遍。根据乙酰-CoA途径，丁酸和/或丁酸盐/酯和/或其衍生物可由单细菌物种通过碳水化合物发酵形成，和/或由一组微生物形成，其中来自其他生物的代谢物作为产丁酸细菌的底物。传统的乙酰-CoA途径涉及一系列的酶，包括(在众多其他酶中)被称为丁酰-CoA转移酶(But)和丁酸激酶(butyrate kinase)(Buk)的两种关键酶。技术人员熟知‘乙酰-CoA途径’，包括编码所述途径的功能机制的酶和其他元件的基因，以及拥有这种途径的肠道细菌物种。
本文所用的术语‘肌醇到丙酸(或丙酸盐/酯)途径基因集’是指编码参与(myo)肌醇转化为丙酸(丙酸盐/酯)或其衍生物的蛋白质的一组基因。在本公开的一个实施方式中，该途径基因集包含编码以下蛋白质的基因：myo-肌醇2-脱氢酶、肌糖脱水酶、表肌醇水解酶、5-脱氧-葡萄糖醛酸异构酶、5-酮基-2-脱氧葡萄糖酸激酶、5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶、甘油醛-3-磷酸酮基-异构酶、甘油醛-3-磷酸脱氢酶、磷酸甘油酸激酶、磷酸甘油酸变位酶、烯醇酶、丙酮酸激酶、丙酮酸-黄素氧还蛋白氧化还原酶、3-含氧酸CoA转移酶、酰基-CoA脱氢酶、烯酰-CoA水合酶、丙烯酰基-CoA脱氢酶/Etf和可选的肌糖异构酶和/或myo-肌醇2-脱氢酶的第二拷贝。
本文所用的术语‘有益的肠道细菌物种’是指栖息在(即先天性的)哺乳动物(如人)肠道中并对其所在的哺乳动物的胃肠道、代谢和其他健康产生一种或多种有益作用(如针对致病菌物种的保护、生产丁酸和/或丁酸盐/酯及其衍生物等)的细菌物种。有益肠道细菌物种的非限制性例子包括乳酸菌(Lactobacillus)属和双歧杆菌(Bifidobacterium)属的乳酸菌。其他有益肠道细菌物种的非限制性例子包括生产丁酸(盐/酯)的细菌物种，其利用乙酰-CoA生产丁酸和/或丁酸盐/酯及其衍生物，例如US2014/0242654、WO 2014/150094或WO2013032328 A1中公开的细菌菌株。致病菌物种可以指栖息在(即先天性的)哺乳动物(如人)肠道并对其所在的哺乳动物的胃肠道健康产生一种或多种有害作用(如感染)的细菌。致病细菌物种的臭名昭著的非限制性例子为生产毒素的艰难梭菌(Clostridiumdifficile)。
本文所用的术语‘有效量’是指达到本文所教导的作用所必需的量。例如，本文所教导的细菌的有效量是指在对象(优选人)中对维持、恢复和/或改善人的胃肠道健康，将(myo)肌醇转化为丙酸/丙酸盐/酯或其衍生物和/或丁酸/丁酸盐/酯或其衍生物，和/或预防和/或治疗本文所述的病症或疾病有效的量。这些病症或疾病包括但不限于肥胖，代谢疾病，例如代谢综合征和胰岛素抵抗或胰岛素抵抗相关的并发症，如血脂异常和2型糖尿病以及内分泌疾病(例如，患有1型糖尿病、库欣病或脂肪代谢障碍综合症的肥胖对象)中的胰岛素抵抗。本领域普通技术人员可以容易地确定有效量而无需过度实验。
本文所用的术语‘由其衍生的菌株’是指通过使用本文所教导的保藏菌株作为起始材料而获得的菌株。由其衍生的菌株可以是突变菌株，它可以通过例如基因工程、辐射、紫外线、化学处理等手段从本发明的菌株中衍生而来。此外，这种衍生物或突变菌株可以是衍生于本文所教导的保藏菌株的菌株，其经历了对特定条件的生长适应，导致衍生菌株的额外益处，例如更快速的生长、在肠道中更好的存活、增强的肌醇到丙酸盐/酯的转化，使用的方法是技术人员所熟知的。优选该衍生物或突变体在功能上等同于本文所教导的保藏菌株。本文所教导的优选衍生物或突变体具有与本文所教导的保藏菌株基本相同的活性或功能，即具有将(myo)肌醇转化为丙酸/丙酸盐/酯和衍生物的能力。该衍生物或突变体对被给予所述衍生物或突变体的哺乳动物(如人或其他哺乳动物)提供的益处与给予保藏菌株情况下的益处基本相同。衍生物或突变体菌株也可以是自发的衍生菌株或突变菌株，具有与本文所述保藏菌株相同的特征。
术语‘适于摄入’或‘营养上可接受的’是指通常被认为用于人(以及其他哺乳动物)摄入是安全的组分或物质。
术语‘代谢综合征’是技术人员所熟知的。在本公开中，该术语包括被(授权的)医疗从业者诊断为“代谢综合征”的所有病症。例如，一位患者可以被诊断为代谢综合征，如果其具有至少两个或至少三个以下特性：
-大腰围-女性的腰围至少测得35英寸(89厘米)，男性的腰围至少测得40英寸(102厘米)；
-高甘油三酯水平-每分升150毫克(mg/dL)，或每升1.7毫摩尔(mmol/L)，或血液中发现的这种类型的脂肪更高；
-″好的″或HDL胆固醇减少-男性的高密度脂蛋白(HDL)胆固醇低于40mg/dL(1.04mmol/L)，或女性的高密度脂蛋白(HDL)胆固醇低于50mg/dL(1.3mmol/L)；
-血压升高-130/85毫米汞柱(mm Hg)或更高；
-空腹血糖升高-100mg/dL(5.6mmol/L)或更高。
术语‘胰岛素抵抗’是技术人员所熟知的。在本公开中，该术语包括被(授权的)医疗从业者诊断为“胰岛素抵抗”的所有病症。例如，胰岛素抵抗可以通过确定和量化胰岛素抵抗的金标准来诊断-(DeFronzo RA，Tobin JD，Andres R 1979).《美国生理学杂志》(TheAmerican Journal of Physiology.)237(3)：E214-23)。这种方法测量的是在不引起低血糖的情况下补偿增加的胰岛素水平所需的葡萄糖量。该过程可能需要约两个小时，通常包括以下步骤。通过外周静脉，以每分钟每m210-120mU的速度输注胰岛素。为了补偿胰岛素的输注，输注20％的葡萄糖以维持血糖水平在5至5.5mmol/L之间。葡萄糖的输注速度是通过每五到十分钟检查一次血糖水平来确定的(Muniyappa R，Lee S，Chen H，Quon MJ(2008年1月).《美国生理学杂志》《内分泌和新陈代谢》(American Journal ofPhysiology.Endocrinology and Metabolism.)294(1)：E15-26)。测试最后三十分钟期间的葡萄糖输注速度确定了胰岛素敏感性。如果需要较高的水平(7.5mg/分钟或更高)，患者是胰岛素敏感的。低水平(4.0mg/分钟或更低)表示胰岛素抵抗。4.0和7.5mg/分钟之间的水平不是确定的，表示″糖耐量受损″，这是胰岛素抵抗的早期迹象。此外，稳态模型评估(HOMA)是一种用于确定和量化胰岛素抵抗的方法，因为它与金标准有合理的相关性。参见，例如，Matthews DR，Hosker JP，Rudenski AS，Naylor BA，Treacher DF，Turner RC(1985).Diabetologia.28(7)：412-9.doi：10.1007/BF00280883.PMID 3899825；和/或A.S.Rudenski；D.R.Matthews；J.C.Levy；R.C.Turner(1991)Metabolism.40(9)：908-917。偏离参考范围的HOMA(-IR)评分可以表示胰岛素抵抗。此外，空腹血清胰岛素水平大于25mU/L或174pmol/L也可被认为是表明胰岛素抵抗。本文所用的术语“胰岛素抵抗”是指外周胰岛素抵抗和/或肝脏胰岛素抵抗。术语‘胰岛素抵抗相关病症’(或并发症)可以指血脂异常。附加或替代性地，该术语也可以指2型糖尿病。此外，术语‘胰岛素抵抗相关病症’(或并发症)可以指内分泌疾病(例如，患有1型糖尿病、库欣病或脂肪代谢障碍综合征的肥胖对象)中的胰岛素抵抗。
本文使用的术语‘约’表示本领域的正常容许范围，例如在平均值的2个标准差内。术语‘约’可以理解为包括最多偏离指定值的10％、9％、8％、7％、6％、5％、4％、3％、2％、1％、0.5％、0.1％、0.05％或0.01％。
本文中使用的术语‘包括’或‘包含’及其变体是指这样一种情况，即所述术语在其非限制性意义上使用，意味着该词后面的项被包括在内，但没有具体提到的项不被排除在外。它还包括更限制性的动词‘基本上由......组成’和‘由......组成’。
用不定冠词‘一个’或‘一种’指示一个/种元素时，并不排除存在多于一个/种元素的可能性，除非上下文明确要求有一个(one)且仅有一个/种元素。因此，不定冠词‘一个’或‘一种’通常意为‘至少一个/种’。
术语‘增加’和‘增加的水平’以及术语‘减少’和‘减少的水平’指的是显著增加或显著减少的能力，或指显著增加的水平或显著减少的水平。通常，当水平比对照组或参考组中的相应水平分别高出或低于至少5％，例如，10％、15％、20％、25％、30％、35％、40％、45％、50％时，该水平是被增加或减少的。或者，当样品中的水平与对照或参考组中的水平相比在统计学上显著增加或减少时，其可以是被增加或减少的。
附图说明
图1.根据本公开的细菌能够高效地将myo-肌醇发酵成丙酸(盐/酯)。该实验进行了两次。
图2A/2B.鉴定的肌醇至丙酸(盐/酯)的途径。
图3A/3B.显示了不同的厌氧菌(Anaerostipes)菌株显示的代谢myo-肌醇的能力
图4.在厌氧菌(Anaerostipes)分离株的NCBI基因组中肌醇途径基因的存在
序列表
Figure BDA0003503944760000231
Figure BDA0003503944760000232
Figure BDA0003503944760000241
Figure BDA0003503944760000242
Figure BDA0003503944760000243
Figure BDA0003503944760000251
Figure BDA0003503944760000261
Figure BDA0003503944760000262
Figure BDA0003503944760000271
Figure BDA0003503944760000272
Figure BDA0003503944760000273
Figure BDA0003503944760000281
Figure BDA0003503944760000282
Figure BDA0003503944760000283
Figure BDA0003503944760000291
Figure BDA0003503944760000292
Figure BDA0003503944760000301
Figure BDA0003503944760000302
Figure BDA0003503944760000303
Figure BDA0003503944760000311
Figure BDA0003503944760000321
Figure BDA0003503944760000322
Figure BDA0003503944760000331
Figure BDA0003503944760000332
Figure BDA0003503944760000341
Figure BDA0003503944760000342
Figure BDA0003503944760000343
Figure BDA0003503944760000351
Figure BDA0003503944760000352
Figure BDA0003503944760000361
Figure BDA0003503944760000362
Figure BDA0003503944760000363
Figure BDA0003503944760000371
Figure BDA0003503944760000372
Figure BDA0003503944760000373
Figure BDA0003503944760000381
Figure BDA0003503944760000382
Figure BDA0003503944760000391
Figure BDA0003503944760000392
Figure BDA0003503944760000401
如果说明书中公开的序列与序列表中公开的序列不一致，则以说明书中公开的序列为优选。替代性地，也可以使用序列表中的序列。
实验支持
包含myo-肌醇至丙酸(盐/酯)途径的细菌
本发明人发现，根据本公开，myo-肌醇可以作为一种先前从健康婴儿的粪便中分离出来的细菌(例如鼠李厌氧菌(Anaerostipes rhamnosivorans)的碳和能量来源(Bui等2014 International Journal of Systematic and Evolutionary Microbiology 64：787-793)。
图1显示了该细菌能够高效地将myo-肌醇发酵成丙酸(盐/酯)。该实验进行了两次。
蛋白质组学
在鼠李厌氧菌(Anaerostipes rhamnosivorans)的封闭基因组中已经鉴定了完整的肌醇发酵途径，因此可以将其引入任何选择的细菌中。
蛋白质组学的方法
为了鉴定参与该途径的蛋白质，用液相色谱-质谱/质谱法检测了用两种不同底物生长的培养物中的蛋白质丰度。
鼠李厌氧菌(Anaerostipes rhamnosivorans)在含有40mM myo-肌醇或含有40mM鼠李糖作为碳和能量来源的100ml碳酸氢盐缓冲培养基中生长，设4个重复。
在4℃下4700g离心20分钟收集指数期的细胞。细胞沉淀被洗涤两次并悬浮在0.5ml的100mM Tris-HCl(pH 8)中。蛋白质提取和消化如先前所述进行(Bui等，2015)。消化后，在分析前样品被保存在-20℃。在赛默飞(Thermo)EASY nanoLC1000上，以0.5ul/分钟的流速用乙腈梯度通过向0.10*250mm ReproSil-Pur 120 C18-AQ 1.9μm珠分析柱(内部准备的(prepared in-house))注入4μl样品，进行样品分析。该梯度由在50分钟内用1ml/1甲酸在水中将乙腈从9％增加到34％组成，然后作为柱清洗步骤，在3分钟内将乙腈的百分比快速增加到80％(其中，在乙腈和水二者中1ml/1甲酸和20％水)。通过安装在微交叉(microcross)的废液管(waste line)中的不锈钢针将3.5kV的电喷雾电位直接施加于洗脱液。全扫描正模式FTMS谱是在Q-Exactive HFX(赛默电子(Thermo electron)，美国加利福尼亚州圣荷西)上以轨道阱(Orbitrap)以高分辨率(60000)在m/z 380和1400之间测量的。MS和MSMS AGC目标分别设置为3.106、50000或使用最大的离子注入时间50ms(MS)和25ms(MSMS)。MS扫描中25个最丰富的2-5+带电荷峰的HCD破碎的(分离幅(Isolation width)1.2m/z，24％归一化碰撞能量)MSMS扫描以数据依赖模式记录(阈值1.2e5，选定的m/z+/-10ppm为15s排除时间)。分析用所有MSMS谱获取的LCMS运行，使用MaxQuant 1.6.3.4(Cox等，2008)，使用“特异性胰蛋白酶/P”消化模式，最大限度地进行2次错位裂解，并对Andromeda搜寻器(search engine)进行进一步的默认设置(首次搜寻20ppm肽容许偏差，主要搜寻4.5ppm容许偏差，MSMS片段匹配容许偏差为0.5Da，丙酰胺(C)被设置为固定修饰，而可变修饰被设置为蛋白质N-末端乙酰化和M氧化，其通过非默认设置完成N和Q的脱酰胺基作用(de-amidation)，每个肽的最大修饰数为5(Cox等，2011)。来自NCBI的鼠李厌氧菌(Anaerostipes rhamnosivorans)数据库(CP040058)与一个污染物数据库一起使用，该污染物数据库包含常见污染物的序列，如胰蛋白酶(P00760，牛，和P00761，猪)和人角蛋白(角蛋白K22E(P35908)、角蛋白K1C9(P35527)、角蛋白K2C1(P04264)和角蛋白K1CI(P35527))。启用了“无标签量化”以及“运行间匹配”选项。允许将脱酰胺基作用肽用于蛋白质量化，所有其他的量化设置都保持默认。
使用Perseus 1.6.2.1模块(可在MaxQuant组中获取)对MaxQuant/Andromeda工作流程的输出进行过滤和进一步的生物信息学分析，并对所鉴定的蛋白质的丰度进行分析。接受错误发现率(FDR)小于1％的肽和蛋白质，以及至少有2个鉴定的肽的蛋白质，其中至少一个应当是独特的，至少一个应当是未修饰的。从MaxQuant结果表中删除反向命中(Reversed hit)以及所有显示所有肌醇和鼠李糖注射中归一化无标签定量强度(LFQ)值为0的结果。从MaxQuant获得的蛋白质LFQ MS1强度中提取正态对数。零的“Log LFQ”值被5.9的值所替代(一个比最低的测量值略低的值)以使合理的比率计算成为可能。肌醇和鼠李糖的相对蛋白质定量是通过Perseus进行的，通过使用FDR设置为0.05且S0设置为1获得的“LFQ强度”列进行双样本T检验。使用MaxQuant结果文件用PTXQC(Bielow等，2016)检查nLC-MSMS系统质量。
参考文献：
Bui TPN，Ritari J，Boeren S，de Waard P，Plugge CM，de Vos WM.(2015).一种人肠道共生菌从赖氨酸和阿马多里产物果糖赖氨酸产生丁酸盐/酯(Production ofbutyrate from lysine and the Amadori product fructoselysine by a human gutcommensal.)Nature Communication 6。
Cox，J.；Mann，M.(2008).MaxQuant实现了高肽鉴定率、个体化的p.p.b.范围质量精度和全蛋白质组的蛋白质量化(MaxQuant enables high peptide identificationrates，individualized p.p.b.-range mass accuracies and proteome-wide proteinquantification.)Nature Biotechnology 26(12)：1367-1372。
Cox，N.Neuhauser，A.Michalski，R.A.Scheltema，J.V.Olsen和M.Mann(2011).Andromeda：整合到MaxQuant的肽搜寻器(Andromeda：A Peptide Search EngineIntegrated into the MaxQuant.)Environment.Journal of Proteome Research.10(4)：1794-1805。
Bielow，C.，G.Mastrobuoni和S.Kempa(2016).蛋白质组学质量控制：MaxQuant结果的质量控制软件(Proteomics Quality Control：Quality Control Software forMaxQuant Results.)Journal of Proteome Research 15(3)：777-787。
有益作用
众所周知，膳食补充myo-肌醇可以减少胰岛素抵抗。然而，其发生机制尚不清楚。本发明人认为myo-肌醇可能具有间接的有益作用。
本发明人设想有益于宿主的是myo-肌醇的代谢转化，而不是myo-肌醇本身。因此，值得注意的是，鼠李厌氧菌(A.rhamnosivorans)生产丁酸(盐/酯)和(特别是)丙酸(盐/酯)确定是有益于患者的(Hamer等2008 Pharmacology&Therapeutics 27：104-119；Hosseini等2011 Nutrition Reviews 69：245-258)。
因此，给患者补充根据本公开的细菌(例如鼠李厌氧菌(A.rhamnosivorans))或者，替代性地，补充myo-肌醇和鼠李厌氧菌(A.rhamnosivorans)二者，通过附加的丙酸盐/酯和丁酸盐/酯的生产，对改善胰岛素抵抗提供直接或协同作用。
治疗
患者按照以下指示的3个治疗方案进行治疗：
治疗1：6周，每天两次空腹补充。
治疗2：6周，每天两次补充根据本公开的细菌(即鼠李厌氧菌(A.rhamnosivorans))的108个活细胞。
治疗3：6周，每天两次补充根据本公开的细菌(即鼠李厌氧菌(A.rhamnosivorans))的108个活细胞和10mg myo-肌醇的组合。
Figure BDA0003503944760000441
预计在更大的患者队列中可以得到类似于上表所示的推定作用的结果。
其他宿主细菌
另一种宿主细菌，即大肠杆菌(Escherichia coli)，根据标准方法用根据本发明的基因集转染，其包括：myo-肌醇2-脱氢酶、肌糖脱水酶、表肌醇水解酶、5-脱氧-葡萄糖醛酸异构酶、5-酮基-2-脱氧葡萄糖酸激酶、5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶、甘油醛-3-磷酸酮醇-异构酶、甘油醛-3-磷酸脱氢酶、磷酸甘油酸激酶、磷酸甘油酸变位酶、烯醇酶、丙酮酸激酶、丙酮酸-黄素氧还蛋白氧化还原酶、3-酮酸CoA转移酶、酰基-CoA脱氢酶、烯酰-CoA水合酶、丙烯酰基-CoA脱氢酶/Etf和肌糖异构酶。据发现，宿主细菌能够在厌氧条件下将(myo)肌酸酯转化为丙酸(盐/酯)。
Figure BDA0003503944760000461
序列表
<110> 瓦格宁根大学(Wageningen Universiteit)
<120> 包含myo-肌醇至丙酸途径的细菌
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<170> PatentIn version 3.5
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ggggcgttta cggtaccggg tgacggatgt attgattttg atccgatctt taaggtgctt 780
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Gly Ala Phe Thr Val Pro Gly Asp Gly Cys Ile Asp Phe Asp Pro Ile
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gccacaagac agccggaccc ggtgctccag cagttagaaa agagtgacag tctctctaca 420
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gctgtgtgca ttgcactctc ccaggatgta gaaggagaat cttatgattt ccctgactat 600
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gaccttgtaa aagtcattaa agaagcgaaa aatccgttag tgatcgtggg cggaggtgtg 720
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ggagagagcc aggcaggaaa aagtgcctgc aagtcaagcc acccttactg cttaggagga 840
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aatgtaaaaa tggtgacgat caacaacaat aaatatcatg catataaaat ggatgcagta 1020
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gcagcattgt gcaaaatccg tgaggtcatt gatgaagacg ctaatattgt gacagcaggg 1320
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gcagaatacg gatattcctg catgggatat gaagtggcgg gagcgctcgg cgtaaagatg 1440
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tgcggatttg gctgtatcaa caaccttcag atgaatcatg gagtgggaag tcttgcaaca 1620
gagttcagat accgcgatga aaacaatgag atcaagggtg atctgatccc ggttgactat 1680
gcaaaagtcg gagaaggata cggactcaag acgtacagtg taagaacgat caaagagctg 1740
gaggaagcat tgatcgatgc taagaaacag gacgttgcca cattgatcga cttgaaggtc 1800
attccgaaaa caatgacaga cggttacaaa tcatggtgga acgtaggtat tgcgacaact 1860
tctgtgaaag aaagcgtgca gaaagcatgt gaaggagtat tggaaggccg caaaaacgca 1920
agacagtatt ag 1932
<210> 8
<211> 643
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 8
Met Ser Thr Thr Arg Met Thr Val Ala Gln Ala Leu Val Lys Phe Leu
1 5 10 15
Asp Asn Gln Tyr Val Glu Phe Asp Gly Glu Glu Thr Lys Phe Val Glu
20 25 30
Gly Phe Phe Thr Ile Phe Gly His Gly Ile Ala Val Gly Leu Gly Glu
35 40 45
Ala Leu Asp Ser Asn Pro Gly Ser Leu Lys Val Leu Gln Gly Arg Asn
50 55 60
Glu Gln Gly Met Cys His Val Ala Thr Ala Tyr Ala Lys Gln Asn Arg
65 70 75 80
Arg Arg Lys Ile Ile Pro Cys Ala Ser Ser Val Gly Pro Gly Ala Ala
85 90 95
Asn Met Val Thr Ala Ala Ala Thr Ala Thr Val Asn Asn Ile Pro Leu
100 105 110
Leu Val Val Pro Ser Asp Thr Phe Ala Thr Arg Gln Pro Asp Pro Val
115 120 125
Leu Gln Gln Leu Glu Lys Ser Asp Ser Leu Ser Thr Thr Thr Asn Asp
130 135 140
Ala Phe Lys Pro Val Cys Lys Tyr Trp Asp Arg Ile Ile Arg Pro Glu
145 150 155 160
Gln Leu Met Thr Ala Met Val Asn Ala Met Arg Val Leu Thr Asp Pro
165 170 175
Ser Glu Thr Gly Ala Val Cys Ile Ala Leu Ser Gln Asp Val Glu Gly
180 185 190
Glu Ser Tyr Asp Phe Pro Asp Tyr Leu Phe Glu Lys Arg Val His Arg
195 200 205
Ile Thr Arg Pro Cys Ala Val Lys Glu Glu Ile Glu Asp Leu Val Lys
210 215 220
Val Ile Lys Glu Ala Lys Asn Pro Leu Val Ile Val Gly Gly Gly Val
225 230 235 240
Lys Tyr Ser Glu Ala Gly Glu Ala Val Glu Lys Phe Cys Glu Asp Phe
245 250 255
Asn Ile Pro Phe Gly Glu Ser Gln Ala Gly Lys Ser Ala Cys Lys Ser
260 265 270
Ser His Pro Tyr Cys Leu Gly Gly Ile Gly Val Thr Gly Thr Leu Ala
275 280 285
Ala Asn Thr Ile Ala Asp Glu Ala Asp Val Val Ile Ala Val Gly Thr
290 295 300
Arg Leu Ser Asp Phe Thr Thr Gly Ser Lys Gly Gln Phe Lys Asn Pro
305 310 315 320
Asn Val Lys Met Val Thr Ile Asn Asn Asn Lys Tyr His Ala Tyr Lys
325 330 335
Met Asp Ala Val Lys Ala Val Gly Asp Ala Lys Val Thr Val Glu Ala
340 345 350
Leu Ser Ala Arg Leu Lys Glu Glu Gly Tyr Lys Ser Ala Tyr Thr Thr
355 360 365
Glu Ile Gln Asp Ala Lys Ala Ala Trp Asp Lys Glu Met Asp Arg Leu
370 375 380
Ala Asn Ile Glu Tyr Thr Gly Asp Asp Phe Glu Pro Glu Ile Lys Ala
385 390 395 400
Arg Asp Pro Arg Thr Ile Pro Glu Phe Val Lys Leu Thr Gly Gly Leu
405 410 415
Ile Thr Gln Thr Ala Ala Leu Cys Lys Ile Arg Glu Val Ile Asp Glu
420 425 430
Asp Ala Asn Ile Val Thr Ala Gly Gly Ser Leu Pro Ser Cys Met Gln
435 440 445
Arg Ile Trp Thr Thr Asp Lys Arg Gly Gly Tyr His Ala Glu Tyr Gly
450 455 460
Tyr Ser Cys Met Gly Tyr Glu Val Ala Gly Ala Leu Gly Val Lys Met
465 470 475 480
Ala Glu Pro Glu His Glu Ser Tyr Val Val Val Gly Asp Ala Ser Phe
485 490 495
Gln Met Leu His Ser Glu Ile Met Thr Ala Met Gln Glu Lys Gln Lys
500 505 510
Ile Asn Ile Leu Val Phe Asp Asn Cys Gly Phe Gly Cys Ile Asn Asn
515 520 525
Leu Gln Met Asn His Gly Val Gly Ser Leu Ala Thr Glu Phe Arg Tyr
530 535 540
Arg Asp Glu Asn Asn Glu Ile Lys Gly Asp Leu Ile Pro Val Asp Tyr
545 550 555 560
Ala Lys Val Gly Glu Gly Tyr Gly Leu Lys Thr Tyr Ser Val Arg Thr
565 570 575
Ile Lys Glu Leu Glu Glu Ala Leu Ile Asp Ala Lys Lys Gln Asp Val
580 585 590
Ala Thr Leu Ile Asp Leu Lys Val Ile Pro Lys Thr Met Thr Asp Gly
595 600 605
Tyr Lys Ser Trp Trp Asn Val Gly Ile Ala Thr Thr Ser Val Lys Glu
610 615 620
Ser Val Gln Lys Ala Cys Glu Gly Val Leu Glu Gly Arg Lys Asn Ala
625 630 635 640
Arg Gln Tyr
<210> 9
<211> 786
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 9
atgggtaaag tattcggcta tcctgagttt gatgtaaacg gggaaaaggt tttaacaaca 60
tatgacaatg attataaaga aatgctgatg gacatccgcg tcttccgctt aaaagcggga 120
gatgtgaaga ccttctgcaa agaaaaagag gagaccgcgg ttcttttact aaaaggggat 180
gtcgtattct catttgatga aacttccaaa gaagtcacaa gaaaagatgt atttacagaa 240
ggaccttggg cagtacatat ctgcacagga gccaaagtca tagtggaagc aaaggcagac 300
tctgaaatct tggtacagtc cacaatgaat gaccagacat ttgagagtaa attgtatgcg 360
ccggaagatg ctccttgggg atattcctgt gtaggaaagt tcggaaatgt ggctaaacgc 420
cgtgtcaata ccatctttga ccatgacatt gcaccatact ccaacatggt attaggtgaa 480
gtcttaaatg accgcggaaa ctggtcagga tatcttcctc acagacatcc gcagccggaa 540
acttattact tcctgtttga ccatccggaa ggatttgggg caagctttgt gggagaccag 600
gtatttaaga gtacagacgg aagcttctca gcgattccag ggggagaact tcatcctcag 660
gcagtggctc cgggatacca aatgtatact tgctggatga tccgtcatct ggaagggaac 720
ccatggcttc agacagacag aaatgaagac gaacgctacg tttggcttca tgacgcagaa 780
ttctaa 786
<210> 10
<211> 261
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 10
Met Gly Lys Val Phe Gly Tyr Pro Glu Phe Asp Val Asn Gly Glu Lys
1 5 10 15
Val Leu Thr Thr Tyr Asp Asn Asp Tyr Lys Glu Met Leu Met Asp Ile
20 25 30
Arg Val Phe Arg Leu Lys Ala Gly Asp Val Lys Thr Phe Cys Lys Glu
35 40 45
Lys Glu Glu Thr Ala Val Leu Leu Leu Lys Gly Asp Val Val Phe Ser
50 55 60
Phe Asp Glu Thr Ser Lys Glu Val Thr Arg Lys Asp Val Phe Thr Glu
65 70 75 80
Gly Pro Trp Ala Val His Ile Cys Thr Gly Ala Lys Val Ile Val Glu
85 90 95
Ala Lys Ala Asp Ser Glu Ile Leu Val Gln Ser Thr Met Asn Asp Gln
100 105 110
Thr Phe Glu Ser Lys Leu Tyr Ala Pro Glu Asp Ala Pro Trp Gly Tyr
115 120 125
Ser Cys Val Gly Lys Phe Gly Asn Val Ala Lys Arg Arg Val Asn Thr
130 135 140
Ile Phe Asp His Asp Ile Ala Pro Tyr Ser Asn Met Val Leu Gly Glu
145 150 155 160
Val Leu Asn Asp Arg Gly Asn Trp Ser Gly Tyr Leu Pro His Arg His
165 170 175
Pro Gln Pro Glu Thr Tyr Tyr Phe Leu Phe Asp His Pro Glu Gly Phe
180 185 190
Gly Ala Ser Phe Val Gly Asp Gln Val Phe Lys Ser Thr Asp Gly Ser
195 200 205
Phe Ser Ala Ile Pro Gly Gly Glu Leu His Pro Gln Ala Val Ala Pro
210 215 220
Gly Tyr Gln Met Tyr Thr Cys Trp Met Ile Arg His Leu Glu Gly Asn
225 230 235 240
Pro Trp Leu Gln Thr Asp Arg Asn Glu Asp Glu Arg Tyr Val Trp Leu
245 250 255
His Asp Ala Glu Phe
260
<210> 11
<211> 1017
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 11
atgaagtatg ttgaatttga ccagacaaga ccaatggatt tagtactcat cggaagggta 60
gccatcgatt ttaacccggt agattatttc cacccgttat ctgagtgcac taccttcaag 120
aagtatgtgg gaggatctcc ggcaaacatc gcagtgggca tcacaaggca cggaaagaaa 180
gccggattca tcggcaaagt ttctgatgac cagttcggag agtatgtagt agacttcttc 240
aataaagagg gaatcgatac atcccatatt acaaaatgta cgaacggaga aaagcttgga 300
cttaccttta cagaaattct ttccagagaa gaaagcagca tcttaatgta ccgcaactgc 360
atcgcagact tacagttatc tgtggatgac attgacgaag aatacataaa gaacacaaaa 420
gcaatcctgg tttccggaac agcattggca cagagcccat ccagggaagc agtgttaaaa 480
gcagtgatgc ttgccaagaa aaatgataca aagatcatct ttgacattga ctatagagaa 540
tacaactgga aaaattccga tgagatttca atctactatt ctttagtagc cagagaagca 600
gatatcatca tgggatctag agaagaattt gacctgacag aaaaactgat aaaaccgggc 660
agaacagaca aagaatctgc acaggcatgg aacactgaaa atgcaaagat cgttgtcatc 720
aaacatggca aaaaaggatc tacagcatat accaatgacg gaaatgacta ttcaatcaaa 780
ccgttcccgg ttgaggcgtt aaaaggcttt gggggcggag acggatatgc atccggcttc 840
ttatatggaa tatttgaagg atgggatatg atcgagtgtc tggaattcgg aagtgcggaa 900
gcggccatga tggtgagaag ccattcttgt tctgaagaac ttccaaaccc tcaggaagtc 960
aaagacttta tccgcgagac aaaagacaaa tatggcgaaa tgattgcgag agtatag 1017
<210> 12
<211> 338
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 12
Met Lys Tyr Val Glu Phe Asp Gln Thr Arg Pro Met Asp Leu Val Leu
1 5 10 15
Ile Gly Arg Val Ala Ile Asp Phe Asn Pro Val Asp Tyr Phe His Pro
20 25 30
Leu Ser Glu Cys Thr Thr Phe Lys Lys Tyr Val Gly Gly Ser Pro Ala
35 40 45
Asn Ile Ala Val Gly Ile Thr Arg His Gly Lys Lys Ala Gly Phe Ile
50 55 60
Gly Lys Val Ser Asp Asp Gln Phe Gly Glu Tyr Val Val Asp Phe Phe
65 70 75 80
Asn Lys Glu Gly Ile Asp Thr Ser His Ile Thr Lys Cys Thr Asn Gly
85 90 95
Glu Lys Leu Gly Leu Thr Phe Thr Glu Ile Leu Ser Arg Glu Glu Ser
100 105 110
Ser Ile Leu Met Tyr Arg Asn Cys Ile Ala Asp Leu Gln Leu Ser Val
115 120 125
Asp Asp Ile Asp Glu Glu Tyr Ile Lys Asn Thr Lys Ala Ile Leu Val
130 135 140
Ser Gly Thr Ala Leu Ala Gln Ser Pro Ser Arg Glu Ala Val Leu Lys
145 150 155 160
Ala Val Met Leu Ala Lys Lys Asn Asp Thr Lys Ile Ile Phe Asp Ile
165 170 175
Asp Tyr Arg Glu Tyr Asn Trp Lys Asn Ser Asp Glu Ile Ser Ile Tyr
180 185 190
Tyr Ser Leu Val Ala Arg Glu Ala Asp Ile Ile Met Gly Ser Arg Glu
195 200 205
Glu Phe Asp Leu Thr Glu Lys Leu Ile Lys Pro Gly Arg Thr Asp Lys
210 215 220
Glu Ser Ala Gln Ala Trp Asn Thr Glu Asn Ala Lys Ile Val Val Ile
225 230 235 240
Lys His Gly Lys Lys Gly Ser Thr Ala Tyr Thr Asn Asp Gly Asn Asp
245 250 255
Tyr Ser Ile Lys Pro Phe Pro Val Glu Ala Leu Lys Gly Phe Gly Gly
260 265 270
Gly Asp Gly Tyr Ala Ser Gly Phe Leu Tyr Gly Ile Phe Glu Gly Trp
275 280 285
Asp Met Ile Glu Cys Leu Glu Phe Gly Ser Ala Glu Ala Ala Met Met
290 295 300
Val Arg Ser His Ser Cys Ser Glu Glu Leu Pro Asn Pro Gln Glu Val
305 310 315 320
Lys Asp Phe Ile Arg Glu Thr Lys Asp Lys Tyr Gly Glu Met Ile Ala
325 330 335
Arg Val
<210> 13
<211> 837
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 13
atggcattag tcaaaatgaa acagttatta gagcaggcaa aaaaggaaaa cagaggatgc 60
ggtgcattca gtgtgggcaa tatggaaatg gtcaaagggg cgattcaggc agcggaggag 120
atgaatacac cgatcatcct gcagatcgct gaagtgcggc tcgcccattc accgcttcat 180
cttatggggc cgatgatggt gcaggcggca aaagaggcaa aggtggatgt ggcagttcat 240
ctggaccacg gacttaacat tgagactgta aaaaaagcgc tggaactggg atttacctct 300
gttatgctgg atgcatccag agattcgttt gaagaaaata tcagaaaaac aaaagaagtt 360
gtcgctctgg cagcacagta cggagcaacc gtggaagcgg aattagggct ggtaggcgga 420
agcgaagacg gaaagagtga ccatggaatc cagtgcacca agcctcagga cgccaaggtc 480
ttctgtgagc agaccggagt ggatgccctg gccgttgcca ttggaaatgc ccacggggac 540
tatccggtag ctccgacttt ggaatttggt gtattggaag acattcacaa tattactgcc 600
aaaccattgg tgcttcacgg cggaagcggt attacagatg aggatttcag aaaagccatc 660
tctcttggaa tctgcaaagt gaacattgca actgcaagct ttaacagcct gacaaaagaa 720
gtggaaaact atctggagac agaaggaaaa cataattact tcgatatgaa cgaagctatg 780
gtaaagggtg tctatgacaa cgtaaaacgc catatccaga tctttaactg cagataa 837
<210> 14
<211> 278
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 14
Met Ala Leu Val Lys Met Lys Gln Leu Leu Glu Gln Ala Lys Lys Glu
1 5 10 15
Asn Arg Gly Cys Gly Ala Phe Ser Val Gly Asn Met Glu Met Val Lys
20 25 30
Gly Ala Ile Gln Ala Ala Glu Glu Met Asn Thr Pro Ile Ile Leu Gln
35 40 45
Ile Ala Glu Val Arg Leu Ala His Ser Pro Leu His Leu Met Gly Pro
50 55 60
Met Met Val Gln Ala Ala Lys Glu Ala Lys Val Asp Val Ala Val His
65 70 75 80
Leu Asp His Gly Leu Asn Ile Glu Thr Val Lys Lys Ala Leu Glu Leu
85 90 95
Gly Phe Thr Ser Val Met Leu Asp Ala Ser Arg Asp Ser Phe Glu Glu
100 105 110
Asn Ile Arg Lys Thr Lys Glu Val Val Ala Leu Ala Ala Gln Tyr Gly
115 120 125
Ala Thr Val Glu Ala Glu Leu Gly Leu Val Gly Gly Ser Glu Asp Gly
130 135 140
Lys Ser Asp His Gly Ile Gln Cys Thr Lys Pro Gln Asp Ala Lys Val
145 150 155 160
Phe Cys Glu Gln Thr Gly Val Asp Ala Leu Ala Val Ala Ile Gly Asn
165 170 175
Ala His Gly Asp Tyr Pro Val Ala Pro Thr Leu Glu Phe Gly Val Leu
180 185 190
Glu Asp Ile His Asn Ile Thr Ala Lys Pro Leu Val Leu His Gly Gly
195 200 205
Ser Gly Ile Thr Asp Glu Asp Phe Arg Lys Ala Ile Ser Leu Gly Ile
210 215 220
Cys Lys Val Asn Ile Ala Thr Ala Ser Phe Asn Ser Leu Thr Lys Glu
225 230 235 240
Val Glu Asn Tyr Leu Glu Thr Glu Gly Lys His Asn Tyr Phe Asp Met
245 250 255
Asn Glu Ala Met Val Lys Gly Val Tyr Asp Asn Val Lys Arg His Ile
260 265 270
Gln Ile Phe Asn Cys Arg
275
<210> 15
<211> 747
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 15
atgcgtaaaa caatcgtagc aggaaactgg aaaatgaaca aaacacctag cgagacagta 60
gctttagtta atgaattaaa gccattggta gcaagcgagg tttcagatgt tgtcttctgt 120
gtgccggcca tctgtattcc ggcagcactg gaagctgcaa aaggaagtaa catcaacatc 180
ggcgctgaga acatgtattt tgaagagagc ggcgcttaca caggcgagat cgctccgaat 240
atgttaacag acttaggtgt gaaatatgtt atcatcggac attctgagag aagagaatat 300
tttgcagaaa cagatgagac agtgaataaa aaagtcttaa aagcttttga acatggaatt 360
actccaatcg tttgctgcgg tgagacactt gctcagagag agcagggtgt gaccatcgat 420
ttcgtacgcc agcagatcaa gatcgcattc cagggtgtga ctgctgacca ggcaaagaca 480
gctgtcattg catacgaacc gatctgggct atcggaacag gaaaagttgc gacgacagaa 540
caggctcagg aagtatgtaa agcgatccgt gagtgcatcg ctgaagtata cgatcaggca 600
acagcggacg ctattcgtat ccagtacggc ggttctgtat ccgctgcaag tgcaccagaa 660
ttatttgcac aggaagacat cgatggagga ttagtcggtg gagctgcttt aaaaccagac 720
tttggtaaga tcgtgaatta caaataa 747
<210> 16
<211> 248
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 16
Met Arg Lys Thr Ile Val Ala Gly Asn Trp Lys Met Asn Lys Thr Pro
1 5 10 15
Ser Glu Thr Val Ala Leu Val Asn Glu Leu Lys Pro Leu Val Ala Ser
20 25 30
Glu Val Ser Asp Val Val Phe Cys Val Pro Ala Ile Cys Ile Pro Ala
35 40 45
Ala Leu Glu Ala Ala Lys Gly Ser Asn Ile Asn Ile Gly Ala Glu Asn
50 55 60
Met Tyr Phe Glu Glu Ser Gly Ala Tyr Thr Gly Glu Ile Ala Pro Asn
65 70 75 80
Met Leu Thr Asp Leu Gly Val Lys Tyr Val Ile Ile Gly His Ser Glu
85 90 95
Arg Arg Glu Tyr Phe Ala Glu Thr Asp Glu Thr Val Asn Lys Lys Val
100 105 110
Leu Lys Ala Phe Glu His Gly Ile Thr Pro Ile Val Cys Cys Gly Glu
115 120 125
Thr Leu Ala Gln Arg Glu Gln Gly Val Thr Ile Asp Phe Val Arg Gln
130 135 140
Gln Ile Lys Ile Ala Phe Gln Gly Val Thr Ala Asp Gln Ala Lys Thr
145 150 155 160
Ala Val Ile Ala Tyr Glu Pro Ile Trp Ala Ile Gly Thr Gly Lys Val
165 170 175
Ala Thr Thr Glu Gln Ala Gln Glu Val Cys Lys Ala Ile Arg Glu Cys
180 185 190
Ile Ala Glu Val Tyr Asp Gln Ala Thr Ala Asp Ala Ile Arg Ile Gln
195 200 205
Tyr Gly Gly Ser Val Ser Ala Ala Ser Ala Pro Glu Leu Phe Ala Gln
210 215 220
Glu Asp Ile Asp Gly Gly Leu Val Gly Gly Ala Ala Leu Lys Pro Asp
225 230 235 240
Phe Gly Lys Ile Val Asn Tyr Lys
245
<210> 17
<211> 1017
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 17
atggcagtaa aagtagcgat taatggattt ggacgtattg gacgtcttgc attcagacag 60
atgttcggag cagaaggtta tgaagttgta gcaatcaacg atttaacaaa tcctaagatg 120
ttagcacatt tattaaagta tgattctgca cagggaagat atgcattagg cgacaaggta 180
gaagcaaaag aatcttccat cgtagttgac ggaaaagaaa tcgaaatcta cgcagaagca 240
gacgcaacaa aacttccttg gggagaatta gatgttgatg ttgtattaga atgtacagga 300
ttctacacat ctaaagacaa agcatccgca cacgttcagg caggagctaa gaaagttgtt 360
atttctgcgc cagctggaaa tgatcttcca actatcgtat ataatgtaaa ccacgataca 420
ttgacaaaag aagacacagt catctcagca gcatcttgta caacaaactg cttagcacct 480
atggctgatg cactgaacaa gtatgcacca atccagtctg gtatcatgtt aacagtacat 540
gcttacacag gagatcagat gactcttgac ggacctcaga gaaaaggtga cttaagaaga 600
gcacgtgcag ctgcagtcaa catcgtacct aactctacag gtgctgcaaa agctatcgga 660
ttagttatcc cagaattaaa cggaaaatta atcggatctg ctcagcgtgt accggttcct 720
acaggatcaa caacactttt aacagcagtt gttaaaggtg acaatgtaac tgttgaagga 780
atcaacgcag ctatgaaagc agcagcaaca gagtctttcg gatacacaga agaagaatta 840
gtatcttctg acatcatcgg aatcaaatat ggttctttat tcgacgcaac tcagacaatg 900
gttactgaag ttggtgacgg attatatgaa gtacaggttg tttcttggta tgacaacgaa 960
aactcataca caagccagat ggttagaaca atcaaatact ttgcagaatt agcataa 1017
<210> 18
<211> 338
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 18
Met Ala Val Lys Val Ala Ile Asn Gly Phe Gly Arg Ile Gly Arg Leu
1 5 10 15
Ala Phe Arg Gln Met Phe Gly Ala Glu Gly Tyr Glu Val Val Ala Ile
20 25 30
Asn Asp Leu Thr Asn Pro Lys Met Leu Ala His Leu Leu Lys Tyr Asp
35 40 45
Ser Ala Gln Gly Arg Tyr Ala Leu Gly Asp Lys Val Glu Ala Lys Glu
50 55 60
Ser Ser Ile Val Val Asp Gly Lys Glu Ile Glu Ile Tyr Ala Glu Ala
65 70 75 80
Asp Ala Thr Lys Leu Pro Trp Gly Glu Leu Asp Val Asp Val Val Leu
85 90 95
Glu Cys Thr Gly Phe Tyr Thr Ser Lys Asp Lys Ala Ser Ala His Val
100 105 110
Gln Ala Gly Ala Lys Lys Val Val Ile Ser Ala Pro Ala Gly Asn Asp
115 120 125
Leu Pro Thr Ile Val Tyr Asn Val Asn His Asp Thr Leu Thr Lys Glu
130 135 140
Asp Thr Val Ile Ser Ala Ala Ser Cys Thr Thr Asn Cys Leu Ala Pro
145 150 155 160
Met Ala Asp Ala Leu Asn Lys Tyr Ala Pro Ile Gln Ser Gly Ile Met
165 170 175
Leu Thr Val His Ala Tyr Thr Gly Asp Gln Met Thr Leu Asp Gly Pro
180 185 190
Gln Arg Lys Gly Asp Leu Arg Arg Ala Arg Ala Ala Ala Val Asn Ile
195 200 205
Val Pro Asn Ser Thr Gly Ala Ala Lys Ala Ile Gly Leu Val Ile Pro
210 215 220
Glu Leu Asn Gly Lys Leu Ile Gly Ser Ala Gln Arg Val Pro Val Pro
225 230 235 240
Thr Gly Ser Thr Thr Leu Leu Thr Ala Val Val Lys Gly Asp Asn Val
245 250 255
Thr Val Glu Gly Ile Asn Ala Ala Met Lys Ala Ala Ala Thr Glu Ser
260 265 270
Phe Gly Tyr Thr Glu Glu Glu Leu Val Ser Ser Asp Ile Ile Gly Ile
275 280 285
Lys Tyr Gly Ser Leu Phe Asp Ala Thr Gln Thr Met Val Thr Glu Val
290 295 300
Gly Asp Gly Leu Tyr Glu Val Gln Val Val Ser Trp Tyr Asp Asn Glu
305 310 315 320
Asn Ser Tyr Thr Ser Gln Met Val Arg Thr Ile Lys Tyr Phe Ala Glu
325 330 335
Leu Ala
<210> 19
<211> 1194
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 19
atgttaaaca agaaatcagt agatgatatc aacgtaaaag gaaaaaaagt cttagtgcgc 60
tgtgacttca acgttccgct tcaggatgga aagatcacag atgagaaccg tcttgtggca 120
gcacttccta cactaaagaa gttaattgct gacggcggaa agctgatcct ctgctcacac 180
ttaggaaaac caaaagggga accgaaaccg gagttatctc ttgcgccagt agcagaaaga 240
ttaagcgagt tattaggaca ggaagtaaag tttgctgcag atgacaacgt ggtaggaccg 300
aatgcaaaag ctgcggtaga aggaatgcag gacggggatg tcattttact tcagaataca 360
cgctacagag cagaagagac aaagaatgga gaagagttca gcaaagaact tgcaagtctc 420
tgcgatgttt ttgttaatga tgcttttggt accgctcata gagctcactg ctctaacgtg 480
ggagttacaa agttcgtgga cactgcagtt gtaggatatt taatgcagaa agagattgat 540
ttcttaggaa atgcggtcaa caatccggaa cgtcctatgg tcgctatctt gggaggagca 600
aaggtttcct ctaagatctc tgtgatcaat aacctgctag acaaagtcga tactttgatc 660
atcggcggag gtatggcata tactttcatg aaagcattgg gagaagaagt tggagattcc 720
cttctggaag ctgactactt agactacgca aaagaaatga tggacaaggc aaaagaaaaa 780
ggtgtgaact tactgattcc tgttgacact gtagttgctg atgacttctc aaatgacgcc 840
aacatcaaaa ctgttgagag aggcggaatc gaagcaggat ggcagggact tgacatcgga 900
ccaaagacaa gagaactgtt ttcaaatgca ctgaaagatg ccaagactgt agtatggaac 960
ggaccgatgg gatgctttga gatgccgaac tttgcagcag gaaccgttgc agttgcagaa 1020
gcactggcag agatcgacgc tacaactatc attggcggag gagattccgc agcggcagtt 1080
aaccagctcg gattcggaga taagatgact catatctcta caggtggtgg agcatcactg 1140
gaattcctgg aaggaaaaga attaccaggc gttgcagcgg caaacgataa ataa 1194
<210> 20
<211> 397
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 20
Met Leu Asn Lys Lys Ser Val Asp Asp Ile Asn Val Lys Gly Lys Lys
1 5 10 15
Val Leu Val Arg Cys Asp Phe Asn Val Pro Leu Gln Asp Gly Lys Ile
20 25 30
Thr Asp Glu Asn Arg Leu Val Ala Ala Leu Pro Thr Leu Lys Lys Leu
35 40 45
Ile Ala Asp Gly Gly Lys Leu Ile Leu Cys Ser His Leu Gly Lys Pro
50 55 60
Lys Gly Glu Pro Lys Pro Glu Leu Ser Leu Ala Pro Val Ala Glu Arg
65 70 75 80
Leu Ser Glu Leu Leu Gly Gln Glu Val Lys Phe Ala Ala Asp Asp Asn
85 90 95
Val Val Gly Pro Asn Ala Lys Ala Ala Val Glu Gly Met Gln Asp Gly
100 105 110
Asp Val Ile Leu Leu Gln Asn Thr Arg Tyr Arg Ala Glu Glu Thr Lys
115 120 125
Asn Gly Glu Glu Phe Ser Lys Glu Leu Ala Ser Leu Cys Asp Val Phe
130 135 140
Val Asn Asp Ala Phe Gly Thr Ala His Arg Ala His Cys Ser Asn Val
145 150 155 160
Gly Val Thr Lys Phe Val Asp Thr Ala Val Val Gly Tyr Leu Met Gln
165 170 175
Lys Glu Ile Asp Phe Leu Gly Asn Ala Val Asn Asn Pro Glu Arg Pro
180 185 190
Met Val Ala Ile Leu Gly Gly Ala Lys Val Ser Ser Lys Ile Ser Val
195 200 205
Ile Asn Asn Leu Leu Asp Lys Val Asp Thr Leu Ile Ile Gly Gly Gly
210 215 220
Met Ala Tyr Thr Phe Met Lys Ala Leu Gly Glu Glu Val Gly Asp Ser
225 230 235 240
Leu Leu Glu Ala Asp Tyr Leu Asp Tyr Ala Lys Glu Met Met Asp Lys
245 250 255
Ala Lys Glu Lys Gly Val Asn Leu Leu Ile Pro Val Asp Thr Val Val
260 265 270
Ala Asp Asp Phe Ser Asn Asp Ala Asn Ile Lys Thr Val Glu Arg Gly
275 280 285
Gly Ile Glu Ala Gly Trp Gln Gly Leu Asp Ile Gly Pro Lys Thr Arg
290 295 300
Glu Leu Phe Ser Asn Ala Leu Lys Asp Ala Lys Thr Val Val Trp Asn
305 310 315 320
Gly Pro Met Gly Cys Phe Glu Met Pro Asn Phe Ala Ala Gly Thr Val
325 330 335
Ala Val Ala Glu Ala Leu Ala Glu Ile Asp Ala Thr Thr Ile Ile Gly
340 345 350
Gly Gly Asp Ser Ala Ala Ala Val Asn Gln Leu Gly Phe Gly Asp Lys
355 360 365
Met Thr His Ile Ser Thr Gly Gly Gly Ala Ser Leu Glu Phe Leu Glu
370 375 380
Gly Lys Glu Leu Pro Gly Val Ala Ala Ala Asn Asp Lys
385 390 395
<210> 21
<211> 606
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 21
ttgaagttat atatgatgag gcacggagaa actccatgga ataaagtgcg gaggattcag 60
gggcagtcag acgtggatct gagtgaagcg ggcagggaag cagccaggct caccaggaga 120
gcactgaaag atttccattt tgatgcggcc tacacgagcc cgctgagcag agcgagagaa 180
acaggggaga tcatcctgga gggcagaggg atccctctgc tggaggatga acggcttaag 240
gaggccaact tcggacctta tgaaggggca cacatcaatg aattatatga aagagaagaa 300
ccgattctgg atttctttga ccggccggaa cagatggcct atattgaagg agcggagact 360
ccggctcagg tagtagaaag atccaggata tttttagagg aatttatact tccgatggaa 420
aaagaagcag aaagtgtgat cttatttacc cacggagctt tcatccacgg gatgctgact 480
aatatgtatc aaagagagat cagggacttt tggaaaggac cgaagcttaa gaattgttct 540
atcagtacgg ctgaagtcag ggacggtcag ttccgcattt tgagtgaggc tgaggtcttt 600
tactga 606
<210> 22
<211> 201
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 22
Met Lys Leu Tyr Met Met Arg His Gly Glu Thr Pro Trp Asn Lys Val
1 5 10 15
Arg Arg Ile Gln Gly Gln Ser Asp Val Asp Leu Ser Glu Ala Gly Arg
20 25 30
Glu Ala Ala Arg Leu Thr Arg Arg Ala Leu Lys Asp Phe His Phe Asp
35 40 45
Ala Ala Tyr Thr Ser Pro Leu Ser Arg Ala Arg Glu Thr Gly Glu Ile
50 55 60
Ile Leu Glu Gly Arg Gly Ile Pro Leu Leu Glu Asp Glu Arg Leu Lys
65 70 75 80
Glu Ala Asn Phe Gly Pro Tyr Glu Gly Ala His Ile Asn Glu Leu Tyr
85 90 95
Glu Arg Glu Glu Pro Ile Leu Asp Phe Phe Asp Arg Pro Glu Gln Met
100 105 110
Ala Tyr Ile Glu Gly Ala Glu Thr Pro Ala Gln Val Val Glu Arg Ser
115 120 125
Arg Ile Phe Leu Glu Glu Phe Ile Leu Pro Met Glu Lys Glu Ala Glu
130 135 140
Ser Val Ile Leu Phe Thr His Gly Ala Phe Ile His Gly Met Leu Thr
145 150 155 160
Asn Met Tyr Gln Arg Glu Ile Arg Asp Phe Trp Lys Gly Pro Lys Leu
165 170 175
Lys Asn Cys Ser Ile Ser Thr Ala Glu Val Arg Asp Gly Gln Phe Arg
180 185 190
Ile Leu Ser Glu Ala Glu Val Phe Tyr
195 200
<210> 23
<211> 1284
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 23
atggattatt tagagattga aaaggtcata ggaagggaaa ttattgattc caggggaaat 60
cctacagtgg aagcagaagt tcttttagcc ggcgggacaa tcggacgggg cacagcaccc 120
agcggagctt caactggaga atttgaggcg ttggaattaa gagacggaga taaggagcgt 180
tttggaggaa aaggtgtgtc caaggcagtt cataatatta atacgatcat taacgatact 240
ttaaaaggga tggatgcatc cgatacttac gcggtggaca gagcgatgat cagcgtagac 300
ggaacaaagg ataaatcaaa gcttggggcc aatgcgatcc ttgcggtttc gattgcatgc 360
gcaaaggcgg catcggcagg cctggatctg ccattatacc gttttctggg cggtgttaat 420
gccaaccgtc ttccggtgcc gatgatgaac attttaaacg gaggtgccca tgcggccaac 480
accgtcgatg tacaggagtt tatgatcatg cctgtgggag cagaaaattt cagggaagca 540
ctccggtggt gtacggaagt attccacgcc ttggcagctt tgctgaaatc caaagggctg 600
gcaacctccg tgggtgatga aggcgggttt gcgcctgacc ttgcaagtga tgaggaagcc 660
atcgaatata ttttggaagc tgttcaggca gcgggatatg agccgggcag tgattttgtt 720
ctggctatgg atgctgcttc cagcgagtgg aaaggcgcga acaaaggtga atatattctt 780
cctaagagtg gcaagaaatt tacctcagaa gaactggtgg accactggaa atcactttgt 840
gagaaatatc cgatcagctc cattgaggat ggattggatg aggaagactg ggacggctgg 900
aaatacatga cccaggagct tggagagaaa atccagctgg tgggagatga cttatttgta 960
acgaatacgg aacgccttgg aaaaggtatc aagatgggat gcggaaattc tatcttgatc 1020
aagctgaacc agatcggttc tgtgtcggag acattggaag ctattaagat ggcccataaa 1080
gcgggttaca cagcggtcac atcccaccgt tcaggggaga cagaagacac gaccatcgca 1140
gatctcgctg ttgcacttaa taccggacag atcaaaaccg gtgcaccgag cagaagtgag 1200
agggtggcaa aatataatca gcttctgagg attgaagagg aactggggga aagtgccgta 1260
tacccgggag tcggaacatt ttag 1284
<210> 24
<211> 427
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 24
Met Asp Tyr Leu Glu Ile Glu Lys Val Ile Gly Arg Glu Ile Ile Asp
1 5 10 15
Ser Arg Gly Asn Pro Thr Val Glu Ala Glu Val Leu Leu Ala Gly Gly
20 25 30
Thr Ile Gly Arg Gly Thr Ala Pro Ser Gly Ala Ser Thr Gly Glu Phe
35 40 45
Glu Ala Leu Glu Leu Arg Asp Gly Asp Lys Glu Arg Phe Gly Gly Lys
50 55 60
Gly Val Ser Lys Ala Val His Asn Ile Asn Thr Ile Ile Asn Asp Thr
65 70 75 80
Leu Lys Gly Met Asp Ala Ser Asp Thr Tyr Ala Val Asp Arg Ala Met
85 90 95
Ile Ser Val Asp Gly Thr Lys Asp Lys Ser Lys Leu Gly Ala Asn Ala
100 105 110
Ile Leu Ala Val Ser Ile Ala Cys Ala Lys Ala Ala Ser Ala Gly Leu
115 120 125
Asp Leu Pro Leu Tyr Arg Phe Leu Gly Gly Val Asn Ala Asn Arg Leu
130 135 140
Pro Val Pro Met Met Asn Ile Leu Asn Gly Gly Ala His Ala Ala Asn
145 150 155 160
Thr Val Asp Val Gln Glu Phe Met Ile Met Pro Val Gly Ala Glu Asn
165 170 175
Phe Arg Glu Ala Leu Arg Trp Cys Thr Glu Val Phe His Ala Leu Ala
180 185 190
Ala Leu Leu Lys Ser Lys Gly Leu Ala Thr Ser Val Gly Asp Glu Gly
195 200 205
Gly Phe Ala Pro Asp Leu Ala Ser Asp Glu Glu Ala Ile Glu Tyr Ile
210 215 220
Leu Glu Ala Val Gln Ala Ala Gly Tyr Glu Pro Gly Ser Asp Phe Val
225 230 235 240
Leu Ala Met Asp Ala Ala Ser Ser Glu Trp Lys Gly Ala Asn Lys Gly
245 250 255
Glu Tyr Ile Leu Pro Lys Ser Gly Lys Lys Phe Thr Ser Glu Glu Leu
260 265 270
Val Asp His Trp Lys Ser Leu Cys Glu Lys Tyr Pro Ile Ser Ser Ile
275 280 285
Glu Asp Gly Leu Asp Glu Glu Asp Trp Asp Gly Trp Lys Tyr Met Thr
290 295 300
Gln Glu Leu Gly Glu Lys Ile Gln Leu Val Gly Asp Asp Leu Phe Val
305 310 315 320
Thr Asn Thr Glu Arg Leu Gly Lys Gly Ile Lys Met Gly Cys Gly Asn
325 330 335
Ser Ile Leu Ile Lys Leu Asn Gln Ile Gly Ser Val Ser Glu Thr Leu
340 345 350
Glu Ala Ile Lys Met Ala His Lys Ala Gly Tyr Thr Ala Val Thr Ser
355 360 365
His Arg Ser Gly Glu Thr Glu Asp Thr Thr Ile Ala Asp Leu Ala Val
370 375 380
Ala Leu Asn Thr Gly Gln Ile Lys Thr Gly Ala Pro Ser Arg Ser Glu
385 390 395 400
Arg Val Ala Lys Tyr Asn Gln Leu Leu Arg Ile Glu Glu Glu Leu Gly
405 410 415
Glu Ser Ala Val Tyr Pro Gly Val Gly Thr Phe
420 425
<210> 25
<211> 3525
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 25
atggcaagaa aaatgaaaac catggatggt aacacagctg cagcacacgt gtcttacgct 60
tttactgaga cagctgctat ctacccaatt acaccatcct caccaatggc agaatcaaca 120
gaccagtggg caacacaggg aaagaaaaat attttcggac atcctgtaaa attagttgaa 180
atgcagtcag agggcggagc agcaggaact gttcacggat ctcttgcagc aggcgcattg 240
acaactacat acactgcatc tcagggatta ttactgatga ttcctaatat gtacaagatc 300
gcaggtgaat taatgccttg tgtatttgat gtatctgcac gtgcaatcgc atctcatgca 360
ctgaatatct ttggtgatca ctctgacgtt tacgcttgtc gccagacagg ttttgcaatg 420
ctttgcagct ccagcgttca ggaagttatg gacttaggcg ctgttgctca tttatctaca 480
atcaagggaa gcgttccagt tctccatttc ttcgatggat tcagaacatc tcatgagatc 540
cagaagattg aaatgtggga caacgaagat cttgcagata tggtagatta cgatgctctt 600
gaaaagttca gagcaaatgc tttgaatcca gaacatccgg ttctccgcgg atctgctcag 660
aatccagata tcttcttcca ggcaagagaa gcatgcaaca aatactacga tgcattcccg 720
gcaatcgtcg aagattacat gaaccaggtt aatgcaaaga tcggtacaga ttataaatta 780
ttcaactact acggagctgc tgatgctgaa tctgttatca ttgcaatggg atctgtatgt 840
gagactatcg atgagaccat cgattactta acagcaaaag gcgaaaaagt cggtgttgtt 900
aaagtaagac tttacagacc attcgtagct gaaaaattac tcgaagttat cccagagact 960
gttaaaacaa tcaacgtttt agacagaaca aaagaaccgg gatctcttgg agagccatta 1020
tacttagacg ttgtttctgc attaagagga acaaaattcg agcaggtaac aatcaacgga 1080
ggacgttacg gattaggatc caaagataca actcctgctg atatcatctc tgtattcaat 1140
aacaaagata agaaagaatt cacagttgcg atcaacgatg atgtgacaaa cttatctctt 1200
gaaagaggag aagctgtttc ttctacacca gaaagcacag taagctgtaa gttctggggt 1260
cttggagcag atggtaccgt tggtgctaac aagaactcca tcaagatcat cggtgaccac 1320
actgacaaat atgctcaggc atactttgat tatgattcca agaaatccgg tggtgttaca 1380
atttcccact tacgtttcgg cgatgacccg atcaaagcaa cttacctgat caacaaagct 1440
gattttgttg catgtcactg tgctccgtac atgacaaaat acaacatggt tcaggactta 1500
aaagatggcg gaacattctt gttaaactgt agctggccgg tagaagaaat cggagatcat 1560
cttccaggac aggtaaaagc ttacatggca aaacacaaca tcaagttcta tgtgatcgat 1620
ggtatcaaga tcggtaaaga gattggactt ggcggacgta tcaatactgt acttcagtct 1680
gcattcttca aattatctgg aattattccg gaagcagacg cgatccagta tatgaaagac 1740
gctgctactg cttcttacag caagaagggt gatcacatcg ttaagatgaa tcatgacgcg 1800
atcgaagctg gtgctaagag tgttgtagaa gttccggttc ctgctgaatg ggctgactgc 1860
ggagaagaaa gcttattaca tccagtatcc ggagatagaa aagatcttgt tgattatgtt 1920
aacaacattc agaacgctgt caatggacag attggtaaca gccttaaggt aagcgactta 1980
gttccttacg ctgacggtca tatgcctcag ggatctgctg catacgaaaa acgtggagtt 2040
gctgtagacg ttcctacatg gaatccggac aactgtatcc agtgtaactt ctgtgcatat 2100
gtatgtcctc atgcagttat ccgtcctgtt gccatgacag aagcagaact tgctgcagca 2160
ccggaagcta caaaatctct tccgatgacg ggaatgccag attacaaatt tgtaatgaca 2220
actactgttc ttgactgtac aggatgtggt tcttgtgcaa atgtctgccc aggtaagaaa 2280
ggcgagaaag ctcttacaat ggcaccactc gacagcatga gagatcagca ggaagtttac 2340
aactatggac agtctttacc tataaaagaa gatatctttg acaagtttaa accagaatct 2400
gttaagggaa gccagttcaa gaaacctctc cttgagttct caggagcttg tgcaggatgt 2460
ggagagactc catatgcgaa actgatcact cagttattcg gagacagaat gtacattgcc 2520
aatgcgacag gatgttcttc tatctggggt ggttcttcac ctgcaacacc ttacacagta 2580
aacagcgaag gacagggacc ggcttggtct aactcactgt tcgaagacaa tgctgagttt 2640
ggtttaggta tgttcacagg acagaatact ttaagagagc agacaaaaga aaaggttgca 2700
gcattagcag aatctacaga taatgcagat gtaaaagcag cagcggctga atacttagat 2760
acttacacag acggtaagaa aaacggagca gctactaaga aattagttgc agcactggaa 2820
gcttgcggat gtgaagaagg aaaagaaatc cttaagatga aagattactt atctaagaaa 2880
tctcagtgga tcttcggtgg tgacggatgg gcttacgaca tcggctttgg cggtgttgac 2940
catgtacttg caagtggtga agatgttaat atctttgtat tcgatacaga ggtttactct 3000
aacaccggcg gacaggcatc caaatctaca ccggcaggtg cgatcgctca gttcgcagca 3060
gcaggtaagg ctgtgaagaa aaaagacctt gcagcaatcg caatgagcta cggatatgta 3120
tatgttgctc agatctctat gggtgctgat tacaatcaga cagtcaaagc gatcgcagag 3180
gcagaagctt atccaggacc atcactgatc atcggttatg ctccatgtat caaccacggt 3240
atcaagggtg gaatgagcat tgctcagtct gaagaaaaga aagcagttac atcaggatac 3300
tggaacttat tccgtttcaa ccctgaatta gctgaagaag gaaagaatcc attctcatta 3360
gattctaaag agcctacaac agagtacaat gacttcatca tgggtgaggt tcgttacaac 3420
gctcttgctc gccagaatcc tgagagagct aaggagctgt ttgagcaggc agaaaagaat 3480
gccaaagaaa aatatgctcg tttgaaagaa ttagcagata aataa 3525
<210> 26
<211> 1174
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 26
Met Ala Arg Lys Met Lys Thr Met Asp Gly Asn Thr Ala Ala Ala His
1 5 10 15
Val Ser Tyr Ala Phe Thr Glu Thr Ala Ala Ile Tyr Pro Ile Thr Pro
20 25 30
Ser Ser Pro Met Ala Glu Ser Thr Asp Gln Trp Ala Thr Gln Gly Lys
35 40 45
Lys Asn Ile Phe Gly His Pro Val Lys Leu Val Glu Met Gln Ser Glu
50 55 60
Gly Gly Ala Ala Gly Thr Val His Gly Ser Leu Ala Ala Gly Ala Leu
65 70 75 80
Thr Thr Thr Tyr Thr Ala Ser Gln Gly Leu Leu Leu Met Ile Pro Asn
85 90 95
Met Tyr Lys Ile Ala Gly Glu Leu Met Pro Cys Val Phe Asp Val Ser
100 105 110
Ala Arg Ala Ile Ala Ser His Ala Leu Asn Ile Phe Gly Asp His Ser
115 120 125
Asp Val Tyr Ala Cys Arg Gln Thr Gly Phe Ala Met Leu Cys Ser Ser
130 135 140
Ser Val Gln Glu Val Met Asp Leu Gly Ala Val Ala His Leu Ser Thr
145 150 155 160
Ile Lys Gly Ser Val Pro Val Leu His Phe Phe Asp Gly Phe Arg Thr
165 170 175
Ser His Glu Ile Gln Lys Ile Glu Met Trp Asp Asn Glu Asp Leu Ala
180 185 190
Asp Met Val Asp Tyr Asp Ala Leu Glu Lys Phe Arg Ala Asn Ala Leu
195 200 205
Asn Pro Glu His Pro Val Leu Arg Gly Ser Ala Gln Asn Pro Asp Ile
210 215 220
Phe Phe Gln Ala Arg Glu Ala Cys Asn Lys Tyr Tyr Asp Ala Phe Pro
225 230 235 240
Ala Ile Val Glu Asp Tyr Met Asn Gln Val Asn Ala Lys Ile Gly Thr
245 250 255
Asp Tyr Lys Leu Phe Asn Tyr Tyr Gly Ala Ala Asp Ala Glu Ser Val
260 265 270
Ile Ile Ala Met Gly Ser Val Cys Glu Thr Ile Asp Glu Thr Ile Asp
275 280 285
Tyr Leu Thr Ala Lys Gly Glu Lys Val Gly Val Val Lys Val Arg Leu
290 295 300
Tyr Arg Pro Phe Val Ala Glu Lys Leu Leu Glu Val Ile Pro Glu Thr
305 310 315 320
Val Lys Thr Ile Asn Val Leu Asp Arg Thr Lys Glu Pro Gly Ser Leu
325 330 335
Gly Glu Pro Leu Tyr Leu Asp Val Val Ser Ala Leu Arg Gly Thr Lys
340 345 350
Phe Glu Gln Val Thr Ile Asn Gly Gly Arg Tyr Gly Leu Gly Ser Lys
355 360 365
Asp Thr Thr Pro Ala Asp Ile Ile Ser Val Phe Asn Asn Lys Asp Lys
370 375 380
Lys Glu Phe Thr Val Ala Ile Asn Asp Asp Val Thr Asn Leu Ser Leu
385 390 395 400
Glu Arg Gly Glu Ala Val Ser Ser Thr Pro Glu Ser Thr Val Ser Cys
405 410 415
Lys Phe Trp Gly Leu Gly Ala Asp Gly Thr Val Gly Ala Asn Lys Asn
420 425 430
Ser Ile Lys Ile Ile Gly Asp His Thr Asp Lys Tyr Ala Gln Ala Tyr
435 440 445
Phe Asp Tyr Asp Ser Lys Lys Ser Gly Gly Val Thr Ile Ser His Leu
450 455 460
Arg Phe Gly Asp Asp Pro Ile Lys Ala Thr Tyr Leu Ile Asn Lys Ala
465 470 475 480
Asp Phe Val Ala Cys His Cys Ala Pro Tyr Met Thr Lys Tyr Asn Met
485 490 495
Val Gln Asp Leu Lys Asp Gly Gly Thr Phe Leu Leu Asn Cys Ser Trp
500 505 510
Pro Val Glu Glu Ile Gly Asp His Leu Pro Gly Gln Val Lys Ala Tyr
515 520 525
Met Ala Lys His Asn Ile Lys Phe Tyr Val Ile Asp Gly Ile Lys Ile
530 535 540
Gly Lys Glu Ile Gly Leu Gly Gly Arg Ile Asn Thr Val Leu Gln Ser
545 550 555 560
Ala Phe Phe Lys Leu Ser Gly Ile Ile Pro Glu Ala Asp Ala Ile Gln
565 570 575
Tyr Met Lys Asp Ala Ala Thr Ala Ser Tyr Ser Lys Lys Gly Asp His
580 585 590
Ile Val Lys Met Asn His Asp Ala Ile Glu Ala Gly Ala Lys Ser Val
595 600 605
Val Glu Val Pro Val Pro Ala Glu Trp Ala Asp Cys Gly Glu Glu Ser
610 615 620
Leu Leu His Pro Val Ser Gly Asp Arg Lys Asp Leu Val Asp Tyr Val
625 630 635 640
Asn Asn Ile Gln Asn Ala Val Asn Gly Gln Ile Gly Asn Ser Leu Lys
645 650 655
Val Ser Asp Leu Val Pro Tyr Ala Asp Gly His Met Pro Gln Gly Ser
660 665 670
Ala Ala Tyr Glu Lys Arg Gly Val Ala Val Asp Val Pro Thr Trp Asn
675 680 685
Pro Asp Asn Cys Ile Gln Cys Asn Phe Cys Ala Tyr Val Cys Pro His
690 695 700
Ala Val Ile Arg Pro Val Ala Met Thr Glu Ala Glu Leu Ala Ala Ala
705 710 715 720
Pro Glu Ala Thr Lys Ser Leu Pro Met Thr Gly Met Pro Asp Tyr Lys
725 730 735
Phe Val Met Thr Thr Thr Val Leu Asp Cys Thr Gly Cys Gly Ser Cys
740 745 750
Ala Asn Val Cys Pro Gly Lys Lys Gly Glu Lys Ala Leu Thr Met Ala
755 760 765
Pro Leu Asp Ser Met Arg Asp Gln Gln Glu Val Tyr Asn Tyr Gly Gln
770 775 780
Ser Leu Pro Ile Lys Glu Asp Ile Phe Asp Lys Phe Lys Pro Glu Ser
785 790 795 800
Val Lys Gly Ser Gln Phe Lys Lys Pro Leu Leu Glu Phe Ser Gly Ala
805 810 815
Cys Ala Gly Cys Gly Glu Thr Pro Tyr Ala Lys Leu Ile Thr Gln Leu
820 825 830
Phe Gly Asp Arg Met Tyr Ile Ala Asn Ala Thr Gly Cys Ser Ser Ile
835 840 845
Trp Gly Gly Ser Ser Pro Ala Thr Pro Tyr Thr Val Asn Ser Glu Gly
850 855 860
Gln Gly Pro Ala Trp Ser Asn Ser Leu Phe Glu Asp Asn Ala Glu Phe
865 870 875 880
Gly Leu Gly Met Phe Thr Gly Gln Asn Thr Leu Arg Glu Gln Thr Lys
885 890 895
Glu Lys Val Ala Ala Leu Ala Glu Ser Thr Asp Asn Ala Asp Val Lys
900 905 910
Ala Ala Ala Ala Glu Tyr Leu Asp Thr Tyr Thr Asp Gly Lys Lys Asn
915 920 925
Gly Ala Ala Thr Lys Lys Leu Val Ala Ala Leu Glu Ala Cys Gly Cys
930 935 940
Glu Glu Gly Lys Glu Ile Leu Lys Met Lys Asp Tyr Leu Ser Lys Lys
945 950 955 960
Ser Gln Trp Ile Phe Gly Gly Asp Gly Trp Ala Tyr Asp Ile Gly Phe
965 970 975
Gly Gly Val Asp His Val Leu Ala Ser Gly Glu Asp Val Asn Ile Phe
980 985 990
Val Phe Asp Thr Glu Val Tyr Ser Asn Thr Gly Gly Gln Ala Ser Lys
995 1000 1005
Ser Thr Pro Ala Gly Ala Ile Ala Gln Phe Ala Ala Ala Gly Lys
1010 1015 1020
Ala Val Lys Lys Lys Asp Leu Ala Ala Ile Ala Met Ser Tyr Gly
1025 1030 1035
Tyr Val Tyr Val Ala Gln Ile Ser Met Gly Ala Asp Tyr Asn Gln
1040 1045 1050
Thr Val Lys Ala Ile Ala Glu Ala Glu Ala Tyr Pro Gly Pro Ser
1055 1060 1065
Leu Ile Ile Gly Tyr Ala Pro Cys Ile Asn His Gly Ile Lys Gly
1070 1075 1080
Gly Met Ser Ile Ala Gln Ser Glu Glu Lys Lys Ala Val Thr Ser
1085 1090 1095
Gly Tyr Trp Asn Leu Phe Arg Phe Asn Pro Glu Leu Ala Glu Glu
1100 1105 1110
Gly Lys Asn Pro Phe Ser Leu Asp Ser Lys Glu Pro Thr Thr Glu
1115 1120 1125
Tyr Asn Asp Phe Ile Met Gly Glu Val Arg Tyr Asn Ala Leu Ala
1130 1135 1140
Arg Gln Asn Pro Glu Arg Ala Lys Glu Leu Phe Glu Gln Ala Glu
1145 1150 1155
Lys Asn Ala Lys Glu Lys Tyr Ala Arg Leu Lys Glu Leu Ala Asp
1160 1165 1170
Lys
<210> 27
<211> 1560
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 27
atgggaaaag ttaaaattat cacagcagat caggctgctg ccctggtgga ggatcataca 60
acgatcacaa ccagcggatt tgttgccagc ggaatgccgg aagctctcac aaaagctttg 120
gaaaaaagat tcaaagaaac cggatccccc aaaaacctga ctttgtttta tgctgccgcc 180
cagggaaacc gtgacggaag cggcgcggat cattttgccc atgaaggtat gacaaaacgt 240
gtcataggcg gacattggaa catggttcct gcactgggac agatggttct ggacaataaa 300
atcgaaggct ataatctgcc tcagggaaca ctggcacagt tataccgtgc catcgcaggt 360
cacaaacccg gcgttatcag tcatgtagga ttaaatacat ttgctgaccc acgcattgag 420
ggcggtaaat taaatgacat tacaaccgaa gatatcgtcg atgtagttga aatcctggga 480
gaagagaaat tattgtacaa atcgttcccg atcaacatcg gatttatccg cggtacatat 540
gcagatgaac acggcaacgt aactctgtct cacgaatgtg ccaccacaga ggtcacaacc 600
atggctcagg ccgtaaagaa cagcggcgga aaggtcgttg tacaggtaga aaaggtcgtt 660
tcagacggca ccttagatcc aaaattagtc aagatccctg gaatttatgt ggatgccgtt 720
gtggaagtag aagacatgaa ggatcacgaa caatgcgtgg gctgtgatta tgatggttcc 780
atgaccggag acttccgggt tccgttaagc agtcttgagt acccgcctct ttccgccaag 840
aagatcattg gacgcagagc agccatggaa ctgacagaaa acacggttgt aaatctaggc 900
attggtattc cagagtacat ctccatggta gccaacgaag aaggcattgg agattacatg 960
actctgactg tagaggccgg accaatcggc ggtgtacctc agggaggagc taaattcgga 1020
ggcgctgtca atgctgaatg tatcctagat cagccgtacc agtttgattt ctatgacggc 1080
ggcggagttg actatgcatt cttaggactc gcacaggcag ataaagacgg taatatcaac 1140
gtaagcaagt tcggtccaag gattgcgggc tgcggcggtt tcgtcaatat cacccagaac 1200
gcaaaacgct gctacttctg cggaactttt actgcaggag gtctgaagac atccgtaaaa 1260
gacgggaaac ttatcattga ccaggaagga aaatcaaaca aattcctgga taccgtagaa 1320
cagatcacct tcagcggtga atacgcaaat aaagtcggcc agccggttct ctatatcaca 1380
gaacgtgctg tattcgaact cagaaaggac ggcgtctatc tgacagaggt tgcccctggt 1440
atcgatatcc agacacagat catcgatcat atgggatttg ctccaaagat ggaaggaacg 1500
ccaaagttca tggatgaaag aatcttcaaa gatgagctga tgggcctgaa gcacgattaa 1560
<210> 28
<211> 519
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 28
Met Gly Lys Val Lys Ile Ile Thr Ala Asp Gln Ala Ala Ala Leu Val
1 5 10 15
Glu Asp His Thr Thr Ile Thr Thr Ser Gly Phe Val Ala Ser Gly Met
20 25 30
Pro Glu Ala Leu Thr Lys Ala Leu Glu Lys Arg Phe Lys Glu Thr Gly
35 40 45
Ser Pro Lys Asn Leu Thr Leu Phe Tyr Ala Ala Ala Gln Gly Asn Arg
50 55 60
Asp Gly Ser Gly Ala Asp His Phe Ala His Glu Gly Met Thr Lys Arg
65 70 75 80
Val Ile Gly Gly His Trp Asn Met Val Pro Ala Leu Gly Gln Met Val
85 90 95
Leu Asp Asn Lys Ile Glu Gly Tyr Asn Leu Pro Gln Gly Thr Leu Ala
100 105 110
Gln Leu Tyr Arg Ala Ile Ala Gly His Lys Pro Gly Val Ile Ser His
115 120 125
Val Gly Leu Asn Thr Phe Ala Asp Pro Arg Ile Glu Gly Gly Lys Leu
130 135 140
Asn Asp Ile Thr Thr Glu Asp Ile Val Asp Val Val Glu Ile Leu Gly
145 150 155 160
Glu Glu Lys Leu Leu Tyr Lys Ser Phe Pro Ile Asn Ile Gly Phe Ile
165 170 175
Arg Gly Thr Tyr Ala Asp Glu His Gly Asn Val Thr Leu Ser His Glu
180 185 190
Cys Ala Thr Thr Glu Val Thr Thr Met Ala Gln Ala Val Lys Asn Ser
195 200 205
Gly Gly Lys Val Val Val Gln Val Glu Lys Val Val Ser Asp Gly Thr
210 215 220
Leu Asp Pro Lys Leu Val Lys Ile Pro Gly Ile Tyr Val Asp Ala Val
225 230 235 240
Val Glu Val Glu Asp Met Lys Asp His Glu Gln Cys Val Gly Cys Asp
245 250 255
Tyr Asp Gly Ser Met Thr Gly Asp Phe Arg Val Pro Leu Ser Ser Leu
260 265 270
Glu Tyr Pro Pro Leu Ser Ala Lys Lys Ile Ile Gly Arg Arg Ala Ala
275 280 285
Met Glu Leu Thr Glu Asn Thr Val Val Asn Leu Gly Ile Gly Ile Pro
290 295 300
Glu Tyr Ile Ser Met Val Ala Asn Glu Glu Gly Ile Gly Asp Tyr Met
305 310 315 320
Thr Leu Thr Val Glu Ala Gly Pro Ile Gly Gly Val Pro Gln Gly Gly
325 330 335
Ala Lys Phe Gly Gly Ala Val Asn Ala Glu Cys Ile Leu Asp Gln Pro
340 345 350
Tyr Gln Phe Asp Phe Tyr Asp Gly Gly Gly Val Asp Tyr Ala Phe Leu
355 360 365
Gly Leu Ala Gln Ala Asp Lys Asp Gly Asn Ile Asn Val Ser Lys Phe
370 375 380
Gly Pro Arg Ile Ala Gly Cys Gly Gly Phe Val Asn Ile Thr Gln Asn
385 390 395 400
Ala Lys Arg Cys Tyr Phe Cys Gly Thr Phe Thr Ala Gly Gly Leu Lys
405 410 415
Thr Ser Val Lys Asp Gly Lys Leu Ile Ile Asp Gln Glu Gly Lys Ser
420 425 430
Asn Lys Phe Leu Asp Thr Val Glu Gln Ile Thr Phe Ser Gly Glu Tyr
435 440 445
Ala Asn Lys Val Gly Gln Pro Val Leu Tyr Ile Thr Glu Arg Ala Val
450 455 460
Phe Glu Leu Arg Lys Asp Gly Val Tyr Leu Thr Glu Val Ala Pro Gly
465 470 475 480
Ile Asp Ile Gln Thr Gln Ile Ile Asp His Met Gly Phe Ala Pro Lys
485 490 495
Met Glu Gly Thr Pro Lys Phe Met Asp Glu Arg Ile Phe Lys Asp Glu
500 505 510
Leu Met Gly Leu Lys His Asp
515
<210> 29
<211> 1143
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 29
atgaattttg aattaacaga gcagcaggca gccattcagg aaacagcaag gaactttgct 60
cagacagaac tgcagccagg tgtgctggag agagatgcaa acagtgagtt tccggtagat 120
ctttataaga agatggggga tatgggcctg atcggtcttc catatccgaa agaagtcgga 180
ggacagggag ccgattatct ttcttatgca ctggcagtgg aagagatctc aaaagtagat 240
gcctctgtgg gtatttccta ttctgtttcc acctctctgt atggcggaag cattatgaac 300
tctgatgctt ccgttgagaa aaagaatgaa tttctagcac cggtactgtc cggacagcat 360
ttcggatcct ttggactcac agagcccaat gccggatcag acgcaggcgg atgtgtcact 420
gtggctgaaa aagatgggga cgaatacata ttaaatggta tgaagtgttt taacaccaac 480
ggacctttgg ccgattatac agcggtatat gccctgacag aacctgagaa gaaagcaaag 540
ggtctttcct gctttgtagt aaaaaaagga actcctggat tttctgtagg caaggtggag 600
gataagatgg gaatccgctc tgcgcaggtc tctgagatga tcctggaaaa tgtcagagta 660
cctgcagaga atatggtcgt tccatctggg gacggattta agctggccat gaagactttg 720
gatggaggac gcatcggcgt tgccgcgcag gggcttggta tcgcggaggg cgcatttgag 780
atcgcaaaag aatacttaaa gagcagagaa cagttcggca aaccattata taaaaaccag 840
tatcttgcat ttaagatggc ggaacttgaa atggagatcg acgctgcaag atacatgctt 900
tacaaagcgg ctacagataa acacgaggga agatcttact caatcccggc agcaaaggca 960
aaataccttt gtacagaggc cgctatgcat gtgacaacag aagcagtaca gatgttaggt 1020
ggaaatgggt atatgaaggg ttaccatgta gaacgtatga tgagagatgc gaagatcact 1080
cagatctatg agggaaccaa tgaaatccag aagctcgttg taagcggagc tatcttcaga 1140
tag 1143
<210> 30
<211> 380
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 30
Met Asn Phe Glu Leu Thr Glu Gln Gln Ala Ala Ile Gln Glu Thr Ala
1 5 10 15
Arg Asn Phe Ala Gln Thr Glu Leu Gln Pro Gly Val Leu Glu Arg Asp
20 25 30
Ala Asn Ser Glu Phe Pro Val Asp Leu Tyr Lys Lys Met Gly Asp Met
35 40 45
Gly Leu Ile Gly Leu Pro Tyr Pro Lys Glu Val Gly Gly Gln Gly Ala
50 55 60
Asp Tyr Leu Ser Tyr Ala Leu Ala Val Glu Glu Ile Ser Lys Val Asp
65 70 75 80
Ala Ser Val Gly Ile Ser Tyr Ser Val Ser Thr Ser Leu Tyr Gly Gly
85 90 95
Ser Ile Met Asn Ser Asp Ala Ser Val Glu Lys Lys Asn Glu Phe Leu
100 105 110
Ala Pro Val Leu Ser Gly Gln His Phe Gly Ser Phe Gly Leu Thr Glu
115 120 125
Pro Asn Ala Gly Ser Asp Ala Gly Gly Cys Val Thr Val Ala Glu Lys
130 135 140
Asp Gly Asp Glu Tyr Ile Leu Asn Gly Met Lys Cys Phe Asn Thr Asn
145 150 155 160
Gly Pro Leu Ala Asp Tyr Thr Ala Val Tyr Ala Leu Thr Glu Pro Glu
165 170 175
Lys Lys Ala Lys Gly Leu Ser Cys Phe Val Val Lys Lys Gly Thr Pro
180 185 190
Gly Phe Ser Val Gly Lys Val Glu Asp Lys Met Gly Ile Arg Ser Ala
195 200 205
Gln Val Ser Glu Met Ile Leu Glu Asn Val Arg Val Pro Ala Glu Asn
210 215 220
Met Val Val Pro Ser Gly Asp Gly Phe Lys Leu Ala Met Lys Thr Leu
225 230 235 240
Asp Gly Gly Arg Ile Gly Val Ala Ala Gln Gly Leu Gly Ile Ala Glu
245 250 255
Gly Ala Phe Glu Ile Ala Lys Glu Tyr Leu Lys Ser Arg Glu Gln Phe
260 265 270
Gly Lys Pro Leu Tyr Lys Asn Gln Tyr Leu Ala Phe Lys Met Ala Glu
275 280 285
Leu Glu Met Glu Ile Asp Ala Ala Arg Tyr Met Leu Tyr Lys Ala Ala
290 295 300
Thr Asp Lys His Glu Gly Arg Ser Tyr Ser Ile Pro Ala Ala Lys Ala
305 310 315 320
Lys Tyr Leu Cys Thr Glu Ala Ala Met His Val Thr Thr Glu Ala Val
325 330 335
Gln Met Leu Gly Gly Asn Gly Tyr Met Lys Gly Tyr His Val Glu Arg
340 345 350
Met Met Arg Asp Ala Lys Ile Thr Gln Ile Tyr Glu Gly Thr Asn Glu
355 360 365
Ile Gln Lys Leu Val Val Ser Gly Ala Ile Phe Arg
370 375 380
<210> 31
<211> 777
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 31
atgaacaatt tattaatgga agtagaaaac gaagtcgcag ttgtaacaat caacagacca 60
aaatcattaa acgctttaaa cagtgaaact ttagctgagt tagaccagtg ctttacagag 120
atttcaggac gcaaggacat cagagtggtg atcctcacag gatcaggcga aaaatccttt 180
gtagctggtg ctgatatctc tgaaatggtc aatgcaactc ctgcagaagg aagacagatg 240
ggtcttttgg caaaagaagc atttcttaag ttagagacaa tgcctcaggt aaccatcgct 300
gccgtcaacg gttacgctct gggaggcgga tgcgagatct ccatggcatg tgatatccgt 360
gtagctgcgg aaaacgcaaa attcgcacag ccagaaacag gacttggaat tcttccggga 420
ttcggcggaa cacagcgtct ctcccgttta gtaggaaaag gacgcgcaaa ggaattgatc 480
tttacatgtg accagatcga tgccgaagaa gcttacagaa ttggtcttgc aaacaaagta 540
gtgcctcagg cggagctgat cgattactgt aagaagatgg ctgcaaagat catgtccaaa 600
ggaagctacg caatttccct tgcaaaagaa gcgatcaaca caggaatgga cacagactta 660
agcagcggtc ttacattaga agctgactta ttcggacttg cattctccac tgctgacaaa 720
aaagagggta tgacagcatt ccttgaaaaa cgtaaagctg atttaaaaga tttctag 777
<210> 32
<211> 258
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 32
Met Asn Asn Leu Leu Met Glu Val Glu Asn Glu Val Ala Val Val Thr
1 5 10 15
Ile Asn Arg Pro Lys Ser Leu Asn Ala Leu Asn Ser Glu Thr Leu Ala
20 25 30
Glu Leu Asp Gln Cys Phe Thr Glu Ile Ser Gly Arg Lys Asp Ile Arg
35 40 45
Val Val Ile Leu Thr Gly Ser Gly Glu Lys Ser Phe Val Ala Gly Ala
50 55 60
Asp Ile Ser Glu Met Val Asn Ala Thr Pro Ala Glu Gly Arg Gln Met
65 70 75 80
Gly Leu Leu Ala Lys Glu Ala Phe Leu Lys Leu Glu Thr Met Pro Gln
85 90 95
Val Thr Ile Ala Ala Val Asn Gly Tyr Ala Leu Gly Gly Gly Cys Glu
100 105 110
Ile Ser Met Ala Cys Asp Ile Arg Val Ala Ala Glu Asn Ala Lys Phe
115 120 125
Ala Gln Pro Glu Thr Gly Leu Gly Ile Leu Pro Gly Phe Gly Gly Thr
130 135 140
Gln Arg Leu Ser Arg Leu Val Gly Lys Gly Arg Ala Lys Glu Leu Ile
145 150 155 160
Phe Thr Cys Asp Gln Ile Asp Ala Glu Glu Ala Tyr Arg Ile Gly Leu
165 170 175
Ala Asn Lys Val Val Pro Gln Ala Glu Leu Ile Asp Tyr Cys Lys Lys
180 185 190
Met Ala Ala Lys Ile Met Ser Lys Gly Ser Tyr Ala Ile Ser Leu Ala
195 200 205
Lys Glu Ala Ile Asn Thr Gly Met Asp Thr Asp Leu Ser Ser Gly Leu
210 215 220
Thr Leu Glu Ala Asp Leu Phe Gly Leu Ala Phe Ser Thr Ala Asp Lys
225 230 235 240
Lys Glu Gly Met Thr Ala Phe Leu Glu Lys Arg Lys Ala Asp Leu Lys
245 250 255
Asp Phe
<210> 33
<211> 1143
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 33
atggttgaat ttaaattgac aaaagaacag ctgcttgcac agcagatgtt caaagatttc 60
gcagagacag aaatcaagcc aattgctagg gacatggatg aaacagaaga attcagcatg 120
gaactgcttg agaaaatgaa aaaattcggt cttatgggaa ttccatattc caaagaatac 180
ggcggagaag gggcagacgt tttaacttat acactctgta tggaagagat gtctaagtta 240
gatgcttcca caggaatcac aatttccgta catacatcat tgtgctgttc ctgcatcaat 300
gattttgctt cagaagagca gaaacaaaaa tttttacgtc cgttggttga cggttctaaa 360
gtgggatgct ttggtcttac agagccggga gcaggtaccg atgccagcgg tgtgaagaca 420
aatgccgtat tggacggcga tgaatatatc ttaaacggac agaaggtgtt cactacaaac 480
tcaggctttg ccgatacatt tattattttt gcagttacag acaaaactgc aggtacaaga 540
ggtatgtctg catttatcgt ggacaggaat acaccgggat tagaagtcag caagaatatc 600
cctcgtatgg gtatccgtgc tgcgtcaaac tgtgaagttg ctttagttga tgtgagagta 660
ccgaaggaaa acctgatcgc gggcgaggga aaaggatata agatcgctat gtcagcgctg 720
gcaggcggac ggatcggaat cggcgctcag tccgtaggaa tcgcacaggg tgctttaaac 780
gaggccattg catatgtaaa ggaaagaaaa cagttcggaa aaccgatttc taaattccag 840
aatacacagt tcctgatcgc agaactccaa gtgaagatcg acgctgcgcg ccttatggta 900
tggagagcgg caaaatcaaa agacgatcat gaaaactatg ctcctctggc agcagcgtgc 960
aaactgtttg catctgacgt ggcagtggaa gtgacaagag cagccgtaca gcttcttgga 1020
ggatatggat actccagaga atatccggta gagagaatgt accgtgatgc taagatcaca 1080
gagatttacg aaggtacatc tgaagctatg aagatgatcg tcggcggcgg acttttaaga 1140
taa 1143
<210> 34
<211> 380
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 34
Met Val Glu Phe Lys Leu Thr Lys Glu Gln Leu Leu Ala Gln Gln Met
1 5 10 15
Phe Lys Asp Phe Ala Glu Thr Glu Ile Lys Pro Ile Ala Arg Asp Met
20 25 30
Asp Glu Thr Glu Glu Phe Ser Met Glu Leu Leu Glu Lys Met Lys Lys
35 40 45
Phe Gly Leu Met Gly Ile Pro Tyr Ser Lys Glu Tyr Gly Gly Glu Gly
50 55 60
Ala Asp Val Leu Thr Tyr Thr Leu Cys Met Glu Glu Met Ser Lys Leu
65 70 75 80
Asp Ala Ser Thr Gly Ile Thr Ile Ser Val His Thr Ser Leu Cys Cys
85 90 95
Ser Cys Ile Asn Asp Phe Ala Ser Glu Glu Gln Lys Gln Lys Phe Leu
100 105 110
Arg Pro Leu Val Asp Gly Ser Lys Val Gly Cys Phe Gly Leu Thr Glu
115 120 125
Pro Gly Ala Gly Thr Asp Ala Ser Gly Val Lys Thr Asn Ala Val Leu
130 135 140
Asp Gly Asp Glu Tyr Ile Leu Asn Gly Gln Lys Val Phe Thr Thr Asn
145 150 155 160
Ser Gly Phe Ala Asp Thr Phe Ile Ile Phe Ala Val Thr Asp Lys Thr
165 170 175
Ala Gly Thr Arg Gly Met Ser Ala Phe Ile Val Asp Arg Asn Thr Pro
180 185 190
Gly Leu Glu Val Ser Lys Asn Ile Pro Arg Met Gly Ile Arg Ala Ala
195 200 205
Ser Asn Cys Glu Val Ala Leu Val Asp Val Arg Val Pro Lys Glu Asn
210 215 220
Leu Ile Ala Gly Glu Gly Lys Gly Tyr Lys Ile Ala Met Ser Ala Leu
225 230 235 240
Ala Gly Gly Arg Ile Gly Ile Gly Ala Gln Ser Val Gly Ile Ala Gln
245 250 255
Gly Ala Leu Asn Glu Ala Ile Ala Tyr Val Lys Glu Arg Lys Gln Phe
260 265 270
Gly Lys Pro Ile Ser Lys Phe Gln Asn Thr Gln Phe Leu Ile Ala Glu
275 280 285
Leu Gln Val Lys Ile Asp Ala Ala Arg Leu Met Val Trp Arg Ala Ala
290 295 300
Lys Ser Lys Asp Asp His Glu Asn Tyr Ala Pro Leu Ala Ala Ala Cys
305 310 315 320
Lys Leu Phe Ala Ser Asp Val Ala Val Glu Val Thr Arg Ala Ala Val
325 330 335
Gln Leu Leu Gly Gly Tyr Gly Tyr Ser Arg Glu Tyr Pro Val Glu Arg
340 345 350
Met Tyr Arg Asp Ala Lys Ile Thr Glu Ile Tyr Glu Gly Thr Ser Glu
355 360 365
Ala Met Lys Met Ile Val Gly Gly Gly Leu Leu Arg
370 375 380
<210> 35
<211> 798
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 35
atgaaaatcg ttgtttgtgc aaaacaagta ccagatacaa ctgaagtaaa attagatcca 60
aagaccaaca ctctgatcag ggatggtgtt ccgagtatca tcaacccaga tgacaaagcc 120
ggaatcgaag ctgccctgca gttaaaggaa aaatgcccgg gaagcactgt gactgttgtt 180
tccatgggac cgcctcaggc agatgtggca ttgagagaag cacttgctat gggatgtgac 240
gatgcagttc tggtttctga cagagcattc ggaggagcag atacatgggc aacatcttcc 300
actatcgcgg cagcgatcaa aaaattggat tacgatgtca tcatcacagg acgccaggcg 360
attgacggag ataccgctca ggtaggccct cagatcgcag aacatcttgg aattcctcag 420
gtgagctatg tcgaagccct gaatgtggaa ggggaagaca ctttgatcgt ccagaggcag 480
tttgaagacc gccatcagat cattgaagta aagactcctt gcctgatcac tgctttggct 540
gaattggcaa cacctagata tatgacagtc cacggtgcat ttgacgcata cagagaaaaa 600
gaagtcagcg tctggggact tgcagactta gaagacactg tagaccaggc aaatatcggg 660
ttaaaaggat ctcctacaag agtaaagaaa tcctttacaa aacaggccaa aggtgcagga 720
actattttaa aagatttatc agcagacgaa gctgttgcat ccattgttga taaacttcag 780
gaaaagcaca tcatttaa 798
<210> 36
<211> 265
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 36
Met Lys Ile Val Val Cys Ala Lys Gln Val Pro Asp Thr Thr Glu Val
1 5 10 15
Lys Leu Asp Pro Lys Thr Asn Thr Leu Ile Arg Asp Gly Val Pro Ser
20 25 30
Ile Ile Asn Pro Asp Asp Lys Ala Gly Ile Glu Ala Ala Leu Gln Leu
35 40 45
Lys Glu Lys Cys Pro Gly Ser Thr Val Thr Val Val Ser Met Gly Pro
50 55 60
Pro Gln Ala Asp Val Ala Leu Arg Glu Ala Leu Ala Met Gly Cys Asp
65 70 75 80
Asp Ala Val Leu Val Ser Asp Arg Ala Phe Gly Gly Ala Asp Thr Trp
85 90 95
Ala Thr Ser Ser Thr Ile Ala Ala Ala Ile Lys Lys Leu Asp Tyr Asp
100 105 110
Val Ile Ile Thr Gly Arg Gln Ala Ile Asp Gly Asp Thr Ala Gln Val
115 120 125
Gly Pro Gln Ile Ala Glu His Leu Gly Ile Pro Gln Val Ser Tyr Val
130 135 140
Glu Ala Leu Asn Val Glu Gly Glu Asp Thr Leu Ile Val Gln Arg Gln
145 150 155 160
Phe Glu Asp Arg His Gln Ile Ile Glu Val Lys Thr Pro Cys Leu Ile
165 170 175
Thr Ala Leu Ala Glu Leu Ala Thr Pro Arg Tyr Met Thr Val His Gly
180 185 190
Ala Phe Asp Ala Tyr Arg Glu Lys Glu Val Ser Val Trp Gly Leu Ala
195 200 205
Asp Leu Glu Asp Thr Val Asp Gln Ala Asn Ile Gly Leu Lys Gly Ser
210 215 220
Pro Thr Arg Val Lys Lys Ser Phe Thr Lys Gln Ala Lys Gly Ala Gly
225 230 235 240
Thr Ile Leu Lys Asp Leu Ser Ala Asp Glu Ala Val Ala Ser Ile Val
245 250 255
Asp Lys Leu Gln Glu Lys His Ile Ile
260 265
<210> 37
<211> 996
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 37
atgagcagag acgtatatgt attcgctgag cagagagacg gcgaacttca gaaagtcgga 60
atcgaattaa ttggtaaagc aagagaatta gcagatgatc ttggacagca ggtcgttgcc 120
gtgctgcttg gggcaggcgt aaaagaaaaa gcccaggaat tagttgcctg cggtgcagat 180
aaagttgttg tcgtagatga cattatgctg gcagattatg tgacagagcc atacacaaag 240
gcactgacag ctgtgattaa cgcaaaagat cctgagatcg tgctttatgg tgcatcttcc 300
atcggacgtg accttgcccc aagagtatct gcaaggatcc atactggatt gacagcggac 360
tgtactgcac ttgccattga tgaagagaca aagctcctca tgatgacccg tccggcattt 420
ggcggaaata tcatggcgac catcgtgtgt gaagacttcc gtcctcagat ggcaacagtc 480
cgtccaggag taatgaaagc cttggaaaac gatgcatcca gaagcggtga agtggaagag 540
ttcaaagtag aattctctga tgcagacatg aatgtaaaag tccgtgaaac tgtaaagaca 600
gcacataaat ctgtagacat tacagaggct aagatccttg tttccggtgg gcgcggaatc 660
ggaagcgctg acaagttcaa ggtgttagag gaactggcgg atgtcatgga aggtgaagtg 720
tcttcttcca gagcatgtgt agattccgga tggatcagtg ctgaccgcca ggtaggacag 780
acaggaaaga ctgtgcgtcc ggaattatat ctggcctgcg gcatctcagg agcgatccag 840
catgcagccg gtatggagaa ctcagagttt atcgtagcca tcaaccgtga tgaggatgcg 900
ccgatctttg atattgcaga cctcggcatc gttggagact taaataccat cgtaccgaaa 960
cttacagaag ctgtgaaggc ggtaaaagga aaataa 996
<210> 38
<211> 331
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 38
Met Ser Arg Asp Val Tyr Val Phe Ala Glu Gln Arg Asp Gly Glu Leu
1 5 10 15
Gln Lys Val Gly Ile Glu Leu Ile Gly Lys Ala Arg Glu Leu Ala Asp
20 25 30
Asp Leu Gly Gln Gln Val Val Ala Val Leu Leu Gly Ala Gly Val Lys
35 40 45
Glu Lys Ala Gln Glu Leu Val Ala Cys Gly Ala Asp Lys Val Val Val
50 55 60
Val Asp Asp Ile Met Leu Ala Asp Tyr Val Thr Glu Pro Tyr Thr Lys
65 70 75 80
Ala Leu Thr Ala Val Ile Asn Ala Lys Asp Pro Glu Ile Val Leu Tyr
85 90 95
Gly Ala Ser Ser Ile Gly Arg Asp Leu Ala Pro Arg Val Ser Ala Arg
100 105 110
Ile His Thr Gly Leu Thr Ala Asp Cys Thr Ala Leu Ala Ile Asp Glu
115 120 125
Glu Thr Lys Leu Leu Met Met Thr Arg Pro Ala Phe Gly Gly Asn Ile
130 135 140
Met Ala Thr Ile Val Cys Glu Asp Phe Arg Pro Gln Met Ala Thr Val
145 150 155 160
Arg Pro Gly Val Met Lys Ala Leu Glu Asn Asp Ala Ser Arg Ser Gly
165 170 175
Glu Val Glu Glu Phe Lys Val Glu Phe Ser Asp Ala Asp Met Asn Val
180 185 190
Lys Val Arg Glu Thr Val Lys Thr Ala His Lys Ser Val Asp Ile Thr
195 200 205
Glu Ala Lys Ile Leu Val Ser Gly Gly Arg Gly Ile Gly Ser Ala Asp
210 215 220
Lys Phe Lys Val Leu Glu Glu Leu Ala Asp Val Met Glu Gly Glu Val
225 230 235 240
Ser Ser Ser Arg Ala Cys Val Asp Ser Gly Trp Ile Ser Ala Asp Arg
245 250 255
Gln Val Gly Gln Thr Gly Lys Thr Val Arg Pro Glu Leu Tyr Leu Ala
260 265 270
Cys Gly Ile Ser Gly Ala Ile Gln His Ala Ala Gly Met Glu Asn Ser
275 280 285
Glu Phe Ile Val Ala Ile Asn Arg Asp Glu Asp Ala Pro Ile Phe Asp
290 295 300
Ile Ala Asp Leu Gly Ile Val Gly Asp Leu Asn Thr Ile Val Pro Lys
305 310 315 320
Leu Thr Glu Ala Val Lys Ala Val Lys Gly Lys
325 330
<210> 39
<211> 834
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 39
atgaaaatcg gatttaacga agcaactgca ctggaatgta aaggacagtc tctgatggct 60
gacttagaag cgtgtgaaaa atacggattt gattacatcg agatcagatt tgactgtgta 120
aaggattatt tgaaagaaca cacactggaa gaactggcgg actggtttaa aaaccatcat 180
ttaaaaccat gggcttataa taccttgatc ttttttaacc agagagacga agccggagaa 240
aaagagattg acgaagagac tgattttatc attgaagtgt gcaaggccat cggcatgaag 300
atgctgatca ctgttccgtc ctttgatgta aaggataaga gcatcacaga gatcaaagag 360
gaagcagtag aacgtctccg ttatttatcc gataaggtgg gagaagatat taagatatca 420
ctggaattct gcggggcgcc gaactgctcc atcaaccagt ttgggacagc ttacgatgta 480
gtgaaagcaa cagaccgtga caatgtaggg gtaacagtgg ataccttcca tttccatgag 540
atgtgttcta agttagaaga tttagaagca gcggacggaa agaagatctt tgcttaccat 600
ctgaatgact gtgaggatct gcctctggga tcatgcggtg atgataaacg cctgtggccg 660
ggagaaggtg tggtagatca tgcaggaatc gcagctgcct taaagaagat cggattcgac 720
ggggtatgta ccattgaaga attccgtcca gaatattatg aaatgtccca tgacgagaat 780
gtgaaaaagt ctgctgaagt gacaagggat ttcgtagcaa aatactttgc ataa 834
<210> 40
<211> 277
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 40
Met Lys Ile Gly Phe Asn Glu Ala Thr Ala Leu Glu Cys Lys Gly Gln
1 5 10 15
Ser Leu Met Ala Asp Leu Glu Ala Cys Glu Lys Tyr Gly Phe Asp Tyr
20 25 30
Ile Glu Ile Arg Phe Asp Cys Val Lys Asp Tyr Leu Lys Glu His Thr
35 40 45
Leu Glu Glu Leu Ala Asp Trp Phe Lys Asn His His Leu Lys Pro Trp
50 55 60
Ala Tyr Asn Thr Leu Ile Phe Phe Asn Gln Arg Asp Glu Ala Gly Glu
65 70 75 80
Lys Glu Ile Asp Glu Glu Thr Asp Phe Ile Ile Glu Val Cys Lys Ala
85 90 95
Ile Gly Met Lys Met Leu Ile Thr Val Pro Ser Phe Asp Val Lys Asp
100 105 110
Lys Ser Ile Thr Glu Ile Lys Glu Glu Ala Val Glu Arg Leu Arg Tyr
115 120 125
Leu Ser Asp Lys Val Gly Glu Asp Ile Lys Ile Ser Leu Glu Phe Cys
130 135 140
Gly Ala Pro Asn Cys Ser Ile Asn Gln Phe Gly Thr Ala Tyr Asp Val
145 150 155 160
Val Lys Ala Thr Asp Arg Asp Asn Val Gly Val Thr Val Asp Thr Phe
165 170 175
His Phe His Glu Met Cys Ser Lys Leu Glu Asp Leu Glu Ala Ala Asp
180 185 190
Gly Lys Lys Ile Phe Ala Tyr His Leu Asn Asp Cys Glu Asp Leu Pro
195 200 205
Leu Gly Ser Cys Gly Asp Asp Lys Arg Leu Trp Pro Gly Glu Gly Val
210 215 220
Val Asp His Ala Gly Ile Ala Ala Ala Leu Lys Lys Ile Gly Phe Asp
225 230 235 240
Gly Val Cys Thr Ile Glu Glu Phe Arg Pro Glu Tyr Tyr Glu Met Ser
245 250 255
His Asp Glu Asn Val Lys Lys Ser Ala Glu Val Thr Arg Asp Phe Val
260 265 270
Ala Lys Tyr Phe Ala
275
<210> 41
<211> 945
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 41
atgacatata aaatgagaaa aatagtgatc ataggggccg gacatgtggg aaccatgtgc 60
ggcctgagtc ttatgtaccg cggagaagtg gacgaattgg tattcataga catcgataag 120
gaaaaggcat acagccaggc gctggacctt agtgatgccg tctccttcct gccccggcag 180
atcacggtgc gcaccgggga ttatgaagat gtggaggacg ctgacatcat cgttatggcc 240
gctggtgttt ccaggctgcc cggtcagaca aggctggata tgctggacga ttccatccgc 300
atcatgaaag aagtcaccag ccatttaaaa gataagaaga ttcagggcat cctcatcagt 360
atctccaatc ctgccgacat tgtggcggat tatctgagaa aacaactggg ccttccgaga 420
aaccgctgct tcagcaccgg tacttccctg gactcctgcc gtctcagaag gattctttcc 480
caaagaatgc acttagaccg gaattccatt caggcctttg tcatgggaga acacggagat 540
tcccaaatga tcccgttttc tgcggtacat atagccggga aaccattgct tcagtggatg 600
caagatgaac cggaacggta cggaagtctc gatctttcac agattgaaac ggagaccgcc 660
aacgccggcc atgaagtgat cgaaggaaag ggcagcacag agtttggtat cggcatcgcc 720
ctgtccgaga tcgtccagtc cattttccac gattcaaaaa aggtccttcc cgcttcgcct 780
ctgctggaag gagaatatgg acagcatggc gttcacgccg gtgtcccctg cgtgattgga 840
aaagccggaa ttgaaaagat cattgagatc cctctcacag accgggagca agagaaattt 900
gaccattcct gcgatgtgat cagaacgttt attcaagatc tctga 945
<210> 42
<211> 314
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 42
Met Thr Tyr Lys Met Arg Lys Ile Val Ile Ile Gly Ala Gly His Val
1 5 10 15
Gly Thr Met Cys Gly Leu Ser Leu Met Tyr Arg Gly Glu Val Asp Glu
20 25 30
Leu Val Phe Ile Asp Ile Asp Lys Glu Lys Ala Tyr Ser Gln Ala Leu
35 40 45
Asp Leu Ser Asp Ala Val Ser Phe Leu Pro Arg Gln Ile Thr Val Arg
50 55 60
Thr Gly Asp Tyr Glu Asp Val Glu Asp Ala Asp Ile Ile Val Met Ala
65 70 75 80
Ala Gly Val Ser Arg Leu Pro Gly Gln Thr Arg Leu Asp Met Leu Asp
85 90 95
Asp Ser Ile Arg Ile Met Lys Glu Val Thr Ser His Leu Lys Asp Lys
100 105 110
Lys Ile Gln Gly Ile Leu Ile Ser Ile Ser Asn Pro Ala Asp Ile Val
115 120 125
Ala Asp Tyr Leu Arg Lys Gln Leu Gly Leu Pro Arg Asn Arg Cys Phe
130 135 140
Ser Thr Gly Thr Ser Leu Asp Ser Cys Arg Leu Arg Arg Ile Leu Ser
145 150 155 160
Gln Arg Met His Leu Asp Arg Asn Ser Ile Gln Ala Phe Val Met Gly
165 170 175
Glu His Gly Asp Ser Gln Met Ile Pro Phe Ser Ala Val His Ile Ala
180 185 190
Gly Lys Pro Leu Leu Gln Trp Met Gln Asp Glu Pro Glu Arg Tyr Gly
195 200 205
Ser Leu Asp Leu Ser Gln Ile Glu Thr Glu Thr Ala Asn Ala Gly His
210 215 220
Glu Val Ile Glu Gly Lys Gly Ser Thr Glu Phe Gly Ile Gly Ile Ala
225 230 235 240
Leu Ser Glu Ile Val Gln Ser Ile Phe His Asp Ser Lys Lys Val Leu
245 250 255
Pro Ala Ser Pro Leu Leu Glu Gly Glu Tyr Gly Gln His Gly Val His
260 265 270
Ala Gly Val Pro Cys Val Ile Gly Lys Ala Gly Ile Glu Lys Ile Ile
275 280 285
Glu Ile Pro Leu Thr Asp Arg Glu Gln Glu Lys Phe Asp His Ser Cys
290 295 300
Asp Val Ile Arg Thr Phe Ile Gln Asp Leu
305 310
<210> 43
<211> 1176
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 43
atgggaagat ttacattacc tagagatttg tactttggaa aaggatcact tgagacactg 60
aagacgctgg acggaaaaaa agctgtttta gtcatcggcg gcggatctat gaaacgtttt 120
ggatttgtag accaggttgt tgattattta aaagaagcag gcatagagac aaaattaatt 180
gagggagtag agccggaccc ttctgttgag accgtattta aaggtgccga gattatgaga 240
gagtttgaac cggactggat cgtggcaatg ggcggaggat ctccgatcga tgctgcaaaa 300
gctatgtgga tcttctatga acatccggaa accacatttg acgatgtaaa agacccattc 360
acagttccaa aactcagaaa caaagcaaga ttccttgcaa tcccttcaac ttcaggaaca 420
gctacggaag tgacggcatt tgctgttatc acggactaca gttcaggcat taaatatccg 480
ctggcagact ttgagatcac accggatgtt gccattgtag accctgcact ggcagagacg 540
atgcctccga aactgacctc ttatacagga atggatgcac tgacccatgc gattgaagca 600
tatgttgccg gactgcattc accattttca gatcctttgg caatcgatgc catcgagatg 660
gtatttgaca acttaaaagc ttcctatgag ggagacatga ccgcacgtga aaatatgcac 720
tatgcacaat gtcttgcagg aatgtcattc tctaatgcac tgttaggaat tgtacattct 780
ttagcgcata agacaggagc agtttttgat acaggacata tcacacacgg atgtgcgaac 840
gctatctatc ttccgtatgt gatccagttt aatgcaaagg tatgcgaaga ccgctatgca 900
gccattgcaa gaaagatcgg cctccctgga aattccgata aagcactgac actttctttg 960
attgaagcaa tccgggatat gaacaagaag ctgaacattg tttccaacct gaaagatttc 1020
ggaatcaatg aagaagaatt caaccagaag aagaggatga tcgcggagcg tgctgtggca 1080
gacgcatgta caggatctaa tcctagagaa acctctgtag atgacatgga aaaagtgtta 1140
gagtgcatct actacggaaa agacgtaata ttctaa 1176
<210> 44
<211> 391
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 44
Met Gly Arg Phe Thr Leu Pro Arg Asp Leu Tyr Phe Gly Lys Gly Ser
1 5 10 15
Leu Glu Thr Leu Lys Thr Leu Asp Gly Lys Lys Ala Val Leu Val Ile
20 25 30
Gly Gly Gly Ser Met Lys Arg Phe Gly Phe Val Asp Gln Val Val Asp
35 40 45
Tyr Leu Lys Glu Ala Gly Ile Glu Thr Lys Leu Ile Glu Gly Val Glu
50 55 60
Pro Asp Pro Ser Val Glu Thr Val Phe Lys Gly Ala Glu Ile Met Arg
65 70 75 80
Glu Phe Glu Pro Asp Trp Ile Val Ala Met Gly Gly Gly Ser Pro Ile
85 90 95
Asp Ala Ala Lys Ala Met Trp Ile Phe Tyr Glu His Pro Glu Thr Thr
100 105 110
Phe Asp Asp Val Lys Asp Pro Phe Thr Val Pro Lys Leu Arg Asn Lys
115 120 125
Ala Arg Phe Leu Ala Ile Pro Ser Thr Ser Gly Thr Ala Thr Glu Val
130 135 140
Thr Ala Phe Ala Val Ile Thr Asp Tyr Ser Ser Gly Ile Lys Tyr Pro
145 150 155 160
Leu Ala Asp Phe Glu Ile Thr Pro Asp Val Ala Ile Val Asp Pro Ala
165 170 175
Leu Ala Glu Thr Met Pro Pro Lys Leu Thr Ser Tyr Thr Gly Met Asp
180 185 190
Ala Leu Thr His Ala Ile Glu Ala Tyr Val Ala Gly Leu His Ser Pro
195 200 205
Phe Ser Asp Pro Leu Ala Ile Asp Ala Ile Glu Met Val Phe Asp Asn
210 215 220
Leu Lys Ala Ser Tyr Glu Gly Asp Met Thr Ala Arg Glu Asn Met His
225 230 235 240
Tyr Ala Gln Cys Leu Ala Gly Met Ser Phe Ser Asn Ala Leu Leu Gly
245 250 255
Ile Val His Ser Leu Ala His Lys Thr Gly Ala Val Phe Asp Thr Gly
260 265 270
His Ile Thr His Gly Cys Ala Asn Ala Ile Tyr Leu Pro Tyr Val Ile
275 280 285
Gln Phe Asn Ala Lys Val Cys Glu Asp Arg Tyr Ala Ala Ile Ala Arg
290 295 300
Lys Ile Gly Leu Pro Gly Asn Ser Asp Lys Ala Leu Thr Leu Ser Leu
305 310 315 320
Ile Glu Ala Ile Arg Asp Met Asn Lys Lys Leu Asn Ile Val Ser Asn
325 330 335
Leu Lys Asp Phe Gly Ile Asn Glu Glu Glu Phe Asn Gln Lys Lys Arg
340 345 350
Met Ile Ala Glu Arg Ala Val Ala Asp Ala Cys Thr Gly Ser Asn Pro
355 360 365
Arg Glu Thr Ser Val Asp Asp Met Glu Lys Val Leu Glu Cys Ile Tyr
370 375 380
Tyr Gly Lys Asp Val Ile Phe
385 390
<210> 45
<211> 1184
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 45
cgaaagtccg tgaatttttg tgccttaccg cacatcctca gggctgcaga aaaaatgttg 60
aagatcagat tacatatgta aaaaaacaca gcggtgttga gaatgggccg aaaaaggtcc 120
tggtcatcgg ctcatccacg ggatatggcc tggcatcaag gatcaccgct gcattcgggt 180
gcggagcgga taccttgggt gtcatgtttg agagaccggc ggccggtaaa cgtaccgcca 240
ctgccggatg gtataataca gctgcatttg aacaggcggc ggccagagaa ggcttatatg 300
cgaagacggt caacgcagat gcattttcca gggaagtaaa agaccaggtc atccaactga 360
tcaagaagga tttcggtaag gttgacgctg tcatttacag tctggctgca ccgagaagaa 420
cgacagagga cggcacggtt tatcagtctg tcttaaagac aacaggggaa gattttacaa 480
ataagaacct gaaccttaaa gataatacca tcagtgagaa aaccatcgag gctgccacag 540
aggaagaagt gaaagctacc gtgaaggtca tgggcgggga ggactggaag gcatggatcc 600
aggcgcttac cgatgcggat gccattgaaa agggcgcagt caccttcgca tattcttata 660
tcggacctaa gcttacatat cctatctatt ttgagggaac catcggtgcc gcgaagaagc 720
atcttcataa gacggcgggt gagatcaatg aggaattctc aaaggatgga atcaaagcat 780
acatctccgt caataagggg ctggtgacac aggccagttc tgccattccg atcgtaccgc 840
tttatatggc tgtgctgtac cgcgttatga aagaaaaggg acttcatgaa ggctgtatcg 900
aacagatcgt aaggctgttt tctgaaaagg ctgtctttgg acaggccaag acagatgaac 960
agggtctgat ccgtctggat gactgggaac tgcgcccgga agtccaggaa gaagtggaac 1020
gccgctggga gaaggtctgc accgaaaatg tccaggagta ttctgatatt gacggatact 1080
gggatgattt ctaccaaatg ttcggcttcc gtatggatgg agtggactac gaggaggatc 1140
ttgacccttc tgtggatatc ccaagcattt ccggccaaga atag 1184
<210> 46
<211> 398
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 46
Met Lys Ile Ser Pro Lys Val Arg Glu Phe Leu Cys Leu Thr Ala His
1 5 10 15
Pro Gln Gly Cys Arg Lys Asn Val Glu Asp Gln Ile Thr Tyr Val Lys
20 25 30
Lys His Ser Gly Val Glu Asn Gly Pro Lys Lys Val Leu Val Ile Gly
35 40 45
Ser Ser Thr Gly Tyr Gly Leu Ala Ser Arg Ile Thr Ala Ala Phe Gly
50 55 60
Cys Gly Ala Asp Thr Leu Gly Val Met Phe Glu Arg Pro Ala Ala Gly
65 70 75 80
Lys Arg Thr Ala Thr Ala Gly Trp Tyr Asn Thr Ala Ala Phe Glu Gln
85 90 95
Ala Ala Ala Arg Glu Gly Leu Tyr Ala Lys Thr Val Asn Ala Asp Ala
100 105 110
Phe Ser Arg Glu Val Lys Asp Gln Val Ile Gln Leu Ile Lys Lys Asp
115 120 125
Phe Gly Lys Val Asp Ala Val Ile Tyr Ser Leu Ala Ala Pro Arg Arg
130 135 140
Thr Thr Glu Asp Gly Thr Val Tyr Gln Ser Val Leu Lys Thr Thr Gly
145 150 155 160
Glu Asp Phe Thr Asn Lys Asn Leu Asn Leu Lys Asp Asn Thr Ile Ser
165 170 175
Glu Lys Thr Ile Glu Ala Ala Thr Glu Glu Glu Val Lys Ala Thr Val
180 185 190
Lys Val Met Gly Gly Glu Asp Trp Lys Ala Trp Ile Gln Ala Leu Thr
195 200 205
Asp Ala Asp Ala Ile Glu Lys Gly Ala Val Thr Phe Ala Tyr Ser Tyr
210 215 220
Ile Gly Pro Lys Leu Thr Tyr Pro Ile Tyr Phe Glu Gly Thr Ile Gly
225 230 235 240
Ala Ala Lys Lys His Leu His Lys Thr Ala Gly Glu Ile Asn Glu Glu
245 250 255
Phe Ser Lys Asp Gly Ile Lys Ala Tyr Ile Ser Val Asn Lys Gly Leu
260 265 270
Val Thr Gln Ala Ser Ser Ala Ile Pro Ile Val Pro Leu Tyr Met Ala
275 280 285
Val Leu Tyr Arg Val Met Lys Glu Lys Gly Leu His Glu Gly Cys Ile
290 295 300
Glu Gln Ile Val Arg Leu Phe Ser Glu Lys Ala Val Phe Gly Gln Ala
305 310 315 320
Lys Thr Asp Glu Gln Gly Leu Ile Arg Leu Asp Asp Trp Glu Leu Arg
325 330 335
Pro Glu Val Gln Glu Glu Val Glu Arg Arg Trp Glu Lys Val Cys Thr
340 345 350
Glu Asn Val Gln Glu Tyr Ser Asp Ile Asp Gly Tyr Trp Asp Asp Phe
355 360 365
Tyr Gln Met Phe Gly Phe Arg Met Asp Gly Val Asp Tyr Glu Glu Asp
370 375 380
Leu Asp Pro Ser Val Asp Ile Pro Ser Ile Ser Gly Gln Glu
385 390 395
<210> 47
<211> 1434
<212> DNA
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 47
atgctgacaa aaaaaacaaa gattgtttgc acgatggggc ctgcgacaga tgatgatgcg 60
gtgctcaaac agctgatgct ggaaggaatg gatatcgcga ggctgaattt ctctcacggt 120
gaccatgagg aacagcttgg aaggatcaag agaattaaaa gattccgtga agaactgaat 180
attccgatcg cgatcttact ggatacaaaa ggacctgaga tccgtacagg acttctggag 240
acagacggag acgtggaatt aaaagaagga aatgaatttg ttctgaccac aagggacatc 300
aaaggaaatg attctatcgt agcaattaca tacgaagagc ttccgcagga tgtcacagaa 360
ggaaatacaa tcctgatcga tgacggtctg atcgaactga gagtcaaaga gatcaaagac 420
ggaacagata ttgtatgtga aattgtaaac ggcggacttt taggaagccg taagggagtg 480
aacgtaccga acgtgcgcgt aaatcttcct tccatcacag aaaaggataa gagagacatt 540
gagttcggac ttgaaaacgg cattgatttt atcgcggctt ctttcatccg taacgcagat 600
gcagtcaatg agatcaagga catcgtaaaa gcccacaaca tggaagtcgg cgttatctcc 660
aaaattgaaa acgtggaggg tgtggaaaat attgaatcca tcatccaggc ttctgacgga 720
atcatggtag cccgtggaga tttaggtgtg gaaattcccg cagaggaagt tccgtttatg 780
cagaaagcaa tcattaagaa atgcaacaat gcatttaagc cagtcatcac agctacacag 840
atgttagact ctatgatcag aaacccacgt ccgacaagag cggaagtaac agacgttgcc 900
aatgctattt atgacggaac cgatgcgatt atgctttctg gagaaaccgc gaaggggaaa 960
taccctgtgg aggccgtaag gatgatgaac cagatcgcca tctccacaga actgcatctg 1020
gatacgaaga tcaaagattt tcgttccatc tatgtaagcc gtggaatctc agcagcggtt 1080
gcttattctg ctgtacagac tgctcataat attaacgcaa aatgtatcct ggcgtccagt 1140
atgtccggat ttacggcaag gatcgtatct aagttcaaac cggatgcaca gatcattggc 1200
ttgtctccgg atgaagcggt tgtgcgtaag atgcagcttt actggggagt gcgtccgttt 1260
aagtcacata aggcttcctc taccagagaa cttttggatg aagctacgga tatcgtactg 1320
aatgcagatc ttgcacagga gaacgacatc ctggtactga ccggaggagg tccggcagac 1380
caccgtggaa aaggcgtgac aaacatgctg aaagtagtaa aaatcggcga ataa 1434
<210> 48
<211> 477
<212> PRT
<213> 鼠李厌氧菌(Anaerostipes rhamnosivorans)
<400> 48
Met Leu Thr Lys Lys Thr Lys Ile Val Cys Thr Met Gly Pro Ala Thr
1 5 10 15
Asp Asp Asp Ala Val Leu Lys Gln Leu Met Leu Glu Gly Met Asp Ile
20 25 30
Ala Arg Leu Asn Phe Ser His Gly Asp His Glu Glu Gln Leu Gly Arg
35 40 45
Ile Lys Arg Ile Lys Arg Phe Arg Glu Glu Leu Asn Ile Pro Ile Ala
50 55 60
Ile Leu Leu Asp Thr Lys Gly Pro Glu Ile Arg Thr Gly Leu Leu Glu
65 70 75 80
Thr Asp Gly Asp Val Glu Leu Lys Glu Gly Asn Glu Phe Val Leu Thr
85 90 95
Thr Arg Asp Ile Lys Gly Asn Asp Ser Ile Val Ala Ile Thr Tyr Glu
100 105 110
Glu Leu Pro Gln Asp Val Thr Glu Gly Asn Thr Ile Leu Ile Asp Asp
115 120 125
Gly Leu Ile Glu Leu Arg Val Lys Glu Ile Lys Asp Gly Thr Asp Ile
130 135 140
Val Cys Glu Ile Val Asn Gly Gly Leu Leu Gly Ser Arg Lys Gly Val
145 150 155 160
Asn Val Pro Asn Val Arg Val Asn Leu Pro Ser Ile Thr Glu Lys Asp
165 170 175
Lys Arg Asp Ile Glu Phe Gly Leu Glu Asn Gly Ile Asp Phe Ile Ala
180 185 190
Ala Ser Phe Ile Arg Asn Ala Asp Ala Val Asn Glu Ile Lys Asp Ile
195 200 205
Val Lys Ala His Asn Met Glu Val Gly Val Ile Ser Lys Ile Glu Asn
210 215 220
Val Glu Gly Val Glu Asn Ile Glu Ser Ile Ile Gln Ala Ser Asp Gly
225 230 235 240
Ile Met Val Ala Arg Gly Asp Leu Gly Val Glu Ile Pro Ala Glu Glu
245 250 255
Val Pro Phe Met Gln Lys Ala Ile Ile Lys Lys Cys Asn Asn Ala Phe
260 265 270
Lys Pro Val Ile Thr Ala Thr Gln Met Leu Asp Ser Met Ile Arg Asn
275 280 285
Pro Arg Pro Thr Arg Ala Glu Val Thr Asp Val Ala Asn Ala Ile Tyr
290 295 300
Asp Gly Thr Asp Ala Ile Met Leu Ser Gly Glu Thr Ala Lys Gly Lys
305 310 315 320
Tyr Pro Val Glu Ala Val Arg Met Met Asn Gln Ile Ala Ile Ser Thr
325 330 335
Glu Leu His Leu Asp Thr Lys Ile Lys Asp Phe Arg Ser Ile Tyr Val
340 345 350
Ser Arg Gly Ile Ser Ala Ala Val Ala Tyr Ser Ala Val Gln Thr Ala
355 360 365
His Asn Ile Asn Ala Lys Cys Ile Leu Ala Ser Ser Met Ser Gly Phe
370 375 380
Thr Ala Arg Ile Val Ser Lys Phe Lys Pro Asp Ala Gln Ile Ile Gly
385 390 395 400
Leu Ser Pro Asp Glu Ala Val Val Arg Lys Met Gln Leu Tyr Trp Gly
405 410 415
Val Arg Pro Phe Lys Ser His Lys Ala Ser Ser Thr Arg Glu Leu Leu
420 425 430
Asp Glu Ala Thr Asp Ile Val Leu Asn Ala Asp Leu Ala Gln Glu Asn
435 440 445
Asp Ile Leu Val Leu Thr Gly Gly Gly Pro Ala Asp His Arg Gly Lys
450 455 460
Gly Val Thr Asn Met Leu Lys Val Val Lys Ile Gly Glu
465 470 475
PCT/RO/134表
Figure QDA0003570283330000011

Claims (13)

1.一种细菌，其包含允许所述细菌将肌醇转化为丙酸或其盐或酯的基因集，用于预防和/或治疗代谢综合征、胰岛素抵抗或胰岛素抵抗相关病症，其中所述基因集包含编码以下一种或多种蛋白质的基因：myo-肌醇2-脱氢酶、肌糖脱水酶、表肌醇水解酶、5-脱氧-葡萄糖醛酸异构酶、5-酮基-2-脱氧葡萄糖酸激酶、5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶、甘油醛-3-磷酸酮醇-异构酶、甘油醛-3-磷酸脱氢酶、磷酸甘油酸激酶、磷酸甘油酸变位酶、烯醇酶、丙酮酸激酶、丙酮酸-黄素氧还蛋白氧化还原酶、3-含氧酸CoA转移酶、酰基-CoA脱氢酶、烯酰-CoA水合酶、丙烯酰基-CoA脱氢酶/Etf和肌糖异构酶。
2.用于如权利要求1所述用途的细菌，其中，与当所述细菌在不存在肌醇的情况下生长时相比，当所述细菌在存在肌醇的情况下生长时，以下蛋白质的编码基因中的至少一种过表达：myo-肌醇2-脱氢酶、肌糖脱水酶、表肌醇水解酶、5-脱氧-葡萄糖醛酸异构酶、5-酮基-2-脱氧葡萄糖酸激酶、5-酮基-2-脱氧-D-葡糖酸-6磷酸醛缩酶、甘油醛-3-磷酸酮基-异构酶、甘油醛-3-磷酸脱氢酶、磷酸甘油酸激酶、磷酸甘油酸变位酶、烯醇酶、丙酮酸激酶、丙酮酸-黄素氧还蛋白氧化还原酶、3-含氧酸CoA转移酶、酰基-CoA脱氢酶、烯酰-CoA水合酶、丙烯酰基-CoA脱氢酶/Etf和肌糖异构酶。
3.用于如前述条款中任一项所述用途的细菌，其中所述用途是在预防和/或治疗胰岛素抵抗或胰岛素抵抗相关病症中。
4.用于如前述条款中任一项所述用途的细菌，其中所述胰岛素抵抗相关病症选自血脂异常、2型糖尿病和内分泌疾病中的胰岛素抵抗。
5.用于如前述条款中任一项所述用途的细菌，其中所述细菌是人肠道分离细菌。
6.用于如前述条款中任一项所述用途的细菌，其中所述细菌保藏为CBS 140182。
7.用于如前述条款中任一项所述用途的细菌，其中所述细菌被包含在进一步包含生理学上可接受的运载体的组合物中。
8.用于如条款7所述用途的细菌，其中所述组合物是食品组合物，优选乳制品，更优选发酵的乳制品，优选酸奶或酸奶饮料。
9.用于如条款7所述用途的细菌，其中所述组合物是药物组合物，优选是固体剂型，优选胶囊、片剂或粉末。
10.用于如条款7-9中任一项所述用途的细菌，其中在所述组合物中所述细菌以冻干或微囊化形式存在。
11.用于如前述条款中任一项所述用途的细菌，其中所述细菌以106至1015菌落形成单位(CFU)范围内的量存在。
12.用于如前述条款中任一项所述用途的细菌，其中所述细菌与肌醇分别给予、顺序给予或同时给予。
13.用于如前述条款中任一项所述用途的细菌，其用作益生菌。
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