新型抗生素Bagremycins生物合成基因簇的鉴定与解析

项目名称： 新型抗生素Bagremycins生物合成基因簇的鉴定与解析

项目编号： No.31200026

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 微生物学、植物学

项目作者： 叶江

作者单位： 华东理工大学

项目金额： 22万元

中文摘要： 细菌对抗生素日趋严重的耐药性促使人们采用组合生物合成和代谢途径工程策略获得具有新结构和新活性的抗生素，而新型抗生素的筛选及其生物合成机制的揭示将为这些策略的实施提供丰富的物质资源和信息资源。本项目以新型抗生素bagremycins生物合成机制为研究对象，前期工作已经克隆了七个成簇排列的基因，借助基因敲除手段初步确定了其中有四个基因与bagremycins生物合成相关。在此基础上，本项目拟进一步分离、克隆并鉴定bagremycins生物合成全基因簇，调查关键基因、调控基因和抗性基因的功能和作用机理，揭示其生物合成途径及基因表达调控机制，拓展新型天然次级代谢产物合成机制的认识，为其结构优化或利用组合生物合成策略设计更优的抗生素奠定理论基础。

中文关键词： Bagremycins；生物合成基因簇；基因缺失；基因功能；基因表达调控

英文摘要： More antibiotics with new structure and new function have been found by the means of using combinatorial biosynthesis and metabolic pathway engineering strategies so as to respond totheincreasing bacterial resistance to antibiotics. The screening of the new antibiotics and the reveal of the biosynthesis mechanisms will provide abundant material and informational resource for the enforcement of these strategies. Our project take the biosynthetic mechanism of bagremycins as the subject of study and we have already cloned seven genes arranged in a cluster and determined that four genes are related to the biosynthesis of bagremycins. Based on the preliminary work, we are going to further clone and character the whole biosynthetic gene cluster in order to investigate the function and interaction mechanisms of the key genes, regulator genes and resistance genes, clarify its biosynthetic pathway and regulation mechanism of gene expression, and expand the knowledge of synthetic mechanism of novel natural secondary metabolite, which provide the theory foundation for the structural optimization of the antibiotics or obtain more excellent antibiotics by the ways of combinatorial biosynthesis strategy.

英文关键词： Bagremycins；biosynthetic gene cluster；gene deletion；gene function；gene expression regulation