TetR家族蛋白，SCO3201，在天蓝色链霉菌和变铅青链霉菌中下游调控靶基因的鉴定及功能分析

项目名称： TetR家族蛋白，SCO3201，在天蓝色链霉菌和变铅青链霉菌中下游调控靶基因的鉴定及功能分析

项目编号： No.31300046

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 许德麟

作者单位： 暨南大学

项目金额： 25万元

中文摘要： TetR家族转录调控因子SCO3201的过量表达对天蓝色链霉菌的抗生素生产及孢子形成均产生强烈的抑制作用，而对与天蓝色链霉菌有很近亲缘关系的变铅青链霉菌却没有明显的作用。本课题以此现象为基础，计划在二宿主中分别鉴定SCO3201的调控靶基因，并逐一分析靶基因在各自宿主中对抗生素生产及形态分化的作用；分析SCO3201在靶基因启动子区域准确的结合位点；明确SCO3201在胞内对各靶基因转录的调控作用；对比解析SCO3201在天蓝色链霉菌及变铅青链霉菌二宿主中靶基因身份，功能，调控应答等的异同。预期取得的研究成果，不仅可以更全面的鉴明链霉菌次级代谢及形态分化的调控网络，而且还可以为进一步揭示和完善天蓝色链霉菌及变铅青链霉菌抗生素生产调控网络的差异提供支持，解析基因沉默的分子机理，以便日后将模式菌株沉默基因的研究经验应用于急需抗生素的激活与利用上。

中文关键词： 链霉菌；次级代谢；形态分化；抗生素；转录调控

英文摘要： Streptomyces coelicolor and Streptomyces lividans are two model strains of great interest to study the regulation of antibiotic biosynthesis. Indeed, the two strains contain the same functional biosynthetic pathways for secondary metabolites biosynthesis but the latter are weakly expressed in S. lividans and strongly expressed in S. coelicolor. The genomes of these two species include 151 regulators of the TetR family and we have previously demonstrated that the over-expression of one of them (SCO3201) totally switch off the antibiotic production and sporulation in S. coelicolor, but not in S. lividans. The main goal of this study is to identify the downstream regulatory target genes of SCO3201 in S. coelicolor and S. lividans, and to assess their involvement in the antibiotic production. This work is expected to lead a better understanding of the regulatory circuit controlling antibiotic production in Streptomyces lividans and Streptomyces coelicolor, and might allow the identification of the genetic changes underlying the drastically different capabilities of these two strains to produce antibiotic. This understanding should open the possibility, in the future, to transform each Streptomyces strain to S. coelicolor-like over-producing strain by appropriate genetic engineering strategies and thus facilitate the

英文关键词： Streptomyces；secondary metabolism；morphological differetiation；antibiotics；transcriptional regulation