红霉糖多孢菌转录因子PhoP调控网络构建及其参与红霉素合成代谢调控的研究

项目名称： 红霉糖多孢菌转录因子PhoP调控网络构建及其参与红霉素合成代谢调控的研究

项目编号： No.21276079

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 化学工业

项目作者： 叶邦策

作者单位： 华东理工大学

项目金额： 80万元

中文摘要： 通过红霉糖多孢菌高产菌株的基因组测序及发酵过程比较转录组研究，我们发现磷代谢调控因子PhoP在细胞内碳氮磷等营养组份代谢平衡、应激响应及其红霉素合成代谢调控中可能有重要作用。本课题利用生物信息学工具全基因组搜寻Pho-Box结合序列，phoP基因敲除及转录组差异分析等方法确定PhoP调节组及调控网络，探讨PhoP通过GlnR介导调控氮代谢基因转录作用及细胞内氮-磷营养平衡调控及应激机制，鉴定PhoP参与抗生素合成代谢调控的介导蛋白，阐明红霉素合成调控机理并设计相应的代谢工程策略，初步探讨基于PhoP调控机制的菌种改造及发酵工艺优化方法，提高红霉素发酵菌种改良及过程优化效率。

中文关键词： 红霉素合成；营养感知调控蛋白；转录调控；磷代谢；氮代谢

英文摘要： Saccharopolyspora erythraea is a Gram-positive filamentous bacterium used for the industrial-scale production of erythromycin A which is of high clinical importance. To elucidate the mechanisms underlying erythromycin biosynthesis, we sequenced the whole genome of a high-producing strain (E3) obtained by random mutagenesis and screening from the wide-type strain NRRL23338, and compared E3 with NRRL23338 at both the genomic level and the transcriptomic level. We observed that global phosphate regulator PhoP maybe play an important role in phosphate-nitrogen nutrition stress responses and secondary metabolism in S. erythraea. In this study, we will identify the PhoP regulon by using bioinformatics, phoP mutation, and comparative transcriptomic analysis, and also identify the regulators (including their target genes) mediating phosphate, nitrogen metabolism and erythromycin biosynthesis. We further will build and confirm the regulatory network of PhoP-GlnR-AfsR to elucidate the precise mechanisms underlying the erythromycin biosynthesis in S. erythraea.

英文关键词： erythromycin biosybthesis；nutrient-sensing regulator；transcriptional regulation；phosphate metabolism；nitrogen metabolism