放线紫红素在其产生菌天蓝色链霉菌A3(2)中的生物学功能

Antibiotics are produced as secondary metabolites by microorganisms. Their biological functions in other microorganisms, especially pathogens, have been extensively studied and reported. It has also been reported that, as small molecules, antibiotics act as signaling molecules to regulate the growth and gene expression of antibiotic-producing bacteria themselves. However, the physiological and regulatory roles of antibiotics in antibiotic-producing bacteria have not been widely studied. In this project, we aim at studying the physiological effects and regulatory mechanisms of actinorhodin on its producing bacterium Streptomyces coelicolor through genetic, biochemistry, and chemical approaches. Specifically, we will study how the lack of actinorhodin affects the growth and development of Streptomyces coelicolor by knocking out the actinorhodin biosynthetic genes. We will also identify the genes and proteins regulated by the actinorhodin through transcriptomic and proteomic analysis. On this basis, the object of this project is to identify the specific binding ligands of actinorhodin and reveal the regulatory mechanism of actinorhodin on its producing bacteria. The findings of this study will have impact on building high-yielding strains of antibiotic producers to improve antibiotic production. The discovery of antibiotics specific ligands can lead to the finding of specific antibiotic targets.

抗生素作为微生物产生的次级代谢产物，对其他微生物的生物学功能已经被广泛深入的研究和报道。作为小分子代谢物，抗生素也作为信号分子对于其产生菌存在着某些重要的生理作用和影响。但是抗生素对产生菌本身的生理作用和调控作用尚未见广泛报道。本项目在功能基因组学研究基础上，通过遗传学、生物化学、化学等手段阐明放线紫红素对其产生菌天蓝色链霉菌的生理作用和作用机理。通过抗生素合成关键基因的敲除，着重研究放线紫红素缺失对其产生菌生长发育的影响；通过全基因组芯片和蛋白质组学的研究发现受放线紫红素正负调控的基因或蛋白质。在此基础上，利用同位素标记抗生素与异源表达调控蛋白结合，获取与放线紫红素特异性结合的蛋白，并揭示放线紫红素对其产生菌的作用途径。抗生素对其产生菌的生理作用的研究对构建更为优良的抗生素高产菌株具有很好的实际指导意义。抗生素作用靶点的发现可以为其特异药靶的寻找提供借鉴。

本项目在功能基因组学研究基础上，通过遗传学、生物化学、化学等手段阐明放线紫红素对其产生菌天蓝色链霉菌的生理作用和作用机理。通过抗生素合成关键基因的敲除，着重研究放线紫红素缺失对其产生菌生长发育的影响；通过全基因组芯片和蛋白质组学的研究发现受放线紫红素正负调控的基因或蛋白质。在此基础上，利用同位素标记抗生素与异源表达调控蛋白结合，获取与放线紫红素特异性结合的蛋白，并揭示放线紫红素对其产生菌的作用途径。同时还对阿维菌素对其产生菌的生理调控作用、井冈霉素生物合成调控、林可霉素的硝酸盐效应等调控机制进行了深入解析。