hfq和rpoS调控粘质沙雷氏菌灵菌红素合成与逆境适应的分子机制

灵菌红素是粘质沙雷氏菌合成的主要次级代谢产物。因其具有对癌细胞的高度特异性和正常细胞低毒性成为一种非常有潜力的抗癌物质。但关于灵菌红素对于粘质沙雷氏菌的作用和意义，特别是在逆境胁迫下菌种产灵菌红素的退化与逆境适应的机制尚缺乏研究。本课题前期获得了一株高产灵菌红素的粘质沙雷氏菌（红色），并且分别获得了该菌株在不同氮源和长期饥饿胁迫下的突变株（白色）。通过对野生株和突变株的全基因组测序，发现可能分别是rpoS和hfq突变所致。本课题拟通过对rpoS和hfq基因的敲除和回补确定其对于灵菌红素合成的调控以及逆境适应的作用机制。并利用筛选获得的合作株（胁迫处理后仍有野生表型菌株）与欺骗株（缺失突变的白色菌株），探索合作株的“谨慎”代谢与欺骗株的生长优势和节能特性在促进粘质沙雷氏菌种群稳定的作用机制。揭示rpoS和hfq在调控种群适应性进化以及灵菌红素合成中的作用。

Prodigiosin is the main secondary metabolite of Serratia marcescens. Because of its high specificity to cancer cells and low toxicity to normal cells, it has become a very potential anticancer substance. However, the role and significance of prodigiosin in Serratia marcescens, especially the relationship between the reduction of prodigiosin and the adaptation to adversity, are still lacking. In the early stage of this project, a strain of Serratia marcescens (red) with high production of prodigiosin was obtained, and the mutant strains (white) under different nitrogen sources and long-term starvation stress were isolated respectively. Through sequencing the whole genome of wild strains and mutant strains, it was found that they may be caused by rpoS and hfq mutations, respectively. We intend to determine the mechanism of their regulation of prodigiosin synthesis and adversity adaptation by knocking out and supplementing the rpoS and hfq genes. The mechanism of "cautious" metabolism of the cooperative strain and the growth advantage and energy-saving characteristics of the cheating strain in promoting the stability of Serratia marcescens population was explored by using the cooperative strain (the wild phenotype strain still exists after stress treatment) and the cheating strain (the white strain). We want to explore the role of rpoS and hfq in the regulation of adaptive evolution of population and the synthesis of prodigiosin.