地中海拟无枝酸菌“硝酸盐效应”的研究进展  

“Nitrate stimulating effect” in Amycolatopsis mediterranei——from discovery to mechanistic studies

作　　者：邵志会 赵维 王颖 丁晓明[2] 王金 姜卫红 赵国屏[1,2] 

机构地区：[1]中闰科学院植物生理生态研究所合成生物学重点实验室,上海200032 [2]复旦大学生命科学学院微生物学和微生物工程系,上海200438

出　　处：《生物工程学报》2015年第6期845-856,共12页Chinese Journal of Biotechnology

基　　金：国家重点基础研究发展计划(973计划)(No.2012CB721102);国家自然科学基金(Nos.31200021,31121001,31300031)资助~~

摘　　要：地中海拟无枝酸菌"硝酸盐效应"是指发酵基质中的硝酸盐在一定浓度下大幅度促进该菌合成利福霉素,并对初级代谢产生多种影响的现象。针对该效应,本实验室开展了多年的研究,阐明硝酸盐主要通过两个方面促进利福霉素的生物合成:一方面,硝酸盐增加利福霉素生物合成前体的供给(如UDP-葡萄糖、AHBA、丙二酰Co A以及甲基丙二酰Co A等),尤其是通过抑制体内脂肪酸的合成来保障利福霉素前体丙二酰Co A的供给;另一方面,硝酸盐提升利福霉素生物合成酶基因的表达。因此,在充足的利福霉素前体和合成酶系的协同效应下,菌体生成大量的利福霉素。进一步的工作将围绕"硝酸盐效应"的信号分子、信号转导途径以及相关基因的表达调控和翻译后修饰机制等方面展开。Nitrate not only remarkably stimulates the rifamycinbiosynthesis in Amycolatopsismediterranei, but also influences the primary metabolisms, including the inhibition of fatty acids biosynthesis in the bacterial. This phenomenon has been designated as ＂Nitrate Stimulating Effect＂by the late Prof. J.S. Chiaosince its discovery in the 1970’s, and has been found in many other antibiotics-producing actinomycetes subsequently. Based on the research in his laboratory, we have revealed that the nitrate stimulation effect mainly manifests in two aspects over the last two decades. First, nitrate promotes the supply of rifamycin precursors, e.g., UDP-glucose, AHBA, malonyl-Co A and methylmalonyl-Co A. Specifically, the biosynthesis of fatty acids is inhibited by nitrate consequently the acetyl-Co A is shunted into malonyl-Co A. Second, nitrate facilitates the expression of genes in the rifclulsterthat encodes rifamycin biosynthetic enzymes. Following our current understanding, the future research will focus on the signals, the signal transduction pathway and the molecular mechanisms that dictate nitrate-mediated transcriptional and post-translational regulations.

关 键 词：放线菌 地中海拟无枝酸菌 硝酸盐 利福霉素 氮调控 

分 类 号：Q935[生物学—微生物学]