文献类型：期刊文献

英文题名：Transcriptional regulation of a leucine-responsive regulatory protein for directly controlling lincomycin biosynthesis in Streptomyces lincolnensis

作者：Xu, Yurong[1,2];Tang, Yaqian[1];Wang, Nian[1];Liu, Jing[1];Cai, Xinlu[1];Cai, Hongyi[1];Li, Jie[1];Tan, Guoqing[1];Liu, Ruihua[3];Bai, Linquan[5];Zhang, Lixin[1,4];Wu, Hang[1];Zhang, Buchang[1]

机构：[1]Anhui Univ, Sch Life Sci, Inst Phys Sci & Informat Technol, Hefei 230601, Peoples R China;[2]Hefei Normal Univ, Dept Chem & Chem Engn, Hefei 230601, Peoples R China;[3]Xinyu Pharmaceut Co Ltd, Suzhou 234000, Peoples R China;[4]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[5]Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai 200240, Peoples R China

年份：2020

卷号：104

期号：6

起止页码：2575

外文期刊名：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY

收录：;EI(收录号：20200508104869);WOS:【SCI-EXPANDED(收录号:WOS:000517127300024)】；

语种：英文

外文关键词：Leucine-responsive regulatory protein; Metabolic regulation; Streptomyces lincolnensis; Lincomycin; Transcriptional activator

摘要：Leucine-responsive regulatory proteins (Lrps) are a family of transcription factors involved in diverse biological processes in bacteria. So far, molecular mechanism of Lrps for regulating antibiotics biosynthesis in actinomycetes remains largely unexplored. This study, for the first time in Streptomyces lincolnensis, identified an Lrp (named as SLCG_Lrp) associated with lincomycin production. SLCG_Lrp was validated to be a positive regulator for lincomycin biosynthesis by directly stimulating transcription of two structural genes (lmbA and lmbV), three resistance genes (lmrA, lmrB and lmrC), and a regulatory gene (lmbU) within the lincomycin biosynthetic gene (lin) cluster. SLCG_Lrp was transcriptionally self-inhibited and triggered the expression of its adjacent gene SLCG_3127 encoding a LysE superfamily protein. Further, the binding site of SLCG_Lrp in the intergenic region of SLCG_3127 and SLCG_Lrp was precisely identified. Inactivation of SLCG_3127 in S. lincolnensis resulted in yield improvement of lincomycin, which was caused by intracellular accumulation of proline and cysteine. Arginine and phenylalanine were identified as specific regulatory ligands, respectively, to reduce and promote DNA-binding affinity of SLCG_Lrp. We further found that SLCG_Lrp was directly repressed by SLCG_2919, the first identified transcription factor outside lin cluster for lincomycin production. Therefore, our findings revealed SLCG_Lrp-mediated transcriptional regulation of lincomycin biosynthesis. This study extends the understanding of molecular mechanisms underlying lincomycin biosynthetic regulation.