文献类型：期刊文献

英文题名：MarR family regulator LcbR2 activates lincomycin biosynthesis in multiple ways

作者：Wang, Ruida[1,2,3];Chen, Lei[1,2];Zhao, Jiaqi[1,2];Gao, Yu[1,2];Zhou, Tianyu[1,2];Ye, Jiang[1];Wu, Haizhen[1,2];Zhang, Huizhan[1]

机构：[1]East China Univ Sci & Technol, Sch Biotechnol, Dept Appl Biol, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Tarim Univ, Coll Life Sci & Technol, Alar 843300, Peoples R China

年份：2025

卷号：300

外文期刊名：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

收录：;EI(收录号：20250417765652);WOS:【SCI-EXPANDED(收录号:WOS:001413119100001)】；

基金：This work was supported by the National Natural Science Foundation of China (NSFC) (42406126) and the National Key Research and Development Program of China (2021YFC2100600) .

语种：英文

外文关键词：Streptomyces lincolnensis; LcbR2; MarR family; Lincomycin biosynthesis; Transcriptional regulator

摘要：Lincomycin, produced by the actinomycete Streptomyces lincolnensis, is highly effective against Gram-positive bacteria and protozoans, making it widely used in clinical settings. This study identified LcbR2, a MarR family transcriptional regulator, as an activator of lincomycin biosynthesis. Knocking out the lcbR2 gene reduced lincomycin production by 63.0 % without affecting growth or morphology. Quantitative real-time PCR, electrophoretic mobility shift assays, and XylE reporter assays demonstrated that LcbR2 binds to a 13-bp imperfect palindromic sequence-TTGCCnnnnnCAA-, repressing the expression of lcbR2 Further analysis revealed that LcbR2 directly activates the expression of lincomycin biosynthesis genes (lmbD, lmbJ, lmbK, lmbV, and lmbW), enhancing lincomycin production. It also regulates lincomycin resistance genes (lmrA and lmrB), increasing the self-tolerance of S. lincolnensis to lincomycin. Additionally, LcbR2 modulates other regulatory genes (lmbU, adpA, aflQ1, bldD, and lcbR1), affecting lincomycin production in a cascade manner. LcbR2 also influences the expression of genes related to carbon, nitrogen, phosphorus, and sulfur metabolism, indirectly impacting lincomycin production. Moreover, the binding of LcbR2 to DNA can be attenuated by apramycin. This study thus characterized LcbR2 as a novel transcriptional regulator with a broad regulatory scope.