文献类型：期刊文献

英文题名：The protocatechuic acid catabolism regulator PcaV inhibits lincomycin biosynthesis either directly or indirectly through the control of the expression of other regulatory or metabolic genes

作者：Zhou, Tianyu[1,2];Wang, Ruida[1,2,3,4];Jiang, Wenli[1,2];Zhao, Jiaqi;Ye, Jiang;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;[4]Tarim Univ, State Key Lab Incubat Base Conservat & Utilizat Bi, Alar 843300, Peoples R China

年份：2025

卷号：311

外文期刊名：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

收录：;EI(收录号：20251818330903);WOS:【SCI-EXPANDED(收录号:WOS:001494349100001)】；

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; Metabolism regulation; Lincomycin biosynthesis; Transcriptional regulator; Protocatechuic acid catabolism

摘要：Lincomycin, synthesized by Streptomyces lincolnensis, is extensively utilized in clinical settings to treat infections caused by Gram-positive pathogenic bacteria. Understanding the regulatory mechanism of lincomycin biosynthesis is crucial for improving its production. This study identified PcaV, a conserved regulator of protocatechuic acid catabolic genes, as a repressor of lincomycin biosynthesis. Knocking out the pcaV gene enhanced lincomycin production by up to 9.8-fold, and slowed cellular growth. Quantitative real-time PCR and electrophoretic mobility shift assays reconfirmed that PcaV binds to two 12-bp sites within a bidirectional promoter, repressing the expression of the pcaV gene and the pcaIJFHGBL operon. The pcaIJFHGBL operon, in turn, promoted lincomycin biosynthesis. Besides, PcaV directly represses the expression of lmbA, lmbV, lmbW, lmrA, and lmrC from the lincomycin biosynthesis gene cluster, thereby inhibiting lincomycin biosynthesis. It also directly activates the expression of adpA, aflQ1, bldD, glnR, lcbR1, and ramR, known regulators of lincomycin biosynthesis. Additionally, PcaV influences the expression of genes related to phosphorus metabolism, the shikimate pathway, sulfur metabolism, protocatechuic acid anabolism, amino acid metabolism, and nitrogen metabolism, indirectly impacting lincomycin production. This study thus broadens PcaV's regulon and redefines it as a novel pleiotropic regulator and a promising target for engineering antibiotic-producing strains.