文献类型：期刊文献

英文题名：AdpAlin, a Pleiotropic Transcriptional Regulator, Is Involved in the Cascade Regulation of Lincomycin Biosynthesis in Streptomyces lincolnensis

作者：Kang, Yajing[1];Wang, Yingying[1];Hou, Bingbing[1,2];Wang, Ruida[1];Ye, Jiang[2];Zhu, Xiaoyu[1];Wu, Haizhen[1,2];Zhang, Huizhan[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Dept Appl Biol, Shanghai, Peoples R China

年份：2019

卷号：10

外文期刊名：FRONTIERS IN MICROBIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000497438100001)】；

基金：This study was supported by the National Natural Science Foundation of China (NSFC) (31900059), the China Postdoctoral Science Foundation (2019M650079), and the Research Program of State Key Laboratory of Bioreactor Engineering.

语种：英文

外文关键词：AdpA; lincomycin; Streptomyces lincolnensis; transcriptional regulator; cascade regulation

摘要：Lincomycin is one of the most important antibiotics in clinical practice. To further understand the regulatory mechanism on lincomycin biosynthesis, we investigated a pleiotropic transcriptional regulator AdpA(lin) in the lincomycin producer Streptomyces lincolnensis NRRL 2936. Deletion of adpA(lin) (which generated Delta adpA(lin)) interrupted lincomycin biosynthesis and impaired the morphological differentiation. We also found that putative AdpA binding sites were unusually scattered in the promoters of all the 8 putative operons in the lincomycin biosynthetic gene cluster (BGC). In Delta adpA(lin), transcript levels of structural genes in 8 putative operons were decreased with varying degrees, and electrophoretic mobility shift assays (EMSAs) confirmed that AdpA(lin) activated the overall putative operons via directly binding to their promoter regions. Thus, we speculated that the entire lincomycin biosynthesis is under the control of AdpA(lin). Besides, AdpA(lin) participated in lincomycin biosynthesis by binding to the promoter of lmbU which encoded a cluster sited regulator (CSR) LmbU of lincomycin biosynthesis. Results of qRT-PCR and catechol dioxygenase activity assay showed that AdpA(lin) activated the transcription of lmbU. In addition, AdpA(lin) activated the transcription of the bldA by binding to its promoter, suggesting that AdpA(lin) indirectly participated in lincomycin biosynthesis and morphological differentiation. Uncommon but understandable, AdpA(lin) auto-activated its own transcription via binding to its own promoter region. In conclusion, we provided a molecular mechanism around the effect of AdpA(lin) on lincomycin biosynthesis in S. lincolnensis, and revealed a cascade regulation of lincomycin biosynthesis by AdpA(lin), LmbU, and BldA.