文献类型： 外文期刊

作者： Chen, Qiong ¹ ; Zhu, Jianya ³ ; Li, Xingwang ¹ ; Wen, Ying ¹ ;

作者机构： 1.China Agr Univ, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China

2.China Agr Univ, Coll Biol Sci, Beijing 100193, Peoples R China

3.Beijing Acad Agr & Forestry Sci, Inst Fisheries Res, Beijing 100068, Peoples R China

关键词： Streptomyces roseosporus; daptomycin; morphological development; DasR; AdpA

期刊名称：ANTIBIOTICS-BASEL （ 影响因子：5.222； 五年影响因子：5.396 ）

ISSN： 2079-6382

年卷期： 2022 年 11 卷 8 期

页码：

收录情况： SCI

摘要： Daptomycin, produced by Streptomyces roseosporus, is a clinically important cyclic lipopeptide antibiotic used for the treatment of human infections caused by drug-resistant Gram-positive pathogens. In contrast to most Streptomyces antibiotic biosynthetic gene clusters (BGCs), daptomycin BGC has no cluster-situated regulator (CSR) genes. DasR, a GntR-family transcriptional regulator (TR) widely present in the genus, was shown to regulate antibiotic production in model species S. coelicolor by binding to promoter regions of CSR genes. New findings reported here reveal that DasR pleiotropically regulates production of daptomycin and reddish pigment, and morphological development in S. roseosporus. dasR deletion enhanced daptomycin production and morphological development, but reduced pigment production. DasR inhibited daptomycin production by directly repressing dpt structural genes and global regulatory gene adpA (whose product AdpA protein activates daptomycin production and morphological development). DasR-protected regions on dptEp and adpAp contained a 16 nt sequence similar to the consensus DasR-binding site dre in S. coelicolor. AdpA was shown to target dpt structural genes and dptR2 (which encodes a DeoR-family TR required for daptomycin production). A 10 nt sequence similar to the consensus AdpA-binding site was found on target promoter regions dptAp and dptR2p. This is the first demonstration that DasR regulates antibiotic production both directly and through a cascade mechanism. The findings expand our limited knowledge of the regulatory network underlying daptomycin production, and will facilitate methods for construction of daptomycin overproducers.