wblA, a pleiotropic regulatory gene modulating morphogenesis and daptomycin production in Streptomyces roseosporus

被引:34
|
作者
Huang, X. [1 ]
Ma, T. [1 ]
Tian, J. [1 ]
Shen, L. [1 ]
Zuo, H. [1 ]
Hu, C. [1 ]
Liao, G. [1 ]
机构
[1] Southwest Univ, Inst Modern Biopharmaceut, Sch Pharmaceut Sci, Chongqing 400715, Peoples R China
基金
中国国家自然科学基金;
关键词
antibiotics; metabolism; streptococci; streptomycetes; transcriptional regulation; FAMILY TRANSCRIPTIONAL REGULATOR; MORPHOLOGICAL-DIFFERENTIATION; BIOSYNTHESIS; CLUSTER; WHIB; AVERMITILIS; AVERMECTIN; PATHWAY; CLONING; ACID;
D O I
10.1111/jam.13512
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
AimsThe wblA gene, encoding a homologue of the WhiB family protein, was identified in the sequenced genome of daptomycin producer Streptomyces roseosporus. To explore the function of wblA, we construct wblA disruption strains, complemented strains and overexpression strains to test whether it can affect the production of secondary metabolites and morphogenesis. Methods and ResultsWe constructed disruption strains by homologous recombination in S. roseosporus. The disruption mutant of wblA could block aerial mycelium sporulation and enhance the production of daptomycin by 51%. In contrast, overexpression of wblA resulted in significantly decreased the yield of daptomycin. In agreement with it, the transcription of key daptomycin regulatory genes atrA, dptR2 and dptR3 and structural gene dptE remarkably increased in the wblA disruption mutant. ConclusionswblA plays a key role in control of daptomycin biosynthesis and is essential for sporulation. The disruption of wblA could accumulate the transcription level of some key genes involving in daptomycin biosynthesis. Significance and Impact of the StudyDaptomycin is an important antibiotic with potent activity against a variety of Gram-positive pathogens. This study demonstrates that valuable improvement in the yield of daptomycin can be achieved through modulating the expression of wblA transcription regulator.
引用
收藏
页码:669 / 677
页数:9
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