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Overexpression of the Wbl family regulator whiDsbh modulates secondary metabolite biosynthesis in Streptomyces

文献类型： 外文期刊

作者： Zhang, Xuedong 1 ; Wang, Jiabin 1 ; Shi, Haoran 1 ; Zhou, Na 2 ; Li, Shanshan 2 ; Ye, Lan 1 ; Xiang, Wensheng 1 ; Wang, Xiangjing 1 ; Zhang, Yanyan 2 ;

作者机构： 1.Northeast Agr Univ, Key Lab Agr Microbiol Heilongjiang Prov, Harbin 150030, Peoples R China

2.Chinese Acad Agr Sci, Inst Plant Protect, State Key Lab Biol Plant Dis & Insect Pests, Beijing 100193, Peoples R China

关键词： WhiD(sbh); Secondary metabolites; Streptomyces bingchenggensis; ActK/R-KelR regulatory cascade; High-yielding strategies

期刊名称：WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY （ 影响因子：4.2； 五年影响因子：4.6 ）

ISSN： 0959-3993

年卷期： 2025 年 41 卷 5 期

页码：

收录情况： SCI

摘要： Streptomyces species are prolific producers of a diverse array of bioactive secondary metabolites (SMs), which constitute approximately two-thirds of natural product-based pharmaceuticals with significant clinical, agricultural, and biotechnological applications. However, the regulatory mechanisms underlying the biosynthesis of these compounds remain poorly understood, impeding the development of high-yielding strains for industrial production. Herein, we investigated the role of the WhiB-like (Wbl) family transcriptional regulator, WhiD(sbh), in modulating SM production in Streptomyces bingchenggensis BC04. Overexpression of whiD(sbh) in BC04 significantly suppressed milbemycin production by repressing the transcription of the milbemycin biosynthetic gene cluster via the ActK/R-KelR regulatory cascade. Comparative transcriptomic analysis between the whiD(sbh) overexpression strain and BC04 revealed that whiD(sbh) overexpression not only altered the expression of multiple other biosynthetic gene clusters but also impacted genes involved in central carbon metabolism, glutathione biosynthesis, and cofactor synthesis. Furthermore, cross-species genetic analysis demonstrated that whiD(sbh) overexpression enhanced actinorhodin production in Streptomyces coelicolor and avermectin production in Streptomyces avermitilis, while inhibiting the biosynthesis of nemadectin and guvermectin in Streptomyces cyaneogriseus ssp. noncyanogenus and Streptomyces caniferus, respectively. These results expanded our understanding of the regulatory networks controlling SM biosynthesis in Streptomyces and provided beneficial regulatory targets for developing strategies to optimize SM yield.

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