数字农科院2.0

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

文献类型： 外文期刊

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

作者机构：

关键词： ActK/R-KelR regulatory cascade;High-yielding strategies;Secondary metabolites;Streptomyces bingchenggensis;WhiDsbh

期刊名称： World Journal of Microbiology and Biotechnology

ISSN： 0959-3993

年卷期： 2025 年 41 卷 5 期

页码：

收录情况： SCIE（2025版） ; ; EI（2025版）

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, WhiDsbh, in modulating SM production in Streptomyces bingchenggensis BC04. Overexpression of whiDsbh 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 whiDsbh overexpression strain and BC04 revealed that whiDsbh 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 whiDsbh 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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