数字农科院2.0

Scalable secondary metabolite production in Streptomyces using a plug-and-play system

文献类型： 外文期刊

作者： Yang, Bowen;Li, Zilong;Zhang, Jingyu;Qiu, Shiwen;Liu, Xueting;Liang, Zonglin;Yan, Hao;Zhang, Yanyan;Liu, Lihong;Xia, Bing;Bao, Lianqun;Li, Defeng;Zhou, Shanshan;Corre, Christophe;Zhang, Chengyu;Lu, Yinhua;Tan, Gao-Yi;Xia, Xuekui;Li, Shanshan;Zhang, Lixin;Wang, Weishan

作者机构：

关键词： plug-and-play; secondary metabolite; Streptomyces

期刊名称： NATURE BIOTECHNOLOGY

ISSN： 1087-0156

年卷期： 2025 年

页码：

收录情况： SCIE（2025版） ; ; EI（2025版）

摘要： Streptomyces species are producers of bioactive secondary metabolites with clinical, agricultural and biotechnological applications. To scale these strains for industrial production, a plug-and-play system that orchestrates multitarget engineering for maximizing cellular contributions to secondary metabolites is needed. Building on the discovery that distinct quorum-sensing receptors within the Streptomyces genus can recognize an identical DNA-binding site, we build a quorum-sensing-triggered promoter applicable across various Streptomyces. Integrating this promoter with a stabilizer and a multiplexer module, we develop a Streptomyces multiplexed artificial control system (SMARTS) that converts the transient signals of diverse quorum sensing into stable and multiplexed on or off outputs with varying strengths. We build a redesigned native Streptomyces avermitilis for specialized production of the nematicide baiweimectin and a de novo programmed Streptomyces venezuelae for heterologous production of the semisynthesized antitumor drug epidoxorubicin. Notably, the baiweimectin-producing strain was scaled up to a 120-m3 industrial-scale fermentation with a titer of 8.4 g L-1, underscoring the robustness of the SMARTS-based program.

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