文献类型：期刊文献

英文题名：Scalable secondary metabolite production in Streptomyces using a plug-and-play system

作者：Yang, Bowen[1,2,3];Li, Zilong[3,4];Zhang, Jingyu[1,2];Qiu, Shiwen[3];Liu, Xueting[1,2];Liang, Zonglin[3];Yan, Hao[3];Zhang, Yanyan[5];Liu, Lihong[6];Xia, Bing[6];Bao, Lianqun[6];Li, Defeng[3];Zhou, Shanshan[3];Corre, Christophe[7];Zhang, Chengyu[1,2,3];Lu, Yinhua[8];Tan, Gao-Yi[1,2];Xia, Xuekui[9];Li, Shanshan[5];Zhang, Lixin[1,2,10];Wang, Weishan[1,2,3,4,11]

机构：[1]East China Univ Sci & Technol ECUST, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]East China Univ Sci & Technol ECUST, Sch Biotechnol, Shanghai, Peoples R China;[3]Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Divers & Innovat Utilizat, Beijing, Peoples R China;[4]Beijing Key Lab Genet Element Biosourcing & Intell, Beijing, Peoples R China;[5]Chinese Acad Agr Sci, Inst Plant Protect, State Key Lab Biol Plant Dis & Insect Pests, Beijing, Peoples R China;[6]Hebei Xingbai Agrochem Grp Co Ltd, Shijiazhuang, Peoples R China;[7]Univ Warwick, Sch Life Sci, Coventry, England;[8]Shanghai Normal Univ, Coll Life Sci, Shanghai, Peoples R China;[9]Qilu Univ Technol, Shandong Acad Sci, Biol Inst, Jinan, Peoples R China;[10]Shanghai Collaborat Innovat Ctr Biomfg Technol SCI, Shanghai, Peoples R China;[11]Univ Chinese Acad Sci, Beijing, Peoples R China

年份：2025

外文期刊名：NATURE BIOTECHNOLOGY

收录：;EI(收录号：20253419006244);WOS:【SCI-EXPANDED(收录号:WOS:001550327400001)】；

基金：This work was supported by the National Natural Science Foundation of China (W2411016 and 32170095 to W.W. and 32121005 and 32327801 to L.Z.), the National Key Research and Development Program of China (2020YFA0907800 to L.Z. and 2022YFC2105400 to C.Z.), the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences (CAAS-CSCB-202401 to S.L.), the Youth Innovation Promotion Association CAS (Y202027 to W.W.) and the 111 Project (B18022 to L.Z). We would like to thank Z. Fan, G. Ai, E. Li and T. Zhao from IMCAS for the BLI assay, LC-MS/MS analysis, UPLC-MS analysis and flow cytometry assay, respectively.

语种：英文

外文关键词：Biomolecules - Strain

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.