Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces

文献类型： 外文期刊

第一作者： Chu, Liyang

作者： Chu, Liyang;Dong, Zhuoxu;Jin, Pinjiao;Ye, Lan;Wang, Xiangjing;Xiang, Wensheng;Chu, Liyang;Li, Shanshan;Dong, Zhuoxu;Zhang, Yanyan;Jin, Pinjiao;Ye, Lan;Xiang, Wensheng

作者机构：

期刊名称：MICROBIAL BIOTECHNOLOGY （ 影响因子：5.813； 五年影响因子：6.559 ）

ISSN： 1751-7915

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收录情况： SCI

摘要： Exporter engineering is a promising strategy to construct high-yield Streptomyces for natural product pharmaceuticals in industrial biotechnology. However, available exporters are scarce, due to the limited knowledge of bacterial transporters. Here, we built a workflow for exporter mining and devised a tunable plug-and-play exporter (TuPPE) module to improve the production of macrolide biopesticides in Streptomyces. Combining genome analyses and experimental confirmations, we found three ATP-binding cassette transporters that contribute to milbemycin production in Streptomyces bingchenggensis. We then optimized the expression level of target exporters for milbemycin titer optimization by designing a TuPPE module with replaceable promoters and ribosome binding sites. Finally, broader applications of the TuPPE module were implemented in industrial S. bingchenggensis BC04, Streptomyces avermitilis NEAU12 and Streptomyces cyaneogriseus NMWT1, which led to optimal titer improvement of milbemycin A3/A4, avermectin B-1a and nemadectin alpha by 24.2%, 53.0% and 41.0%, respectively. Our work provides useful exporters and a convenient TuPPE module for titer improvement of macrolide biopesticides in Streptomyces. More importantly, the feasible exporter mining workflow developed here might shed light on widespread applications of exporter engineering in Streptomyces to boost the production of other secondary metabolites.

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