A previously unidentified sugar transporter for engineering of high-yield Streptomyces

文献类型： 外文期刊

第一作者： Dong, Zhuoxu

作者： Dong, Zhuoxu;Li, Lei;Wang, Xiangjing;Li, Shanshan;Xiang, Wensheng;Dong, Zhuoxu;Li, Lei;Du, Guozhong;Zhang, Yanyan;Li, Shanshan;Xiang, Wensheng

作者机构：

关键词： Sugar transporter; Transporter engineering; Streptomyces; Strain engineering; Titer improvement

期刊名称：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY （ 影响因子：3.9； 五年影响因子：4.9 ）

ISSN： 0175-7598

年卷期： 2024 年 108 卷 1 期

页码：

收录情况： SCI

摘要： Sugar transporters have significant contributions to regulate metabolic flux towards products and they are general potential targets for engineering of high-yield microbial cell factories. Streptomyces, well-known producers of natural product pharmaceuticals, contain an abundance of sugar transporters, while few of them are well characterized and applied. Here, we report a previously unidentified ATP-binding cassette (ABC) sugar transporter TP6568 found within a Streptomyces avermitilis transposon library, along with its key regulator GM006564. Subsequent in silico molecular docking and genetic experiments demonstrated that TP6568 possessed a broad substrate specificity. It could not only promote uptake of diverse monosaccharides and disaccharides, but also enhance the utilization of industrial carbon sources such as starch, sucrose, and dextrin. Constitutive overexpression of TP6568 resulted in decrease of residual total sugar by 36.16%, 39.04%, 38.40%, and 30.21% in engineered S. avermitilis S0, Streptomyces caniferus NEAU6, Streptomyces bingchenggensis BC-101-4, and Streptomyces roseosporus NRRL 11379 than their individual parent strain, respectively. Production of avermectin B-1a, guvermectin, and milbemycin A3/A4 increased by 75.61%, 56.89%, and 41.13%, respectively. We then overexpressed TP6568 in combination with the regulator GM006564 in a high-yield strain S. avermitilis S45, and further fine-tuning of their overexpression levels boosted production of avermectin B-1a by 50.97% to 7.02 g/L in the engineering strain. Our work demonstrates that TP6568 as a promising sugar transporter may have broad applications in construction of high-yield Streptomyces microbial cell factories for desirable natural product pharmaceuticals.

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[1]A previously unidentified sugar transporter for engineering of high-yield Streptomyces. Dong, Zhuoxu,Li, Lei,Wang, Xiangjing,Xiang, Wensheng,Dong, Zhuoxu,Li, Lei,Du, Guozhong,Zhang, Yanyan,Li, Shanshan,Xiang, Wensheng. 2024

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