期刊
ACS SYNTHETIC BIOLOGY
卷 10, 期 4, 页码 646-669出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.0c00507
关键词
metabolites; cytotoxicity; transporter engineering; efflux transporters
资金
- National Natural Science Foundation of China [21736002, 21606018]
- National Key Research and Development Program of China [2018YFA0901800]
- National Science Fund for Distinguished Young Scholars [21425624]
This study provides insights into efflux transport proteins as potential solutions for enhancing the export of heterologous metabolites from microbial cell systems, including their mechanistic modes of action, selection of appropriate transporters, and future research directions.
Metabolic engineering of microbial hosts for the production of heterologous metabolites and biochemicals is an enabling technology to generate meaningful quantities of desired products that may be otherwise difficult to produce by traditional means. Heterologous metabolite production can be restricted by the accumulation of toxic products within the cell. Efflux transport proteins (transporters) provide a potential solution to facilitate the export of these products, mitigate toxic effects, and enhance production. Recent investigations using knockout lines, heterologous expression, and expression profiling of transporters have revealed candidates that can enhance the export of heterologous metabolites from microbial cell systems. Transporter engineering efforts have revealed that some exhibit flexible substrate specificity and may have broader application potentials. In this Review, the major superfamilies of efflux transporters, their mechanistic modes of action, selection of appropriate efflux transporters for desired compounds, and potential transporter engineering strategies are described for potential applications in enhancing engineered microbial metabolite production. Future studies in substrate recognition, heterologous expression, and combinatorial engineering of efflux transporters will assist efforts to enhance heterologous metabolite production in microbial hosts.
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