Efflux Transporters’ Engineering and Their Application in Microbial Production of Heterologous Metabolites
- Muhammad Saad AhmedMuhammad Saad AhmedInstitute for Synthetic Biosystem/Department of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology (BIT), Beijing 100081, P. R. ChinaDepartment of Biological Sciences, National University of Medical Sciences (NUMS), Abid Majeed Road, The Mall, Rawalpindi 46000, PakistanMore by Muhammad Saad Ahmed
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- Kyle J. LauersenKyle J. LauersenBiological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Kingdom of Saudi ArabiaMore by Kyle J. Lauersen
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- Sana IkramSana IkramBeijing Higher Institution Engineering Research Center for Food Additives and Ingredients, Beijing Technology & Business University (BTBU), Beijing 100048, P. R. ChinaMore by Sana Ikram
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- Chun Li*Chun Li*E-mail: [email protected]Institute for Synthetic Biosystem/Department of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology (BIT), Beijing 100081, P. R. ChinaSynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, Key Laboratory of Systems Bioengineering, Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, P. R. ChinaKey Laboratory for Industrial Biocatalysis, Ministry of Education, Department of Chemical Engineering, Tsinghua University, Beijing 100084, P. R. ChinaMore by Chun Li
Abstract
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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