title: Efflux systems in bacteria and their metabolic engineering applications.
abstract: The production of valuable chemicals from metabolically engineered microbes can be limited by excretion from the cell. Efflux is often overlooked as a bottleneck in metabolic pathways, despite its impact on alleviating feedback inhibition and product toxicity. In the past, it has been assumed that endogenous efflux pumps and membrane porins can accommodate product efflux rates; however, there are an increasing number of examples wherein overexpressing efflux systems is required to improve metabolite production. In this review, we highlight specific examples from the literature where metabolite export has been studied to identify unknown transporters, increase tolerance to metabolites, and improve the production capabilities of engineered bacteria. The review focuses on the export of a broad spectrum of valuable chemicals including amino acids, sugars, flavins, biofuels, and solvents. The combined set of examples supports the hypothesis that efflux systems can be identified and engineered to confer export capabilities on industrially relevant microbes.
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Jones
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA.
authors.forename: Néstor J
authors.initials: NJ
authors.lastname: Hernández Lozada
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA. pfleger@engr.wisc.edu.|Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI, 53706, USA. pfleger@engr.wisc.edu.|, 3629 Engineering Hall, 1415 Engineering Drive, Madison, WI, 53706, USA. pfleger@engr.wisc.edu.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Pfleger
mesh_terms: D001419:Bacteria / Q000235:genetics* / Q000378:metabolism*; D056804:Biofuels; D004138:Dinitrocresols / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D007218:Industrial Microbiology / Q000379:methods; D026901:Membrane Transport Proteins / Q000378:metabolism; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways; D049490:Systems Biology
chemical_list: D056804:Biofuels; D004138:Dinitrocresols; D026901:Membrane Transport Proteins; C024132:4,6-dinitro-o-cresol
keywords: Efflux; Export; Metabolic engineering; Synthetic biology; Toxicity; Transporters