title: Engineering membrane and cell-wall programs for tolerance to toxic chemicals: Beyond solo genes.
abstract: Metabolite toxicity in microbes, particularly at the membrane, remains a bottleneck in the production of fuels and chemicals. Under chemical stress, native adaptation mechanisms combat hyper-fluidization by modifying the phospholipids in the membrane. Recent work in fluxomics reveals the mechanism of how membrane damage negatively affects energy metabolism while lipidomic and transcriptomic analyses show that strains evolved to be tolerant maintain membrane fluidity under stress through a variety of mechanisms such as incorporation of cyclopropanated fatty acids, trans-unsaturated fatty acids, and upregulation of cell wall biosynthesis genes. Engineered strains with modifications made in the biosynthesis of fatty acids, peptidoglycan, and lipopolysaccharide have shown increased tolerance to exogenous stress as well as increased production of desired metabolites of industrial importance. We review recent advances in elucidation of mechanisms or toxicity and tolerance as well as efforts to engineer the bacterial membrane and cell wall.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Molecular Biotechnology Laboratory, Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way, Newark, DE 19711, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Sandoval
authors.affiliation: Department of Chemical and Biomolecular Engineering, Molecular Biotechnology Laboratory, Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way, Newark, DE 19711, USA. Electronic address: epaps@udel.edu.
authors.forename: Eleftherios T
authors.initials: ET
authors.lastname: Papoutsakis
mesh_terms: D000222:Adaptation, Physiological; D001673:Biodegradation, Environmental; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism*; D004785:Environmental Pollutants / Q000378:metabolism* / Q000633:toxicity*; D004926:Escherichia coli / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis; D007220:Industrial Waste; D008070:Lipopolysaccharides / Q000096:biosynthesis; D030781:Organisms, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D010457:Peptidoglycan / Q000096:biosynthesis
chemical_list: D004785:Environmental Pollutants; D005227:Fatty Acids; D007220:Industrial Waste; D008070:Lipopolysaccharides; D010457:Peptidoglycan