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Abstract
<p class="first" id="P2">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,
<i>trans</i>-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.
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