Microbial overproduction of free fatty acids is one route to next generation biofuels such as alkanes, olefins, and fatty acid esters.  Moderate titers of free fatty acids can be achieved by expression of an acyl-acyl carrier protein thioesterase in E. coli, however a next-generation strain has not yet been engineered that can achieve greater than 30% of the maximum theoretical yield.  It was found that fatty acid overproduction results in large reductions in cell viability, compromised membrane integrity, and changes in cell morphology.  To determine a functional basis for these observations, a differential transcriptomic, proteomic, and lipidomic analysis was conducted that compared fatty acid overproducing strains to non-overproducing control strains.  Altered expression levels were evident for numerous genes and proteins related to membrane stresses, proton motive force dissipation, and cell envelope composition.  These findings and successive iterations of strain engineering based on functional genomics guided hypotheses will be discussed.

Functional genomics guided strain improvement for fatty acid overproduction in Escherichia coli

243rd National Meeting (2012)

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