Engineering Escherichia coli to synthesize free fatty acids

Abstract

Fatty acid metabolism has received significant attention as a route for producing high-energy density, liquid transportation fuels and high-value oleochemicals from renewable feedstocks. If microbes can be engineered to produce these compounds at yields that approach the theoretical limits of 0.3-0.4 g/g glucose, then processes can be developed to replace current petrochemical technologies. Here, we review recent metabolic engineering efforts to maximize production of free fatty acids (FFA) in Escherichia coli, the first step towards production of downstream products. To date, metabolic engineers have succeeded in achieving higher yields of FFA than any downstream products. Regulation of fatty acid metabolism and the physiological effects of fatty acid production will also be reviewed from the perspective of identifying future engineering targets.

Figure I

Metabolic pathways for biosynthesis of fatty acids (a,b), β-oxidation (c), and production of high-value chemicals from intermediates in fatty acid metabolism (d).

Figure I

FFA export from Gram-negative bacteria.

Figure II

Impact of thioesterase specificity on membrane saturation.