Enhanced production of branched-chain fatty acids by replacing β-ketoacyl-(acyl-carrier-protein) synthase III (FabH)

Biotechnology and Bioengineering
Wen JiangFuzhong Zhang

Abstract

Branched-chain fatty acids (BCFAs) are important precursors for the production of advanced biofuels with improved cold-flow properties. Previous efforts in engineering type II fatty acid synthase (FAS) for BCFA production suffered from low titers and/or the co-production of a large amount of straight-chain fatty acids (SCFAs), making it nearly impossible for further conversion of BCFAs to branched biofuels. Synthesis of both SCFAs and BCFAs requires FabH, the only β-ketoacyl-(acyl-carrier-protein) synthase in Escherichia coli that catalyzes the initial condensation reaction between malonyl-ACP and a short-chain acyl-CoA. In this study, we demonstrated that replacement of the acetyl-CoA-specific E. coli FabH with a branched-chain-acyl-CoA-specific FabH directed the flux to the synthesis of BCFAs, resulting in a significant enhancement in BCFA titer compared to a strain containing both acetyl-CoA- and branched-chain-acyl-CoA-specific FabHs. We further demonstrated that the composition of BCFAs can be tuned by engineering the upstream pathway to control the supply of different branched-chain acyl-CoAs, leading to the production either even-chain-iso-, odd-chain-iso-, or odd-chain-anteiso-BCFAs separately. Overall, the top-performi...Continue Reading

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Citations

Oct 30, 2016·Metabolic Engineering·Gayle J BentleyFuzhong Zhang
Sep 12, 2017·Environmental Microbiology·Edna BodeHelge B Bode
Nov 2, 2017·Biotechnology for Biofuels·Wen JiangFuzhong Zhang
Apr 24, 2019·Biotechnology for Biofuels·Wenqin BaiFuzhong Zhang
Nov 7, 2019·Journal of Biotechnology·Jeong Sang YiByung-Gee Kim
Mar 16, 2017·Current Opinion in Biotechnology·Chonglong WangSeon-Won Kim
Jul 5, 2019·Metabolic Engineering·Garrett W RoellYinjie J Tang
Jun 23, 2021·Chemical Reviews·Pedro PaivaPedro A Fernandes

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