Tailored fatty acid synthesis via dynamic control of fatty acid elongation

Journal Article · Tue Jul 09 04:00:00 EDT 2013 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1307129110· OSTI ID:1211353

Torella, JP; Ford, TJ; Kim, SN; Chen, AM; Way, JC; Silver, PA

Medium-chain fatty acids (MCFAs, 4-12 carbons) are valuable as precursors to industrial chemicals and biofuels, but are not canonical products of microbial fatty acid synthesis. We engineered microbial production of the full range of even-and odd-chain-length MCFAs and found that MCFA production is limited by rapid, irreversible elongation of their acyl-ACP precursors. To address this limitation, we programmed an essential ketoacyl synthase to degrade in response to a chemical inducer, thereby slowing acyl-ACP elongation and redirecting flux from phospholipid synthesis to MCFA production. Our results show that induced protein degradation can be used to dynamically alter metabolic flux, and thereby increase the yield of a desired compound. The strategy reported herein should be widely useful in a range of metabolic engineering applications in which essential enzymes divert flux away from a desired product, as well as in the production of polyketides, bioplastics, and other recursively synthesized hydrocarbons for which chain-length control is desired.

• Sponsoring Organization: USDOE Advanced Research Projects Agency - Energy (ARPA-E)
• DOE Contract Number: AR0000079
• OSTI ID: 1211353
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 28 Vol. 110; ISSN 0027-8424
• Country of Publication: United States
• Language: English