Enhancing fatty acid production in Escherichia coli by Vitreoscilla hemoglobin overexpression
- 6 August 2016
- journal article
- other
- Published by Wiley in Biotechnology & Bioengineering
- Vol. 114 (2), 463-467
- https://doi.org/10.1002/bit.26067
Abstract
Our recent 13C-metabolic flux analysis (13C-MFA) study indicates that energy metabolism becomes a rate-limiting factor for fatty acid overproduction in E. coli strains (after “Push-Pull-Block” based genetic modifications). To resolve this bottleneck, Vitreoscilla hemoglobin (VHb, a membrane protein facilitating O2 transport) was introduced into a fatty-acid-producing strain to promote oxygen supply and energy metabolism. The resulting strain, FAV50, achieved 70% percent higher fatty acid titer than the parent strain in micro-aerobic shake tube cultures. In high cell-density bioreactor fermentations, FAV50 achieved free fatty acids at a titer of 7.02 g/L (51% of the theoretical yield). In addition to “Push-Pull-Block-Power” strategies, our experiments and flux balance analysis also revealed the fatty acid over-producing strain is sensitive to metabolic burden and oxygen influx, and thus a careful evaluation of the cost-benefit tradeoff with the guidance of fluxome analysis will be fundamental for the rational design of synthetic biology strains. Biotechnol. Bioeng. 2017;114: 463–467.Funding Information
- National Science Foundation (DBI 1356669, MCB1453147)
- Human Frontier Science Program (RGY0076/2015)
- National Science Foundation (CBET 1438125)
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