Redirecting carbon flux into malonyl-CoA to improve resveratrol titers: Proof of concept for genetic interventions predicted by OptForce computational framework

Namita Bhan, Peng Xu, Omar Khalidi, Mattheos A.G. Koffas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Malonyl-CoA is the limiting precursor for the overexpression of an array of heterologous pathways in bacteria, such as flavanones, polyketides, microdiesel and poly-unsaturated omega-3 fatty acids. Previously, we have been able to develop a strain with higher carbon flux to acetyl-coA and malonyl-CoA by carrying out genetic interventions predicted by OptForce framework. Here we carried out the same interventions in a resveratrol producing strain and obtained a 60% increase in the yield giving the highest titer of 1.6. g/L obtained in lab scale fermentation without the addition of expensive fatty acid pathway inhibitors such as cerulenin. The positive genetic alterations involved overexpression of pyruvate dehydrogenase multi-enzyme complex (PDH), phosphoglycerate kinase (PGK), glyceraldehyde-3-phosphate dehydrogenase (GapA) and deletion of fumarase (FumC). This work presents the development of an alternative source of resveratrol with possible applications in pharmaceutical, nutraceutical and food industry.

Original languageEnglish
Pages (from-to)109-114
Number of pages6
JournalChemical Engineering Science
Volume103
DOIs
StatePublished - 5 Nov 2013
Externally publishedYes

Keywords

  • Malonyl CoA
  • Metabolic engineering
  • OptForce
  • Resveratrol
  • Stoichiometric-based modeling
  • Synthetic biology

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