Investigating E. coli Coculture for Resveratrol Production with 13C Metabolic Flux Analysis

Jaeseung Hong, Dae Kyun Im, Min Kyu Oh

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Resveratrol, a phytoalexin produced by plants, has several beneficial effects in humans. It can be produced using Escherichia coli by introducing only three heterologous genes: TAL, 4CL, and STS. However, the resveratrol synthesis pathway requires two precursors, tyrosine and acetyl-CoA, which are produced by two branched central metabolic pathways. Therefore, overexpression of these genes in E. coli results in the production of only trace amounts of resveratrol. In this study, we attempted to produce resveratrol via coculture of two engineered strains in which the two metabolic pathways are activated. The first strain was engineered to produce p-coumaric acid using tyrosine as a precursor, which can be synthesized by the pentose phosphate pathway. The second strain produced resveratrol by combining p-coumaric acid from the first strain and malonyl-CoA synthesized from acetyl-CoA, which is produced by the glycolytic pathway. In total, 55.7 mg/L of resveratrol was produced from 20 g/L of glucose via coculture of these two strains in glucose minimal medium without any supplements. The metabolic fluxes in each of the strains producing resveratrol were successfully investigated by 13C metabolic flux analysis. The results showed that the balance between the citric acid cycle and the malonyl-CoA supply node was important for resveratrol production.

Original languageEnglish
Pages (from-to)3466-3473
Number of pages8
JournalJournal of agricultural and food chemistry
Issue number11
Publication statusPublished - 2020 Mar 18

Bibliographical note

Funding Information:
This study was supported by the National Research Foundation of Korea funded by the Korean Government (2012M1A2A2026560 and 2017R1A2B4008758).

Publisher Copyright:
Copyright © 2020 American Chemical Society.


  • C-MFA
  • E. coli
  • coculture
  • metabolic engineering
  • resveratrol

ASJC Scopus subject areas

  • General Chemistry
  • General Agricultural and Biological Sciences


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