De novo production of resveratrol from glucose or ethanol by engineered Saccharomyces cerevisiae
Journal article, 2015

Resveratrol is a natural antioxidant compound, used as food supplement and cosmetic ingredient. Microbial production of resveratrol has until now been achieved by supplementation of expensive substrates, p-coumaric acid or aromatic amino acids. Here we engineered the yeast Saccharomyces cerevisiae to produce resveratrol directly from glucose or ethanol via tyrosine intermediate. First we introduced the biosynthetic pathway, consisting of tyrosine ammonia-lyase from Herpetosiphon aurantiacus, 4-coumaryl-CoA ligase from Arabidopsis thaliana and resveratrol synthase from Vitis vinifera, and obtained 2.73±0.05mgL-1 resveratrol from glucose. Then we over-expressed feedback-insensitive alleles of ARO4 encoding 3-deoxy-D-arabino-heptulosonate-7-phosphate and ARO7 encoding chorismate mutase, resulting in production of 4.85±0.31mgL-1 resveratrol from glucose as the sole carbon source. Next we improved the supply of the precursor malonyl-CoA by over-expressing a post-translational de-regulated version of the acetyl-CoA carboxylase encoding gene ACC1; this strategy further increased resveratrol production to 6.39±0.03mgL-1. Subsequently, we improved the strain by performing multiple-integration of pathway genes resulting in resveratrol production of 235.57±7.00mgL-1. Finally, fed-batch fermentation of the final strain with glucose or ethanol as carbon source resulted in a resveratrol titer of 415.65 and 531.41mgL-1, respectively.

Saccharomyces cerevisiae



Metabolic engineering


M. Li

Technical University of Denmark (DTU)

K. R. Kildegaard

Technical University of Denmark (DTU)

Yun Chen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

A. Rodriguez

Technical University of Denmark (DTU)

I. Borodina

Technical University of Denmark (DTU)

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Metabolic Engineering

1096-7176 (ISSN) 1096-7184 (eISSN)

Vol. 32 1-11

Areas of Advance

Life Science Engineering (2010-2018)

Subject Categories

Bioinformatics and Systems Biology



More information

Latest update