De Novo Biosynthesis of Caffeic Acid from Glucose by Engineered Saccharomyces cerevisiae

Caffeic acid is a plant phenolic compound possessing extensive pharmacological activities. Here, we identified that p-coumaric acid 3-hydroxylase from Arabidopsis thaliana was capable of hydroxylating p-coumaric acid to form caffeic acid in Saccharomyces cerevisiae. Then, we introduced a combined caffeic acid biosynthetic pathway into S. cerevisiae and obtained 0.183 mg L–1 caffeic acid from glucose. Next we improved the tyrosine biosynthesis in S. cerevisiae by blocking the pathway flux to aromatic alcohols and eliminating the tyrosine-induced feedback inhibition resulting in caffeic acid production of 2.780 mg L–1. Finally, the medium was optimized, and the highest caffeic acid production obtained was 11.432 mg L–1 in YPD medium containing 4% glucose. This study opens a route to produce caffeic acid from glucose in S. cerevisiae and establishes a platform for the biosynthesis of caffeic acid derived metabolites.