Biosynthesis of Caffeic Acid from Glucose by Engineered .

Caffeic acid is a plant phenolic compound possessing extensive pharmacological activities. Here, we identified that -coumaric acid 3-hydroxylase from was capable of hydroxylating -coumaric acid to form caffeic acid in . Then, we introduced a combined caffeic acid biosynthetic pathway into and obtained 0.183 mg L caffeic acid from glucose. Next we improved the tyrosine biosynthesis in 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. Finally, the medium was optimized, and the highest caffeic acid production obtained was 11.432 mg L in YPD medium containing 4% glucose. This study opens a route to produce caffeic acid from glucose in and establishes a platform for the biosynthesis of caffeic acid derived metabolites.