Cinnamic acid and p-coumaric acid are metabolized to 4-hydroxybenzoic acid by Yarrowia lipolytica

Abstract

The transition towards a bioeconomy requires the microbial production of various products from renewable resources such as lignocellulosic hydrolysate. Yarrowia lipolytica has been explored as a potential production host for flavonoid synthesis due to its high tolerance to aromatic acids and ability to supply malonyl-CoA. However, little is known about its ability to consume the precursors cinnamic and p-coumaric acid. In this study, we demonstrate that Y. lipolytica can consume these precursors through multiple pathways that are partially dependent on the cultivation medium. We constructed a collection of 15 P450 protein knock-out strains to identify the genes responsible for the reaction and identified YALI1_B28430g as the gene encoding for a protein with a trans-cinnamate 4-monooxygenase activity that converts cinnamic acid to p-coumaric acid and named it TCM1. p-Coumaric acid in turn is further converted to 4-hydroxybenzoic acid. Our findings provide new insight into the metabolic capabilities of Y. lipolytica and will be essential for the future construction of better flavonoid production strains.