Metabolic Engineering for Resveratrol Production Based on Modularization of Metabolic Pathways in Escherichia coli

Separating metabolic pathways for microbial chemical production is a promising approach for allocating resources based on target compounds. We modularized an artificial resveratrol biosynthetic pathway in Escherichia coli to supply p-coumaric acid and malonyl-CoA as precursors independently via the coutilization of glucose and xylose. The optimization of resveratrol synthetic gene expression, sugar concentration, and Corynebacterium glutamicum pyc overexpression improved the resveratrol titer in the engineered strain. Furthermore, introducing acetate into the malonyl-CoA supply module as a third carbon source resulted in an increased resveratrol titer. The cultivation of a strain overexpressing pyc and resveratrol synthetic genes in a 1-L bioreactor produced 273.5 mg/L resveratrol. The modularization of metabolic pathways to supply p-coumaric acid and malonyl-CoA from independent sources, such as sugars and acetate, enabled resveratrol production. Overall, this study contributes to the high production of chemicals whose biosynthetic pathways require multiple precursors such as polyketide.