Microbial Biosynthesis of Natural Esters via Enzyme and Metabolic Engineering

Esters are vital compounds with wide-ranging applications in food, fragrance, and pharmaceuticals, yet their sustainable supply increasingly relies on microbial biosynthesis. Acyltransferases (ATFs), particularly BAHD family members, catalyze the esterification of alcohols with acyl-CoA donors, a central step in generating structurally diverse esters in vivo. This review highlights recent progress in ATF-mediated microbial biosynthesis of three representative classes: short-chain fatty acid esters (SCFAEs), monoterpenyl esters (MTEs), and aromatic esters (AEs). Advances in enzyme discovery, protein engineering, and metabolic pathway reprogramming have expanded substrate scope, improved catalytic efficiency, and enabled titers from milligram to gram scale. Nonetheless, challenges remain in achieving high activity, selectivity, and stereochemical fidelity under industrial conditions. We summarize strategies including co-culture systems, non-natural precursor biosynthetic pathways, high-throughput screening, and rational enzyme engineering. Future perspectives emphasize developing a precision precursor supply for ATF-mediated esterification, elucidating ATF structure-function relationships, and optimizing downstream processing to achieve efficient, scalable, and sustainable microbial production of diverse natural esters.