Microbial production of L-methionine and its precursors using systems metabolic engineering.

L-methionine is an essential amino acid with versatile applications in food, feed, cosmetics and pharmaceuticals. At present, the production of L-methionine mainly relies on chemical synthesis, which conflicts with the concern over serious environmental problems and sustainable development goals. In recent years, microbial production of natural products has been amply rewarded with the emergence and rapid development of system metabolic engineering. However, efficient L-methionine production by microbial fermentation remains a great challenge due to its complicated biosynthetic pathway and strict regulatory mechanism. Additionally, the engineered production of L-methionine precursors, L-homoserine, O-succinyl-L-homoserine (OSH) and O-acetyl-L-homoserine (OAH), has also received widespread attention because they can be catalyzed to L-methionine via a high-efficiently enzymatic reaction in vitro, which is also a promising alternative to chemical route. This review provides a comprehensive overview on the recent advances in the microbial production of L-methionine and its precursors, highlighting the challenges and potential solutions for developing L-methionine microbial cell factories from the perspective of systems metabolic engineering, aiming to offer guidance for future engineering.