Metabolic engineering strategies of Corynebacterium glutamicum for sulfur-containing amino acid production: current...

Sulfur-containing amino acids (e.g., L-methionine, L-cysteine) are crucial bioactive substances in pharmaceutical, food, feed, and cosmetics industries. Compared with traditional chemical synthesis, which suffers from environmental pollution and complicated chiral separation processes, microbial cell factories have emerged as a promising platform for their biomanufacturing due to advantages of sustainability and precise catalysis. However, current research predominantly focuses on Escherichia coli, whereas studies on Corynebacterium glutamicum remain relatively limited despite its established prowess in amino acid production. Focusing on C. glutamicum, this review delineates the biosynthetic routes, regulatory constraints, and physiological factors involved in L-methionine and L-cysteine biosynthesis, particularly from the perspective of carbon-sulfur-nitrogen metabolic synergy. It further identifies key limitations associated with sulfur assimilation, precursor allocation, feedback regulation, cofactor balance, product export, and fermentation performance. Based on these constraints, targeted metabolic engineering strategies are discussed, and the remaining challenges and development priorities for sulfur-containing amino acid biosynthesis in C. glutamicum are highlighted.