Emerging strategies for enhanced glutathione biosynthesis and its biomedical applications

Glutathione (GSH), a ubiquitous bioactive tripeptide, plays a central role in antioxidant defense, detoxification, and cellular metabolism. This review highlights advanced strategies to enhance GSH production, emphasizing strain improvement via traditional mutagenesis and genetic engineering. Optimization of microbial fermentation through carbon source selection, amino acid precursors, and ATP regeneration combined with metabolic engineering approaches, has significantly improved GSH yields in Saccharomyces cerevisiae and Escherichia coli. Clinically, GSH is used in managing liver diseases, oxidative stress, and immune dysfunction. Emerging applications, particularly in oncology, show promise. This review also compares production methods such as chemical synthesis, enzymatic catalysis, and microbial fermentation, highlighting microbial fermentation for its sustainability, cost-efficiency, and scalability. Future research should focus on refining detection methods, elucidating GSH's therapeutic mechanisms, and broadening its applications across pharmaceuticals, nutrition, and cosmetics.