Recent advances in microbial biosynthesis of L-cysteine and its derivative sulfur-containing antioxidants

Sulfur is an essential element for life, and most microorganisms are actively involved in the global sulfur cycle through sulfur oxidation and sulfate reduction pathways. Among sulfur-containing metabolites, L-cysteine plays a central role as a precursor to various thiol-based antioxidants, including glutathione, mycothiol, ergothioneine, and taurine. These compounds are critical for maintaining redox homeostasis, modulating oxidative stress responses, and mediating cellular signaling. However, the complexity of L-cysteine metabolism and the inherently low sulfur conversion efficiency present major obstacles to the large-scale biosynthesis and application of sulfur-containing antioxidants. This review provides a comprehensive overview of the sulfur assimilation ability of inorganic sulfur sources in microorganisms and summarizes the metabolic pathways and regulatory mechanisms of sulfur-containing antioxidants mediated by L-cysteine in different strains. In particular, this review focuses on the regulation of sulfur-containing antioxidants on redox balance during oxidative stress. Furthermore, we discuss their potential applications in the selection and expansion of microorganisms, the exploration and regulation of novel metabolic targets, and the coordination of carbon/sulfur modules. By coordinating the yield of target products, they can regulate the balance of oxidative and reduction pressures. These insights provide promising strategies to alleviate oxidative stress during industrial fermentation and to facilitate the development of robust microbial chassis strains.