Ergothioneine biosynthesis: The present state and future prospect.

Ergothioneine (ERG), a rare natural thio-histidine derivative with potent antioxidant properties and diverse biological functions, is widely utilized in food processing, cosmetics, pharmaceuticals, and nutritional supplements. Current bioproduction methods for ERG primarily depend on fermenting edible mushrooms. However, with the advancement in synthetic biology, an increasing number of genetically engineered microbial hosts have been developed for ERG production, including , , and . Given the involvement of multiple precursor substances in ERG synthesis, it is crucial to employ diverse strategies to regulate the metabolic flux of ERG synthesis. This review comprehensively evaluates the physiological effects and safety considerations associated with ERG, along with the recent advancements in catalytic metabolic pathway for ERG production using synthetic biology tools. Finally, the review discusses the challenges in achieving efficient ERG production and the strategies to address these challenges using synthetic biology tools. This review provides a literature analysis and strategies guidance for the further application of novel synthetic biology tools and strategies to improve ERG yield.