Abstract:Ergothioneine is a multifunctional physiological cytoprotector,with broad application in foods,beverage,medicine,cosmetics and so on.Biosynthesis is an increasingly favored method in the production of ergothioneine.This paper summarizes the new progress in the identification of key pathways,the mining of key enzymes,and the development of natural edible mushroom species and high-yield engineering strains for ergothioneine biosynthesis in recent years.Through this review,we aim to reveal the molecular mechanism of ergothioneine biosynthesis and then employ the methods of fermentation engineering,metabolic engineering,and synthetic biology to greatly increase the yield of ergothioneine.