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Background  Ergothioneine (EGT) has a unique antioxidant ability and diverse beneficial effects on human health. But the content of EGT is very low in its natural producing organisms such as  Mycobacterium smegmatis  and mushrooms. Therefore, it is necessary to highly efficient heterologous production of EGT in food-grade yeasts such as  Saccharomyces cerevisiae .    Results  Two EGT biosynthetic genes were cloned from the mushroom  Grifola frondosa  and successfully heterologously expressed in  Saccharomyces cerevisiae  EC1118 strain in this study. By optimization of the fermentation conditions of the engineered strain  S. cerevisiae  EC1118, the 11.80 mg/L of EGT production was obtained. With daily addition of 1% glycerol to the culture medium in the fermentation process, the EGT production of the engineered strain  S. cerevisiae  EC1118 can reach up to 20.61 mg/L.    Conclusion  A successful EGT de novo biosynthetic system of  S. cerevisiae  containing only two genes from mushroom  Grifola frondosa  was developed in this study. This system provides promising prospects for the large scales production of EGT for human health.

Successful biosynthesis of natural antioxidant ergothioneine in Saccharomyces cerevisiae required only two genes from Grifola frondosa