Regioselectivity of the Oxidative C–S Bond Formation in Ergothioneine and Ovothiol Biosyntheses

Ergothioneine (5) and ovothiol (8) are two novel thiol-containing natural products. Their C–S bonds are formed by oxidative coupling reactions catalyzed by EgtB and OvoA enzymes, respectively. In this work, it was discovered that in addition to catalyzing the oxidative coupling between histidine and cysteine (1 → 6 conversion), OvoA can also catalyze a direct oxidative coupling between hercynine (2) and cysteine (2 → 4 conversion), which can shorten the ergothioneine biosynthetic pathway by two steps.