Radical mediated ring formation in the biosynthesis of the hypermodified tRNA base wybutosine

•Wybutosine is a hypermodified tRNA base.•Biosynthesis of wybutosine requires pyruvate.•TYW1 is a member of the radical SAM superfamily.•TYW1 catalyzes a complex radical-mediated ring formation of the unique tricyclic ring of wybutosine. Wyosine and its derivatives are highly modified, acid labile tricyclic bases found at position 37 of tRNAPhe in archaea and eukarya. The formation of the common 4-demethylwyosine structural feature entails condensation of pyruvate and N-methylguanosine catalyzed by TYW1. This review will focus on the mechanism of this complex radical mediated transformation.