Self-sacrifice in radical S-adenosylmethionine proteins

The radical SAM superfamily of metalloproteins catalyze the reductive cleavage of S-adenosyl-l-methionine to generate a 5′-deoxyadenosyl radical (5′-dA) intermediate that is obligate for turnover. The 5′-dA acts as a potent oxidant, initiating turnover by abstracting a hydrogen atom from an appropriate substrate. A special class of these enzymes use this strategy to functionalize unactivated C–H bonds by insertion of sulfur atoms. This review will describe the characterization of three members of this class — biotin synthase, lipoyl synthase, and MiaB protein — each of which has been shown to cannibalize itself during turnover.