Radical S-adenosylmethionine enzymes: Mechanism, control and function

Abstract

Covering: January 2007 to March 2011

The radical SAM superfamily of enzymes use an iron sulfur cluster to reduce S-adenosylmethionine, which leads to the formation of a highly reactive intermediate, usually the 5′-deoxyadenosyl radical. This potent oxidant is able to functionalize relatively inert substrates, including unactivated C–H bonds. This reactivity is evidently useful, as radical SAM enzymes are widely distributed throughout metabolism and catalyze some of the most complex and elegant biotransformations. In the first part of this review, the focus is on the mechanism of radical formation, including the features shared across the family, followed by a discussion of recent evidence for variations in cluster binding motifs and the mechanism of radical formation. In the second part, we survey how radical SAM chemistry has been applied to biosynthesis.