Radicals from S-adenosylmethionine and their application to biosynthesis.

The radical SAM superfamily of enzymes catalyzes a broad spectrum of biotransformations by employing a common obligate intermediate, the 5'-deoxyadenosyl radical (DOA). Radical formation occurs via the reductive cleavage of S-adenosylmethionine (SAM or AdoMet). The resultant highly reactive primary radical is a potent oxidant that enables the functionalization of relatively inert substrates, including unactivated C-H bonds. The reactions initiated by the DOA are breathtaking in their efficiency, elegance and in many cases, the complexity of the biotransformation achieved. This review describes the common features shared by enzymes that generate the DOA and the intriguing variations or modifications that have recently been reported. The review also highlights selected examples of the diverse biotransformations that ensue.