S-Adenosyl Methionine: One Electron and Two Electron Reaction Manifolds in Biosyntheses

Abstract

S-Adenosylmethionine (SAM), likely an ancient molecule in biological systems, is known for delivery of a [CH3+] equivalent to a host of cellular metabolites containing nucleophilic N, O, S, and C centers via heterolytic cleavage of the CH3–S bond in SAM. SAM can also undergo catalyzed hemolytic cleavage of that CH3–S bond by iron/sulfur-containing enzymes that use the resultant 5′-deoxyadenosyl radical for carbon-based radical chemistry on specific substrates. Bioinformatic analysis indicates >50 000 such enzymes in microbial data bases. All these iron/sulfur cluster enzymes are predicted to be sensitive to autoxidation so, in contrast/complementarity to O2-based homolytic chemistry which is by definition aerobic, the SAM radical enzymes function anaerobically.