[Perspective] A radically unexpected mechanism

The S-adenosylmethionine (SAM) radical enzyme superfamily plays a central role in the biosynthesis of many vitamins, cofactors, and antibiotics. Radical SAM enzymes catalyze challenging chemical reactions such as C-H bond activation (1), ring contraction (2), and molecular skeletal rearrangements (3, 4). They overcome the dif culty of these reactions by forming a highly oxidizing radical species, 5′-deoxyadenosyl (5′-dAdo·), from SAM and a reduced iron-sulfur cluster (5). This radical speci