Making and breaking carbon-carbon bonds in class C radical SAM methyltransferases.

Radical S-adenosylmethionine (SAM) enzymes utilize a [4Fe-4S]1+ cluster and S-(5'-adenosyl)-L-methionine, (SAM), to generate a highly reactive radical and catalyze what is arguably the most diverse set of chemical reactions for any known enzyme family. At the heart of radical SAM catalysis is a highly reactive 5'-deoxyadenosyl radical intermediate (5'-dAdo●) generated through reductive cleavage of SAM or nucleophilic attack of the unique iron of the [4Fe-4S]+ cluster on the 5' C atom of SAM. Spectroscopic studies reveal the 5'-dAdo● is transiently captured in an FeC bond (Ω species). In the presence of substrate, homolytic scission of this metal‑carbon bond regenerates the 5'-dAdo● for catalytic hydrogen atom abstraction. While reminiscent of the adenosylcobalamin mechanism, radical SAM enzymes appear to encompass greater catalytic diversity. In this review we discuss recent developments for radical SAM enzymes involved in unique chemical rearrangements, specifically regarding class C radical SAM methyltransferases. Illuminating this class of radical SAM enzymes is especially significant as many enzymes have been shown to play critical roles in pathogenesis and the synthesis of novel antimicrobial compounds.