Radical SAM enzymes in methylation and methylthiolation

Abstract

Radical S-adenosyl-L-methionine (SAM) enzymes are a large and diverse superfamily with functions ranging from enzyme activation through a single H atom abstraction to complex organic and metal cofactor synthesis involving a series of steps. Though these enzymes carry out a variety of functions, they share common structural and mechanistic characteristics. All of them contain a site-differentiated [4Fe–4S] cluster, ligated by a CX₃CX₂C or similar motif, which binds SAM at the unique iron. The [4Fe–4S]¹⁺ state of the cluster reductively cleaves SAM to produce a 5′-deoxyadenosyl radical, which serves to initiate the diverse reactions catalyzed by these enzymes. Recent highlights in the understanding of radical SAM enzymes will be presented, with a particular emphasis on enzymes catalyzing methylation and methythiolation reactions.