Radical AdoMet enzymes in complex metal cluster biosynthesis

Radical S-adenosylmethionine (AdoMet) enzymes comprise a large superfamily of proteins that engage in a diverse series of biochemical transformations through generation of the highly reactive 5′-deoxyadenosyl radical intermediate. Recent advances into the biosynthesis of unique iron–sulfur (FeS)-containing cofactors such as the H-cluster in [FeFe]-hydrogenase, the FeMo-co in nitrogenase, as well as the iron–guanylylpyridinol (FeGP) cofactor in [Fe]-hydrogenase have implicated new roles for radical AdoMet enzymes in the biosynthesis of complex inorganic cofactors. Radical AdoMet enzymes in conjunction with scaffold proteins engage in modifying ubiquitous FeS precursors into unique clusters, through novel amino acid decomposition and sulfur insertion reactions. The ability of radical AdoMet enzymes to modify common metal centers to unusual metal cofactors may provide important clues into the stepwise evolution of these and other complex bioinorganic catalysts. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.

► Radical AdoMet enzymes in modifying common iron–sulfur clusters are surveyed.
► Advances of radical AdoMet maturases in metal cofactor biosynthesis are reviewed.
► Biosynthetic mechanisms involving radical AdoMet enzymes are highlighted.
► Diversity of motifs that impart cluster modification functionality is discussed.