Journey on the Radical SAM Road as an Accidental Pilgrim.

Radical S-adenosyl-l-methionine (SAM) enzymes catalyze a diverse group of complex transformations in all aspects of cellular physiology. These metalloenzymes bind SAM to a 4Fe-4S cluster and reductively cleave SAM to generate a 5'-deoxyadenosyl radical, which generally initiates the catalytic cycle by catalyzing a H atom to activate the substrate for subsequent chemistry. This perspective will focus on our discovery of several members of this superfamily of enzymes, with a particular emphasis on the current state of the field, challenges, and outlook.