Abstract
Radical S-adenosyl-l-methionine (SAM) enzymes catalyze radical mediated chemical transformations notable for their diversity. The radical mediated reactions that take place in their catalytic cycles can be characterized with respect to one or more phases of initiation, propagation, and termination. Mechanistic models abound regarding these three phases of catalysis being regularly informed and updated by new discoveries that offer insights into their detailed workings. However, questions continue to be raised that touch on fundamental aspects of their mechanistic enzymology. Radical SAM enzymes are consequently far from fully understood, and this Perspective aims to outline some of the current models of radical SAM chemistry with an emphasis on lines of investigation that remain to be explored.