Radical S-adenosyl-L-methionine (rSAM) enzymes catalyze diverse and complex radical mediated transformations. These enzymes reductively cleave SAM to generate a 5’-deoxyadenosyl radical (dAdo•), which initiates transformation of the substrate. rSAM enzymes are widely distributed in naturally occurring biosynthetic pathways, including those that generate ribosomally produced and posttranslationally modified polypeptides (RiPPs). We have carried out extensive biochemical studies of members of the rSAM RiPP maturase enzymes that produce thioether crosslink in their cognate substrate. This presentation will focus on our work leveraging detailed biochemical insights into development of a rSAM-based system introducing thioether crosslinks in RiPPs. Current progress and breadth of transformations catalyzed will be discussed.