Abstract
Class C radical SAM methyltransferases catalyze a diverse array of difficult chemical transformations in the biosynthesis of a range of compounds of biomedical importance. Phylogenetic analysis suggests that all of these enzymes are related to "CpdH" (formerly "HemN") and "HemW", proteins with essential roles in anaerobic heme biosynthesis and heme transport, respectively. These functions are essential to anaerobic metabolism in Escherichia coli. Interestingly, evolution has come full circle, and the divergence of this protein sequence/fold has resulted in the class C radical SAM methyltransferases. Several pathogenic organisms have further adapted this fold to catalyze the anaerobic degradation of heme. In this review, we summarize what is known about the mechanism of anaerobic heme degradation and the evolutionary implications.