S-Adenosylmethionine-Dependent Radical Formation in Anaerobic Systems

In this chapter we will review some recent and exciting developments in the formation of radical-containing enzymes that are mediated through the cleavage of S-adenosylmethionine (SAM). The three enzyme systems, pyruvate formate lyase (PFL) and its activating enzyme (AE), lysine 2,3-aminomutase (LAM), and a SAM-dependent anaerobic ribonucleotide reductase (ARR) each use a 5'-deoxyadenosyl radical derived from SAM as a B12 surrogate. In the case of LAM the radical cofactor functions in a catalytic manner with respect to substrate and is responsible for the generation of substrate radical intermediates. For PFL and ARR, the radical cofactor is utilized stoichiometrically with respect to the enzyme to generate an enzyme radical localized on a glycine residue. These systems define a new role for SAM in enzymatic catalysis and will certainly be the subject of continued intensive research in the future.