Almost all known aerobic oxidation processes depend on transition metals or small aromatic molecules for O2 activation. However, several recent reports hint at alternative ways by which enzymes might utilize triplet O2 to oxidize singlet biomolecules. If true this would allow for novel opportunities in biocatalyst design but it might also suggest that small and large molecules not previously considered redox catalysts might be a source for significant oxidative stress related to aging and infective disease. We propose that a cysteine residue oxidixed to sulfenic acid within an appropriately evolved enzyme active site may serve as a redox catalyst by engaging in one- electron transfers. This proposal integrates thermodynamic considerations and experimental observations on small molecules but clearly departs from traditional enzymology. We identified a bacterial formylglycine-generating enzyme as an ideal model to test this proposal. This enzyme has been structurally characterized but its mechanism remains elusive.