Sulfatases are widespread enzymes, found from prokaryotes to eukaryotes and involved in many biochemical processes. To be active, all known sulfatases undergo a unique post-translational modification leading to the conversion of a critical active-site residue, i.e., a serine or a cysteine, into a C alpha-formylglycine (FGly). Two different systems are involved in sulfatase maturation. One, named FGE, is an oxygen-dependent oxygenase and has been fully characterized. The other one, a member of the so-called "radical SAM" super-family, has been only preliminary investigated. This latter system allows the maturation of sulfatases in strictly anaerobic conditions and has thus been named anSME (anaerobic Sulfatase Maturating Enzyme). Our results provide the first experimental evidence that anSME are iron-sulfur enzymes able to perform the reductive cleavage of SAM and thus belong to the radical SAM super-family. Furthermore, they demonstrate that anSME are able to efficiently oxidize cysteine into FGly in an oxygen-independent manner.