Reductive Cleavage of Sulfoxide and Sulfone by Two Radical S-Adenosyl-l-methionine Enzymes.

Sulfoxides and sulfones are commonly found in nature as a result of thioether oxidation, whereas only a very few enzymes have been found to metabolize these compounds. Utilizing the strong reduction potential of the [4Fe-4S] cluster of radical S-adenosyl-l-methionine (SAM) enzymes, we herein report the first enzyme-catalyzed reductive cleavage of sulfoxide and sulfone. We show two radical SAM enzymes, tryptophan lyase NosL and the class C radical SAM methyltransferase NosN, are able to act on a sulfoxide SAHO and a sulfone SAHO, both of which are structurally similar to SAM. NosL cleaves all of the three bonds (i.e., S-C(5'), S-C(γ), and S-O) connecting the sulfur center of SAHO, with a preference for S-C(5') bond cleavage. Similar S-C cleavage activity was also found for SHAO, but no S-O cleavage was observed. In contrast to NosL, NosN almost exclusively cleaves the S-C(5') bonds of SAHO and SAHO with much higher efficiencies. Our study provides valuable insights into the [4Fe-4S] cluster-mediated reduction reactions and highlights the remarkable catalytic promiscuity of radical SAM enzymes.