A glycyl radical enzyme enables hydrogen sulfide production by the human intestinal bacterium<i>Bilophila wadsworthia</i>

Abstract

Hydrogen sulfide (H₂S) production in the intestinal microbiota has many contributions to human health and disease. An important source of H₂S in the human gut is anaerobic respiration of sulfite released from the abundant dietary and host-derived organic sulfonate substrate in the gut, taurine (2-aminoethanesulfonate). However, the enzymes that allow intestinal bacteria to access sulfite from taurine have not yet been identified. Here we decipher the complete taurine desulfonation pathway in <i>Bilophila wadsworthia</i> 3.1.6 using differential proteomics, in vitro reconstruction with heterologously produced enzymes, and identification of critical intermediates. An initial deamination of taurine to sulfoacetaldehyde by a known taurine:pyruvate aminotransferase is followed, unexpectedly, by reduction of sulfoacetaldehyde to isethionate (2-hydroxyethanesulfonate) by an NADH-dependent reductase. Isethionate is then cleaved to sulfite and acetaldehyde by a previously uncharacterized glycyl radical enzyme (GRE), isethionate sulfite-lyase (IslA). The acetaldehyde produced is oxidized to acetyl-CoA by a dehydrogenase, and the sulfite is reduced to H₂S by dissimilatory sulfite reductase. This unique GRE is also found in <i>Desulfovibrio desulfuricans</i> DSM642 and <i>Desulfovibrio alaskensis</i> G20, which use isethionate but not taurine; corresponding knockout mutants of <i>D. alaskensis</i> G20 did not grow with isethionate as the terminal electron acceptor. In conclusion, the novel radical-based C-S bond-cleavage reaction catalyzed by IslA diversifies the known repertoire of GRE superfamily enzymes and enables the energy metabolism of <i>B. wadsworthia</i> This GRE is widely distributed in gut bacterial genomes and may represent a novel target for control of intestinal H₂S production.