Publications

• A glycyl radical enzyme enables hydrogen sulfide production by the human intestinal bacterium Bilophila wadsworthia.

  Peck S.C., Denger K., Burrichter A., Irwin S.M., Balskus E.P., Schleheck D.

  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 i ... >> More

  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. << Less

  Proc. Natl. Acad. Sci. U.S.A. 116:3171-3176(2019) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Radical-mediated C-S bond cleavage in C2 sulfonate degradation by anaerobic bacteria.

  Xing M., Wei Y., Zhou Y., Zhang J., Lin L., Hu Y., Hua G., Urs A.N.N., Liu D., Wang F., Guo C., Tong Y., Li M., Liu Y., Ang E.L., Zhao H., Yuchi Z., Zhang Y.

  Bacterial degradation of organosulfonates plays an important role in sulfur recycling, and has been extensively studied. However, this process in anaerobic bacteria especially gut bacteria is little known despite of its potential significant impact on human health with the production of toxic H<su ... >> More

  Bacterial degradation of organosulfonates plays an important role in sulfur recycling, and has been extensively studied. However, this process in anaerobic bacteria especially gut bacteria is little known despite of its potential significant impact on human health with the production of toxic H₂S. Here, we describe the structural and biochemical characterization of an oxygen-sensitive enzyme that catalyzes the radical-mediated C-S bond cleavage of isethionate to form sulfite and acetaldehyde. We demonstrate its involvement in pathways that enables C2 sulfonates to be used as terminal electron acceptors for anaerobic respiration in sulfate- and sulfite-reducing bacteria. Furthermore, it plays a key role in converting bile salt-derived taurine into H₂S in the disease-associated gut bacterium Bilophila wadsworthia. The enzymes and transporters in these anaerobic pathways expand our understanding of microbial sulfur metabolism, and help deciphering the complex web of microbial pathways involved in the transformation of sulfur compounds in the gut. << Less

  Nat. Commun. 10:1609-1609(2019) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.