A glycyl radical enzyme enables hydrogen sulfide production by the human intestinal bacterium Bilophila wadsworthia
A glycyl radical enzyme enables hydrogen sulfide production by the human intestinal bacterium Bilophila wadsworthia
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DOI：
10.1073/pnas.1815661116
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发表时间：
2019-02-19
影响因子：
11.1
通讯作者：
Schleheck, David
中科院分区：
文献类型：
--
作者：
Peck, Spencer C.;Denger, Karin;Schleheck, David
肠道微生物区系中产生的硫化氢对人类健康和疾病有许多贡献。人体肠道中硫化氢的一个重要来源是肠道中丰富的膳食和宿主来源的有机磺酸盐底物牛磺酸(2-氨基乙磺酸盐)释放的亚硫酸盐的无氧呼吸。然而，允许肠道细菌从牛磺酸中获得亚硫酸盐的酶还没有确定。在这里，我们使用差异蛋白质组学、异源产生的酶的体外重建和关键中间体的鉴定来破译Bilophila wadsworth 3.1.6中完整的牛磺酸脱磺途径。一种已知的牛磺酸：丙酮酸氨基转移酶最初将牛磺酸脱氨为磺乙醛，然后意外地通过依赖于NADH的还原酶将磺乙醛还原为异硫酸酯(2-羟基乙磺酸盐)。然后，异硫酸酯被一种以前未知的甘氨酰自由基酶(GRE)--异硫酸酯亚硫酸盐裂解酶(ISLA)裂解成亚硫酸盐和乙醛。产生的乙醛被脱氢酶氧化为乙酰辅酶A，亚硫酸盐被异化亚硫酸盐还原酶还原为硫化氢。这种独特的GRE也存在于脱硫弧菌DSM642和阿拉斯加脱硫弧菌G20中，它们使用异硫酸盐而不使用牛磺酸；相应的阿拉斯加脱硫弧菌G20基因敲除突变体不能以异硫酸盐作为末端电子受体生长。综上所述，ISLA催化的基于自由基的新型C-S键断裂反应丰富了已知的GRE超家族酶系，并使瓦兹沃斯芽孢杆菌的能量代谢成为可能。这种GRE广泛分布于肠道细菌基因组中，可能成为控制肠道硫化氢产生的新靶点。
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 Bilophila wadsworthia 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 Desulfovibrio desulfuricans DSM642 and Desulfovibrio alaskensis G20, which use isethionate but not taurine; corresponding knockout mutants of D. alaskensis 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 B. wadsworthia. This GRE is widely distributed in gut bacterial genomes and may represent a novel target for control of intestinal H2S production.