Abstract:
The sulfite-reducing bacterium Bilophila wadsworthia, a common human intestinal pathobiont, is unique in its ability to metabolize a wide variety of sulfonates to generate sulfite as a terminal electron acceptor (TEA). The resulting formation of H2S is implicated in inflammation and colon cancer. l-cysteate, an oxidation product of l-cysteine, is among the sulfonates metabolized by B. wadsworthia, although the enzymes involved remain unknown. Here we report a pathway for l-cysteate dissimilation in B. wadsworthia RZATAU, involving isomerization of l-cysteate to d-cysteate by a cysteate racemase (BwCuyB), followed by cleavage into pyruvate, ammonia and sulfite by a d-cysteate sulfo-lyase (BwCuyA). The strong selectivity of BwCuyA for d-cysteate over l-cysteate was rationalized by protein structural modeling. A homolog of BwCuyA in the marine bacterium Silicibacter pomeroyi (SpCuyA) was previously reported to be a l-cysteate sulfo-lyase, but our experiments confirm that SpCuyA too displays a strong selectivity for d-cysteate. Growth of B. wadsworthia with cysteate as the electron acceptor is accompanied by production of H2S and induction of BwCuyA. Close homologs of BwCuyA and BwCuyB are present in diverse bacteria, including many sulfate- and sulfite-reducing bacteria, suggesting their involvement in cysteate degradation in different biological environments.
摘要:
亚硫酸盐还原细菌Bilophilawadsworthia,一种常见的人类肠道疾病,独特之处在于其代谢多种磺酸盐以产生亚硫酸盐作为末端电子受体(TEA)的能力。由此产生的H2S的形成与炎症和结肠癌有关。l-半胱氨酸,L-半胱氨酸的氧化产物,是B.wadsworthia代谢的磺酸盐之一,尽管所涉及的酶仍然未知。在这里,我们报道了B.wadsworthiaRZATAU中l-半胱氨酸异化的途径,涉及通过半胱氨酸消旋酶(BwCuyB)将l-半胱氨酸异构化为d-半胱氨酸,然后卵裂成丙酮酸,氨和亚硫酸盐通过d-半胱氨酸磺基裂解酶(BwCuyA)。BwCuyA对d-半胱氨酸对l-半胱氨酸的强选择性通过蛋白质结构建模来合理化。先前有报道称,海洋细菌硅化杆菌pomeroyi(SpCuyA)中的BwCuyA同系物是一种l-半胱氨酸磺基裂解酶,但我们的实验证实SpCuyA对d-半胱氨酸也显示出强选择性。以半胱氨酸作为电子受体的B.wadsworthia的生长伴随着H2S的产生和BwCuyA的诱导。BwCuyA和BwCuyB的紧密同源物存在于不同的细菌中,包括许多硫酸盐和亚硫酸盐还原菌,表明它们参与不同生物环境中的半胱氨酸降解。