Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
J Bacteriol. 2010 Mar;192(5):1184-92. doi: 10.1128/JB.01372-09. Epub 2010 Jan 8.
In many bacteria, LuxS functions as a quorum-sensing molecule synthase. However, it also has a second, more central metabolic function in the activated methyl cycle (AMC), which generates the S-adenosylmethionine required by methyltransferases and recycles the product via methionine. Helicobacter pylori lacks an enzyme catalyzing homocysteine-to-methionine conversion, rendering the AMC incomplete and thus making any metabolic role of H. pylori LuxS (LuxS(Hp)) unclear. Interestingly, luxS(Hp) is located next to genes annotated as cysK(Hp) and metB(Hp), involved in other bacteria in cysteine and methionine metabolism. We showed that isogenic strains carrying mutations in luxS(Hp), cysK(Hp), and metB(Hp) could not grow without added cysteine (whereas the wild type could), suggesting roles in cysteine synthesis. Growth of the DeltaluxS(Hp) mutant was restored by homocysteine or cystathionine and growth of the DeltacysK(Hp) mutant by cystathionine only. The DeltametB(Hp) mutant had an absolute requirement for cysteine. Metabolite analyses showed that S-ribosylhomocysteine accumulated in the DeltaluxS(Hp) mutant, homocysteine in the DeltacysK(Hp) mutant, and cystathionine in the DeltametB(Hp) mutant. This suggests that S-ribosylhomocysteine is converted by LuxS(Hp) to homocysteine (as in the classic AMC) and thence by CysK(Hp) to cystathionine and by MetB(Hp) to cysteine. In silico analysis suggested that cysK-metB-luxS were acquired by H. pylori from a Gram-positive source. We conclude that cysK-metB-luxS encode the capacity to generate cysteine from products of the incomplete AMC of H. pylori in a process of reverse transsulfuration. We recommend that the misnamed genes cysK(Hp) and metB(Hp) be renamed mccA (methionine-to-cysteine-conversion gene A) and mccB, respectively.
在许多细菌中，LuxS 作为群体感应分子合成酶发挥作用。然而，它在激活甲基循环（AMC）中也具有第二个更核心的代谢功能，该循环生成甲基转移酶所需的 S-腺苷甲硫氨酸，并通过蛋氨酸回收产物。幽门螺杆菌缺乏催化同型半胱氨酸向蛋氨酸转化的酶，导致 AMC 不完整，因此幽门螺杆菌 LuxS（LuxS（Hp））的任何代谢作用都不清楚。有趣的是，luxS（Hp）位于被注释为 cysK（Hp）和 metB（Hp）的基因旁边，这些基因在其他细菌中参与半胱氨酸和蛋氨酸代谢。我们表明，携带 luxS（Hp）、cysK（Hp）和 metB（Hp）突变的同基因菌株在没有添加半胱氨酸的情况下无法生长（而野生型可以），这表明它们在半胱氨酸合成中具有作用。DeltaluxS（Hp）突变体的生长可以通过同型半胱氨酸或胱硫醚恢复，而 DeltacysK（Hp）突变体的生长仅通过胱硫醚恢复。DeltametB（Hp）突变体绝对需要半胱氨酸。代谢物分析表明，S-核糖同型半胱氨酸在 DeltaluxS（Hp）突变体中积累，同型半胱氨酸在 DeltacysK（Hp）突变体中积累，胱硫醚在 DeltametB（Hp）突变体中积累。这表明 S-核糖同型半胱氨酸由 LuxS（Hp）转化为同型半胱氨酸（如经典 AMC 中那样），然后由 CysK（Hp）转化为胱硫醚，由 MetB（Hp）转化为半胱氨酸。计算机分析表明，cysK-metB-luxS 是幽门螺杆菌从革兰氏阳性源获得的。我们得出结论，cysK-metB-luxS 编码了幽门螺杆菌不完全 AMC 的产物转化为半胱氨酸的能力，这是一个反向转硫过程。我们建议将命名不当的基因 cysK（Hp）和 metB（Hp）分别更名为 mccA（蛋氨酸向半胱氨酸转化基因 A）和 mccB。
