One pathway can incorporate either adenine or dimethylbenzimidazole as an α-axial ligand of B12 cofactors in Salmonella enterica
One pathway can incorporate either adenine or dimethylbenzimidazole as an α-axial ligand of B12 cofactors in Salmonella enterica
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DOI：
10.1128/jb.01386-07
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发表时间：
2008-02-01
影响因子：
3.2
通讯作者：
Roth, John R.
中科院分区：
文献类型：
--
作者：
Anderson, Peter J.;Lango, Jozsef;Roth, John R.
类柯啉（维生素B-12样）辅因子含有各种α-轴向配体，包括5，6-二甲基苯并咪唑（DMB）或腺嘌呤。肠道沙门氏菌（Salmonella enterica）仅在厌氧条件下产生咕啉环，但它可以通过导入“不完全”的咕啉类化合物（如cobinamide（Cbi））并加入适当的α-和β-轴配体，在有氧条件下形成“完全”的咕啉类化合物。在有氧条件下，S.如果给予维生素B-12，肠杆菌进行乙醇胺的类咕啉依赖性降解，但只有当还提供DMB时，肠杆菌才能从外源性Cbi制备B-12。分离的突变体在不添加DMB的情况下降解乙醇胺的能力将Cbi转化为假B-12辅因子（具有腺嘌呤作为α-轴向配体）。突变导致游离腺嘌呤水平增加，并将腺嘌呤（而不是DMB）作为α-配体。当向这些突变体提供DMB时，假B-12辅因子的合成停止，并产生B-12辅因子，表明DMB调节游离腺嘌呤作为α-配体的产生或掺入。野生型细胞在丙二醇加Cbi的有氧生长过程中产生假B-12辅因子，并且可以将假维生素B-12用于它们所有的类咕啉依赖性酶。辅酶伪B-12辅因子的合成需要在辅酶B-12的形成中安装DMB的相同酶（CobT、CobU、CobS和CobC）。模型描述的机制和控制的α-轴向配体安装。
Corrinoid (vitamin B-12-like) cofactors contain various alpha-axial ligands, including 5,6-dimethylbenzimidazole (DMB) or adenine. The bacterium Salmonella enterica produces the corrin ring only under anaerobic conditions, but it can form "complete" corrinoids aerobically by importing an "incomplete" corrinoid, such as cobinamide (Cbi), and adding appropriate alpha- and beta-axial ligands. Under aerobic conditions, S. enterica performs the corrinoid-dependent degradation of ethanolamine if given vitamin B-12, but it can make B-12 from exogenous Cbi only if DMB is also provided. Mutants isolated for their ability to degrade ethanolamine without added DMB converted Cbi to pseudo-B-12 cofactors (having adenine as an alpha-axial ligand). The mutations cause an increase in the level of free adenine and install adenine (instead of DMB) as an alpha-ligand. When DMB is provided to these mutants, synthesis of pseudo-B-12 cofactors ceases and B-12 cofactors are produced, suggesting that DMB regulates production or incorporation of free adenine as an alpha-ligand. Wild-type cells make pseudo-B-12 cofactors during aerobic growth on propanediol plus Cbi and can use pseudo-vitamin B-12 for all of their corrinoid-dependent enzymes. Synthesis of coenzyme pseudo-B-12 cofactors requires the same enzymes (CobT, CobU, CobS, and CobC) that install DMB in the formation of coenzyme B-12. Models are described for the mechanism and control of alpha-axial ligand installation.