Aerobic synthesis of vitamin B12:: ring contraction and cobalt chelation

Aerobic synthesis of vitamin B12:: ring contraction and cobalt chelation
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DOI:
10.1042/bst0330815
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发表时间:
2005-08-01
影响因子:
3.9
通讯作者:
Warren, MJ
Warren, MJ
中科院分区:
生物学3区
文献类型:
--
作者:
Heldt, D;Lawrence, AD;Warren, MJ

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综述了维生素 B-12(钴胺素)生物合成的有氧生物合成途径。特别关注环收缩过程,由此除去四吡咯衍生的大环的完整碳原子。之前的工作已经证实,这一化学要求较高的步骤是通过一种称为 CobG 的单加氧酶的作用来促进的,该酶会生成羟基内酯中间体。这种单加氧酶同时含有非血红素铁和 Fe-S 中心,但有关其机制的信息知之甚少。最近的研究表明,在荚膜红杆菌等细菌中,CobG 被一种称为 CobZ 的同功能蛋白取代。该蛋白质已被证明含有黄素、血红素和铁硫中心。提出了一种机制来解释 CobZ 的功能。有氧钴胺素生物合成途径的另一个有趣的方面是钴插入,它与叶绿素合成中的镁螯合过程有一些相似之处。讨论了钴螯合的遗传要求和随后金属离子的还原。
The aerobic biosynthetic pathway for vitamin B-12 (cobalamin) biosynthesis is reviewed. Particular attention is focused on the ring contraction process, whereby an integral carbon atom of the tetrapyrrole-derived macrocycle is removed. Previous work had established that this chemically demanding step is facilitated by the action of a mono-oxygenase called CobG, which generates a hydroxy lactone intermediate. This mono-oxygenase contains both a non-haem iron and an Fe-S centre, but little information is known about its mechanism. Recent work has established that in bacteria such as Rhodobacter capsulatus, CobG is substituted by an isofunctional protein called CobZ. This protein has been shown to contain flavin, haem and Fe-S centres. A mechanism is proposed to explain the function of CobZ. Another interesting aspect of the aerobic cobalamin biosynthetic pathway is cobalt insertion, which displays some similarity to the process of magnesium chelation in chlorophyll synthesis. The genetic requirements of cobalt chelation and the subsequent reduction of the metal ion are discussed.