Total Synthesis, Structure, and Biological Activity of Adenosylrhodibalamin, the Non-Natural Rhodium Homologue of Coenzyme B12.
Total Synthesis, Structure, and Biological Activity of Adenosylrhodibalamin, the Non-Natural Rhodium Homologue of Coenzyme B12.
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DOI：
10.1002/anie.201603738
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发表时间：
2016-09-05
影响因子：
16.6
通讯作者：
Kraeutler, Bernhard
中科院分区：
文献类型：
--
作者：
Widner, Florian J.;Lawrence, Andrew D.;Deery, Evelyne;Heldt, Dana;Frank, Stefanie;Gruber, Karl;Wurst, Klaus;Warren, Martin J.;Kraeutler, Bernhard
B12 在维生素中是独一无二的，因为它只能由某些原核生物生物合成。其合成的复杂性与其独特的钴咕啉结构有关，该结构对于 B12 生物化学至关重要，并使辅酶 B12 (AdoCbl) 非常适合酶促自由基反应。然而，为什么钴如此适合其在 B12 依赖性酶中的作用？为了解决这个问题，我们考虑用铑取代 AdoCbl 中的钴，生成铑类似物 5'-脱氧-5'-腺苷铑二巴胺 (AdoRbl)。 AdoRbl 通过从头全合成法制备，涉及生物和化学步骤。在蛋氨酸合酶的微生物生物测定中发现 AdoRbl 在体内无活性，并且充当 AdoCbl 依赖性二醇脱水酶的体外抑制剂。 AdoRbl 的溶液 NMR 研究揭示了与 AdoCbl 相似的结构。然而，AdoRbl 的晶体结构表明，corrin 配体与 RhIII 的配合明显优于与 CoIII 的配合，这挑战了当前有关 corrin 进化的观点。
B12 is unique among the vitamins as it is biosynthesized only by certain prokaryotes. The complexity of its synthesis relates to its distinctive cobalt corrin structure, which is essential for B12 biochemistry and renders coenzyme B12 (AdoCbl) so intriguingly suitable for enzymatic radical reactions. However, why is cobalt so fit for its role in B12‐dependent enzymes? To address this question, we considered the substitution of cobalt in AdoCbl with rhodium to generate the rhodium analogue 5′‐deoxy‐5′‐adenosylrhodibalamin (AdoRbl). AdoRbl was prepared by de novo total synthesis involving both biological and chemical steps. AdoRbl was found to be inactive in vivo in microbial bioassays for methionine synthase and acted as an in vitro inhibitor of an AdoCbl‐dependent diol dehydratase. Solution NMR studies of AdoRbl revealed a structure similar to that of AdoCbl. However, the crystal structure of AdoRbl revealed a conspicuously better fit of the corrin ligand for RhIII than for CoIII, challenging the current views concerning the evolution of corrins.
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