1071

Structure, function, and biosynthesis of nickel–dependent enzymes

Marila Alfano and Christine Cavazza

Nickel was a key player in catalyst development. However, according to the nickel famine theory, the drastic diminution of nickel availability on earth would be correlated to the existence of only nine nickel enzymes in archaea, bacteria, plants and primitive eukaryotes, while no nickel enzyme has been found in mammalian species. Despite their scarcity, they are often essential, playing key functions in diverse metabolic processes, such as energy metabolism and virulence, and functioning as either redox or non‐redox enzymes. These enzymes often possess unique metallocofactors, requiring highly specific and complex biosynthetic pathways. Nickel enzymes, present in archaea, bacteria, plants and primitive eukaryotes are divided into redox and non‐redox enzymes and play key functions in diverse metabolic processes, such as energy metabolism and virulence. They catalyze various reactions by using active sites of diverse complexities, such as mononuclear nickel in Ni‐superoxide dismutase, glyoxylase I and acireductone dioxygenase, dinuclear nickel in urease, heteronuclear metalloclusters in [NiFe]‐carbon monoxide dehydrogenase, acetyl‐CoA decarbonylase/synthase and [NiFe]‐hydrogenase, and even more complex cofactors in methyl‐CoM reductase and lactate racemase. The presence of metalloenzymes in a cell necessitates a tight regulation of metal homeostasis, in order to maintain the appropriate intracellular concentration of nickel while avoiding its toxicity. As well, the biosynthesis and insertion of nickel active sites often require specific and elaborated maturation pathways, allowing the correct metal to be delivered and incorporated into the target enzyme. In this review, the phylogenetic distribution of nickel enzymes will be briefly described. Their tridimensional structures as well as the complexity of their active sites will be discussed. In view of the latest findings on these enzymes, a special focus will be put on the biosynthesis of their active sites and nickel activation of apo‐enzymes. https://onlinelibrary.wiley.com/doi/abs/10.1002/pro.3836

中文翻译：

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1071

镍依赖性酶的结构，功能和生物合成

玛莉拉·阿尔法诺（Marila Alfano）和克里斯汀·卡瓦扎（Christine Cavazza）

镍是催化剂开发中的关键角色。但是，根据饥荒镍理论，地球上镍的利用率急剧下降与古细菌，细菌，植物和原始真核生物中仅存在9种镍酶有关，而在哺乳动物物种中未发现镍酶。尽管缺乏，但它们通常是必不可少的，它们在多种代谢过程（例如能量代谢和毒力）中发挥关键作用，并充当氧化还原酶或非氧化还原酶。这些酶通常具有独特的金属因子，需要高度特异性和复杂的生物合成途径。存在于古细菌，细菌，植物和原始真核生物中的镍酶分为氧化还原酶和非氧化还原酶，并在多种代谢过程中发挥关键作用，例如能量代谢和毒力。它们通过使用各种复杂性的活性位点来催化各种反应，例如镍超氧化物歧化酶中的单核镍，乙醛酸酶I和降re酮双加氧酶，脲酶中的双核镍，[NiFe]-一氧化碳脱氢酶中的异核金属簇合物，乙酰基-CoA脱羰酶/合酶。和[NiFe]-氢化酶，甚至是甲基-CoM还原酶和乳酸消旋酶中更复杂的辅因子。细胞中金属酶的存在需要严格调节金属稳态，以维持适当的细胞内镍浓度，同时避免其毒性。同样，镍活性位点的生物合成和插入通常需要特定且精心设计的成熟途径，从而可以传递正确的金属并将其掺入目标酶中。在这篇综述中，将简要描述镍酶的系统发育分布。将讨论它们的三维结构及其活动站点的复杂性。鉴于这些酶的最新发现，将特别关注其活性位点的生物合成和脱辅酶的镍活化。https://onlinelibrary.wiley.com/doi/abs/10.1002/pro.3836