The acetyl coenzyme A synthase (ACS) enzyme plays a central role in the metabolism of anaerobic bacteria and archaea, catalyzing the reversible synthesis of acetyl-CoA from CO and a methyl group through a series of nickel-based organometallic intermediates. Owing to the extreme complexity of the native enzyme systems, the mechanism by which this catalysis occurs remains poorly understood. In this work, we have developed a protein-based model for the Ni_P center of acetyl coenzyme A synthase using a nickel-substituted azurin protein (NiAz). NiAz is the first model nickel protein system capable of accessing three (Ni^I/Ni^II/Ni^III) distinct oxidation states within a physiological potential range in aqueous solution, a critical feature for achieving organometallic ACS activity, and binds CO and −CH₃ groups with biologically relevant affinity. Characterization of the Ni^I–CO species through spectroscopic and computational techniques reveals fundamentally similar features between the model NiAz system and the native ACS enzyme, highlighting the potential for related reactivity in this model protein. This work provides insight into the enzymatic process, with implications toward engineering biological catalysts for organometallic processes.

中文翻译：

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镍金属蛋白模型中的多电子化学：乙酰辅酶A合酶的机制意义。

乙酰辅酶A合酶（ACS）酶在厌氧细菌和古细菌的代谢中起关键作用，通过一系列镍基有机金属中间体催化从CO和甲基可逆合成乙酰辅酶A。由于天然酶系统的极端复杂性，对该催化发生的机理仍知之甚少。在这项工作中，我们使用镍取代的天青蛋白（NiAz）开发了基于蛋白质的乙酰辅酶A合酶Ni _P中心模型。NiAz是第一个能够访问三种（Ni ^I / Ni ^II / Ni ^III）在水溶液的生理电势范围内具有独特的氧化态，这是实现有机金属ACS活性的关键特征，并以生物学相关的亲和力结合CO和-CH ₃基团。通过光谱学和计算技术对Ni ^I –CO物种的表征揭示了模型NiAz系统与天然ACS酶之间基本相似的特征，从而突出了该模型蛋白中相关反应的潜力。这项工作提供了对酶促过程的深入了解，对工程化有机金属过程的生物催化剂具有启示意义。