Thioester synthesis by a designed nickel enzyme models prebiotic energy conversion.
Thioester synthesis by a designed nickel enzyme models prebiotic energy conversion.
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DOI：
10.1073/pnas.2123022119
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发表时间：
2022-07-26
影响因子：
11.1
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中科院分区：
文献类型：
--
作者：
乙酰辅酶 A 合酶 (ACS) 是原始微生物固碳和节能的基石金属酶，为从二氧化碳生成液体燃料提供了路线图，但 ACS 的工作原理仍存在争议。在这里，我们通过构建一种执行类似化学反应的人造金属酶来深入了解这一过程。我们证明了 NiI 物质和有序底物结合在生物有机金属碳-碳键形成反应中的中介作用。此外，我们还表征了乙酰基镍物质，它能够生化合成活化的硫酯。除了提供理解天然酶机制的框架之外，这项工作还为利用这些化学原理的合成催化剂提供了设计指南，并提供了对生命起源前能量转换过程进化的见解。由二氧化碳等生命前体形成的碳-碳键代表了所有原始生命过程的基础。在现存生物体中，该反应由一氧化碳脱氢酶 (CODH)/乙酰辅酶 A 合酶 (ACS) 进行，该酶在古老的 Wood-Ljungdahl 代谢途径中进行基石反应，合成关键的生物代谢物乙酰辅酶 A。尽管其意义重大，但人们对这种转变缺乏基本的理解，这阻碍了利用类似化学的努力。为了解决这些知识差距，我们在天青蛋白支架内设计了一种人工金属酶，作为 ACS 的结构、功能和机制模型。我们证明了 NiI 物质的中介作用以及在一碳 ACS 底物的生物有机金属碳-碳键形成反应中有序底物结合的要求。使用时间分辨光学、电子顺磁共振和 X 射线吸收光谱结合量子化学计算，对乙酰基镍中间体的电子和几何结构进行了表征。此外，我们证明镍-乙酰基物质在化学上能够在硫醇加成后选择性酰基转移以生物合成活化的硫酯。与天然酶进行类比，提出了通过该 ACS 模型产生硫酯的机制。这种基本的 ACS 模型提供了对酶促过程的基本见解，对原始 ACS 样蛋白的进化具有重要意义。最终，这些发现为开发高活性催化剂提供了策略，用于从一碳基质可持续生成液体燃料，并具有在从能源存储到环境修复等不同领域的广泛应用的潜力。
Acetyl coenzyme A synthase (ACS) is the cornerstone metalloenzyme in carbon fixation and energy conservation in primordial microorganisms and offers a roadmap for generating liquid fuels from carbon dioxide, but how ACS works remains debated. Here we gain insight into this process by constructing an artificial metalloenzyme that performs analogous chemistry. We demonstrate the intermediacy of the NiI species and ordered substrate binding in the bioorganometallic carbon–carbon bond-forming reaction. In addition, we characterize the nickel-acetyl species, which is competent for biochemical synthesis of an activated thioester. Beyond providing a framework for understanding the native enzymatic mechanism, this work provides design guidelines for synthetic catalysts that harness these chemical principles and offers insight into the evolution of prebiotic energy conversion processes. The formation of carbon–carbon bonds from prebiotic precursors such as carbon dioxide represents the foundation of all primordial life processes. In extant organisms, this reaction is carried out by the carbon monoxide dehydrogenase (CODH)/acetyl coenzyme A synthase (ACS) enzyme, which performs the cornerstone reaction in the ancient Wood–Ljungdahl metabolic pathway to synthesize the key biological metabolite, acetyl-CoA. Despite its significance, a fundamental understanding of this transformation is lacking, hampering efforts to harness analogous chemistry. To address these knowledge gaps, we have designed an artificial metalloenzyme within the azurin protein scaffold as a structural, functional, and mechanistic model of ACS. We demonstrate the intermediacy of the NiI species and requirement for ordered substrate binding in the bioorganometallic carbon–carbon bond-forming reaction from the one-carbon ACS substrates. The electronic and geometric structures of the nickel-acetyl intermediate have been characterized using time-resolved optical, electron paramagnetic resonance, and X-ray absorption spectroscopy in conjunction with quantum chemical calculations. Moreover, we demonstrate that the nickel-acetyl species is chemically competent for selective acyl transfer upon thiol addition to biosynthesize an activated thioester. Drawing an analogy to the native enzyme, a mechanism for thioester generation by this ACS model has been proposed. The fundamental insight into the enzymatic process provided by this rudimentary ACS model has implications for the evolution of primitive ACS-like proteins. Ultimately, these findings offer strategies for development of highly active catalysts for sustainable generation of liquid fuels from one-carbon substrates, with potential for broad applications across diverse fields ranging from energy storage to environmental remediation.
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影响因子：
15
作者：
Barondeau, DP;Lindahl, PA
通讯作者：
Lindahl, PA
影响因子：
15
作者：
George, SJ;Seravalli, J;Ragsdale, SW
通讯作者：
Ragsdale, SW
影响因子：
4
作者：
Ariyananda, Piyal W. G.;Kieber-Emmons, Matthew T.;Riordan, Charles G.
通讯作者：
Riordan, Charles G.
影响因子：
56.9
作者：
Huber, C;Eisenreich, W;Wächtershäusher, G
通讯作者：
Wächtershäusher, G
影响因子：
2.5
作者：
Hatsui, T;Takata, Y;Kosugi, N
通讯作者：
Kosugi, N