Nath Shounak, Griego Leonel, Mirica Liviu M
Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Nat Commun. 2025 Jun 4;16(1):5177. doi: 10.1038/s41467-025-60163-z.
Given the urgent need to develop new methods of CO/CO utilization, understanding the mechanism of acetyl-CoA synthase (ACS)-a primordial nickel-containing enzyme that converts these gases into a source of cellular energy-is crucial; however, conflicting hypotheses and a dearth of well-characterized bioorganometallic intermediates have hindered a proper understanding of its mechanism. Herein, we report a functional model system that supports several organometallic intermediates proposed for ACS, including the long sought-after Ni(methyl)(CO) species, and promotes all key reaction steps during catalysis: methylation, carbonylation, and thiolysis. Our investigations provide the following key mechanistic insights that are directly relevant to ACS: (i) the binding of a second CO molecule to the Ni center promotes migratory insertion, (ii) both paramagnetic and diamagnetic Ni intermediates are involved, (iii) one-electron oxidation of the Ni(acetyl)(thiolate) species drives a fast reductive elimination, and (iv) a random binding order of the methyl and CO groups to the Ni center is feasible.
鉴于开发一氧化碳（CO）/一氧化碳利用新方法的迫切需求，了解乙酰辅酶A合成酶（ACS）的机制至关重要，ACS是一种原始的含镍酶，可将这些气体转化为细胞能量来源；然而，相互矛盾的假设以及缺乏充分表征的生物有机金属中间体阻碍了对其机制的正确理解。在此，我们报告了一个功能模型系统，该系统支持为ACS提出的几种有机金属中间体，包括长期以来寻找的Ni(甲基)(CO)物种，并促进催化过程中的所有关键反应步骤：甲基化、羰基化和硫解。我们的研究提供了以下与ACS直接相关的关键机制见解：（i）第二个CO分子与Ni中心的结合促进迁移插入，（ii）顺磁性和抗磁性Ni中间体均参与其中，（iii）Ni(乙酰基)(硫醇盐)物种的单电子氧化驱动快速还原消除，以及（iv）甲基和CO基团与Ni中心的随机结合顺序是可行的。
