The mechanism of acetyl-CoA synthase through the lens of a nickel model system

从镍模型系统的角度探讨乙酰辅酶A合成酶的机制

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Abstract

Given the urgent need to develop new methods of CO(2)/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(II)(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.

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