The mechanism of acetyl-CoA synthase through the lens of a nickel model system
Abstract Given the urgent need to develop new methods of CO2/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-char...
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60163-z |
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| author | Shounak Nath Leonel Griego Liviu M. Mirica |
| author_facet | Shounak Nath Leonel Griego Liviu M. Mirica |
| author_sort | Shounak Nath |
| collection | DOAJ |
| description | Abstract Given the urgent need to develop new methods of CO2/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 NiII(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. |
| format | Article |
| id | doaj-art-e68dfd9e7db84031ab45bfcfdfced5c7 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e68dfd9e7db84031ab45bfcfdfced5c72025-08-20T02:05:38ZengNature PortfolioNature Communications2041-17232025-06-0116111010.1038/s41467-025-60163-zThe mechanism of acetyl-CoA synthase through the lens of a nickel model systemShounak Nath0Leonel Griego1Liviu M. Mirica2Department of Chemistry, University of Illinois Urbana-ChampaignDepartment of Chemistry, University of Illinois Urbana-ChampaignDepartment of Chemistry, University of Illinois Urbana-ChampaignAbstract Given the urgent need to develop new methods of CO2/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 NiII(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.https://doi.org/10.1038/s41467-025-60163-z |
| spellingShingle | Shounak Nath Leonel Griego Liviu M. Mirica The mechanism of acetyl-CoA synthase through the lens of a nickel model system Nature Communications |
| title | The mechanism of acetyl-CoA synthase through the lens of a nickel model system |
| title_full | The mechanism of acetyl-CoA synthase through the lens of a nickel model system |
| title_fullStr | The mechanism of acetyl-CoA synthase through the lens of a nickel model system |
| title_full_unstemmed | The mechanism of acetyl-CoA synthase through the lens of a nickel model system |
| title_short | The mechanism of acetyl-CoA synthase through the lens of a nickel model system |
| title_sort | mechanism of acetyl coa synthase through the lens of a nickel model system |
| url | https://doi.org/10.1038/s41467-025-60163-z |
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