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Updated: Jun 26, 2025

Versatile CO2 Transformations into Complex Products: A One-pot Two-step Strategy
Published on: November 9, 2019
Coupling CO2 Reduction and Acetyl-CoA Formation: The Role of a CO Capturing Tunnel in Enzymatic Catalysis
Jakob Ruickoldt1, Jae-Hun Jeoung1, Maik Alexander Rudolph2
1Humboldt-Universität zu Berlin, Institut für Biologie, Unter den Linden 6, 10099, Berlin, Germany.
Abstract:
The bifunctional CO-dehydrogenase/acetyl-CoA synthase (CODH/ACS) complex couples the reduction of CO2 to the condensation of CO with a methyl moiety and CoA to acetyl-CoA. Catalysis occurs at two sites connected by a tunnel transporting the CO. In this study, we investigated how the bifunctional complex and its tunnel support catalysis using the CODH/ACS from Carboxydothermus hydrogenoformans as a model. Although CODH/ACS adapted to form a stable bifunctional complex with a secluded substrate tunnel, catalysis and CO transport is even more efficient when two monofunctional enzymes are coupled. Efficient CO channeling appears to be ensured by hydrophobic binding sites for CO, which act in a bucket-brigade fashion rather than as a simple tube. Tunnel remodeling showed that opening the tunnel increased activity but impaired directed transport of CO. Constricting the tunnel impaired activity and CO transport, suggesting that the tunnel evolved to sequester CO rather than to maximize turnover.
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