In two studies that have just been published in the renowned journal Nature Catalysis, the research teams show how the two nickel-containing enzymes carbon monoxide dehydrogenase (CODH) and acetyl-CoA synthase (ACS) convert carbon dioxide into activated acetic acid. These detailed insights into the mechanism provide new approaches for the development of synthetic catalysts that could utiliseCO2 as a raw material.
Two enzymes - how structural changes control the reaction
The investigations focus on two enzymes in which nickel and iron ions are linked in a unique way in the active centres: CODH and ACS. These enzymes work hand in hand to convert CO? first into carbon monoxide (CO) and then into acetyl-CoA, an activated acetic acid. This reaction chain is an essential part of the so-called Wood-Ljungdahl pathway, one of the oldest biological processes for carbon fixation. In a study, the scientists from Humboldt-Universit?t zu Berlin, in cooperation with scientists from TU Berlin, showed that the nickel ion in the active centre of CODH not only binds CO?, but also provides the electrons required for the reaction. This flexibility makes the nickel ion the key element in CO? conversion. Using a combination of X-ray diffraction and spectroscopy on enzyme crystals, it was possible for the first time to visualise all catalytically relevant states with the bound reaction partners in the enzyme at atomic resolution.
"Since our first structure of Ni-containing carbon monoxide dehydrogenases in 2001, I have wondered why these enzymes need Ni ions. Only our new work provides an answer, which lies in the unusual coordination of nickel," says Prof Holger Dobbek, head of the Structural Biology and Biochemistry research group at Humboldt-Universit?t zu Berlin. And Yudhajeet Basak, first author of the study, adds: "By understanding the ancient mechanisms ofCO2 fixation, we can apply them to the development of novel catalysts that could accelerate the transition to a carbon-neutral industry."
A complementary study led by Prof. Petra Wendler from the University of Potsdam investigated how the binding of small molecules at the nickel centre of the ACS triggers large-scale structural changes in the enzyme. Using high-resolution cryo-electron microscopy, the researchers were able to visualise six previously unknown intermediate states of the enzyme. The results show that the enzymes do not work rigidly, but that ligand bonds trigger dynamic movements that control the course of the reaction.
Relevance for climate protection and sustainable chemistry
The findings are not only important for basic research. They could also show how biological catalysis principles can be transferred to technical processes. In the future, synthetic catalysts modelled on these enzymes could efficiently convert CO? into valuable chemical products - an important contribution to a more sustainable circular economy.
Further publications
Yudhajeet Basak, Christian Lorent, Jae-Hun Jeoung, Ingo Zebger, Holger Dobbek. Metalloradical-driven enzymaticCO2 reduction by a dynamic Ni--Fe cluster. Nature Catalysis (2025) 10.1038/s41929-025-01388-5
Jakob Ruickoldt, Julian Kreibich, Thomas Bick, Jae-Hun Jeoung, Benjamin Duffus, Silke Leimkühler, Holger Dobbek, Petra Wendler. Ligand binding to a Ni--Fe cluster orchestrates conformational changes of the CO-dehydrogenase--acetyl-CoA synthase complex. Nature Catalysis (2025) 10.1038/s41929-025-01365-y
Contact
Prof Dr Holger Dobbek
Department of Biology, Humboldt-Universit?t zu Berlin
Tel.: 030 2093-49842
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Dr Christian Lorent
Department of Chemistry at the Technical University of Berlin
Prof Dr Petra Wendler
Department of Biology and Biochemistry at the University of Potsdam
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