In a pioneering work, the chemists Prof. Petra Wendler and Dr. Jakob Ruickoldt achieved outstanding success. With the help of revolutionary cryo-electron microscopy, they unraveled the reaction cycle of the enzyme complex CO-dehydrogenase-acetyl-CoA-synthase (CODH/ACS). This complex of enzymes has been conserved in living entities for some 3.5 billion years of evolution. First, it serves as an essential input for powering next-generation biotechnological carbon fixation processes. The work was recently published by researchers in the journal Nature Catalysis. This effort is a major step forward in our understanding of the enzymatic processes underlying carbon dioxide fixation.
The research used a technique called high-resolution cryo-electron microscopy to study complex enzymatic processes down to the molecular detail. Ruickoldt and Wendler fabricated the sample holder and loaded samples for analysis. This painstaking effort resulted in a level of clarity to their observations that was unparalleled. This approach allowed them to probe six different, intermediate states of CODH/ACS. They explored how different molecules interact with the active center throughout the enzyme’s reaction cycle.
Insights from Cryo-Electron Microscopy
Cryo-electron microscopy (cryo-EM) has emerged as a valuable resource in this research. This gave the researchers unprecedented insight into the binding states of CODH/ACS. It was the first time they had looked into this with the help of this approach. According to Prof. Wendler, “The different binding states of CODH/ACS have not yet been investigated using cryo-EM.”
Additional innovation and insight led the researchers to the astonishing conclusion that CO reacts with a methyl group and coenzyme A to generate acetyl-CoA. This finding is crucial, as it describes for the first time how the complex machinery that executes carbon fixation works. Dr. Ruickoldt elaborated on their findings:
“Our cryo-EM maps of six intermediate states of the CODH/ACS are so highly resolved that the molecules bound to the metal center can be clearly correlated with the movements of the protein.”
These insights provide a molecular-level understanding of how selective interaction with the active site promotes reactive intermediate stabilization to drive reaction evolution toward productive outcomes.
Importance of Preventing Side Reactions
Crio-electron microscopy provides a key benefit in this investigation. It inhibits side reactions and maintains useful reaction intermediates. The researchers underscored how valuable this new insight is. It is the key to unlocking the full catalytic potential of this ancient enzyme complex for biotechnological applications.
As the world pays more attention to sustainability, knowing how to achieve and maximize efficient carbon fixation processes is key.
“By using this method, we have discovered how the binding of the different molecules prepares the active center for the next reaction step and thus prevents side reactions and the loss of valuable reaction intermediates. This knowledge will help to utilize the catalysis of the ancient enzyme complex for biotechnological carbon fixation.”
The results of this study identify new directions for research into CO2 fixation methods going forward. Fortunately, scientists are furiously working to create new carbon capture and storage technologies. Lessons gained from CODH/ACS can propel future biotechnological innovations needed to address climate change and other challenges.
Implications for Future Research
The research is available under its DOI 10.1038/s41929-025-01365-y and was freely downloaded on July 14, 2025 from phys.org. The impact of this research goes beyond fundamental science — it may help shape future approaches to environmental improvement and carbon reduction.
The study has been made accessible through its DOI 10.1038/s41929-025-01365-y and was retrieved on July 14, 2025, from phys.org. The implications of this research extend beyond basic science, potentially influencing future strategies for environmental sustainability and carbon management.