Researchers from the Institut de Biologie Structurale, the Max Planck Institute for Marine Microbiology, and the Max Planck Institute of Molecular Cell Biology and Genetics have unraveled a key step in the conversion of the toxic carbon monoxide into ethanol performed by the bacterium Clostridium autoethanogenum.
The study, published in Nature Chemical Biology, reveals the key role of a tungsten-containing enzyme in this remarkable process, bringing new insight into the sustainable production of biofuels from industrial gases.
Converting a toxic waste gas into an energetic resource : a solved mystery
Clostridium autoethanogenum is a fascinating microbe capable of surviving on pure carbon monoxide (CO), a gas deadly to most living organisms, including human beings. The gas is mainly converted into ethanol, making the microbe a promising actor in the synthesis of biofuels. Yet, despite its industrial relevance, the exact mechanism by which this organism converts CO into alcohol has remained poorly understood until now. Notably, one of the steps proposed in the process, the conversion of acetate into acetaldehyde, was questioned within the scientific community.
In this work, the researchers demonstrated that aldehyde:ferredoxin oxidoreductase (AFOR) is responsible for the key step in cellular ethanol production. AFOR is notable for containing tungsten, the heaviest element used in biological systems. The scientists succeeded in purifying the enzyme and resolved its three-dimensional structure at atomic resolution using X-ray crystallography, thus allowing them to describe the precise organization of the tungsten-based catalytic site and its surroundings.
After extensive experimentation, the researchers also found a way to reactivate the enzyme, which was initially inactive after purification. They were then able to demonstrate the enzyme’s ability to reduce a wide range of substrates, paving the way for the production of alcohols other than ethanol.
An unfavorable reaction is enabled through enzymatic cooperation
To confirm that the reaction could indeed take place in living cells, the researchers reconstituted an artificial enzymatic pathway in vitro. By recreating the enzymatic coupling occurring in the cell, they demonstrated that the conversion of acetate to ethanol is biologically achievable under physiological conditions.
These results fill a gap in our understanding of the metabolism of C. autoethanogenum and pave the way for new metabolic engineering strategies for the production of biofuels and molecules of interest from industrial gases. This breakthrough represents a further step towards a circular carbon economy, where waste gases could become renewable energy resources.
References : Carbon monoxide-driven bioethanol production operates via a tungsten-dependent catalyst. Olivier N. Lemaire, Mélissa Belhamri, Anna Shevchenko, Tristan Wagner. Nature Chemical Biology 2025 ; https://www.nature.com/articles/s41589-025-02055-3
Contact : Tristan Wagner & Olivier Lemaire (IBS/Extremophiles and Large Molecular Assemblies Group)