Anaerobic carbon fixation in ancient prokaryotes

Most of us were taught that plants are the main source of fixing carbon from carbon dioxide. Some of us even had to memorize the enzymes and reactions of the Calvin Cycle including the complicated reaction catalyzed by rubisco, the main CO₂ fixing enzyme. [Fixing Carbon: the Rubisco Reaction].

We were led to believe that plants were the main source of sugars and other organic molecules but that's because undergraduate biochemistry education emphasizes human biochemistry. Photosynthesis and plants are only important because they are food. We were also taught, incorrectly, that photosynthesis is defined as a carbon-fixation process. [What is photosynthesis?]

It turns out that the Calvin Cycle isn't restricted to plants and it doesn't even require oxygen. Anaerobic bacteria also have a version of the Calvin Cycle and they are perfectly capable of fixing carbon without a major energy source like photosynthesis. [Carbon Dioxide Fixation in the Dark Ocean]

This makes sense since the earliest forms of life had to be able to turn inorganic molecules (e.g. CO₂) into organic molecules so they had to be able to fix carbon. Current models of the origin of life are referred to as Metabolism First models because they postulate that life began with simple metabolic reactions that made organic molecules from inorganic molecules. One of the most important of these early reactions is the fixation of two molecules of CO₂ into a two carbon compound (acetate).

This early pathway is thought to resemble the modern Wood-Ljungdahl pathway (WLP) that's common in bacteria. It is responsible for about 20% of biological carbon fixation today. The pathway is also known as the reductive acetyl-coenzyme A (acetyl-CoA) pathway and the main enzymes responsible for this reaction are carbon monoxide dehydrogenase (CODH) and acetyl-CoA synthase (ACS).

The two enzymes form a complex where the first step is the conversion of CO₂ to CO (carbon monoxide) and the second step is the joining of two carbons to produce acetate as shown in this figure from a news article in Science.

The figure is based on a paper by Yin et al. (2025) in the same issue of Science. Yin et al. worked out the mechanism from a cryo-EM version of the structure. The most interesting part of the mechanism is that it involves multiple iron-sulphur-nickel complexes ([4Fe-4S]-Ni-Ni) and that probably reflect the ancient mechanism that was catalyzed by iron complexes before proteins evolved.

Note also that the reaction does not require large inputs of external energy in the form of ATP.

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Yin, M.D., Lemaire, O.N., Rosas Jiménez, J.G., Belhamri, M., Shevchenko, A., Hummer, G., Wagner, T. and Murphy, B.J. (2025) Conformational dynamics of a multienzyme complex in anaerobic carbon fixation. Science 387:498-504. doi: [