High CO2 levels drive the TCA cycle backwards towards autotrophy

Lydia Steffens, Eugenio Pettinato, Thomas M. Steiner, Achim Mall, Simone König, Wolfgang Eisenreich () and Ivan A. Berg ()
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Lydia Steffens: University of Münster
Eugenio Pettinato: University of Münster
Thomas M. Steiner: Technische Universität München
Achim Mall: University of Bergen
Simone König: University of Münster
Wolfgang Eisenreich: Technische Universität München
Ivan A. Berg: University of Münster

Nature, 2021, vol. 592, issue 7856, 784-788

Abstract: Abstract It has recently been shown that in anaerobic microorganisms the tricarboxylic acid (TCA) cycle, including the seemingly irreversible citrate synthase reaction, can be reversed and used for autotrophic fixation of carbon1,2. This reversed oxidative TCA cycle requires ferredoxin-dependent 2-oxoglutarate synthase instead of the NAD-dependent dehydrogenase as well as extremely high levels of citrate synthase (more than 7% of the proteins in the cell). In this pathway, citrate synthase replaces ATP-citrate lyase of the reductive TCA cycle, which leads to the spending of one ATP-equivalent less per one turn of the cycle. Here we show, using the thermophilic sulfur-reducing deltaproteobacterium Hippea maritima, that this route is driven by high partial pressures of CO2. These high partial pressures are especially important for the removal of the product acetyl coenzyme A (acetyl-CoA) through reductive carboxylation to pyruvate, which is catalysed by pyruvate synthase. The reversed oxidative TCA cycle may have been functioning in autotrophic CO2 fixation in a primordial atmosphere that is assumed to have been rich in CO2.

Date: 2021
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DOI: 10.1038/s41586-021-03456-9

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