Design and implementation of aerobic and ambient CO2-reduction as an entry-point for enhanced carbon fixation

Ari Satanowski (), Daniel G. Marchal, Alain Perret, Jean-Louis Petit, Madeleine Bouzon, Volker Döring, Ivan Dubois, Hai He, Edward N. Smith, Virginie Pellouin, Henrik M. Petri, Vittorio Rainaldi, Maren Nattermann, Simon Burgener, Nicole Paczia, Jan Zarzycki, Matthias Heinemann, Arren Bar-Even and Tobias J. Erb ()
Additional contact information
Ari Satanowski: Max Planck Institute for Terrestrial Microbiology
Daniel G. Marchal: Max Planck Institute for Terrestrial Microbiology
Alain Perret: Université Paris-Saclay
Jean-Louis Petit: Université Paris-Saclay
Madeleine Bouzon: Université Paris-Saclay
Volker Döring: Université Paris-Saclay
Ivan Dubois: Université Paris-Saclay
Hai He: Max Planck Institute for Terrestrial Microbiology
Edward N. Smith: University of Groningen
Virginie Pellouin: Université Paris-Saclay
Henrik M. Petri: Max Planck Institute for Terrestrial Microbiology
Vittorio Rainaldi: Max Planck Institute of Molecular Plant Physiology
Maren Nattermann: Max Planck Institute for Terrestrial Microbiology
Simon Burgener: Max Planck Institute for Terrestrial Microbiology
Nicole Paczia: Max Planck Institute for Terrestrial Microbiology
Jan Zarzycki: Max Planck Institute for Terrestrial Microbiology
Matthias Heinemann: University of Groningen
Arren Bar-Even: Max Planck Institute of Molecular Plant Physiology
Tobias J. Erb: Max Planck Institute for Terrestrial Microbiology

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract The direct reduction of CO2 into one-carbon molecules is key to highly efficient biological CO2-fixation. However, this strategy is currently restricted to anaerobic organisms and low redox potentials. In this study, we introduce the CORE cycle, a synthetic metabolic pathway that converts CO2 to formate at aerobic conditions and ambient CO2 levels, using only NADPH as a reductant. Combining theoretical pathway design and analysis, enzyme bioprospecting and high-throughput screening, modular assembly and adaptive laboratory evolution, we realize the CORE cycle in vivo and demonstrate that the cycle supports growth of E. coli by supplementing C1-metabolism and serine biosynthesis from CO2. We further analyze the theoretical potential of the CORE cycle as a new entry-point for carbon in photorespiration and autotrophy. Overall, our work expands the solution space for biological carbon reduction, offering a promising approach to enhance CO2 fixation processes such as photosynthesis, and opening avenues for synthetic autotrophy.

Date: 2025
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DOI: 10.1038/s41467-025-57549-4

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