Design and implementation of aerobic and ambient CO2-reduction as an entry-point for enhanced carbon fixation
The direct reduction of CO<sub>2</sub> into one-carbon molecules is key to highly efficient biological CO<sub>2</sub>-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 CO<sub>2</sub> to formate at aerobic conditions and ambient CO<sub>2</sub> 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 CO<sub>2</sub>. 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 CO<sub>2</sub> fixation processes such as photosynthesis, and opening avenues for synthetic autotrophy.
Authors
- Virginie Pellouin
- Alain Perret (ORCID: https://orcid.org/0000-0002-8896-1978)
- Vittorio Rainaldi (ORCID: https://orcid.org/0000-0003-3921-368X)
- Maren Nattermann (ORCID: https://orcid.org/0000-0003-0649-8447)
- Matthias Heinemann (ORCID: https://orcid.org/0000-0002-5512-9077)
- Ivan Dubois
- Arren Bar‐Even (ORCID: https://orcid.org/0000-0002-1039-4328)
- Jan Zarzycki (ORCID: https://orcid.org/0000-0002-6307-6497)
- Ari Satanowski (ORCID: https://orcid.org/0000-0003-0775-4799)
- Volker Döring (ORCID: https://orcid.org/0000-0002-9453-6572)
- Jean‐Louis Petit (ORCID: https://orcid.org/0000-0002-8566-0571)
- Simon Burgener (ORCID: https://orcid.org/0000-0003-3703-168X)
- Hai He (ORCID: https://orcid.org/0000-0003-1223-2813)
- Edward Smith (ORCID: https://orcid.org/0000-0002-6628-323X)
- Madeleine Bouzon (ORCID: https://orcid.org/0000-0002-9581-6584)
- Daniel G. Marchal (ORCID: https://orcid.org/0009-0002-1314-4583)
- Tobias J. Erb (ORCID: https://orcid.org/0000-0003-3685-0894)
- Nicole Paczia (ORCID: https://orcid.org/0000-0003-3859-8186)
- Henrik M. Petri (ORCID: https://orcid.org/0009-0003-1147-4826)
Institutions
- Centre National de la Recherche Scientifique (FR)
- University of Groningen (NL)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Université Paris-Saclay (FR)
- Max Planck Institute of Molecular Plant Physiology (DE)
- Genoscope (FR)
- CEA Paris-Saclay (FR)
- Loewe Center for Synthetic Microbiology (DE)
- Max Planck Institute for Terrestrial Microbiology (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1038/s41467-025-57549-4
- Citations
- 19
- Primary Topic
- Microbial Metabolic Engineering and Bioproduction
- Type
- article
- Field-Weighted Citation Impact
- 15.31
Funders
- International Max Planck Research School for Environmental, Cellular and Molecular Microbiology
- European Commission
- Max-Planck-Gesellschaft
- Horizon 2020 Framework Programme
- Deutsches Elektronen-Synchrotron