One-carbon fixation via the synthetic reductive glycine pathway exceeds yield of the Calvin cycle

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Abstract

One-carbon feedstocks such as formate could be promising renewable substrates for sustainable microbial production of food, fuels and chemicals. Here we replace the native energy-inefficient Calvin–Benson–Bassham cycle in Cupriavidus necator with the more energy-efficient reductive glycine pathway for growth on formate and CO2. In chemostats, our engineered strain reached a 17% higher biomass yield than the wild type and a yield higher than any natural formatotroph using the Calvin cycle. This shows the potential of synthetic metabolism to realize sustainable, bio-based production.

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Dronsella, B., Orsi, E., Schulz-Mirbach, H., Benito-Vaquerizo, S., Yilmaz, S., Glatter, T., … Claassens, N. J. (2025). One-carbon fixation via the synthetic reductive glycine pathway exceeds yield of the Calvin cycle. Nature Microbiology, 10(3), 646–653. https://doi.org/10.1038/s41564-025-01941-9

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