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Engineered synthetic one-carbon fixation exceeds yield of the Calvin Cycle

Dronsella, B. B.; Orsi, E.; Benito-Vaquerizo, S.; Glatter, T.; Bar-Even, A.; Erb, T. J.; Claassens, N. J.

2022-10-20 synthetic biology
10.1101/2022.10.19.512895 bioRxiv
Show abstract

One-carbon (C1) feedstocks derived from CO2 and renewable electricity, such as formate, are promising substrates for sustainable production of chemicals, food and fuels. Energetically more efficient, engineered C1-fixation pathways were proposed to increase biomass yields above their natural counterparts, but have so far not been shown to achieve this. Here, we replace the native energy-inefficient Calvin-Benson-Bassham (CBB) cycle in Cupriavidus necator by genomic integration of the synthetic reductive glycine pathway for growth on formate. Our final engineered strain reaches a higher biomass yield than the CBB-cycle-utilizing wild type, showing for the first time that efficiencies found in natural metabolism can be exceeded via a synthetic pathway. This yield increase demonstrates the potential of synthetic metabolism and is an important step towards realizing truly sustainable, economically feasible bio-based production.

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