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

One-carbon (C1) feedstocks like formate could be energetically efficient substrates for sustainable microbial production of food, fuels and chemicals. Here, we replace the native energy-inefficient Calvin-Benson-Bassham (CBB) cycle in Cupriavidus necator with the more energy-efficient reductive glycine pathway for growth on formate and CO2. In chemostats, our engineered strain reaches a 17% higher biomass yield than the wild type, or any natural formatotroph using the Calvin cycle. This demonstrates the potential of synthetic metabolism to realize sustainable, bio-based production.