Synthetic Formatotrophs for One‐Carbon Biorefinery

The use of CO(2) as a carbon source in biorefinery is of great interest, but the low solubility of CO(2) in water and the lack of efficient CO(2) assimilation pathways are challenges to overcome. Formic acid (FA), which can be easily produced from CO(2) and more conveniently stored and transported than CO(2), is an attractive CO(2)‐equivalent carbon source as it can be assimilated more efficiently than CO(2) by microorganisms and also provides reducing power. Although there are native formatotrophs, they grow slowly and are difficult to metabolically engineer due to the lack of genetic manipulation tools. Thus, much effort is exerted to develop efficient FA assimilation pathways and synthetic microorganisms capable of growing solely on FA (and CO(2)). Several innovative strategies are suggested to develop synthetic formatotrophs through rational metabolic engineering involving new enzymes and reconstructed FA assimilation pathways, and/or adaptive laboratory evolution (ALE). In this paper, recent advances in development of synthetic formatotrophs are reviewed, focusing on biological FA and CO(2) utilization pathways, enzymes involved and newly developed, and metabolic engineering and ALE strategies employed. Also, future challenges in cultivating formatotrophs to higher cell densities and producing chemicals from FA and CO(2) are discussed.