Reinforcing carbon fixation: CO2 reduction replacing and supporting carboxylation

Carbon dioxide enters the biosphere via one of two mechanisms: carboxylation, in which CO 2 is attached to an existing metabolite, or reduction, in which CO 2 is converted to formate or carbon monoxide before further assimilation. Here, we focus on the latter mechanism which usually receives less attention. To better understand the possible advantages of the ‘reduction-first’ approach, we compare the two general strategies according to the kinetics of the CO 2 -capturing enzymes, and the resource consumption of the subsequent pathways. We show that the best CO 2 reducing enzymes can compete with the best carboxylases. We further demonstrate that pathways that fix CO 2 by first reducing it to formate could have an advantage over the majority of their carboxylation-only counterparts in terms of ATP-efficiency and hence biomass yield. We discuss and elaborate on the challenges of implementing ‘reduction-first’ pathways, including the thermodynamic barrier of CO 2 reduction. We believe that pathways based on CO 2 reduction are a valuable addition to nature's arsenal for capturing inorganic carbon and could provide promising metabolic solutions that have been previously overlooked.