Reinforcing carbon fixation: CO 2 reduction replacing and supporting carboxylation

Carbon dioxide enters the biosphere via one of two mechanisms: carboxylation, in which CO is attached to an existing metabolite, or reduction, in which CO 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 -capturing enzymes, and the resource consumption of the subsequent pathways. We show that the best CO reducing enzymes can compete with the best carboxylases. We further demonstrate that pathways that fix CO 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 reduction. We believe that pathways based on CO reduction are a valuable addition to nature's arsenal for capturing inorganic carbon and could provide promising metabolic solutions that have been previously overlooked.