Artificial mediators, protein carriers, and catalyst architecture in C1 bioconversion

Biological conversion of one-carbon (C1) feedstocks frequently requires coupling oxidative and reductive reactions through an appropriate electron-transfer pathway. The combination of carbon monoxide dehydrogenase (CODH), which oxidizes CO to CO₂, and formate dehydrogenase (FDH), which reduces CO₂ to formate, serves as a representative model for examining this requirement. CODH-FDH coupling has been investigated in cell-free systems, whereas intracellular and distributed configurations provide emerging or prospective routes for extending this reaction across different biological environments. However, the relationship between electron carrier selection and system implementation is not one-to-one. Small artificial mediators such as viologens can connect physically separated enzymes or cells when they can access the relevant redox components, whereas protein carriers such as ferredoxins generally favor arrangements in which compatible partners share an accessible intracellular environment. When reactions are divided between cell populations, the connection may instead depend on a diffusible redox metabolite or an engineered conductive interface. Carrier mobility, accessibility across physical boundaries, partner recognition, and chemical stability constrain the range of system arrangements available for C1 bioconversion. Using CODH and FDH as a representative model, this Mini Review examines how electron-carrier properties and spatial organization shape C1 bioconversion architectures under process-relevant conditions.