One-carbon (C1) feedstocks, such as carbon monoxide (CO), formate (HCO2H), methanol (CH3OH), and methane (CH4), can be obtained either through stepwise electrochemical reduction of CO2 with renewable electricity or via processing of organic side streams. These C1 substrates are increasingly investigated in biotechnology as they can contribute to a circular carbon economy. In recent years, noncanonical redox cofactors (NCRCs) emerged as a tool to generate synthetic electron circuits in cell factories to maximize electron transfer within a pathway of interest. Here, we argue that expanding the use of NCRCs in the context of C1-driven bioprocesses will boost product yields and facilitate challenging redox transactions that are typically out of the scope of natural cofactors due to inherent thermodynamic constraints.@en

Fermentation processes are used to sustainably produce chemicals and as such contribute to the transition to a circular economy. The maximum theoretical yield of a conversion can only be approached if all electrons present in the substrate end up in the product. Control over the electrons is therefore crucial. However, electron transfer via redox cofactors results in a diffuse distribution of electrons over metabolism. To overcome this challenge, we propose to apply non-canonical redox cofactors (NRCs) in metabolic networks: cofactors that channel electrons exclusively from substrate to product, forming orthogonal circuits for electron transfer.

@en