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.