Catalysts speed up reactions that would otherwise be slow or require harsh conditions. In biological systems, enzymes often rely on helper molecules, cofactors, that can beexpensive and unstable for industrial use. Self-sufficient heterogeneous biocatalysts(ssHBs) offer a new generation of catalytic systems in which both enzyme and cofactorare co-immobilized on the same porous support, enabling cofactor recycling andreducing operating costs.

But how do these systems actually work? In this study, we combined theoretical modeling and experimental data to uncover the rules that govern ssHB performance.Inspired by the Sabatier principle, we proposed that maximum enzyme activity isachieved when cofactor binding is neither too strong nor too weak. Our model linksenzyme activity to the thermodynamics of cofactor-polymer interactions and predictsa characteristic volcano-shaped activity curve. We validated this with NADH-dependent dehydrogenases immobilized on cationic polymer-coated agarose beads.This work opens the door to the rational design of more efficient and economicalbiocatalytic systems.