Boosting of enzymatic cascades by intermediates: Theoretical analysis and model-based optimization

A recent paper demonstrated that adding intermediates of an enzymatic cascade reaction at the start of the reaction process can increase the space-time yield significantly. This method was coined boosting by intermediates (BBI) and can potentially increase the productivity of enzymatic cascade reaction systems. BBI remains largely unexplored, and its mechanism, potential, and limitations are not fully understood. In this short communication, the theoretical background of the method is revealed by studying four chemical reaction networks that exhibit boosting through intermediates. The dynamics of these networks are studied via the quasi-steady state approximation and numerical solutions. A novel graphical method that can be used to deduce which intermediates boost linear, redox-neutral enzymatic cascade reaction networks is presented. Further, how such a reaction process can be designed using model-based optimization is demonstrated.