Design of oscillatory dynamics in numerical simulations of compartment-based enzyme systems

Enzymatic reactions that yield non-neutral products are known to involve feedback due to the bell-shaped pH-rate curve of the enzyme. Compartmentalizing the reaction has been shown to lead to transport-driven oscillations in theory; however, there have been few reproducible experimental examples. Our objective was to determine how the conditions could be optimized to achieve pH oscillations. We employed numerical simulations to investigate the hydrolysis of ethyl acetate in a confined esterase enzyme system, examining the influence of key factors on its behavior. Specific parameter ranges that lead to bistability and self-sustained pH oscillations and the importance of fast base transport for oscillations in this acid-producing system are highlighted. Suggestions are made to expand the parameter space for the occurrence of oscillations, including modifying the maximum of the enzyme pH-rate curve and increasing the negative feedback rate. This research not only sheds light on the programmable nature of enzyme-driven pH regulation but also furthers knowledge on the optimal design of such feedback systems for experimentalists. (c) 2023 Author(s).