Design principles and control of non-cooperative oscillatory enzymatic reactions

Oscillatory phenomena are often observed in enzyme systems due to feedback regulation, with a classic motif for persistent oscillation being a three-component negative feedback loop. Delay and high cooperativity are proposed as essential for the oscillation in these motifs. This study focuses on designing and optimizing oscillatory biochemical reactions using three-node enzymatic networks without cooperativity. Our findings revealed that improving the specificity constant – the so-called kinetic efficiency – and selecting the optimal topology can greatly increase the probability and frequency of oscillation in biochemical reactions. Inspired by pharmacology, various moderators were utilized to enhance the specificity constant, demonstrating how various oscillatory regimes can be reached with a given topology.