Strong current response to slow modulation: A metabolic case-study

We study the current response to periodic driving of a crucial biochemical reaction network, namely, substrate inhibition. We focus on the conversion rate of substrate into product under time-varying metabolic conditions, modeled by a periodic modulation of the product concentration. We find that the system exhibits a strong nonlinear response to small driving frequencies both for the mean time-averaged current and for the fluctuations. For the first, we obtain an analytic formula by coarse-graining the original model to a solvable one. The result is nonperturbative in the modulation amplitude and frequency. We then refine the picture by studying the stochastic dynamics of the full system using a large deviation approach that allows us to show the resonant effect at the level of the time-averaged variance and signal-to-noise ratio. Finally, we discuss how this nonequilibrium effect may play a role in metabolic and synthetic networks.