Stochasticity in Metabolism: Oxidative Stress Response Phenotypes As Emergent Consequences of Network Topology

Bimodal killing under H2O2 stress is computationally recapitulated in the Escherichia coli iJO1366 genome-scale metabolic model, emerging from metabolic network topology during stochastic exploration.

• Why it matters: ROS are difficult to measure due to reactivity and short half-lives, and prior simulations were limited by small ODE models and scarce kinetic parameters.
• What they did: The authors recast ROS dynamics as flux-balance analysis using COBRA and CPLEX, augmenting iJO1366 with 84 spontaneous oxidation, 14 redox, and 9 detoxification reactions, then stochastically sampled solutions with GapSplit.
• The result: The killing and survival recovery phases arise solely from network topology, with steady-state conservation biasing detoxification when central carbon metabolism reaches capacity, yielding Mode 1 (spare detoxification via Ahp) and Mode 2 (no spare detoxification).