Interplay of Gene Expression Noise and Ultrasensitive Dynamics Affects Bacterial Operon Organization
A. When copy numbers of enzymes A and B are matched, transient changes in production and consumption flux are matched, resulting in maintenance of a low concentration of metabolic intermediate. An increase in expression of A, unmatched by a change in expression of B, can cause the production flux of metabolic intermediate to exceed the saturation point of flux through enzyme B, resulting in accumulation of metabolic intermediate. B. Simulated timecourse of metabolic intermediate in cotranscribed and uncoupled configurations of the linear metabolic pathway model. C. Steady state response of metabolic intermediate to changes in the ratio of production flux to consumption flux (solid line), with stochastic simulation timecourses of intermediate in cotranscribed and uncoupled linear metabolic pathway module configurations plotted with respect to changing flux balance. Results represent the single ribosome binding site model (translational coupling), but are qualitatively the same for multiple ribosome binding sites as well.