Chemostat‐cultivated Escherichia coli at high dilution rate: Multiple steady states and drift

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Abstract
The representation of metabolic network reaction kinetics in a scaled, polynomial form can allow for the prediction of multiple steady states. The polynomial formalism is used to study chemostat‐cultured Escherichia coli which has been observed to exhibit two multiple steady states under ammonium ion‐limited growth conditions: a high cell density–low ammonium ion concentration steady state and a low cell density–high ammonium ion concentration steady state. Additionally, the low‐cell‐density steady state has been observed to drift to the high‐cell‐density steady state. Inspection of the steady‐state rate expressions for the ammonium ion transport/assimilation network (in polynomial form) suggests that at low ammonium ion concentrations, two steady states are possible. One corresponds to heavy use of the glutamine synthetase‐glutamate synthase (GLNS–GS) branch and the second to heavy use of the glutamate dehydrogenase (GDH) branch. Realization of the predicted intracellular steady states is also found to be dependent on the parameters of the transport process. Moreover, the two steady states differ in where their energy intensity lies. To explain the drift, GLNS, which is inducible under low ammonium ion concentrations, is suggested to be a “memory element.” A chemostat‐based model is developed to illustrate that perturbations in dilution rate can lead to drift between the two steady states provided that the disturbance in dilution rate is sufficiently large and/or long in duration.