A metabolic model of cellular energetics and carbon flux during aerobic Escherichia coli fermentation

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Abstract
An integrated metabolic model for the production of acetate by Escherichia coli growing on glucose under aerobic conditions was presented previously (Ko et al., 1993). The resulting model equations can be used to explain phenomena often observed with industrial fermentations, i.e., increased acetate production which follows from high glucose uptake rate, a low dissolved oxygen concentration, a high specific growth rate, or a combination of these conditions. However, several questions still need to be addressed. First, cell composition is growth rate and media dependent. Second, the macromolecular composition varied between E. coli strains. And finally, a model that represents the carbon fluxes between the Embden–Meyerhof–Parnas (EMP) and the hexose monophosphate (HMP) pathways when cells are subject to internal and/or external stresses is still not well defined. In the present work, we have made an effort to account for these effects, and the resulting model equations show good agreement for wild‐type and recombinant E. coli experimental data for the acetate concentration, the onset of acetate secretion, and cell yield based on glucose. These results are useful for optimizing aerobic E. coli fermentation processes. More specifically, we have determined the EMP pathway carbon flux profiles required by the integrated metabolic model for an accurate fit of the acetic acid profile data from a wild‐type E. coli strain ML308. These EMP carbon flux profiles were correlated with a dimensionless measurement of biomass and then used to predict the acetic acid profiles for E. coli strain F‐122 expressing human immunodeficiency virus‐(HIV528) β‐galactosidase fusion protein. The effect of different macromolecular compositions and growth rates between these two E. coli strains required a constant scaling factor for improved quantitative predictions.