Dynamic modeling of aerobic growth of Shewanella oneidensis. Predicting triauxic growth, flux distributions, and energy requirement for growth

A model-based analysis is conducted to investigate metabolism of Shewanella oneidensis MR-1 strain in aerobic batch culture, which exhibits an intriguing growth pattern by sequentially consuming substrate (i.e., lactate) and by-products (i.e., pyruvate and acetate). A general protocol is presented for developing a detailed network-based dynamic model for S. oneidensis based on the Lumped Hybrid Cybernetic Model (L-HCM) framework. The L-HCM, although developed from only limited data, is shown to accurately reproduce exacting dynamic metabolic shifts, and provide reasonable estimates of energy requirement for growth. Flux distributions in S. oneidensis predicted by the L-HCM compare very favorably with 13C-metabolic flux analysis results reported in the literature. Predictive accuracy is enhanced by incorporating measurements of only a few intracellular fluxes, in addition to extracellular metabolites. The L-HCM developed here for S. oneidensis is consequently a promising tool for the analysis of intracellular flux distribution and metabolic engineering.

► A cybernetic model is developed for S. oneidensis based on limited dynamic growth data. ► The model accurately predicts dynamic metabolic switches exhibiting triauxic growth pattern. ► Predictions made of intracellular flux distributions correlate well with 13C-MFA results. ► Energy requirement for growth is also reasonably estimated from limited data only. ► With these features, the developed model emerges as a promising tool for metabolic engineering.