This study presents a detailed modelling framework for the co-production of polyhydroxybutyrate (PHB) and ectoine during Halomonas bluephagenesis TD1.0 batch fermentation. The model effectively captures the complex interactions among glucose, nitrogen, biomass, and intracellular product accumulation during aerobic shake-flask cultivation in a MM63 minimal salts medium. The key feature of the model is the integration of a nonlinear, derivative-free optimization approach across all experimental datasets, enabling consistent parameter estimation and rigorous model validation. The model was validated using dynamic batch fermentation data with varying initial glucose concentrations, while separate limitation and inhibition experiments were conducted for both glucose and nitrogen to support the identification of substrate-dependent kinetics. Simulation results reveal that nitrogen depletion serves as the principal trigger for metabolic regulation, redirecting carbon flux from biomass formation toward PHB accumulation. This is in good agreement with experimental data and with observations reported in the literature for other PHB-producing organisms. Ectoine synthesis is shown to be tightly coupled to active cell growth under nutrient-replete conditions. The model also identifies key inhibition effects of substrate and accumulated products that influence both biomass formation and metabolite synthesis. These findings demonstrate the ability of the model to predict system dynamics under varying glucose conditions and highlight its potential as a predictive tool for optimizing and scaling PHB and ectoine production in industrial bioprocesses.
Hojaji et al. (Sun,) studied this question.
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