Mathematical modelling and process optimization of a continuous 5-stage bioreactor cascade for production of poly[-(R)-3-hydroxybutyrate] by Cupriavidus necator.
Acetone-Butanol-Ethanol (ABE)-fermentation with Clostridium acetobutylicum is a biphasic fermentation process. The formation of organic acids in the so called acidogenesis has to precede the economically interesting phase of solvent formation called solventogenesis. A separation of these metabolic phases in two or more stages of continuously run bioreactors has been successfully applied earlier (Bahl et al., 1982). However no comprehensive mathematical modeling was performed for these multi-stage processes. We now established a new experimental model system, consisting of a cascade of continuous-stirred tank reactors (CCSTR). This arrangement enables us to gain insight into metabolic phases of the ABE-fermentation with an unprecedented resolution. Experimental data collected at two dilution rates are used here to verify a mathematical model of the continuous ABE-fermentation process. This model takes into account subpopulation dynamics, meaning that a differentiation between cells with enzyme equipments adapted to acidogenic, transition and solventogenic metabolism, respectively, is made. Applying our model we found that with the differentiation from acidogenic cells to solventogenic cells takes places in the first bioreactor stage at a dilution rate of 0.042 h-1, while this process is shifted to the second and third bioreactor at a dilution rate of 0.092 h-1. Thus we conclude that the pH alone is not sufficient to trigger the metabolic switch between acidogenesis and solventogenesis.