A systems biology approach to investigate the effect of pH-induced gene regulation on solvent production by Clostridium acetobutylicum in continuous culture

SysMO is a European transnational funding and research initiative on "Systems Biology of Microorganisms".

The goal pursued by SysMO was to record and describe the dynamic molecular processes going on in unicellular microorganisms in a comprehensive way and to present these processes in the form of computerized mathematical models.

Systems biology will raise biomedical and biotechnological research to a new quality level and contribute markedly to progress in understanding. Pooling European research ...

Systems Biology of Clostridium acetobutylicum - a possible answer to dwindling crude oil reserves

This model assumes a phenotypic switch between an acid- and solvent-forming population caused by the changing pH levels. The two phenotypes differ in their transcriptomic, proteomic, and ,thus, their metabolomic profile. Because the growth rates of these phenotypes depends on the extracellular pH, the initiation of the pH-shift results in a significant decline of the acidogenic population. Simultaneously, the solvent-forming population rises and establishes an new steady state.

The model is build ...

An ODE model representing the metabolic network governing acid and solvent production by Clostridium acetobutylicum (Haus et al. BMC Systems Biology 2011, 5:10), incorporating the effect of pH upon gene regulation and subsequent end-product levels. This model describes the third of four experiments in which the pH of the culture was shifted. For this experiment acidogenesis at pH 5.7 was maintained for 121 hours, after which the pH control was stopped, allowing the natural metabolic shift to the ...

An ODE model representing the metabolic network governing acid and solvent production by Clostridium acetobutylicum (Haus et al. BMC Systems Biology 2011, 5:10), incorporating the effect of pH upon gene regulation and subsequent end-product levels. This model describes the last of four experiments in which the pH of the culture was shifted. For this experiment the pH shift was reversed compared to the first three (shift from pH 4.5 to 5.7), with the pH control switched off after 129 hours. ...

An ODE model representing the metabolic network governing acid and solvent production by Clostridium acetobutylicum (Haus et al. BMC Systems Biology 2011, 5:10), incorporating the effect of pH upon gene regulation and subsequent end-product levels. This model describes the second of four experiments in which the pH of the culture was shifted. For this experiment acidogenesis at pH 5.7 was maintained for 137.5 hours, after which the pH control was stopped, allowing the natural metabolic shift to ...

An ODE model representing the metabolic network governing acid and solvent production by Clostridium acetobutylicum (Haus et al. BMC Systems Biology 2011, 5:10), incorporating the effect of pH upon gene regulation and subsequent end-product levels. This model describes the first of four experiments in which the pH of the culture was shifted. For this experiment acidogenesis at pH 5.7 was maintained for 137 hours, after which the pH control was stopped, allowing the natural metabolic shift to the ...

An ODE model representing the metabolic network governing acid and solvent production by Clostridium acetobutylicum, incorporating the effect of pH upon gene regulation and subsequent end-product levels.

The zip file containes 4 models (in SBML), each representing slightly different experimental conditions.

The acetone-butanol-ethanol (ABE) fermentation of Clostridium acetobutylicum attracts new attention because it provides a potential alternative for the synthesis of value added chemicals to petroleum and other fossil reserves. This fermentative metabolic process comprises two distinct metabolic states that differ in their product spectrum. Growing on starch or sugars the predominant fermentation products are acetate and butyrate during acidogenesis (high pH). In contrast, C. acetobutylicum produces ...

This presentation given at the 5th International Beilstein Symposium presents the development of a model for the pH-induced shift in C. acetobutylicum. Starting from experimental information, the model construction and underlying assumptions are explained. Furthermore, the required additions to the metabolic and genetic network caused by the used experimentals setup are established.

The established metabolic and genetic model is compared to dynamic shift experiments starting at acidogenesis and ...