Clostridium acetobutylicum

Comparison of the transcriptome at steady state in acidogenesis and at steady state in solventogenesis.

Investigation of the dynamic switch at pH values between 5.8 and 4.5 (pH 5.5, 5.3, 5.1, 4.9, 4.7 and 4.5).

Investigation of all steady state pH-values between pH 5.7 and 4.5 (pH 5.5, 5.3, 5.1, 4.9, 4.7).

Measurements of acetone, butanol, acetate, butyrate and ethanol taken during dynamic shift (pH 5.8, 5.5, 5.3, 5.1, 4.9, 4.7, 4.5) and at steady state (pH 5.7, 5.5, 5.3, 5.1, 4.9, 4.7, 4.5).

Using Taverna for mining and MATLAB for conversion into specific formats (cytoscape, SBTOOLBOX2)

Cytoscape based analysis and yED based representation of clostridial Reactomes

Using PCA, three components, beam size 8.
Clustering via MCL from Biolayout Express 3D

Data is taken from "Genome-Wide Gene Expression Analysis of the Switch between Acidogenesis and Solventogenesis in Continuous Cultures of Clostridium acetobutylicum." Grimmler et al. 2011
DOI: 10.1159/000320973

Steady state study of the effect of altering gene regulation on yields of end-products, focusing on butanol.

Time-dependent simulations of the dynamic switch between acidogenesis and solventogenesis based on the metabolic network and pH-dependent regulation of the enzymes.

Here, we use hyperbolic tangents to fit experimental data of AB fermentation in C. acetobutylicum in continous culture at steady state for different external pHs. The estimated parameters are used to define acidogenic and solventogenic phase. Furthermore, an transition phase is identified which cannot be assigned to acidogenesis or solventogenesis.

Several plots compare the fits to the experimental data.

This function estimates the parameters of growth functions of the acid-forming and solvent-forming population observed in 'forward'-shift experiments of phosphate-limited continuous cultures of C. acetobutylicum. The parameters are used in the 'Two-Populations'-Model of the pH-induced metabolic shift.

It assumed that the found behaviour of the optical density during these experiments results from a phenotypic switch caused by the changing pH level.

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
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The fitted function describes the pH-drop during 'forward'-shift experiments and the increase of the pH during 'reverse'-shift experiments. The estimated parameters are used to compute the changing pH level in the models of the pH.induced metabolic shift in continuous cultures under phosphate limitation of C. acetobutylicum. Furthermore, the parameters can be applied to join different independent experiments into a single data set.

To fit the changing pH level, an exponential function and a
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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
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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.
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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
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Bacillus subtilis cells may opt to forgo normal cell division and instead form spores if subjected to certain environmental stimuli, for example nutrient deficiency or extreme temperature. The gene regulation net-work governing sporulation initiation accordingly incorporates a variety of signals and is of significant complexity. The present model (Bulletin of Mathematical Biology (2011) 73:181–211) includes four of these signals: nutrient levels, DNA damage, the products of the competence genes,
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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.