pH-dependent steady states of ABE fermetation in C. acetobutylicum

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.

Creator: Thomas Millat

Submitter: Thomas Millat

Model of the pH-induced metabolic shift in phosphate-limited continuous cultures of C. acetobutylicum assuming a phenotypic switch

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 ...

Creators: Thomas Millat, Graeme Thorn, Olaf Wolkenhauer, John King

Submitter: Thomas Millat

A shift in the dominant phenotype governs the pH-induced metabolic switch of Clostridium acetobutylicumin phosphate-limited continuous cultures

Abstract (Expand)

In response to changing extracellular pH levels, phosphate-limited continuous cultures of Clostridium acetobutylicum reversibly switches its metabolism from the dominant formation of acids to the … prevalent production of solvents. Previous experimental and theoretical studies have revealed that this pH-induced metabolic switch involves a rearrangement of the intracellular transcriptomic, proteomic and metabolomic composition of the clostridial cells. However, the influence of the population dynamics on the observations reported has so far been neglected. Here, we present a method for linking the pH shift, clostridial growth and the acetone-butanol-ethanol fermentation metabolic network systematically into a model which combines the dynamics of the external pH and optical density with a metabolic model. Furthermore, the recently found antagonistic expression pattern of the aldehyde/alcohol dehydrogenases AdhE1/2 and pH-dependent enzyme activities have been included into this combined model. Our model predictions reveal that the pH-induced metabolic shift under these experimental conditions is governed by a phenotypic switch of predominantly acidogenic subpopulation towards a predominantly solventogenic subpopulation. This model-driven explanation of the pH-induced shift from acidogenesis to solventogenesis by population dynamics casts an entirely new light on the clostridial response to changing pH levels. Moreover, the results presented here underline that pH-dependent growth and pH-dependent specific enzymatic activity play a crucial role in this adaptation. In particular, the behaviour of AdhE1 and AdhE2 seems to be the key factor for the product formation of the two phenotypes, their pH-dependent growth, and thus, the pH-induced metabolic switch in C. acetobutylicum.

Editor:

Date Published: 3rd May 2013

Publication Type: Not specified

Butyrate re-assimilation in C. acetobutylicum re-evaluated using modeling

This presentation reports about the results from an investigation of a ClosTron-mutant lacking CoA-transferase activity. Using our two-population model developed for the wild type of C. acetobutylicum, we analyse the changes in the formation of products caused by that mutation. In particular, we focus on the investigation of the acid re-assimilation after the initiation of the pH shift. Our comparison of experimental data and simulation unravels that an CoA-independent re-assimilation mechanism ...

Creator: Thomas Millat

Submitter: Thomas Millat

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