Open Access Research article

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

Sylvia Haus1, Sara Jabbari2*, Thomas Millat1, Holger Janssen3, Ralf-Jörg Fischer3, Hubert Bahl3, John R King2 and Olaf Wolkenhauer14

Author Affiliations

1 University of Rostock, Institute of Computer Science, Department of Systems Biology & Bioinformatics, 18051 Rostock, Germany

2 University of Nottingham, School of Mathematical Sciences, University Park, Nottingham, NG7 2RD, UK

3 University of Rostock, Institute of Biological Sciences, Division of Microbiology, 18051 Rostock, Germany

4 Stellenbosch Institute for Advanced Study, Stellenbosch 7600, South Africa

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BMC Systems Biology 2011, 5:10  doi:10.1186/1752-0509-5-10

Published: 19 January 2011



Clostridium acetobutylicum is an anaerobic bacterium which is known for its solvent-producing capabilities, namely regarding the bulk chemicals acetone and butanol, the latter being a highly efficient biofuel. For butanol production by C. acetobutylicum to be optimized and exploited on an industrial scale, the effect of pH-induced gene regulation on solvent production by C. acetobutylicum in continuous culture must be understood as fully as possible.


We present an ordinary differential equation model combining the metabolic network governing solvent production with regulation at the genetic level of the enzymes required for this process. Parameterizing the model with experimental data from continuous culture, we demonstrate the influence of pH upon fermentation products: at high pH (pH 5.7) acids are the dominant product while at low pH (pH 4.5) this switches to solvents. Through steady-state analyses of the model we focus our investigations on how alteration in gene expression of C. acetobutylicum could be exploited to increase butanol yield in a continuous culture fermentation.


Incorporating gene regulation into the model of solvent production by C. acetobutylicum enables an accurate representation of the pH-induced switch to solvent production to be obtained and theoretical investigations of possible synthetic-biology approaches to be pursued. Steady-state analyses suggest that, to increase butanol yield, alterations in the expression of single solvent-associated genes are insufficient; a more complex approach targeting two or more genes is required.