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

Research output: Contribution to journalArticle

Abstract

Background: 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.Results: 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.Conclusions: 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.

Details

Authors
  • Sylvia Haus
  • Sara Jabbari
  • Thomas Millat
  • Holger Janssen
  • Ralf Jörg Fischer
  • Hubert Bahl
  • John R. King
  • Olaf Wolkenhauer
External organisations
  • University of Rostock
  • University of Nottingham
  • Stellenbosch Institute for Advanced Study
Research areas and keywords

Keywords

  • Acetoacetate, Butanol Production, Butanol, Metabolic Network, Continuous Culture
Original languageEnglish
Article number10
JournalBMC Systems Biology
Volume5
Publication statusPublished - 2011 Jan 19
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes