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

Haus, Sylvia LU ; Jabbari, Sara; Millat, Thomas; Janssen, Holger; Fischer, Ralf Jörg; Bahl, Hubert; King, John R. and Wolkenhauer, Olaf (2011) In BMC Systems Biology 5.
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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Acetoacetate, Butanol Production, Butanol, Metabolic Network, Continuous Culture
in
BMC Systems Biology
volume
5
publisher
BioMed Central
external identifiers
  • scopus:78651478840
ISSN
1752-0509
DOI
10.1186/1752-0509-5-10
language
English
LU publication?
no
id
7b6be034-3567-45e1-881e-2d0e551c2b28
date added to LUP
2019-07-02 10:29:04
date last changed
2019-10-23 06:20:43
@article{7b6be034-3567-45e1-881e-2d0e551c2b28,
  abstract     = {<p>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.</p>},
  articleno    = {10},
  author       = {Haus, Sylvia and Jabbari, Sara and Millat, Thomas and Janssen, Holger and Fischer, Ralf Jörg and Bahl, Hubert and King, John R. and Wolkenhauer, Olaf},
  issn         = {1752-0509},
  keyword      = {Acetoacetate,Butanol Production,Butanol,Metabolic Network,Continuous Culture},
  language     = {eng},
  month        = {01},
  publisher    = {BioMed Central},
  series       = {BMC Systems Biology},
  title        = {A systems biology approach to investigate the effect of pH-induced gene regulation on solvent production by Clostridium acetobutylicum in continuous culture},
  url          = {http://dx.doi.org/10.1186/1752-0509-5-10},
  volume       = {5},
  year         = {2011},
}