A systems biology approach to investigate the effect of pH-induced gene regulation on solvent production by Clostridium acetobutylicum in continuous culture.
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.
University of Rostock, Institute of Computer Science, Department of Systems Biology & Bioinformatics, 18051 Rostock, Germany.
Sylvia
S
Haus
Sara
S
Jabbari
Thomas
T
Millat
Holger
H
Janssen
Ralf-Jörg
RJ
Fischer
Hubert
H
Bahl
John R
JR
King
Olaf
O
Wolkenhauer
D000096:Acetone / Q000378:metabolism; D000440:Butanols / Q000378:metabolism; D046969:Clostridium acetobutylicum / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D046508:Culture Techniques; D005285:Fermentation; D015964:Gene Expression Regulation, Bacterial; D005818:Genetic Engineering; D006863:Hydrogen-Ion Concentration; D053858:Metabolic Networks and Pathways / Q000235:genetics; D055432:Metabolomics; D008954:Models, Biological; D040901:Proteomics; D012997:Solvents / Q000378:metabolism*; D049490:Systems Biology / Q000379:methods*
D000440:Butanols; D012997:Solvents; D000096:Acetone
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