Integrative modelling of pH-dependent enzyme activity and transcriptomic regulation of the acetone–butanol–ethanol fermentation of Clostridium acetobutylicum in continuous culture

Authors

  • Thomas Millat,

    Corresponding author
    • University of Rostock, Institute of Computer Science, Department of Systems Biology & Bioinformatics, Rostock, Germany
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  • Holger Janssen,

    1. University of Rostock, Institute of Biological Sciences, Division of Microbiology, Rostock, Germany
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    • Present address: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
  • Hubert Bahl,

    1. University of Rostock, Institute of Biological Sciences, Division of Microbiology, Rostock, Germany
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  • Ralf-Jörg Fischer,

    1. University of Rostock, Institute of Biological Sciences, Division of Microbiology, Rostock, Germany
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  • Olaf Wolkenhauer

    1. University of Rostock, Institute of Computer Science, Department of Systems Biology & Bioinformatics, Rostock, Germany
    2. Institute for Advanced Study (STIAS), Wallenberg Research Centre, Stellenbosch University, Stellenbosch, South Africa
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  • Funding InformationThe authors acknowledge support by the German Federal Ministry for Education and Research (BMBF) as part of the European Transnational Network – Systems Biology of Microorganisms (SysMo) – within the BaCell-SysMo and COSMIC consortia (FKZ 0313981D, 0315782D, 0313978F and 0315784E).

For correspondence. E-mail thomas.millat@uni-rostock.de; Tel. (+49) (0)381 498 7573; Fax (+49) (0)381 498 7572.

Summary

In a continuous culture under phosphate limitation the metabolism of Clostridium acetobutylicum depends on the external pH level. By comparing seven steady-state conditions between pH 5.7 and pH 4.5 we show that the switch from acidogenesis to solventogenesis occurs between pH 5.3 and pH 5.0 with an intermediate state at pH 5.1. Here, an integrative study is presented investigating how a changing external pH level affects the clostridial acetone–butanol–ethanol (ABE) fermentation pathway. This is of particular interest as the biotechnological production of n-butanol as biofuel has recently returned into the focus of industrial applications. One prerequisite is the furthering of the knowledge of the factors determining the solvent production and their integrative regulations. We have mathematically analysed the influence of pH-dependent specific enzyme activities of branch points of the metabolism on the product formation. This kinetic regulation was compared with transcriptomic regulation regarding gene transcription and the proteomic profile. Furthermore, both regulatory mechanisms were combined yielding a detailed projection of their individual and joint effects on the product formation. The resulting model represents an important platform for future developments of industrial butanol production based on C. acetobutylicum.

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