Present address: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Integrative modelling of pH-dependent enzyme activity and transcriptomic regulation of the acetone–butanol–ethanol fermentation of Clostridium acetobutylicum in continuous culture
Article first published online: 21 JAN 2013
© 2013 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 6, Issue 5, pages 526–539, September 2013
How to Cite
Millat, T., Janssen, H., Bahl, H., Fischer, R.-J. and Wolkenhauer, O. (2013), Integrative modelling of pH-dependent enzyme activity and transcriptomic regulation of the acetone–butanol–ethanol fermentation of Clostridium acetobutylicum in continuous culture. Microbial Biotechnology, 6: 526–539. doi: 10.1111/1751-7915.12033
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).
- Issue published online: 14 AUG 2013
- Article first published online: 21 JAN 2013
- Manuscript Accepted: 10 DEC 2012
- Manuscript Received: 23 JUL 2012
- German Federal Ministry for Education and Research (BMBF). Grant Numbers: FKZ 0313981D, 0315782D, 0313978F, 0315784E
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.