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Bioprocess and Biosystems Engineering

, Volume 24, Issue 6, pp 395–403 | Cite as

A small metabolic flux model to identify transient metabolic regulations in Saccharomyces cerevisiae

  • Christoph Herwig
  • Urs von Stockar
Original Papers

Abstract.

The understanding of dynamic metabolic regulations is important for physiological studies and strain characterization tasks. The present study combined transient experiments with online metabolic flux analysis (MFA) in order to quantify metabolic regulations, namely carbon catabolite repression of respiration and transient acetic-acid production, in Saccharomyces cerevisiae during aerobic growth on glucose. The aim was to investigate which additional information can be gained from using a small metabolic flux model to study transient growth provoked by shift-up and shift-down experiments, compared to online monitoring alone. The MFA model allowed us to propose new correlations between pathways of the central metabolism. A linear correlation between glycolytic flux and respiratory capacity holds for shift-down and shift-up experiments. This confirmed that respiratory functions were subjected to carbon catabolite repression and suggested that respiratory capacity is controlled by the glycolytic flux rather than the glucose influx. Furthermore, the model showed that control of repression of respiration by the glycolytic flux was a dynamic phenomenon. Co-factor balancing within the MFA model showed that transient acetic-acid production indicated a transient limitation in another part of the central metabolism but not in oxidative phosphorylation. However, at super-critical growth rates and when coupling of anabolism and catabolism is resumed, the limitation shifts to oxidative phosphorylation, with the consequence that ethanol is formed. The online application of small metabolic flux models to transient experiments enhanced the physiological insight into transient growth and opens up the use of transient experiments as an efficient tool to understand dynamic metabolic regulations.

Keywords

Saccharomyces Cerevisiae Oxidative Phosphorylation Metabolic Regulation Central Metabolism Glycolytic Flux 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Christoph Herwig
    • 1
  • Urs von Stockar
    • 1
  1. 1.Laboratory of Chemical and Biochemical Engineering, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland

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