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

The understanding of dynamic metabolic regulations is important for physiol. studies and strain characterization tasks. The present study combined transient expts. with online metabolic flux anal. (MFA) in order to quantify metabolic regulations, namely carbon catabolite repression of respiration and transient acetic-acid prodn., in Saccharomyces cerevisiae during aerobic growth on glucose. The aim was to investigate which addnl. information can be gained from using a small metabolic flux model to study transient growth provoked by shift-up and shift-down expts., compared to online monitoring alone. The MFA model allowed us to propose new correlations between pathways of the central metab. A linear correlation between glycolytic flux and respiratory capacity holds for shift-down and shift-up expts. 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 prodn. indicated a transient limitation in another part of the central metab. but not in oxidative phosphorylation. However, at super-crit. 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 expts. enhanced the physiol. insight into transient growth and opens up the use of transient expts. as an efficient tool to understand dynamic metabolic regulations. [on SciFinder (R)]