A new model for the aerobic metabolism of yeast allows the detailed analysis of the metabolic regulation during glucose pulse

- A new detailed kinetic model of aerobic energy metabolism of yeast is presented.
- Analysis of dynamics of metabolites after a glucose pulse
- Kinetics of PDC, ADH and PDH bypass pave the way for the onset of the Crabtree effect.
- TCA cycle can operate in two branches after a glucose pulse.
- Flux through the TCA cycle is regulated in two blocks.

The onset of aerobic fermentation (the so-called Crabtree effect) in yeast has long been of interest. However, the underlying mechanisms at the metabolic level are not yet fully understood. We developed a detailed kinetic model of the aerobic central metabolism of Saccharomyces cerevisiae comprising glycolysis, TCA cycle and major transport reactions across the mitochondrial membrane to investigate this phenomenon. It is the first one of this extent in the literature. The model is able to reproduce experimental steady state fluxes and time-course behavior after a glucose pulse. Due to the lack of parameter identifiability in the model, we analyze a model ensemble consisting of a set of differently parameterized models for robust findings. The model predicts that the cooperativity of pyruvate decarboxylase with respect to pyruvate and the capacity difference between alcohol dehydrogenase and the pyruvate dehydrogenase bypass play a major role for the onset of the Crabtree effect.