• Crabtree effect;
  • metabolic regulation;
  • yeast physiology;
  • Saccharomyces cerevisiae;
  • Candida rugosa;
  • Yarrowia lipolytica


Key distinguishing characteristics of yeast glucose metabolism are the relative proportions of fermentation and respiration. Crabtree-positive yeast species exhibit a respirofermentative metabolism, whereas aerobic species respire fully without secretion of fermentation byproducts. Physiological data suggest a gradual transition in different species between these two states. Here, we investigate whether this gradual transition also occurs at the intracellular level by quantifying the intracellular metabolism of Saccharomyces cerevisiae, Saccharomyces bayanus, Saccharomyces exiguus, Kluyveromyces thermotolerans, Yarrowia lipolytica, Pichia angusta and Candida rugosa by 13C-flux analysis and metabolomics. Different from the extracellular physiology, the intracellular fluxes through the tricarboxylic acid cycle fall into two classes where the aerobic species exhibit much higher respiratory fluxes at otherwise similar glycolytic fluxes. More generally, we found the intracellular metabolite concentrations to be primarily species-specific. The sole exception of a metabolite-flux correlation in a species-overarching manner was found for fructose-1,6-bisphosphate and dihydroxyacetone-phosphate, indicating a conservation of the functional properties around these two metabolites.