Cellular constraints and limited resources govern the metabolic strategies of cells to adapt to environmental conditions. Under excess glucose conditions, many yeasts switch from high-yield respiratory metabolism to low-yield fermentation, a phenomenon called the Crabtree effect in yeast, or the Warburg effect in mammalian cells. Which constraints cause this effect is still under debate.
Here we study the Crabtree-negative, fully respiratory yeast Pichia kluyveri and compare it to the Crabtree-positive yeast Saccharomyces cerevisiae from a resource allocation perspective. By integrating quantitative physiology and proteomics into genome-scale proteome-constrained models, we find that the Crabtree effect is determined by the composition of the electron transport chain and is rather sensitive to (often poorly characterized) catalytic constants of mitochondrial enzymes and complexes. This suggests that the “proteome efficiency” - a concept in need of a proper definition that will be addressed - of respiration versus fermentation varies between species. This variation likely reflects evolutionary and ecological history and remains to be explained.
This study advances our understanding of the role of proteome constraints and proteome efficiency in governing cellular metabolism of yeasts, and that of eukaryotic cells at large.