Adaptations in metabolism and protein translation give rise to the Crabtree effect in yeast

Significance Overflow metabolism, referred to as the Crabtree effect in yeast, is the seemingly wasteful strategy of using aerobic fermentation instead of the more efficient respiration for energy generation. This allows cells to grow faster at high glucose availability. Although well-studied, the underlying reasons that not all yeasts experience the Crabtree effect while still able to grow at comparable rates as yeasts exhibiting the effect, are not known. We combined physiological and proteome quantification with metabolic modeling to perform a quantitative comparison of four yeasts, two exhibiting and two not exhibiting the Crabtree effect, under glucose excess conditions. Our analyses provide insight into the underlying causes of the Crabtree effect, demonstrating a coupling to adaptations in both metabolism and protein translation.