Adaptations in metabolism and protein translation give rise to the Crabtree effect in yeast, 2021, Carl Malina et al

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.

Abstract
Aerobic fermentation, also referred to as the Crabtree effect in yeast, is a well-studied phenomenon that allows many eukaryal cells to attain higher growth rates at high glucose availability. Not all yeasts exhibit the Crabtree effect, and it is not known why Crabtree-negative yeasts can grow at rates comparable to Crabtree-positive yeasts. Here, we quantitatively compared two Crabtree-positive yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and two Crabtree-negative yeasts, Kluyveromyces marxianus and Scheffersomyces stipitis, cultivated under glucose excess conditions. Combining physiological and proteome quantification with genome-scale metabolic modeling, we found that the two groups differ in energy metabolism and translation efficiency. In Crabtree-positive yeasts, the central carbon metabolism flux and proteome allocation favor a glucose utilization strategy minimizing proteome cost as proteins translation parameters, including ribosomal content and/or efficiency, are lower. Crabtree-negative yeasts, however, use a strategy of maximizing ATP yield, accompanied by higher protein translation parameters. Our analyses provide insight into the underlying reasons for the Crabtree effect, demonstrating a coupling to adaptations in both metabolism and protein translation.

https://www.pnas.org/content/118/51/e2112836118