期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2112836118
关键词
Crabtree effect; yeast; systems biology; proteomics; constraint-based modeling
资金
- Novo Nordisk Foundation
- Knut and Alice Wallenberg Foundation
- Chalmers University of Technology
The Crabtree effect, observed in many eukaryotic cells, allows for higher growth rates at high glucose availability. Differences in energy metabolism and protein translation efficiency play a key role in distinguishing between Crabtree-positive and Crabtree-negative yeasts.
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.
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