Adaptations in metabolism and protein translation give rise to the Crabtree effect in yeast
Journal article, 2021

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.

Constraint-based modeling

Proteomics

Systems biology

Yeast

Crabtree effect

Author

Carl Malina

Wallenberg Center for Protein Research (WCPR)

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Rosemary Brown

Chalmers, Physics, Chemical Physics

Novo Nordisk Foundation

Johan Björkeroth

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Eduard Kerkhoven

Novo Nordisk Foundation

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Jens B Nielsen

Technical University of Denmark (DTU)

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

BioInnovation Institute

Novo Nordisk Foundation

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 118 51 e2112836118

Subject Categories

Biochemistry and Molecular Biology

Bioprocess Technology

Other Industrial Biotechnology

DOI

10.1073/pnas.2112836118

PubMed

34903663

More information

Latest update

5/26/2023