Global rewiring of cellular metabolism renders Saccharomyces cerevisiae Crabtree negative
Journal article, 2018

Saccharomyces cerevisiae is a Crabtree-positive eukaryal model organism. It is believed that the Crabtree effect has evolved as a competition mechanism by allowing for rapid growth and production of ethanol at aerobic glucose excess conditions. This inherent property of yeast metabolism and the multiple mechanisms underlying it require a global rewiring of the entire metabolic network to abolish the Crabtree effect. Through rational engineering of pyruvate metabolism combined with adaptive laboratory evolution (ALE), we demonstrate that it is possible to obtain such a global rewiring and hereby turn S. cerevisiae into a Crabtree-negative yeast. Using integrated systems biology analysis, we identify that the global rewiring of cellular metabolism is accomplished through a mutation in the RNA polymerase II mediator complex, which is also observed in cancer cells expressing the Warburg effect.

Author

Zongijie Dai

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Mingtao Huang

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Yun Chen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Verena Siewers

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Jens B Nielsen

Beijing University of Chemical Technology

Technical University of Denmark (DTU)

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Nature Communications

2041-1723 (ISSN)

Vol. 9 1 3059

Subject Categories

Cell Biology

Bioinformatics (Computational Biology)

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

DOI

10.1038/s41467-018-05409-9

More information

Latest update

9/4/2018 2