Differential glucose repression in common yeast strains in response to HXK2 deletion

Authors

  • Anne Kümmel,

    1. Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
    Search for more papers by this author
  • Jennifer Christina Ewald,

    1. Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
    2. Competence Center for Systems Physiology and Metabolic Diseases, Zurich, Switzerland
    3. Life Science Zurich PhD Program on Systems Biology of Complex Diseases, Zurich, Switzerland
    Search for more papers by this author
  • Sarah-Maria Fendt,

    1. Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
    2. Competence Center for Systems Physiology and Metabolic Diseases, Zurich, Switzerland
    3. Life Science Zurich PhD Program on Systems Biology of Complex Diseases, Zurich, Switzerland
    Search for more papers by this author
  • Stefan Jasper Jol,

    1. Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
    2. Life Science Zurich PhD Program on Systems Biology of Complex Diseases, Zurich, Switzerland
    Search for more papers by this author
  • Paola Picotti,

    1. Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
    Search for more papers by this author
  • Ruedi Aebersold,

    1. Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
    2. Competence Center for Systems Physiology and Metabolic Diseases, Zurich, Switzerland
    3. Institute for Systems Biology, Seattle, WA, USA
    4. Faculty of Science, University of Zurich, Zurich, Switzerland
    Search for more papers by this author
  • Uwe Sauer,

    1. Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
    2. Competence Center for Systems Physiology and Metabolic Diseases, Zurich, Switzerland
    Search for more papers by this author
  • Nicola Zamboni,

    1. Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
    2. Competence Center for Systems Physiology and Metabolic Diseases, Zurich, Switzerland
    Search for more papers by this author
  • Matthias Heinemann

    1. Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
    2. Competence Center for Systems Physiology and Metabolic Diseases, Zurich, Switzerland
    3. Molecular Systems Biology, Groningen Biomolecular Sciences and Biotechnology Institute, Groningen, The Netherlands
    Search for more papers by this author

  • Editor: Hyun Ah Kang

  • Present address: Anne Kümmel, Novartis Institutes for BioMedical Research, Basel, Switzerland.

Correspondence: Matthias Heinemann, Institute of Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli-Str. 16, Zurich 8093, Switzerland. Tel.: +41 44 6326366; fax: +41 44 6331051; e-mail: heinemann@imsb.biol.ethz.ch

Abstract

Under aerobic, high glucose conditions, Saccharomyces cerevisiae exhibits glucose repression and thus a predominantly fermentative metabolism. Here, we show that two commonly used prototrophic representatives of the CEN.PK and S288C strain families respond differently to deletion of the hexokinase 2 (HXK2) – a key player in glucose repression: In CEN.PK, growth rate collapses and derepression occurs on the physiological level, while the S288C descendant FY4 Δhxk2 still grows like the parent strain and shows a fully repressed metabolism. A CEN.PK Δhxk2 strain with a repaired adenylate cyclase gene CYR1 maintains repression but not growth rate. A comparison of the parent strain's physiology, metabolome, and proteome revealed higher metabolic rates, identical biomass, and byproduct yields, suggesting a lower Snf1 activity and a higher protein kinase A (PKA) activity in CEN.PK. This study highlights the importance of the genetic background in the processes of glucose signaling and regulation, contributes novel evidence on the overlap between the classical glucose repression pathway and the cAMP/PKA signaling pathway, and might have the potential to resolve some of the conflicting findings existing in the field.

Ancillary