title: Differential glucose repression in common yeast strains in response to HXK2 deletion.
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 Deltahxk2 still grows like the parent strain and shows a fully repressed metabolism. A CEN.PK Deltahxk2 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.
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Kümmel
authors.forename: Jennifer Christina
authors.initials: JC
authors.lastname: Ewald
authors.forename: Sarah-Maria
authors.initials: SM
authors.lastname: Fendt
authors.forename: Stefan Jasper
authors.initials: SJ
authors.lastname: Jol
authors.forename: Paola
authors.initials: P
authors.lastname: Picotti
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
authors.forename: Nicola
authors.initials: N
authors.lastname: Zamboni
authors.forename: Matthias
authors.initials: M
authors.lastname: Heinemann
mesh_terms: D000332:Aerobiosis; D018533:Biomass; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000172:deficiency* / Q000378:metabolism*; D055442:Metabolome; D008954:Models, Biological; D020543:Proteome / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins; C490214:HXK2 protein, S cerevisiae; D006593:Hexokinase; D005947:Glucose