title: Modulating the distribution of fluxes among respiration and fermentation by overexpression of HAP4 in Saccharomyces cerevisiae.
abstract: The tendency of Saccharomyces cerevisiae to favor alcoholic fermentation over respiration is a complication in aerobic, biomass-directed applications of this yeast. Overproduction of Hap4p, a positive transcriptional regulator of genes involved in respiratory metabolism, has been reported to positively affect the balance between respiration and fermentation in aerobic glucose-grown batch cultures. In this study, the effects of HAP4 overexpression have been quantified in the prototrophic S. cerevisiae strain CEN.PK 113-7D under a variety of growth conditions. In aerobic glucose-limited chemostat cultures, overexpression of HAP4 increased the specific growth rate at which aerobic fermentation set in by about 10% relative to the isogenic wild-type. Upon relief of glucose-limited conditions, the HAP4-overexpressing strain produced slightly less ethanol than the wild-type strain. The effect of Hap4p overproduction was most drastic in aerobic, glucose-grown chemostat cultures in which ammonium was limiting. In such cultures, the biomass yield on glucose was double that of the wild-type.
authors.affiliation: Kluwer Laboratory of Biotechnology, Delft University of Technology, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: van Maris
authors.forename: B M
authors.initials: BM
authors.lastname: Bakker
authors.forename: M
authors.initials: M
authors.lastname: Brandt
authors.forename: A
authors.initials: A
authors.lastname: Boorsma
authors.forename: M J
authors.initials: MJ
authors.lastname: Teixeira de Mattos
authors.forename: L A
authors.initials: LA
authors.lastname: Grivell
authors.forename: J T
authors.initials: JT
authors.lastname: Pronk
authors.forename: J
authors.initials: J
authors.lastname: Blom
mesh_terms: D000332:Aerobiosis; D018533:Biomass; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D000431:Ethanol / Q000378:metabolism*; D005285:Fermentation; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D010101:Oxygen Consumption; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D023081:CCAAT-Binding Factor; D003470:Culture Media; C061437:HAP4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000431:Ethanol; D005947:Glucose