title: Dynamics of glycolytic regulation during adaptation of Saccharomyces cerevisiae to fermentative metabolism.
abstract: The ability of baker's yeast (Saccharomyces cerevisiae) to rapidly increase its glycolytic flux upon a switch from respiratory to fermentative sugar metabolism is an important characteristic for many of its multiple industrial applications. An increased glycolytic flux can be achieved by an increase in the glycolytic enzyme capacities (V(max)) and/or by changes in the concentrations of low-molecular-weight substrates, products, and effectors. The goal of the present study was to understand the time-dependent, multilevel regulation of glycolytic enzymes during a switch from fully respiratory conditions to fully fermentative conditions. The switch from glucose-limited aerobic chemostat growth to full anaerobiosis and glucose excess resulted in rapid acceleration of fermentative metabolism. Although the capacities (V(max)) of the glycolytic enzymes did not change until 45 min after the switch, the intracellular levels of several substrates, products, and effectors involved in the regulation of glycolysis did change substantially during the initial 45 min (e.g., there was a buildup of the phosphofructokinase activator fructose-2,6-bisphosphate). This study revealed two distinct phases in the upregulation of glycolysis upon a switch to fermentative conditions: (i) an initial phase, in which regulation occurs completely through changes in metabolite levels; and (ii) a second phase, in which regulation is achieved through a combination of changes in V(max) and metabolite concentrations. This multilevel regulation study qualitatively explains the increase in flux through the glycolytic enzymes upon a switch of S. cerevisiae to fermentative conditions and provides a better understanding of the roles of different regulatory mechanisms that influence the dynamics of yeast glycolysis.
authors.affiliation: Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: van den Brink
authors.forename: André B
authors.initials: AB
authors.lastname: Canelas
authors.forename: Walter M
authors.initials: WM
authors.lastname: van Gulik
authors.forename: Jack T
authors.initials: JT
authors.lastname: Pronk
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Heijnen
authors.forename: Johannes H
authors.initials: JH
authors.lastname: de Winde
authors.forename: Pascale
authors.initials: P
authors.lastname: Daran-Lapujade
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000332:Aerobiosis; D000693:Anaerobiosis; D019149:Bioreactors; D003470:Culture Media; D005285:Fermentation; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D010101:Oxygen Consumption; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014199:Trehalose / Q000378:metabolism
chemical_list: D003470:Culture Media; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D014199:Trehalose; D005947:Glucose