An excess of glycolytic enzymes under glucose‐limited conditions may enable Saccharomyces cerevisiae to adapt to nutrient availability

Abstract

Microorganisms, including the budding yeast Saccharomyces cerevisiae, express glycolytic proteins to a maximal capacity that (largely) exceeds the actual flux through the enzymes, especially at low growth rates. An open question is if this apparent expression level is really an overcapacity, or maintains the (optimal) enzyme capacity needed to carry flux at (very) low substrate availability. Here, we use computational modelling to suggest that yeast maintains a genuine excess of glycolytic enzymes at low specific growth rates. During fast fermentative growth at high glucose levels, the observed expression of the glycolytic enzymes matched the predicted optimal levels. We suggest that the excess glycolytic capacity at low glucose levels is a preparatory strategy in the adaptation to sugar fluctuations in the environment.

Elevated energy costs of biomass production in mitochondrial-respiration deficientSaccharomyces cerevisiae

“…Anticipation of presence of oxygen might also explain why S. cerevisiae can grow anaerobically, albeit slowly, without unsaturated fatty acid- or ergosterol supplementation, which is a common technique in laboratory cultivation (Dekker et al, 2019). In general, cells show anticipatory expression of metabolic enzymes when the selection pressure for the transient growth rate is absent: we have recently suggested a similar phenomenon for glycolytic enzymes for aerobic glucose-limited cultures (Grigaitis and Teusink, 2022). Also, glycolytic enzymes show similar levels in both minimal and rich media despite the differences in glycolytic flux (Björkeroth et al, 2020).…”

“…S. cerevisiae intensively ferments glucose into ethanol in glucose-excess conditions (Blank and Sauer, 2004), yet, fluctuations of nutrient levels are a frequent phenomenon in both natural and biotechnologically-relevant environments (Haringa et al, 2016). There, oscillations of glucose availability, for instance, are handled by anticipatory protein expression (Grigaitis and Teusink, 2022; van den Brink et al, 2008). Thus the cells in glucose-scarce conditions are indeed primed to consume the incoming flux of nutrients and store the released energy in the high-energy bonds of the ATP molecule.…”

The deubiquitinase Ubp3/Usp10 constrains glucose-mediated mitochondrial repression via phosphate budgeting

“…Glucose-6 phosphate (G6P) is the central node in glucose metabolism where carbon- allocations are made towards distinct metabolic arms, primarily: glycolysis, the pentose phosphate pathway (PPP), and trehalose biosynthesis (Figure 2A). High glycolytic enzymes ensure maximum glycolytic flux when sufficient glucose is present (Grigaitis & Teusink, 2022). We first investigated what happens to glycolytic enzyme amounts in ubp3Δ cells.…”

“…Ubp3 can control this process (Figure 1), by allowing high glycolytic flux by maintaining the amounts of the glycolytic enzymes phosphofructokinase (Pfk1) and GAPDH (Tdh2 and Tdh3). At high rate of fermentation and growth in S. cerevisiae , glycolytic enzymes levels are optimal for maintaining the high glycolytic rate, and therefore, change in the enzyme levels will have a direct, proportionate effect on flux (Grigaitis & Teusink, 2022). The loss of Ubp3 results in decreased glycolytic flux, due to a decrease in these key enzymes, collectively resulting in a systems-level, mass-action based rewiring of glucose metabolism where more G6P is routed towards trehalose synthesis and the PPP (Figure 2, Figure 5H).…”

Elevated energy costs of biomass production in mitochondrial respiration-deficientSaccharomyces cerevisiae

“…S. cerevisiae intensively ferments glucose into ethanol in glucose-excess conditions (Blank and Sauer 2004 ), yet, fluctuations of nutrient levels are a frequent phenomenon in both natural and biotechnologically-relevant environments (Haringa et al 2016 ). There, oscillations of glucose availability, for instance, are handled by anticipatory protein expression (van den Brink et al 2008 , Grigaitis and Teusink 2022 ). Thus the cells in glucose-scarce conditions are indeed primed to consume the incoming flux of nutrients and store the released energy in the high-energy bonds of the ATP molecule.…”