A systems biology approach to study glucose repression in the yeast <i>Saccharomyces cerevisiae</i>

Westergaard, Steen Lund; Oliveira, Ana Paula; Bro, Christoffer; Olsson, Lisbeth; Nielsen, Jens

doi:10.1002/bit.21135

Cited by 73 publications

(80 citation statements)

References 46 publications

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“…This enzyme plays a key role in the regulation of central carbon metabolism for two reasons (Westergaard et al, 2007). It catalyses the first step of glycolysis, i.e.…”

Section: Sfp1 Might Play a Role At The Crossroads Of Glycolysis Regulmentioning

confidence: 99%

Saccharomyces cerevisiae SFP1: at the crossroads of central metabolism and ribosome biogenesis

et al. 2008

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Saccharomyces cerevisiae SFP1 is required for nutrient-dependent regulation of ribosome biogenesis and cell size. A mutant deleted for SFP1 shows specific traits, including a slow growth phenotype, especially when growing on glucose. We recently analysed the physiology of an sfp1D mutant and its isogenic reference strain in chemostat cultures. This approach was successful in revealing the effects of nutrients on the activity of Sfp1 independent of growth rate-related feedback. In the present work we exposed carbon-limited cultures of an sfp1D mutant and its reference strain to sudden glucose excess. This allowed us to study the effect of SFP1 deletion on cell physiology when the cells are forced to exploit their maximum growth potential; this is similar to what happens in shake-flask cultures but with no bias due to growth rate differences. We show that nutrients differentiallly affect the role of Sfp1 in cell-size modulation and in transcriptional control. Furthermore, we report that while Sfp1 is necessary for the efficient glucose-dependent regulation of ribosome biogenesis genes, it is not required for the proper induction of ribosomal protein genes in response to glucose excess. Finally, our data suggest a role for Sfp1 in the regulation of glycolysis, further underlining its involvement in the network that links ribosome biogenesis and cell metabolism.

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“…This enzyme plays a key role in the regulation of central carbon metabolism for two reasons (Westergaard et al, 2007). It catalyses the first step of glycolysis, i.e.…”

Section: Sfp1 Might Play a Role At The Crossroads Of Glycolysis Regulmentioning

confidence: 99%

Saccharomyces cerevisiae SFP1: at the crossroads of central metabolism and ribosome biogenesis

et al. 2008

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“…The two mutants reported to be partially glucose repression negative (hexokinase 2, hxk2; and F-box protein component of the SCF ubiquitin-ligase complex, grr1) are central components in the major regulatory pathway of glucose repression (Westergaard et al, 2007), while the hap2 mutant, which is unable to derepress, lacks an essential subunit of the Hap2p/3p/4p/5p CCAAT-binding complex, which in the wild-type activates transcription of TCA cycle genes and genes involved in Fig. 3.…”

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confidence: 99%

Correlation between TCA cycle flux and glucose uptake rate during respiro-fermentative growth of Saccharomyces cerevisiae

Heyland

Blank

2009

Microbiology

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Glucose repression of the tricarboxylic acid (TCA) cycle in Saccharomyces cerevisiae was investigated under different environmental conditions using 13C-tracer experiments. Real-time quantification of the volatile metabolites ethanol and CO2 allowed accurate carbon balancing. In all experiments with the wild-type, a strong correlation between the rates of growth and glucose uptake was observed, indicating a constant yield of biomass. In contrast, glycerol and acetate production rates were less dependent on the rate of glucose uptake, but were affected by environmental conditions. The glycerol production rate was highest during growth in high-osmolarity medium (2.9 mmol g−1 h−1), while the highest acetate production rate of 2.1 mmol g−1 h−1 was observed in alkaline medium of pH 6.9. Under standard growth conditions (25 g glucose l−1 , pH 5.0, 30 °C) S. cerevisiae had low fluxes through the pentose phosphate pathway and the TCA cycle. A significant increase in TCA cycle activity from 0.03 mmol g−1 h−1 to about 1.7 mmol g−1 h−1 was observed when S. cerevisiae grew more slowly as a result of environmental perturbations, including unfavourable pH values and sodium chloride stress. Compared to experiments with high glucose uptake rates, the ratio of CO2 to ethanol increased more than 50 %, indicating an increase in flux through the TCA cycle. Although glycolysis and the ethanol production pathway still exhibited the highest fluxes, the net flux through the TCA cycle increased significantly with decreasing glucose uptake rates. Results from experiments with single gene deletion mutants partially impaired in glucose repression (hxk2, grr1) indicated that the rate of glucose uptake correlates with this increase in TCA cycle flux. These findings are discussed in the context of regulation of glucose repression.

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“…Most eukaryotic cells, including yeasts and humans, can sense the availability of carbon sources in their surroundings and, in the presence of their favorite sugar (often glucose), they transport glucose into the cell and use it through the glycolysis pathway to produce energy (Westergaard et al 2006). The example E 6 describes this causality between glucose and glycolysis.…”

Section: Example 13mentioning

confidence: 99%

“…This prior background theory B 6 cannot logically explain E 6 , and thus there are some missing links between B 6 and E 6 . In recent work (Westergaard et al 2006), it has been made known that a signal triggered by Snf3 leads to induce Hxt, and then glucose can be moved into the cell via the transporter Hxt. Then, H 6 , which describes these cellular regulations, is a considerable hypothesis.…”

Section: Example 13mentioning

confidence: 99%

Inverse subsumption for complete explanatory induction

2011

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Modern explanatory inductive logic programming methods like Progol, Residue procedure, CF-induction, HAIL and Imparo use the principle of inverse entailment (IE). Those IE-based methods commonly compute a hypothesis in two steps: by first constructing an intermediate theory and next by generalizing its negation into the hypothesis with the inverse of the entailment relation. Inverse entailment ensures the completeness of generalization. On the other hand, it imposes many non-deterministic generalization operators that cause the search space to be very large. For this reason, most of those methods use the inverse relation of subsumption, instead of entailment. However, it is not clear how this logical reduction affects the completeness of generalization. In this paper, we investigate whether or not inverse subsumption can be embedded in a complete induction procedure; and if it can, how it is to be realized. Our main result is a new form of inverse subsumption that ensures the completeness of generalization. Consequently, inverse entailment can be reduced to inverse subsumption without losing the completeness for finding hypotheses in explanatory induction.

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A systems biology approach to study glucose repression in the yeast Saccharomyces cerevisiae

Cited by 73 publications

References 46 publications

Saccharomyces cerevisiae SFP1: at the crossroads of central metabolism and ribosome biogenesis

Saccharomyces cerevisiae SFP1: at the crossroads of central metabolism and ribosome biogenesis

Correlation between TCA cycle flux and glucose uptake rate during respiro-fermentative growth of Saccharomyces cerevisiae

Inverse subsumption for complete explanatory induction

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