Abstract
Central carbon metabolism is controlled by modulating the protein abundance profiles of enzymes that maintain the essential systems in living organisms. In this study, metabolic adaptation mechanisms in the model organism Saccharomyces cerevisiae were investigated by direct determination of enzyme abundance levels in 30 wild type and mutant strains. We performed a targeted proteome analysis using S. cerevisiae strains that lack genes encoding the enzymes responsible for central carbon metabolism. Our analysis revealed that at least 30% of the observed variations in enzyme abundance levels could be explained by global regulatory mechanisms. A enzyme-enzyme co-abundance analysis revealed that the abundances of enzyme proteins involved in the trehalose metabolism and glycolysis changed in a coordinated manner under the control of the transcription factors for global regulation. The remaining variations were derived from local mechanisms such as a mutant-specific increase in the abundances of remote enzymes. The proteome data also suggested that, although the functional compensation of the deficient enzyme was attained by using more resources for protein biosynthesis, available resources for the biosynthesis of the enzymes responsible for central metabolism were not abundant in S. cerevisiae cells. These results showed that global and local regulation of enzyme abundance levels shape central carbon metabolism in S. cerevisiae by using a limited resource for protein biosynthesis.
Highlights
Central carbon metabolism is an essential system of the living organisms
Do not always correlate with their gene expression levels [19, 23, 24], and the relative contribution of these regulation to the maintenance of central carbon metabolism remains unclear. We have addressed this issue by the direct determination of enzyme abundance in the single gene-deletion mutant strains of S. cerevisiae by targeted proteomics using liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS)
Protein abundance profiles of the central metabolism-related enzymes were obtained from the wild type (BY4742), 29 single-gene deletion strains lacking enzyme genes responsible for the central carbon metabolism and a gene encoding transcriptional activator (Fig 1 and S1 Table)
Summary
Central carbon metabolism is an essential system of the living organisms. Active ethanol fermentation by the budding yeast, Saccharomyces cerevisiae, is a model of the eukaryotic central metabolism due to its importance in brewing industries, as well as its similarity to the Warburg effect in cancer cells [1]. It has been revealed that glycolytic flux is maintained via a complex. Targeted proteome analysis of single-gene deletion strains of Saccharomyces cerevisia
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