• Juliane Caroline Schulz, Mattia Zampieri, Stefanie Wanka, Christian von Mering, and Uwe Sauer.
• Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, 8093 Zürich, Switzerland.
• Sci Signal. 2014 Nov 25; 7 (353): rs6.

AbstractProtein phosphorylation is a widespread posttranslational modification that regulates almost all cellular functions. To investigate the large number of phosphorylation events with unknown functions, we monitored the concentrations of several hundred intracellular metabolites in Saccharomyces cerevisiae yeast strains with deletions of 118 kinases or phosphatases. Whereas most deletion strains had no detectable difference in growth compared to wild-type yeast, two-thirds of deletion strains had alterations in metabolic profiles. For about half of the kinases and phosphatases encoded by the deleted genes, we inferred specific regulatory roles on the basis of knowledge about the affected metabolic pathways. We demonstrated that the phosphatase Ppq1 was required for metal homeostasis. Combining metabolomic data with published phosphoproteomic data in a stoichiometric model enabled us to predict functions for phosphorylation in the regulation of 47 enzymes. Overall, we provided insights and testable predictions covering greater than twice the number of known phosphorylated enzymes in yeast, suggesting extensive phosphorylation-dependent regulation of yeast metabolism. Copyright © 2014, American Association for the Advancement of Science.

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