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Minor Isozymes Tailor Yeast Metabolism to Carbon Availability.

Author(s): Bradley, Patrick H; Gibney, Patrick A; Botstein, David; Troyanskaya, Olga G; Rabinowitz, Joshua D

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dc.contributor.authorBradley, Patrick H-
dc.contributor.authorGibney, Patrick A-
dc.contributor.authorBotstein, David-
dc.contributor.authorTroyanskaya, Olga G-
dc.contributor.authorRabinowitz, Joshua D-
dc.date.accessioned2020-02-25T20:10:59Z-
dc.date.available2020-02-25T20:10:59Z-
dc.date.issued2019-01en_US
dc.identifier.citationBradley, Patrick H, Gibney, Patrick A, Botstein, David, Troyanskaya, Olga G, Rabinowitz, Joshua D. (2019). Minor Isozymes Tailor Yeast Metabolism to Carbon Availability.. mSystems, 4 (1), 10.1128/mSystems.00170-18en_US
dc.identifier.issn2379-5077-
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/pr10778-
dc.description.abstractIsozymes are enzymes that differ in sequence but catalyze the same chemical reactions. Despite their apparent redundancy, isozymes are often retained over evolutionary time, suggesting that they contribute to fitness. We developed an unsupervised computational method for identifying environmental conditions under which isozymes are likely to make fitness contributions. This method analyzes published gene expression data to find specific experimental perturbations that induce differential isozyme expression. In yeast, we found that isozymes are strongly enriched in the pathways of central carbon metabolism and that many isozyme pairs show anticorrelated expression during the respirofermentative shift. Building on these observations, we assigned function to two minor central carbon isozymes, aconitase 2 (ACO2) and pyruvate kinase 2 (PYK2). ACO2 is expressed during fermentation and proves advantageous when glucose is limiting. PYK2 is expressed during respiration and proves advantageous for growth on three-carbon substrates. PYK2's deletion can be rescued by expressing the major pyruvate kinase only if that enzyme carries mutations mirroring PYK2's allosteric regulation. Thus, central carbon isozymes help to optimize allosteric metabolic regulation under a broad range of potential nutrient conditions while requiring only a small number of transcriptional states.en_US
dc.format.extent1 - 19en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofmSystemsen_US
dc.rightsFinal published version. This is an open access article.en_US
dc.titleMinor Isozymes Tailor Yeast Metabolism to Carbon Availability.en_US
dc.typeJournal Articleen_US
dc.identifier.doidoi:10.1128/mSystems.00170-18-
dc.identifier.eissn2379-5077-
pu.type.symplectichttp://www.symplectic.co.uk/publications/atom-terms/1.0/journal-articleen_US

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