Growth-limiting intracellular metabolites in yeast growing under diverse nutrient limitations. Author Viktor Boer, Christopher Crutchfield, Patrick Bradley, David Botstein, Joshua Rabinowitz Publication Year 2010 Type Journal Article Abstract Microbes tailor their growth rate to nutrient availability. Here, we measured, using liquid chromatography-mass spectrometry, >100 intracellular metabolites in steady-state cultures of Saccharomyces cerevisiae growing at five different rates and in each of five different limiting nutrients. In contrast to gene transcripts, where approximately 25% correlated with growth rate irrespective of the nature of the limiting nutrient, metabolite concentrations were highly sensitive to the limiting nutrient's identity. Nitrogen (ammonium) and carbon (glucose) limitation were characterized by low intracellular amino acid and high nucleotide levels, whereas phosphorus (phosphate) limitation resulted in the converse. Low adenylate energy charge was found selectively in phosphorus limitation, suggesting the energy charge may actually measure phosphorus availability. Particularly strong concentration responses occurred in metabolites closely linked to the limiting nutrient, e.g., glutamine in nitrogen limitation, ATP in phosphorus limitation, and pyruvate in carbon limitation. A simple but physically realistic model involving the availability of these metabolites was adequate to account for cellular growth rate. The complete data can be accessed at the interactive website http://growthrate.princeton.edu/metabolome. Keywords Carbon, Glucose, Nitrogen, Gene Expression Profiling, Gene Expression Regulation, Fungal, Saccharomyces cerevisiae, Cluster Analysis, Models, Biological, Phosphates, RNA, Messenger, Metabolome, Quaternary Ammonium Compounds, Phosphorus, Extracellular Space, Intracellular Space Journal Mol Biol Cell Volume 21 Issue 1 Pages 198-211 Date Published 01/2010 Alternate Journal Mol. Biol. Cell Google ScholarBibTeXEndNote X3 XML