ammonium toxicity and potassium limitation in yeast在酵母毒性和钾铵限制.pdfVIP

PLoS BIOLOGY Ammonium Toxicity and Potassium Limitation in Yeast David C. Hess1,2*, Wenyun Lu1,3, Joshua D. Rabinowitz1,3, David Botstein1,2 1 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America, 2 Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America, 3 Department of Chemistry, Princeton University, Princeton, New Jersey, United States of America DNA microarray analysis of gene expression in steady-state chemostat cultures limited for potassium revealed a surprising connection between potassium and ammonium: potassium limits growth only when ammonium is the nitrogen source. Under potassium limitation, ammonium appears to be toxic for Saccharomyces cerevisiae. This ammonium toxicity, which appears to occur by leakage of ammonium through potassium channels, is recapitulated under high-potassium conditions by over-expression of ammonium transporters. Although ammonium toxicity is well established in metazoans, it has never been reported for yeast. To characterize the response to ammonium toxicity, we examined the filtrates of these cultures for compounds whose excretion might serve to detoxify the ammonium (such as urea in mammals). Using liquid chromatography–tandem mass spectrometry to assay for a wide array of metabolites, we detected excreted amino acids. The amounts of amino acids excreted increased in relation to the severity of growth impairment by ammonium, suggesting that amino acid excretion is used by yeast for ammonium detoxification. Citation: Hess DC, Lu W, Rabinowitz JD, Botstein D (2006) Ammonium toxicity and potassium limitation in yeast