Project description:Metabolite concentrations can regulate gene expression, which can in turn regulate metabolic activity. The extent to which functionally related transcripts and metabolites show similar patterns of concentration changes, however, remains unestablished. We have therefore measured and analyzed the metabolomic (previously published in Brauer et al., PMID 17159141) and transcriptional responses (presented here) of Saccharomyces cerevisiae to carbon and nitrogen starvation.
Project description:In response to limited nitrogen and abundant carbon sources, diploid Saccharomyces cerevisiae strains undergo a filamentous transition in cell growth as part of pseudohyphal differentiation. Use of the disaccharide maltose as the principal carbon source, in contrast to the preferred nutrient monosaccharide glucose, has been shown to induce a hyper-filamentous growth phenotype in a strain deficient for GPA2 which codes for a Galpha protein component that interacts with the glucose-sensing receptor Gpr1p to regulate filamentous growth. In this report, we compare the global transcript and proteomic profiles of wild-type and Gpa2p deficient diploid yeast strains grown on both rich and nitrogen starved maltose media. We find that deletion of GPA2 results in significantly different transcript and protein profiles when switching from rich to nitrogen starvation media. The results are discussed with a focus on the genes associated with carbon utilization, or regulation thereof, and a model for the contribution of carbon sensing/metabolism-based signal transduction to pseudohyphal differentiation is proposed. Keywords: Saccharomyces cerevisiae, nitrogen starvation, maltose, pseudohyphal differentiation, yeast, expression profiling
Project description:Metabolite concentrations can regulate gene expression, which can in turn regulate metabolic activity. The extent to which functionally related transcripts and metabolites show similar patterns of concentration changes, however, remains unestablished. We have therefore measured and analyzed the metabolomic (previously published in Brauer et al., PMID 17159141) and transcriptional responses (presented here) of Saccharomyces cerevisiae to carbon and nitrogen starvation. The transcriptomes of filter cultures of FY4 (a prototrophic, Mata derivative of S288C presented by Winston et al., PMID 7762301) were sampled during exponential growth in minimal media and at 10, 30, 60, 120, 240, and 480 minutes following a switch to media lacking ammonium (nitrogen starvation) or D-glucose (carbon starvation). Transcriptional profiles were measured using an Agilent Yeast Oligo Microarray (V2), with the zero timepoint (i.e. exponential growth) as the reference sample. This yielded 2 time-courses of 6 time-points each. Further information is available in the accompanying manuscript.
Project description:Metabolic and transcriptional dynamics during the transition from carbon limitation to nitrogen limitation in Saccharomyces cerevisiae
Project description:Reprogramming a non-methylotrophic industrial host, such as Saccharomyces cerevisiae, to a synthetic methylotroph reprents a huge challenge due to the complex regulation in yeast. Through TMC strategy together with ALE strategy, we completed a strict synthetic methylotrophic yeast that could use methanol as the sole carbon source. However, how cells respond to methanol and remodel cellular metabolic network on methanol were not clear. Therefore, genome-scale transcriptional analysis was performed to unravel the cellular reprograming mechanisms underlying the improved growth phenotype.
Project description:Fatty acid synthesis is closely linked to nutrient availability and cellular energetic status. The committed step in fatty acid synthesis is the acetyl CoA carboxylase. Eukaryotes have two genes encoding acetyl CoA carboxylases, one encoding a cytosolic enzyme and another coding for a mitochondrial enzyme. They catalyze the synthesis of malonyl CoA in the cytosol and the mitochondria, respectively. While cytosolic malonyl CoA is the precursor for fatty acid synthesis, mitochondrial malonyl CoA controls the transfer of fatty acyl group into the mitochondria by inhibiting carnitine/palmitoyl transferase activity and thus, regulates β-oxidation. In Saccharomyces cerevisiae, β-oxidation is restricted to the peroxisomes, raising the question of the function of the mitochondrial isoform (HFA1). In this study, we replaced the cytosolic Acc1 with Hfa1 expressed in the cytosol by removing the mitochondrial leader peptide, under control of the HFA1 promoter. We studied fatty acid synthesis and transcription profiles in this strain during starvation for carbon or nitrogen, using glucose or ethanol as the carbon source. Under all the conditions studied, the key sensor of energetic status, Snf1, was activated, indicating active inhibition of fatty acid synthesis. The pool size of fatty acids was smaller when Acc1 was replaced with truncated Hfa1 for fatty acid synthesis. Yet, the transcription profiles were similar in both the cases. These results point towards the conclusion that Hfa1 is either catalytically less efficient or it is more sensitive to inhibition by Snf1. Gene expression from a strain of Saccharomyces cerevisiae where cytosolic fatty acid synthesis occurs by mitochondrial acetyl CoA carboxylase (without its mitochondrial leader peptide) is compared with that in a reference strain while growing in chemostats on carbon or nitrogen starvation using glucose or ethanol as the carbon source.
Project description:Saccharomyces cerevisiae is an excellent microorganism for industrial succinic acid production, but high succinic acid concentration will inhibit the growth of Saccharomyces cerevisiae then reduce the production of succinic acid. Through analysis the transcriptomic data of Saccharomyces cerevisiae with different genetic backgrounds under different succinic acid stress, we hope to find the response mechanism of Saccharomyces cerevisiae to succinic acid.