Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden.
Genetics (Impact Factor: 5.96). 03/2012; 190(3):885-929. DOI: 10.1534/genetics.111.133306
Source: PubMed

ABSTRACT Ever since the beginning of biochemical analysis, yeast has been a pioneering model for studying the regulation of eukaryotic metabolism. During the last three decades, the combination of powerful yeast genetics and genome-wide approaches has led to a more integrated view of metabolic regulation. Multiple layers of regulation, from suprapathway control to individual gene responses, have been discovered. Constitutive and dedicated systems that are critical in sensing of the intra- and extracellular environment have been identified, and there is a growing awareness of their involvement in the highly regulated intracellular compartmentalization of proteins and metabolites. This review focuses on recent developments in the field of amino acid, nucleotide, and phosphate metabolism and provides illustrative examples of how yeast cells combine a variety of mechanisms to achieve coordinated regulation of multiple metabolic pathways. Importantly, common schemes have emerged, which reveal mechanisms conserved among various pathways, such as those involved in metabolite sensing and transcriptional regulation by noncoding RNAs or by metabolic intermediates. Thanks to the remarkable sophistication offered by the yeast experimental system, a picture of the intimate connections between the metabolomic and the transcriptome is becoming clear.

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    • "A part from yeasts (S. cerevisiae, Schizosaccharomyces pombe) where PTR2 expression is induced by either the presence of amino acids or dipeptides (Kitamura et al., 2012; Ljungdahl and Daignan-Fornier, 2012), very little is known on the regulation of PTR genes in filamentous fungi, with the exception of H. cylindrosporum (Benjdia et al., 2006). A sequence showing high similarity to PTR genes was recently found to be expressed during growth on protein-containing substrates in the ectomycorrhizal fungus P. involutus (Shah et al., 2013). "
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    ABSTRACT: Arbuscular mycorrhizal fungi (AMF), which form an ancient and widespread mutualistic symbiosis with plants, are a crucial but still enigmatic component of the plant microbiome. Nutrient exchange has probably been at the heart of the success of this plant-fungus interaction since the earliest days of plants on land. To characterize genes from the fungal partner involved in nutrient exchange, and presumably important for the functioning of the AM symbiosis, genome-wide transcriptomic data obtained from the AMF Rhizophagus irregularis were exploited. A gene sequence, showing amino acid sequence and transmembrane domains profile similar to members of the PTR2 family of fungal oligopeptide transporters, was identified and called RiPTR2. The functional properties of RiPTR2 were investigated by means of heterologous expression in Saccharomyces cerevisiae mutants defective in either one or both of its di/tripeptide transporter genes PTR2 and DAL5. These assays showed that RiPTR2 can transport dipeptides such as Ala-Leu, Ala-Tyr or Tyr-Ala. From the gene expression analyses it seems that RiPTR2 responds to different environmental clues when the fungus grows inside the root and in the extraradical phase.
    Frontiers in Plant Science 09/2014; 5(436). DOI:10.3389/fpls.2014.00436 · 3.95 Impact Factor
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    • "Another major difference between the YPD and YNB-ammonia media is the quality of the nitrogen source, influencing the yeasts' growth rate (faster on YPD than on YNB). A third major difference is the availability of all amino acids in YPD medium, whereas YNB-ammonia-grown cells need to synthesize their own amino acids (Magasanik and Kaiser 2002; Ljungdahl and Daignan-Fornier 2012). Although it is still not obvious if and how the Vps proteins may be connected to the presence of external amino acids, we speculate that our data do not exclude the possibility that Vps proteins could be required for Gln3 relocation to the nucleus at multiple steps other than only those associated with protein trafficking to the vacuole. "
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    ABSTRACT: Nitrogen catabolite repression (NCR) is the regulatory pathway through which Saccharomyces cerevisiae responds to the available nitrogen status and selectively utilizes rich nitrogen sources in preference to poor ones. Expression of NCR-sensitive genes is mediated by two transcription activators, Gln3 and Gat1, in response to provision of a poorly used nitrogen source or following treatment with the TORC1 inhibitor, rapamycin. During nitrogen excess, the transcription activators are sequestered in the cytoplasm in a Ure2-dependent fashion. Here, we show that Vps components are required for Gln3 localization and function in response to rapamycin treatment when cells are grown in defined yeast nitrogen base but not in complex yeast peptone dextrose medium. On the other hand, Gat1 function was altered in vps mutants in all conditions tested. A significant fraction of Gat1, like Gln3, is associated with light intracellular membranes. Further, our results are consistent with the possibility that Ure2 might function downstream of the Vps components during the control of GATA factor-mediated gene expression. These observations demonstrate distinct media-dependent requirements of vesicular trafficking components for wild-type responses of GATA factor localization and function. As a result, the current model describing participation of Vps system components in events associated with translocation of Gln3 into the nucleus following rapamycin treatment or growth in nitrogen-poor medium requires modification.
    MicrobiologyOpen 06/2014; 3(3). DOI:10.1002/mbo3.168 · 2.21 Impact Factor
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    • "In our study, majority of common QTLs among traits could be group based on amino acid structure, in agreement with the observed patterns of phenotypic co-variation and indicating co-evolution of traits [48]. Part of the detected pleiotropy in our study could be explained by the fact that amino acids with similar structure converged into the same pathway under the control of common factors [49], along with functional relationships to co-ordinately regulate nitrogen assimilation [50]. Another possible explanation for the observed pleiotropy is that most amino acid permeases can transport more than one type of amino acid. "
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    ABSTRACT: Different populations within a species represent a rich reservoir of allelic variants, corresponding to an evolutionary signature of withstood environmental constraints. Saccharomyces cerevisiae strains are widely utilised in the fermentation of different kinds of alcoholic beverages, such as, wine and sake, each of them derived from must with distinct nutrient composition. Importantly, adequate nitrogen levels in the medium are essential for the fermentation process, however, a comprehensive understanding of the genetic variants determining variation in nitrogen consumption is lacking. Here, we assessed the genetic factors underlying variation in nitrogen consumption in a segregating population derived from a cross between two main fermenter yeasts, a Wine/European and a Sake isolate. By linkage analysis we identified 18 main effect QTLs for ammonium and amino acids sources. Interestingly, majority of QTLs were involved in more than a single trait, grouped based on amino acid structure and indicating high levels of pleiotropy across nitrogen sources, in agreement with the observed patterns of phenotypic co-variation. Accordingly, we performed reciprocal hemizygosity analysis validating an effect for three genes, GLT1, ASI1 and AGP1. Furthermore, we detected a widespread pleiotropic effect on these genes, with AGP1 affecting seven amino acids and nine in the case of GLT1 and ASI1. Based on sequence and comparative analysis, candidate causative mutations within these genes were also predicted. Altogether, the identification of these variants demonstrate how Sake and Wine/European genetic backgrounds differentially consume nitrogen sources, in part explaining independently evolved preferences for nitrogen assimilation and representing a niche of genetic diversity for the implementation of practical approaches towards more efficient strains for nitrogen metabolism.
    PLoS ONE 01/2014; 9(1):e86533. DOI:10.1371/journal.pone.0086533 · 3.23 Impact Factor
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