The <i>Saccharomyces cerevisiae ARO1</i> gene An example of the co‐ordinate regulation of five enzymes on a single biosynthetic pathway

Duncan, Kenneth; Edwards, Ruairidh; Coggins, John R.

doi:10.1016/0014-5793(88)81036-6

Cited by 39 publications

(19 citation statements)

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“…The aromatic amino acids tryptophan, tyrosine, and phenylalanine are synthesized from chorismate (51). As shown previously (21,36,50), all four genes encoding enzymes required for chorismate synthesis (ARO1, ARO2, ARO3, and ARO4) and three of the four genes encoding enzymes that convert chorismate to tryptophan (TRP2, TRP3, TRP4, and TRP5) were found to be Gcn4p targets. ARO2 belongs to the class of Gcn4p targets that were not strongly induced by 3AT but required Gcn4p to prevent its repression in severely starved cells (Fig.…”

Section: Fig 3 a Fraction Of Gcn4p Target Genes Is Induced By 3at Isupporting

confidence: 77%

Transcriptional Profiling Shows that Gcn4p Is a Master Regulator of Gene Expression during Amino Acid Starvation in Yeast

Natarajan

Meyer

Jackson

et al. 2001

Molecular and Cellular Biology

686

737

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Starvation for amino acids induces Gcn4p, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. In an effort to identify all genes regulated by Gcn4p during amino acid starvation, we performed cDNA microarray analysis. Data from 21 pairs of hybridization experiments using two different strains derived from S288c revealed that more than 1,000 genes were induced, and a similar number were repressed, by a factor of 2 or more in response to histidine starvation imposed by 3-aminotriazole (3AT). Profiling of a gcn4⌬ strain and a constitutively induced mutant showed that Gcn4p is required for the full induction by 3AT of at least 539 genes, termed Gcn4p targets. Genes in every amino acid biosynthetic pathway except cysteine and genes encoding amino acid precursors, vitamin biosynthetic enzymes, peroxisomal components, mitochondrial carrier proteins, and autophagy proteins were all identified as Gcn4p targets. Unexpectedly, genes involved in amino acid biosynthesis represent only a quarter of the Gcn4p target genes. Gcn4p also activates genes involved in glycogen homeostasis, and mutant analysis showed that Gcn4p suppresses glycogen levels in amino acid-starved cells. Numerous genes encoding protein kinases and transcription factors were identified as targets, suggesting that Gcn4p is a master regulator of gene expression. Interestingly, expression profiles for 3AT and the alkylating agent methyl methanesulfonate (MMS) overlapped extensively, and MMS induced GCN4 translation. Thus, the broad transcriptional response evoked by Gcn4p is produced by diverse stress conditions. Finally, profiling of a gcn4⌬ mutant uncovered an alternative induction pathway operating at many Gcn4p target genes in histidine-starved cells.In response to environmental perturbations, Saccharomyces cerevisiae cells elicit rapid transcriptional reprogramming involving both activation and repression of gene expression. Transcriptional activator proteins function by binding to specific promoter elements, called upstream activating sequences (UASs) in yeast cells, and recruiting the transcriptional machinery. Thus, transcriptional stimulation requires the expression and function of an activator and the appropriate UAS element in the promoters of its target genes. A plethora of mechanisms are known to regulate the activity or expression of transcriptional activators in response to specific signals. For example, in cells grown on glucose, Gal80p inhibits the ability of Gal4p to activate transcription of genes encoding galactosemetabolizing enzymes, whereas Gal3p alleviates this inhibition on galactose medium (83). The transcriptional activators Pho4p, Swi5p, and Yap1p are regulated by the coupling of their nuclear localization to the levels of inorganic phosphate, cell cycle and mother-daughter status, or oxidative stress, respectively (reviewed in reference 52). Starvation for amino acids, purines, and glucose limitation induces the synthesis of Gcn4p, a bZIP transcriptional activator of amino acid biosynthetic gene...

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Section: Fig 3 a Fraction Of Gcn4p Target Genes Is Induced By 3at Isupporting

confidence: 77%

Transcriptional Profiling Shows that Gcn4p Is a Master Regulator of Gene Expression during Amino Acid Starvation in Yeast

Natarajan

Meyer

Jackson

et al. 2001

Molecular and Cellular Biology

686

737

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“…Aro1 is a pentafunctional protein that catalyzes five steps in the biosynthesis of chorismate. Chorismate is a precursor of tryptophan, tyrosine, and phenylalanine (Duncan et al 1988). Aro2 is a bifunctional chorismate synthase and flavin reductase, which catalyzes the conversion of 5-enolpyruvylshikimate 3-phosphate to form chorismate (Jones et al 1991).…”

Section: Resultsmentioning

confidence: 99%

Global Screening of Genes Essential for Growth in High-Pressure and Cold Environments: Searching for Basic Adaptive Strategies Using a Yeast Deletion Library

Abe

Minegishi

2008

Genetics

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Microorganisms display an optimal temperature and hydrostatic pressure for growth. To establish the molecular basis of piezo-and psychroadaptation, we elucidated global genetic defects that give rise to susceptibility to high pressure and low temperature in Saccharomyces cerevisiae. Here we present 80 genes including 71 genes responsible for high-pressure growth and 56 responsible for low-temperature growth with a significant overlap of 47 genes. Numerous previously known cold-sensitive mutants exhibit marked high-pressure sensitivity. We identified critically important cellular functions: (i) amino acid biosynthesis, (ii) microautophagy and sorting of amino acid permease established by the exit from rapamycin-induced growth arrest/Gap1 sorting in the endosome (EGO/GSE) complex, (iii) mitochondrial functions, (iv) membrane trafficking, (v) actin organization mediated by Drs2-Cdc50, and (vi) transcription regulated by the Ccr4-Not complex. The loss of EGO/GSE complex resulted in a marked defect in amino acid uptake following high-pressure and low-temperature incubation, suggesting its role in surface delivery of amino acid permeases. Microautophagy and mitochondrial functions converge on glutamine homeostasis in the target of rapamycin (TOR) signaling pathway. The localization of actin requires numerous associated proteins to be properly delivered by membrane trafficking. In this study, we offer a novel route to gaining insights into cellular functions and the genetic network from growth properties of deletion mutants under high pressure and low temperature.

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“…As low production of PCA might be explained by the competition of the 3-DHS dehydratases with the 3-DHS dehydrogenase activity of the common aromatic amino acid biosynthesis pathway, we blocked the production of phenylalanine, tryptophan, and tyrosine at the level of 3-DHS by the elimination of 3-DHS dehydrogenase activity. In yeast, this reaction is mediated by the pentafunctional enzyme Arom (encoded by ARO1) (12,13), which mediates the stepwise conversion of 3-DAHP to 5-enolpyruvyl-shikimate-3-phosphate via 3-DHS. Therefore, it was necessary to block only the 3-DHS dehydrogenase activity without affecting the dehydroquinate synthase and dehydroquinate dehydratase activities, which convert 3-DAHP to 3-DHS.…”

Section: Aay67850 Aad50377 Aay67851mentioning

confidence: 99%

Biosynthesis of cis , cis -Muconic Acid and Its Aromatic Precursors, Catechol and Protocatechuic Acid, from Renewable Feedstocks by Saccharomyces cerevisiae

Weber

Brückner

Weinreb

et al. 2012

Appl Environ Microbiol

155

170

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Adipic acid is a high-value compound used primarily as a precursor for the synthesis of nylon, coatings, and plastics. Today it is produced mainly in chemical processes from petrochemicals like benzene. Because of the strong environmental impact of the production processes and the dependence on fossil resources, biotechnological production processes would provide an interesting alternative. Here we describe the first engineered Saccharomyces cerevisiae strain expressing a heterologous biosynthetic pathway converting the intermediate 3-dehydroshikimate of the aromatic amino acid biosynthesis pathway via protocatechuic acid and catechol into cis,cis-muconic acid, which can be chemically dehydrogenated to adipic acid. The pathway consists of three heterologous microbial enzymes, 3-dehydroshikimate dehydratase, protocatechuic acid decarboxylase composed of three different subunits, and catechol 1,2-dioxygenase. For each heterologous reaction step, we analyzed several potential candidates for their expression and activity in yeast to compose a functional cis,cis-muconic acid synthesis pathway. Carbon flow into the heterologous pathway was optimized by increasing the flux through selected steps of the common aromatic amino acid biosynthesis pathway and by blocking the conversion of 3-dehydroshikimate into shikimate. The recombinant yeast cells finally produced about 1.56 mg/liter cis,cis-muconic acid.

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The Saccharomyces cerevisiae ARO1 gene An example of the co‐ordinate regulation of five enzymes on a single biosynthetic pathway

Cited by 39 publications

References 40 publications

Transcriptional Profiling Shows that Gcn4p Is a Master Regulator of Gene Expression during Amino Acid Starvation in Yeast

Transcriptional Profiling Shows that Gcn4p Is a Master Regulator of Gene Expression during Amino Acid Starvation in Yeast

Global Screening of Genes Essential for Growth in High-Pressure and Cold Environments: Searching for Basic Adaptive Strategies Using a Yeast Deletion Library

Biosynthesis of cis , cis -Muconic Acid and Its Aromatic Precursors, Catechol and Protocatechuic Acid, from Renewable Feedstocks by Saccharomyces cerevisiae

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