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Volume 148, Issue 5

The gene of encodes a tyrosine-sensitive DAHP synthase: evolution, functional conservation and phenotype of Aro3p-, Aro4p-deficient mutants

The GenBank accession number for the sequence reported in this paper is U53216.

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Abstract

The enzyme 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP) synthase catalyses the first step in aromatic amino acid biosynthesis in prokaryotes, plants and fungi. Cells of contain two catalytically redundant DAHP synthases, encoded by the genes and , whose activities are feedback-inhibited by phenylalanine and tyrosine, respectively. / gene transcription is controlled by . The authors previously cloned an gene orthologue from and found that: (1) it can complement an double mutation in , an effect inhibited by excess phenylalanine, and (2) a homozygous -deletion mutant of is phenotypically Aro, suggesting the existence of another isozyme(s). They now report the identification and functional characterization of the orthologue of Aro4p. The two Aro4p enzymes share 68% amino acid identity. Phylogenetic analysis places the fungal DAHP synthases in a cluster separate from prokaryotic orthologues and suggests that and arose from a single gene via a gene duplication event early in fungal evolution. mRNA is elevated upon amino acid starvation, consistent with the presence of three putative Gcn4p-responsive elements (GCREs) in the gene promoter sequence. complements an double mutation in , an effect inhibited by excess tyrosine. The authors engineered Δ/Δ Δ:: cells of (with one wild-type copy of placed under control of the repressible promoter) and found that they fail to grow in the absence of aromatic amino acids when expression is repressed, and that this growth defect can be partially rescued by aromatic amino acids and certain aromatic amino acid pathway intermediates. It is concluded that, like , contains two DAHP synthases required for the first step in the aromatic amino acid biosynthetic pathway.

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Keyword(s): 3AT, 3-aminotriazole , 5-FOA, 5-fluoroorotic acid , aromatic amino acids , DAHP, 3-deoxy-D-arabinoheptulosonate 7-phosphate , GCN4 , GCRE, Gcn4p-responsive element , MET3 promoter , pathogenic fungi , SC, synthetic complete and UTR, untranslated region
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2002-05-01
2024-04-27
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The ARO4 gene of Candida albicans encodes a tyrosine-sensitive DAHP synthase: evolution, functional conservation and phenotype of Aro3p-, Aro4p-deficient mutantsThe GenBank accession number for the sequence reported in this paper is U53216.
Microbiology 148, 1291 (2002); https://doi.org/10.1099/00221287-148-5-1291
/content/journal/micro/10.1099/00221287-148-5-1291
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