The THI5 gene family of Saccharomyces cerevisiae: Distribution of homologues among the hemiascomycetes and functional redundancy in the aerobic biosynthesis of thiamin from pyridoxine

Raymond Wightman, Peter A. Meacock

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The THI5 gene family of Saccharomyces cerevisiae comprises four highly conserved members named THI5 (YFL058w), THI11 (YJR156c), THI12 (YNL332w) and THI13 (YDL244w). Each gene copy is located within the subtelomeric region of a different chromosome and all are homologues of the Schizosaccharomyces pombe nmt1 gene which is thought to function in the biosynthesis of hydroxymethylpyrimidine (HMP), a precursor of vitamin B1, thiamin. A comprehensive phylogenetic study has shown that the existence of THI5 as a gene family is exclusive to those yeasts of the Saccharomyces sensu stricto subgroup. To determine the function and redundancy of each of the S. cerevisiae homologues, all combinations of the single, double, triple and quadruple deletion mutants were constructed using a PCR-mediated gene-disruption strategy. Phenotypic analyses of these mutant strains have shown the four genes to be functionally redundant in terms of HMP formation for thiamin biosynthesis; each promotes synthesis of HMP from the pyridoxine (vitamin B6) biosynthetic pathway. Furthermore, growth studies with the quadruple mutant strain support a previous proposal of an alternative HMP biosynthetic pathway that operates in yeast under anaerobic growth conditions. Comparative analysis of mRNA levels has revealed subtle differences in the regulation of the four genes, suggesting that they respond differently to nutrient limitation.
    Original languageEnglish
    Pages (from-to)1447-1460
    Number of pages13
    JournalMicrobiology
    Volume149
    Issue number6
    DOIs
    Publication statusPublished - 1 Jun 2003

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