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Gene Review:

FOL1 - trifunctional dihydropteroate...

Saccharomyces cerevisiae S288c

Synonyms: Folic acid synthesis protein FOL1, N0848, YNL256W

Hong, S.P. et al., Iliades, P. et al., Güldener, U. et al., Meneau, I. et al., Bayly, A.M. et al., et al.

Iliades, Berglez, Meshnick, Macreadie, Iliades, Meshnick, Macreadie,

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Disease relevance of FOL1

Therefore, we chose to model the P. jirovecii mutations in the Saccharomyces cerevisiae FAS protein (encoded by FOL1) via its expression in Escherichia coli [1].

High impact information on FOL1

Fol1p is exclusively localized to mitochondria as shown by fluorescence microscopy and immune electronmicroscopy [2].
FOL1 is an essential gene and the nongrowth phenotype of the fol1 deletion leads to a recessive auxotrophy for folinic acid (5'-formyltetrahydrofolate) [2].
Protein binding was increased by tetrahydrofolate, and use of a fol1 deletion mutant indicated the involvement of a folate in the in vivo glycine response [3].
The use of stronger promoters to drive FOL1 expression led to increased sulfamethoxazole resistance when para-aminobenzoic acid (pABA) levels were elevated [4].
Here, yeast strains have been constructed to study the effects of FOL1 expression on growth and sulfa drug resistance [4].

Biological context of FOL1

The folic acid synthesis pathway in the folate utilising isolates was restored via transformation with FOL1 or FOL3 expression plasmids and transformants were tested for resistance to sulfamethoxazole (SMX) [5].

Associations of FOL1 with chemical compounds

However, high FOL1 expression levels resulted in increased susceptibility to sulfamethoxazole in pABA free media [4].
Site-directed mutagenesis of the Saccharomyces cerevisiae dihydropteroate synthase FOL1 gene to study Pneumocystis jirovecii mutations in the orthologue gene FAS [6].

Analytical, diagnostic and therapeutic context of FOL1

Single or double mutations identical to those observed in the DHPS domain of the P. jiroveci FAS gene were introduced by in vitro site-directed mutagenesis into alleles of the S. cerevisiae FOL1 gene, which is the orthologue of the P. jiroveci FAS gene [7].

References

Analysis of Pneumocystis jirovecii DHPS alleles implicated in sulfamethoxazole resistance using an Escherichia coli model system. Iliades, P., Meshnick, S.R., Macreadie, I.G. Microb. Drug Resist. (2005) [Pubmed]
Characterization of the Saccharomyces cerevisiae Fol1 protein: starvation for C1 carrier induces pseudohyphal growth. Güldener, U., Koehler, G.J., Haussmann, C., Bacher, A., Kricke, J., Becher, D., Hegemann, J.H. Mol. Biol. Cell (2004) [Pubmed]
Control of expression of one-carbon metabolism genes of Saccharomyces cerevisiae is mediated by a tetrahydrofolate-responsive protein binding to a glycine regulatory region including a core 5'-CTTCTT-3' motif. Hong, S.P., Piper, M.D., Sinclair, D.A., Dawes, I.W. J. Biol. Chem. (1999) [Pubmed]
Promoter strength of folic acid synthesis genes affects sulfa drug resistance in Saccharomyces cerevisiae. Iliades, P., Berglez, J., Meshnick, S., Macreadie, I. Microb. Drug Resist. (2003) [Pubmed]
Folic acid utilisation related to sulfa drug resistance in Saccharomyces cerevisiae. Bayly, A.M., Berglez, J.M., Patel, O., Castelli, L.A., Hankins, E.G., Coloe, P., Hopkins Sibley, C., Macreadie, I.G. FEMS Microbiol. Lett. (2001) [Pubmed]
Site-directed mutagenesis of the Saccharomyces cerevisiae dihydropteroate synthase FOL1 gene to study Pneumocystis jirovecii mutations in the orthologue gene FAS. Meneau, I., Sanglard, D., Bille, J., Hauser, P.M. J. Eukaryot. Microbiol. (2003) [Pubmed]
Pneumocystis jiroveci dihydropteroate synthase polymorphisms confer resistance to sulfadoxine and sulfanilamide in Saccharomyces cerevisiae. Meneau, I., Sanglard, D., Bille, J., Hauser, P.M. Antimicrob. Agents Chemother. (2004) [Pubmed]

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