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Gene Review

ERG11  -  sterol 14-demethylase

Saccharomyces cerevisiae S288c

Synonyms: CYP51, CYPLI, Cytochrome P450 51, Cytochrome P450-14DM, Cytochrome P450-LIA1, ...
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Disease relevance of ERG11


High impact information on ERG11


Chemical compound and disease context of ERG11

  • Folding requirements are different between sterol 14alpha-demethylase (CYP51) from Mycobacterium tuberculosis and human or fungal orthologs [7].

Biological context of ERG11


Anatomical context of ERG11

  • This modified enzyme was heterologously expressed at a level of 2.5 nmol of Erg11p/mg of protein as an integral endoplasmic reticulum protein [13].
  • CYP51 and FUS enzymes were located in membranes and produced a Soret peak at 448 nm in the reduced CO difference spectrum [1].
  • The Ks of plant CYP51 for LAB170250F (0.29 microM) and gamma-ketotriazole (0.40 microM) calculated from the type-II sp2 nitrogen-binding spectra were in better agreement with their reported effects as plant CYP51 inhibitors than values previously determined with plant microsomes [14].
  • Effects of buthiobate (S-butyl S'-p-tert-butylbenzyl N-3-pyridyldithiocarbonimidate), a fungicide which inhibits lanosterol 14 alpha-demethylation catalyzed by a cytochrome P-450 (P-450 14DM) of yeast, on cytochrome P-450 of rat liver microsomes were studied [15].

Associations of ERG11 with chemical compounds

  • Repression of ERG11 expression was dependent upon the ROX1 repressor and additional repressor(s) designated as Old (overexpression of lanosterol demethylase) [16].
  • We have determined that ERG11 message levels increase during growth on glucose, in the presence of heme, and during oxygen limiting growth conditions and, unexpectedly, during anaerobic growth [16].
  • These strains were reported to synthesize some ergosterol, indicating that they contained leaky mutations in both ERG11 and ERG3, thereby making it impossible to determine whether the removal of the C-14 methyl group was required for aerobic viability [17].
  • The activity of BMS-207147 was minimally affected by overexpression of the gene encoding the efflux pump MDR1, but MIC increases were observed with changes in ERG11 and with overexpression of the CDR transporter gene [18].
  • Select ERG11 alleles were expressed in Saccharomyces cerevisiae; all of the alleles tested conferred reduced susceptibility to fluconazole [11].

Physical interactions of ERG11


Enzymatic interactions of ERG11


Regulatory relationships of ERG11


Other interactions of ERG11

  • Northern (RNA) analysis revealed that the single-deletion mutants had a marked increase in message for the undeleted ERG3 and ERG11 genes [8].
  • To explore ERG27 regulation, an erg11 null strain was generated [22].
  • When grown under azole drug pressure, the parental, heterozygous deletion and reconstructed strains of CaUPC2 upregulate the ERG2 and ERG11 ergosterol biosynthesis genes, while the homozygous deletion strain shows no such upregulation [23].
  • Furthermore, NADPH-cytochrome P450 reductase (CPR1), another component in this P450 system, appears to be coordinately regulated with ERG11 [16].
  • Expression was increased two- to fourfold in erg11, erg6 and erg24 backgrounds [22].

Analytical, diagnostic and therapeutic context of ERG11

  • Real-time quantitative PCR was used to measure expression levels of genes encoding efflux pumps, ERG11 and two control genes, ACT1 and PMA1, in a collection of 14 fluconazole-susceptible Candida albicans isolates [11].
  • Northern blot analyses revealed overexpression of the MDR1 gene in all isolates, which in some isolates was accompanied by elevated levels of CDR1/CDR2 and ERG11 expression [24].
  • Sequence analysis of the polymerase chain reaction-amplified ERG11 gene of selected azole-resistant isolates identified D116E and V488I amino acid alterations in Erg11p that are known to be conserved in fluconazole-resistant strains [24].
  • Localization experiments employing microscopic inspection and cell fractionation revealed that Erg11p in contrast to Erg7p is associated with the endoplasmic reticulum (ER) [20].
  • In this work, we have analysed the level of transcription of the CYP51 gene in correlation with cytochrome P450 enzymatic activity after treatment with several chemical agents known to interact with cytochrome P450 [25].


  1. Characterization of Saccharomyces cerevisiae CYP51 and a CYP51 fusion protein with NADPH cytochrome P-450 oxidoreductase expressed in Escherichia coli. Venkateswarlu, K., Kelly, D.E., Kelly, S.L. Antimicrob. Agents Chemother. (1997) [Pubmed]
  2. Sterol 14 alpha-demethylase, an abundant and essential mixed-function oxidase. Waterman, M.R., Lepesheva, G.I. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  3. Molecular modelling of lanosterol 14 alpha-demethylase (CYP51) from Saccharomyces cerevisiae via homology with CYP102, a unique bacterial cytochrome P450 isoform: quantitative structure-activity relationships (QSARs) within two related series of antifungal azole derivatives. Lewis, D.F., Wiseman, A., Tarbit, M.H. J. Enzym. Inhib. (1999) [Pubmed]
  4. Evidence for an interaction between the CYP1(HAP1) activator and a cellular factor during heme-dependent transcriptional regulation in the yeast Saccharomyces cerevisiae. Fytlovich, S., Gervais, M., Agrimonti, C., Guiard, B. EMBO J. (1993) [Pubmed]
  5. A yeast sterol auxotroph (erg25) is rescued by addition of azole antifungals and reduced levels of heme. Gachotte, D., Pierson, C.A., Lees, N.D., Barbuch, R., Koegel, C., Bard, M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  6. Dap1p, a heme-binding protein that regulates the cytochrome P450 protein Erg11p/Cyp51p in Saccharomyces cerevisiae. Mallory, J.C., Crudden, G., Johnson, B.L., Mo, C., Pierson, C.A., Bard, M., Craven, R.J. Mol. Cell. Biol. (2005) [Pubmed]
  7. Folding requirements are different between sterol 14alpha-demethylase (CYP51) from Mycobacterium tuberculosis and human or fungal orthologs. Lepesheva, G.I., Podust, L.M., Bellamine, A., Waterman, M.R. J. Biol. Chem. (2001) [Pubmed]
  8. Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility. Geber, A., Hitchcock, C.A., Swartz, J.E., Pullen, F.S., Marsden, K.E., Kwon-Chung, K.J., Bennett, J.E. Antimicrob. Agents Chemother. (1995) [Pubmed]
  9. Post-translational regulation of Saccharomyces cerevisiae proteins tagged with the hormone-binding domains of mammalian nuclear receptors. Launhardt, H., Munder, T. Mol. Gen. Genet. (2000) [Pubmed]
  10. ROX1 and ERG regulation in Saccharomyces cerevisiae: implications for antifungal susceptibility. Henry, K.W., Nickels, J.T., Edlind, T.D. Eukaryotic Cell (2002) [Pubmed]
  11. Application of real-time quantitative PCR to molecular analysis of Candida albicans strains exhibiting reduced susceptibility to azoles. Chau, A.S., Mendrick, C.A., Sabatelli, F.J., Loebenberg, D., McNicholas, P.M. Antimicrob. Agents Chemother. (2004) [Pubmed]
  12. Cytochrome P450 lanosterol 14 alpha-demethylase (ERG11) and manganese superoxide dismutase (SOD1) are adjacent genes in Saccharomyces cerevisiae. Turi, T.G., Kalb, V.F., Loper, J.C. Yeast (1991) [Pubmed]
  13. Generation of a complete, soluble, and catalytically active sterol 14 alpha-demethylase-reductase complex. Lamb, D.C., Kelly, D.E., Venkateswarlu, K., Manning, N.J., Bligh, H.F., Schunck, W.H., Kelly, S.L. Biochemistry (1999) [Pubmed]
  14. Optimized expression and catalytic properties of a wheat obtusifoliol 14alpha-demethylase (CYP51) expressed in yeast. Complementation of erg11Delta yeast mutants by plant CYP51. Cabello-Hurtado, F., Taton, M., Forthoffer, N., Kahn, R., Bak, S., Rahier, A., Werck-Reichhart, D. Eur. J. Biochem. (1999) [Pubmed]
  15. Effects of buthiobate, a fungicide, on cytochrome P-450 of rat liver microsomes. Yoshida, Y., Aoyama, Y. J. Pharmacobio-dyn. (1985) [Pubmed]
  16. Multiple regulatory elements control expression of the gene encoding the Saccharomyces cerevisiae cytochrome P450, lanosterol 14 alpha-demethylase (ERG11). Turi, T.G., Loper, J.C. J. Biol. Chem. (1992) [Pubmed]
  17. Sterol synthesis and viability of erg11 (cytochrome P450 lanosterol demethylase) mutations in Saccharomyces cerevisiae and Candida albicans. Bard, M., Lees, N.D., Turi, T., Craft, D., Cofrin, L., Barbuch, R., Koegel, C., Loper, J.C. Lipids (1993) [Pubmed]
  18. In vitro antifungal activity of BMS-207147 and itraconazole against yeast strains that are non-susceptible to fluconazole. Fung-Tomc, J.C., White, T.C., Minassian, B., Huczko, E., Bonner, D.P. Diagn. Microbiol. Infect. Dis. (1999) [Pubmed]
  19. Biodiversity of the P450 catalytic cycle: yeast cytochrome b5/NADH cytochrome b5 reductase complex efficiently drives the entire sterol 14-demethylation (CYP51) reaction. Lamb, D.C., Kelly, D.E., Manning, N.J., Kaderbhai, M.A., Kelly, S.L. FEBS Lett. (1999) [Pubmed]
  20. Flux of sterol intermediates in a yeast strain deleted of the lanosterol C-14 demethylase Erg11p. Ott, R.G., Athenstaedt, K., Hrastnik, C., Leitner, E., Bergler, H., Daum, G. Biochim. Biophys. Acta (2005) [Pubmed]
  21. Factors affecting homologous overexpression of the Saccharomyces cerevisiae lanosterol 14 alpha-demethylase gene. Weber, J.M., Ponti, C.G., Käppeli, O., Reiser, J. Yeast (1992) [Pubmed]
  22. Isolation, characterization, and regulation of the Candida albicans ERG27 gene encoding the sterol 3-keto reductase. Pierson, C.A., Jia, N., Mo, C., Lees, N.D., Sturm, A.M., Eckstein, J., Barbuct, R., Bard, M. Med. Mycol. (2004) [Pubmed]
  23. Role of Candida albicans transcription factor Upc2p in drug resistance and sterol metabolism. Silver, P.M., Oliver, B.G., White, T.C. Eukaryotic Cell (2004) [Pubmed]
  24. Resistance mechanisms in fluconazole-resistant Candida albicans isolates from vaginal candidiasis. Cernicka, J., Subik, J. Int. J. Antimicrob. Agents (2006) [Pubmed]
  25. Expression of cytochrome P450 in yeast after different chemical treatments. Del Carratore, R., Morichetti, E., Cecchini, E., Bronzetti, G., Gallo, E., Galeotti, C.L. Carcinogenesis (1992) [Pubmed]
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