Cited by 19Antifungal resistance and susceptibilityFungal and yeast genetics researchPlant biochemistry and biosynthesis

Isolation, characterization, and regulation of the CandidaalbicansERG27 gene encoding the sterol 3-keto reductase

Pierson, C. A., Jia, N., Mo, C., Lees, N. D., Sturm, A. M., Eckstein, J., Barbuch, R., Bard, M.·2004·Medical Mycology

Abstract

The Candida albicans ERG27 gene which encodes the 3-keto reductase enzyme required for sterol C-4 demethylation was isolated and found to encode a 349 amino acid protein that is 60% identical at the amino acid level to the Saccharomyces cerevisiae Erg27p. A C. albicans erg27 null was created in a strain containing an integrated ERG27 rescue cassette under the control of the pMAL2 inducible promoter. The C. albicans erg27 strain was able to grow only in the presence of maltose indicating that the ERG27 gene is essential. The C. albicans erg27 null showed complete loss of both 3-keto reductase and oxidosqualene cyclase (Erg7p) activities compromising all sterol synthesis. These results suggest that Erg27p inhibitors might be effective antifungals. To explore ERG27 regulation, an erg11 null strain was generated. C. albicans erg6 and erg24 mutants were also employed along with the inhibitors, itraconazole and zaragozic acid A, to characterize ERG27 expression using Northern analysis. Expression was increased two- to fourfold in erg11, erg6 and erg24 backgrounds. However, itraconazole which targets Erg11p (lanosterol demethylase) increased ERG27 expression 10-fold and zaragozic acid A which targets the Erg9p (squalene synthase) increased ERG27 expression fivefold. The azole and erg11 results support other observations that azoles may affect non-sterol targets.

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Crossref · 10.1080/1369378032000141471

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  • ERG1, ERG7, ERG9, ERG25, ERG26, and ERG27 are essential, while ERG2, ERG3, ERG5, ERG6, and ERG24 are considered non-essential in ergosterol biosynthesis.

    “By using the technology of gene disruption and controlled gene expression, ERG1 , ERG7 , ERG9 , ERG25 , ERG26 , and ERG27 have been proved to be essential, while ERG2 , ERG3 , ERG5 , ERG6 , and ERG24 are considered to be non-essential in ergosterol biosynthesis.”

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Authors
Pierson, C. A., Jia, N., Mo, C., Lees, N. D., Sturm, A. M., Eckstein, J., Barbuch, R., & Bard, M.
Affiliations
  • Indiana University – Purdue University Indianapolis (US)
  • Eli Lilly (United States) (US)
Corresponding author
Pierson, C. A.
Venue
Medical Mycology
Published
2004-01
Volume
42
Issue
5
Pages
461-473
ISSN
  • 0268-1218 (ISSN-L)
  • 1369-3786
  • 1460-2709
OpenAlex
W2027579286
Cited by
19
References
41
Citations by year
2024: 1 · 2023: 2 · 2020: 1 · 2019: 1 · 2016: 1 · 2012: 2
FWCI
0.64
Type
journal article
Language
en
Open access
closed
Locations
  • Medical Mycology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Burroughs Wellcome Fund
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
Keywords
Candida albicans, ergosterol biosynthesis, ERG6, gene expression regulation, itraconazole, zaragozic acid A, antifungal drug targets, oxidosqualene cyclase
MeSH terms
Amino Acid Sequence, Base Sequence, Candida albicans, Ergosterol, Genes, Fungal, Molecular Sequence Data, Oxidoreductases, Saccharomyces cerevisiae, Gene Expression Regulation, Fungal, Gene Deletion, Sequence Analysis, DNA, Genes, Essential, Saccharomyces cerevisiae Proteins

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