Distribution and diversity of cytochrome p450 monooxygenases in the fungal class tremellomycetes

Olufunmilayo Olukemi Akapo, Tiara Padayachee, Wanping Chen, Abidemi Paul Kappo, Jae Hyuk Yu, David Nelson, Khajamohiddin Syed

Research output: Contribution to journalArticle

Abstract

Tremellomycetes, a fungal class in the subphylum Agaricomycotina, contain well-known opportunistic and emerging human pathogens. The azole drug fluconazole, used in the treatment of diseases caused by some species of Tremellomycetes, inhibits cytochrome P450 monooxygenase CYP51, an enzyme that converts lanosterol into an essential component of the fungal cell membrane ergosterol. Studies indicate that mutations and over-expression of CYP51 in species of Tremellomycetes are one of the reasons for fluconazole resistance. Moreover, the novel drug, VT-1129, that is in the pipeline is reported to exert its effect by binding and inhibiting CYP51. Despite the importance of CYPs, the CYP repertoire in species of Tremellomycetes has not been reported to date. This study intends to address this research gap. Comprehensive genome-wide CYP analysis revealed the presence of 203 CYPs (excluding 16 pseudo-CYPs) in 23 species of Tremellomycetes that can be grouped into 38 CYP families and 72 CYP subfamilies. Twenty-three CYP families are new and three CYP families (CYP5139, CYP51 and CYP61) were conserved across 23 species of Tremellomycetes. Pathogenic cryptococcal species have 50% fewer CYP genes than non-pathogenic species. The results of this study will serve as reference for future annotation and characterization of CYPs in species of Tremellomycetes.

Original languageEnglish (US)
Article number2889
JournalInternational journal of molecular sciences
Volume20
Issue number12
DOIs
StatePublished - Jun 2 2019

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Fluconazole
cytochromes
Mixed Function Oxygenases
Cytochrome P-450 Enzyme System
drugs
Genes
Fungal Structures
Lanosterol
azoles
annotations
Ergosterol
Azoles
pathogens
genome
Pathogens
Cell membranes
mutations
Pharmaceutical Preparations
genes
enzymes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Distribution and diversity of cytochrome p450 monooxygenases in the fungal class tremellomycetes. / Akapo, Olufunmilayo Olukemi; Padayachee, Tiara; Chen, Wanping; Kappo, Abidemi Paul; Yu, Jae Hyuk; Nelson, David; Syed, Khajamohiddin.

In: International journal of molecular sciences, Vol. 20, No. 12, 2889, 02.06.2019.

Research output: Contribution to journalArticle

Akapo, Olufunmilayo Olukemi ; Padayachee, Tiara ; Chen, Wanping ; Kappo, Abidemi Paul ; Yu, Jae Hyuk ; Nelson, David ; Syed, Khajamohiddin. / Distribution and diversity of cytochrome p450 monooxygenases in the fungal class tremellomycetes. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 12.
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