Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEVSF75)

• DME Name: Cytochrome P450 monooxygenase 51A (cyp51A)
• Synonyms: Sterol 14-alpha demethylase; Ergosterol biosynthesis protein cyp51A; AFUA_4G06890; cyp51A; erg11A
• Gene Name: cyp51A
• UniProt ID: CP51A_ASPFU
• INTEDE ID: DME1664
• Gene ID: 3509526
• EC Number:
  EC: 1.14.14.154
  Oxidoreductase
  Oxygen paired donor oxidoreductase
  Flavin/flavoprotein donor oxidoreductase
  EC: 1.14.14.154
• Lineage:
  Species: Aspergillus fumigatus
  Kingdom: Fungi
  Phylum: Ascomycota
  Class: Eurotiomycetes
  Order: Eurotiales
  Family: Aspergillaceae
  Genus: Aspergillus
  Species: Aspergillus fumigatus
• Tissue Distribution: Primarily distributed in human lung.
• Sequence:
  MVPMLWLTAYMAVAVLTAILLNVVYQLFFRLWNRTEPPMVFHWVPYLGSTISYGIDPYKF
  FFACREKYGDIFTFILLGQKTTVYLGVQGNEFILNGKLKDVNAEEVYSPLTTPVFGSDVV
  YDCPNSKLMEQKKFIKYGLTQSALESHVPLIEKEVLDYLRDSPNFQGSSGRVDISAAMAE
  ITIFTAARALQGQEVRSKLTAEFADLYHDLDKGFTPINFMLPWAPLPHNKKRDAAHARMR
  SIYVDIITQRRLDGEKDSQKSDMIWNLMNCTYKNGQQVPDKEIAHMMITLLMAGQHSSSS
  ISAWIMLRLASQPKVLEELYQEQLANLGPAGPDGSLPPLQYKDLDKLPFHQHVIRETLRI
  HSSIHSIMRKVKSPLPVPGTPYMIPPGRVLLASPGVTALSDEHFPNAGCWDPHRWENQAT
  KEQENDKVVDYGYGAVSKGTSSPYLPFGAGRHRCIGEKFAYVNLGVILATIVRHLRLFNV
  DGKKGVPETDYSSLFSGPMKPSIIGWEKRSKNTSK
• Function: This enzyme is involved in the biosynthesis of ergosterol, and as a cytochrome P-450 (heme-thiolate) protein acts on a range of steroids with a 14alpha-methyl group, such as obtusifoliol and lanosterol. And it catalyses a hydroxylation and a reduction of the 14alpha-methyl group, followed by a second hydroxylation, resulting in the elimination of formate and formation of a 14(15) double bond.
• KEGG Pathway:
  Biosynthesis of secondary metabolites (afm01110)
  Metabolic pathways (afm01100)
  Steroid biosynthesis (afm00100)

Molecular Interaction Atlas (MIA) of This DME

3 Investigative Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dihydrolanosterol	DMG0PXI	N. A.	N. A.	Investigative	[1], [2]
Lanosterol	DMHN74V	Discovery agent	N.A.	Investigative	[1], [2]
Obtusifoldienol	DMA63FQ	N. A.	N. A.	Investigative	[1], [2]

References

• [1] The fungal CYP51s: their functions, structures, related drug resistance, and inhibitors. Front Microbiol. 2019 Apr 24;10:691.
• [2] Lung colonization by Aspergillus fumigatus is controlled by ZNF77. Nat Commun. 2018 Sep 20;9(1):3835.