ID CP51_PICKU Reviewed; 414 AA.
AC Q02315;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 08-NOV-2023, entry version 101.
DE RecName: Full=Lanosterol 14-alpha demethylase;
DE EC=1.14.14.154;
DE AltName: Full=CYPLI;
DE AltName: Full=Cytochrome P450 51;
DE AltName: Full=Cytochrome P450-14DM;
DE AltName: Full=Cytochrome P450-LIA1;
DE AltName: Full=Sterol 14-alpha demethylase;
DE Flags: Fragment;
GN Name=CYP51;
OS Pichia kudriavzevii (Yeast) (Issatchenkia orientalis).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Pichiaceae; Pichia.
OX NCBI_TaxID=4909;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 6258 / CBS 573 / DSM 6128 / JCM 1609 / NBRC 1064 / NRRL Y-413;
RX PubMed=7989540; DOI=10.1128/jcm.32.8.1902-1907.1994;
RA Burgener-Kairuz P., Zuber J.P., Jaunin P., Buchman T.G., Bille J.,
RA Rossier M.;
RT "Rapid detection and identification of Candida albicans and Torulopsis
RT (Candida) glabrata in clinical specimens by species-specific nested PCR
RT amplification of a cytochrome P-450 lanosterol-alpha-demethylase (L1A1)
RT gene fragment.";
RL J. Clin. Microbiol. 32:1902-1907(1994).
CC -!- FUNCTION: Sterol 14alpha-demethylase that plays a critical role in the
CC third module of ergosterol biosynthesis pathway, being ergosterol the
CC major sterol component in fungal membranes that participates in a
CC variety of functions (By similarity). The third module or late pathway
CC involves the ergosterol synthesis itself through consecutive reactions
CC that mainly occur in the endoplasmic reticulum (ER) membrane (By
CC similarity). In filamentous fungi, during the initial step of this
CC module, lanosterol (lanosta-8,24-dien-3beta-ol) can be metabolized to
CC eburicol (By similarity). Sterol 14alpha-demethylase catalyzes the
CC three-step oxidative removal of the 14alpha-methyl group (C-32) of both
CC these sterols in the form of formate, and converts eburicol and
CC lanosterol to 14-demethyleburicol (4,4,24-trimethylergosta-8,14,24(28)-
CC trienol) and 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol,
CC respectively, which are further metabolized by other enzymes in the
CC pathway to ergosterol (By similarity). Can also use substrates not
CC intrinsic to fungi, such as 24,25-dihydrolanosterol (DHL), producing
CC 4,4-dimethyl-8,14-cholestadien-3-beta-ol, but at lower rates than the
CC endogenous substrates (By similarity). {ECO:0000250|UniProtKB:P10613,
CC ECO:0000250|UniProtKB:P10614, ECO:0000250|UniProtKB:Q4WNT5}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-methyl steroid + 3 O2 + 3 reduced [NADPH--
CC hemoprotein reductase] = a Delta(14) steroid + formate + 4 H(+) + 4
CC H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:54028, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:138029, ChEBI:CHEBI:138031; EC=1.14.14.154;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54029;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-methyl steroid + O2 + reduced [NADPH--hemoprotein
CC reductase] = a 14alpha-hydroxymethyl steroid + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68060, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:138029, ChEBI:CHEBI:176901;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68061;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-hydroxymethyl steroid + O2 + reduced [NADPH--
CC hemoprotein reductase] = a 14alpha-formyl steroid + H(+) + 2 H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68064,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:176901, ChEBI:CHEBI:176902;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68065;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-formyl steroid + O2 + reduced [NADPH--hemoprotein
CC reductase] = a Delta(14) steroid + formate + 2 H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68068, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:138031,
CC ChEBI:CHEBI:176902; Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68069;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lanosterol + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] =
CC 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 4
CC H(+) + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:25286, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:16521, ChEBI:CHEBI:17813,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.154;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25287;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 32-
CC hydroxylanosterol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:75103, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16521, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:166806; Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75104;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-hydroxylanosterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 32-oxolanosterol + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:75107, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:166681, ChEBI:CHEBI:166806;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75108;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-oxolanosterol + O2 + reduced [NADPH--hemoprotein reductase]
CC = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 2
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:75111, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:17813, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:166681;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75112;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eburicol + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] =
CC 14-demethyleburicol + formate + 4 H(+) + 4 H2O + 3 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:75439, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:70315, ChEBI:CHEBI:194330;
CC Evidence={ECO:0000250|UniProtKB:P10613};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75440;
CC Evidence={ECO:0000250|UniProtKB:P10613};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eburicol + O2 + reduced [NADPH--hemoprotein reductase] = 32-
CC hydroxyeburicol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:75427, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:70315,
CC ChEBI:CHEBI:194328; Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75428;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-hydroxyeburicol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 32-oxoeburicol + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:75431, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:194328, ChEBI:CHEBI:194329;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75432;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-oxoeburicol + O2 + reduced [NADPH--hemoprotein reductase] =
CC 14-demethyleburicol + formate + 2 H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:75435, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:194329, ChEBI:CHEBI:194330;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75436;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 1/6.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; S75391; AAB32680.1; -; Genomic_DNA.
DR AlphaFoldDB; Q02315; -.
DR SMR; Q02315; -.
DR VEuPathDB; FungiDB:C5L36_0D02200; -.
DR eggNOG; KOG0684; Eukaryota.
DR UniPathway; UPA00770; UER00754.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0008398; F:sterol 14-demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd11042; CYP51-like; 1.
DR Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR PANTHER; PTHR24286; CYTOCHROME P450 26; 1.
DR PANTHER; PTHR24286:SF24; LANOSTEROL 14-ALPHA DEMETHYLASE; 1.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; Cytochrome P450; 1.
PE 3: Inferred from homology;
KW Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding;
KW Monooxygenase; Oxidoreductase; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism.
FT CHAIN 1..>414
FT /note="Lanosterol 14-alpha demethylase"
FT /id="PRO_0000052007"
FT NON_TER 414
SQ SEQUENCE 414 AA; 46981 MW; A23CCD0EE1F3A72D CRC64;
MPWVGSAVVY GMQPYEFFEN CRKQHGDVFS FLLLGKVMTV YLGPKGHEFV LNAKLSDVSA
EDAYTHLTTP VFGKGVIYDC PNWKLMEQKK FAKVALTKES FIRYVPLIKD EMLKYFNANF
RGDSGKTDVL KSQSEMTLFT ASRSLFGDAL RNRLDASYAE MYSDLDKGFT PLNFVFSYLP
LPNYWKRDAA HKNISNTYLD LINTKRAGGE IKNEDLVDAL LKNSVYKDGT RMTDEELAHL
MIGVLMGGQH TSSATSAWFL LHLGEKPQLQ EEIYREIQSV LGENFERELT YDDLQKLDLV
NATIKETLRL HMPLHSIFRK VTRDLPVPNT SYIVPKGHYV LISPGYTMLS ERYFPNASEF
QPHRWDEIKS IDGGISFGAE GENAKETVDY GFGKISKGVA SPYLPFGGGR HRCT
//
