ID   HTYF_ASPRU              Reviewed;         683 AA.
AC   K0E690;
DT   25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT   28-NOV-2012, sequence version 1.
DT   03-AUG-2022, entry version 28.
DE   RecName: Full=Cytochrome P450 monooxygenase htyF {ECO:0000303|PubMed:22998630};
DE            EC=1.-.-.- {ECO:0000305|PubMed:22998630};
DE   AltName: Full=L-homotyrosine biosynthetic cluster protein A {ECO:0000303|PubMed:22998630};
GN   Name=htyF {ECO:0000303|PubMed:22998630};
OS   Aspergillus rugulosus (Emericella rugulosa).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX   NCBI_TaxID=41736;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PATHWAY, AND BIOTECHNOLOGY.
RC   STRAIN=ATCC 58397 / NRRL 11440;
RX   PubMed=22998630; DOI=10.1021/ja307220z;
RA   Cacho R.A., Jiang W., Chooi Y.H., Walsh C.T., Tang Y.;
RT   "Identification and characterization of the echinocandin B biosynthetic
RT   gene cluster from Emericella rugulosa NRRL 11440.";
RL   J. Am. Chem. Soc. 134:16781-16790(2012).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the de novo generation of L-homotyrosine from acetyl-CoA and
CC       4-hydroxyphenyl-pyruvate (PubMed:22998630). L-homotyrosine is a
CC       building block of echinocandin B, a fungal lipidated cyclic hexapeptide
CC       that acts as an antifungal agent (PubMed:22998630). L-homotyrosine 4-
CC       hydroxyphenyl-pyruvate first undergoes an aldol-type condensation by
CC       htyA with the C-2 of acetyl-CoA followed by the release of CoA to form
CC       2-(4-hydroxybenzyl)-malate (PubMed:22998630). This is followed by
CC       isomerization of 2-(4-hydroxy-benzyl)-malate to 3-(4-hydroxybenzyl)-
CC       malate by htyD (PubMed:22998630). Thereafter, 3-(4-hydroxybenzyl)-
CC       malate undergoes decarboxylation and oxidation to form 2-oxo-4-(4-
CC       hydroxybenzyl)butanoic acid, coupled to reduction of NAD(+) to NADH by
CC       htyC (PubMed:22998630). The product then undergoes transamination
CC       catalyzed by htyB to form L-homotyrosine (PubMed:22998630).
CC       {ECO:0000269|PubMed:22998630}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Antifungal biosynthesis. {ECO:0000305|PubMed:22998630}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- BIOTECHNOLOGY: Due to their effectiveness as antifungal agents,
CC       echinocandin derivatives can be used for the treatment of human
CC       invasive candidiasis (PubMed:22998630). {ECO:0000269|PubMed:22998630}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; JX421685; AFT91399.1; -; Genomic_DNA.
DR   AlphaFoldDB; K0E690; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   GO; GO:0008152; P:metabolic process; IEA:UniProt.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW   Oxidoreductase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..683
FT                   /note="Cytochrome P450 monooxygenase htyF"
FT                   /id="PRO_0000443833"
FT   TRANSMEM        8..28
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        588..608
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         481
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
FT   CARBOHYD        29
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        581
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   683 AA;  77153 MW;  2463A14340ACAD73 CRC64;
     MLATDSTPAL LAASVVLAVS LVSYVIQLNR SRTHRAFWAS HPWVGVRDEW FSGARTKLRI
     VTSVREMVED GFHRFSQFKT AFALPNIGEP PWLVLPPASL REFLAKPDAD LDHNIIHEEQ
     LQNYYTQGAL GHHAATIPLQ FDVVRRQLTR ELPLVAAALH DELHKSFQDY WGTDTIAAKQ
     IDLLATCFKI VTRTANRVFI GADICRSEAF LEHLRRYSDA VGRAGIIIRL FPRWLRPVVT
     PAVTVWYRRD LAVCREICVP VIRCRVQQTI EKRKDVDCTW KAPVDVLQWL IEAALRRNDA
     AELDPLLLTQ RLLMLNFVSI ETTSMAITHA IADLYGSADA DSFIAGLQEE CERALPHGEL
     WTKAQLDNLV RIDSAIRESM RVSDFSHIQL PRLVANPHGV DFQSTGNPPL HVPPGIRLCV
     PAHSIHRDPA LYPDPLTYNA FRFVIEPSVG AGDATEPAPK QASLATTTDS FLVFGHGRHA
     CPGRFFAAHL MKLMLAYIVR HYDVARLTQP VDKQTTECTK APFHMEYGGG PLAYMGHSLT
     GATRLQDTLC FMKFDSSQYL DTSPIVTIPS YIYWPSLNTM NQSSKYSLYV FVVLVACVAA
     LFIGIGIYQM YHPLDRDNAA YREVPHEQRA YMRKAGSPPA FSKFIYRLYC PNIQWKVKRC
     IGVLFLLFAY YNSRLRLSSA TKN