ID   ERII_HERER              Reviewed;         552 AA.
AC   A0A1V0QSE9;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   07-JUN-2017, sequence version 1.
DT   03-AUG-2022, entry version 15.
DE   RecName: Full=Cytochrome P450 monooxyhenase eriI {ECO:0000303|PubMed:28371074};
DE            EC=1.-.-.- {ECO:0000269|PubMed:31535864};
DE   AltName: Full=Erinacine biosynthesis cluster protein IA {ECO:0000303|PubMed:28371074};
GN   Name=eriI {ECO:0000303|PubMed:28371074};
OS   Hericium erinaceus (Lion's mane mushroom) (Hydnum erinaceus).
OC   Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC   Russulales; Hericiaceae; Hericium.
OX   NCBI_TaxID=91752;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INDUCTION.
RX   PubMed=28371074; DOI=10.1002/anie.201700565;
RA   Yang Y.L., Zhang S., Ma K., Xu Y., Tao Q., Chen Y., Chen J., Guo S.,
RA   Ren J., Wang W., Tao Y., Yin W.B., Liu H.;
RT   "Discovery and characterization of a new family of diterpene cyclases in
RT   bacteria and fungi.";
RL   Angew. Chem. Int. Ed. 56:4749-4752(2017).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=31535864; DOI=10.1021/jacs.9b08935;
RA   Liu C., Minami A., Ozaki T., Wu J., Kawagishi H., Maruyama J.I., Oikawa H.;
RT   "Efficient reconstitution of basidiomycota diterpene erinacine gene cluster
RT   in ascomycota host Aspergillus oryzae based on genomic DNA sequences.";
RL   J. Am. Chem. Soc. 141:15519-15523(2019).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of erinacines, cyathane-xylosides that show
CC       unique biological activities, including leishmanicidal activity,
CC       stimulating activity for nerve growth-factor synthesis, and agonistic
CC       activity toward the kappa opioid receptor (PubMed:31535864). The
CC       geranylgeranyl diphosphate (GGPP) synthase eriE catalyzes the first
CC       step in erinacines biosynthesis via conversion of farnesyl
CC       pyrophosphate and isopentyl pyrophosphate into geranylgeranyl
CC       pyrophosphate (GGPP) (PubMed:31535864). GGPP is then substrate of the
CC       diterpene cyclase eriG for the production of cyatha-3,12-diene
CC       (PubMed:28371074). EriG is unable to use geranyl diphosphate (GPP) or
CC       farnesyl diphosphate (FPP) as substrates (PubMed:28371074). The
CC       cytochrome P450 monooxygenase eriI then hydroxylates cyatha-3,12-diene
CC       at C-14 of the seven-membered ring to produce erinacol, which is
CC       further hydroxylated at C-15 by the cytochrome P450 monooxygenase eriC
CC       to yield cyathadiol (PubMed:31535864). The cytochrome P450
CC       monooxygenase eriA then catalyzes C-11 hydroxylation in the presence of
CC       the short chain dehydrogenase/reductase (SDR) eriH, which leads to the
CC       production of cyathatriol (PubMed:31535864). The acetyltransferase eriL
CC       converts cyathatriol into 11-O-acetyl-cyathatriol (PubMed:31535864).
CC       The SDR eriH catalyzes further oxidation of 11-O-acetyl-cyathatriol
CC       into 1-O-acetylcyathin A3 (PubMed:31535864). Finally, the glycosyl
CC       transferase eriJ tranfers xylose from UDP-xylose onto C-14 of 11-O-
CC       acetyl-cyathatriol to form eracine Q (PubMed:31535864). EriJ is also
CC       able to convert 11-O-acetyl-cyathatriol to eracine Q2 by using UDP-D-
CC       glucose as cosubstrate, but at a lower rate (PubMed:31535864). In the
CC       absence of eriL and eriJ, the SDR eriH is able to convert cyathatriol
CC       to cyathin A3; this is likely a switching mechanism in the biosynthesis
CC       of cyathins (C-14 ketogroup)and erinacines (C-14 glycosylated group)
CC       (PubMed:31535864). The roles of the SDR eriB, the polyprenyl
CC       transferase eriF and the dehydrogenase eriK have still to be identified
CC       (Probable). {ECO:0000269|PubMed:28371074, ECO:0000269|PubMed:31535864,
CC       ECO:0000305|PubMed:31535864}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:31535864}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: Expression is induced under erinacine P-producing
CC       conditions. {ECO:0000269|PubMed:28371074}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; KY683784; ARE72246.1; -; mRNA.
DR   AlphaFoldDB; A0A1V0QSE9; -.
DR   SMR; A0A1V0QSE9; -.
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   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW   Oxidoreductase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..552
FT                   /note="Cytochrome P450 monooxyhenase eriI"
FT                   /id="PRO_0000452920"
FT   TRANSMEM        9..26
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         495
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        50
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        447
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   552 AA;  61682 MW;  7B5C9FF59F2F2004 CRC64;
     MSLHLSQDFA LKASAAVAVL LLAAWVRLRR RIQSKISNIP GPKPTSLLGN YSQLHSAEKG
     WEFFDEIHAK YGNVCRISTP VGCNDIIYLA DPLALNHMNR RDEAKFDDPH EIHIMLQMVL
     GNKGLGATSG AEHHRQRKFL NPVFGPSYLR HMPPLFYEVT HRFLDAMRIL CADGQREIDM
     SHWGTRVSLE FVGKGAIGFE LDSLAIDSKP NLYGEEMKQG FVALSTPAAR LAMKYFLPRI
     ASLRTPKFNR WLLNLVPSPL VTIVKNFVWE LDANSRTMFQ QKKEALLKGG DALSEQSSKG
     KDLMTALIRE HVLVDRADKV DEEEATSHFR TLLFAATDTS SSAILRTIQL LAEHPDVQTR
     LREEINTAKA DADGDLSYEK LLALPLLDAV YRETLRLYPP ASYIDRVAHE DVVLPLAFPI
     TGVDGTQMSE LVVPKGTVVT MSIVGVNRST AIWGPDALVW NPDRWLAPLP ETVKSSKMPG
     ITSSIMTFLD GKRHCLGYRY VQMELKILIS EIVCTLAFAP TEKHAKIEWP MGLTLSPFVD
     GKMSMPLKVS LA