ERIA_HERER
ID ERIA_HERER Reviewed; 527 AA.
AC A0A1V0QSE7;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Cytochrome P450 monooxyhenase eriA {ECO:0000303|PubMed:28371074};
DE EC=1.-.-.- {ECO:0000269|PubMed:31535864};
DE AltName: Full=Erinacine biosynthesis cluster protein A {ECO:0000303|PubMed:28371074};
GN Name=eriA {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, INDUCTION, AND PATHWAY.
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; KY683776; ARE72238.1; -; mRNA.
DR AlphaFoldDB; A0A1V0QSE7; -.
DR SMR; A0A1V0QSE7; -.
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; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
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..527
FT /note="Cytochrome P450 monooxyhenase eriA"
FT /id="PRO_0000452918"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 453
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 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 527 AA; 58356 MW; 837C891C2574A52F CRC64;
MDTSQLLTLW NDRASQLGVV DLSLLGVGAV IAFAWLFSGG KKARTPPGPR PLPILGNLLS
IPTTHPWKIY DKWCRDNNSD LMYLRLPGGN GILVLNTMKA ATDLLVKRST IYSDRPQSIM
LSDLMGMSWV FGLMQYGDAW KQHRRLFHRE FEGSTAVRMH AQNAARRLLQ RLLNSNVNYA
RDMQLTTGDM ILSATYGITP KSEDDYFIKL AEGLVGALAV VAGGGFLVDL IPPMRWIPRW
FPGGGFKKQA DEWKGLGVTA RSVPFNHVKE QLANGTAPLS IASHFLAAHQ EDDESTNESK
EFMQNILAEA YLGGAGATVG TLCTFTLAMA LNPDVQKRAQ AAIDEALHGE RLPDFTDFGN
IPYMDALLNE ILRWHPGAPL GLFHSSNKDD VYEGYLVPKG TFISPNVWAI LHDPAVYGED
VDEFRPERFL TKDGKRNDIP DSEIAFGFGR RICPGRTMGR DTLWITSASI LATFDITNPV
DKEGKPLDPA SIEYSNSMSS RPPYFDCTFK LRSKAAEALV RNGLNEA
