ERIH_HERER
ID ERIH_HERER Reviewed; 252 AA.
AC A0A1V0QSC6;
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=Short-chain dehydrogenase/reductase eriH {ECO:0000303|PubMed:28371074};
DE EC=1.1.1.- {ECO:0000269|PubMed:31535864};
DE AltName: Full=Erinacine biosynthesis cluster protein H {ECO:0000303|PubMed:28371074};
GN Name=eriH {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], AND FUNCTION.
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: Short-chain dehydrogenase/reductase; part of the gene cluster
CC that mediates the biosynthesis of erinacines, cyathane-xylosides that
CC show 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 -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31535864}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; KY683783; ARE72245.1; -; mRNA.
DR AlphaFoldDB; A0A1V0QSC6; -.
DR SMR; A0A1V0QSC6; -.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW NAD; NADP; Oxidoreductase.
FT CHAIN 1..252
FT /note="Short-chain dehydrogenase/reductase eriH"
FT /id="PRO_0000452922"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 8..16
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 9..39
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16544"
FT BINDING 35..36
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 68..70
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 158..162
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 162
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16544"
FT BINDING 191..193
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 252 AA; 25869 MW; 8E421E5113BB4A89 CRC64;
MSAKGVAIIT GAAQGIGRAI VVRLAADGFD VAVNDLPNDA QVAKLTELAE EIRATGRKAI
VVPGDISQEA IVEKIVADTV EQLGGVDVMV ANAGICELSP IVSTSVEQWD TTQAVNLRGV
FLCFKHAGKQ MLAQGRPGRL IGGGSLGGFS GLPMGSAYAA SKAGMRALTH SAARELGPSG
ITANSYAPGI VATPLTIGNY GQEFLDSQKA TCAVNDNGTP EDIAALVSFL ASKESRFITG
QTIMIDGGRL NI
