ERIB_HERER
ID ERIB_HERER Reviewed; 316 AA.
AC A0A1V0QS34;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=Short-chain dehydrogenase/reductase eriB {ECO:0000303|PubMed:28371074};
DE EC=1.1.1.- {ECO:0000305|PubMed:28371074};
DE AltName: Full=Erinacine biosynthesis cluster protein B {ECO:0000303|PubMed:28371074};
GN Name=eriB {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].
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.
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 -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; KY683777; ARE72239.1; -; mRNA.
DR AlphaFoldDB; A0A1V0QS34; -.
DR SMR; A0A1V0QS34; -.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW NAD; NADP; Oxidoreductase.
FT CHAIN 1..316
FT /note="Short-chain dehydrogenase/reductase eriB"
FT /id="PRO_0000452921"
FT ACT_SITE 197
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 32..40
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 59..60
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 89..91
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 197..201
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 230..232
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 316 AA; 34726 MW; 8E9E3A06C94146E5 CRC64;
MGNALAVYRD TFPPSPTYSV NDVPDLTGKI IIVTGGNTGL GKETIKVLLQ HNATVYLAAR
SPSKAKAAID ELRDMTGKEA LFLQLDLSDL KSIKESARQF LEKEKKLDVL LNNAGVMMSP
IEQLTKDGYD LQFGTNVLGH FYFTKLLLPL LLSTAKTTGE ARVVTLSSGA GLMVDEIDFN
TLKDSPARKK LGTTKLYMQS KLGNMVFSLE LARRYADQGI ISTSINPGTL KSDLARYVDS
LIYKLILKII SYPVPMGTLS PLYAATYPDG KSLNGKYLKP WAREGELSKT ATDPELGKEL
WTWMEEQVAP FESNAS
