ERIK_HERER
ID ERIK_HERER Reviewed; 599 AA.
AC P0DO29;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 1.
DT 03-AUG-2022, entry version 5.
DE RecName: Full=Dehydrogenase eriK {ECO:0000303|PubMed:31535864};
DE EC=1.1.-.- {ECO:0000305|PubMed:31535864};
DE AltName: Full=Erinacine biosynthesis cluster protein K {ECO:0000303|PubMed:31535864};
DE Flags: Precursor;
GN Name=eriK {ECO:0000303|PubMed:31535864};
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 [GENOMIC DNA], AND 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).
RN [2]
RP 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).
CC -!- FUNCTION: Dehydrogenase; part of the gene cluster that mediates the
CC biosynthesis of erinacines, cyathane-xylosides that show unique
CC biological activities, including leishmanicidal activity, stimulating
CC activity for nerve growth-factor synthesis, and agonistic activity
CC toward the kappa opioid receptor (PubMed:31535864). The geranylgeranyl
CC diphosphate (GGPP) synthase eriE catalyzes the first step in erinacines
CC biosynthesis via conversion of farnesyl pyrophosphate and isopentyl
CC pyrophosphate into geranylgeranyl pyrophosphate (GGPP)
CC (PubMed:31535864). GGPP is then substrate of the diterpene cyclase eriG
CC for the production of cyatha-3,12-diene (PubMed:28371074). EriG is
CC unable to use geranyl diphosphate (GPP) or farnesyl diphosphate (FPP)
CC as substrates (PubMed:28371074). The cytochrome P450 monooxygenase eriI
CC then hydroxylates cyatha-3,12-diene at C-14 of the seven-membered ring
CC to produce erinacol, which is further hydroxylated at C-15 by the
CC cytochrome P450 monooxygenase eriC to yield cyathadiol
CC (PubMed:31535864). The cytochrome P450 monooxygenase eriA then
CC catalyzes C-11 hydroxylation in the presence of the short chain
CC dehydrogenase/reductase (SDR) eriH, which leads to the production of
CC cyathatriol (PubMed:31535864). The acetyltransferase eriL converts
CC cyathatriol into 11-O-acetyl-cyathatriol (PubMed:31535864). The SDR
CC eriH catalyzes further oxidation of 11-O-acetyl-cyathatriol into 1-O-
CC acetylcyathin A3 (PubMed:31535864). Finally, the glycosyl transferase
CC eriJ tranfers xylose from UDP-xylose onto C-14 of 11-O-acetyl-
CC cyathatriol to form eracine Q (PubMed:31535864). EriJ is also able to
CC convert 11-O-acetyl-cyathatriol to eracine Q2 by using UDP-D-glucose as
CC cosubstrate, but at a lower rate (PubMed:31535864). In the absence of
CC eriL and eriJ, the SDR eriH is able to convert cyathatriol to cyathin
CC A3; this is likely a switching mechanism in the biosynthesis of
CC 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=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:E4QP00};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q12062}.
CC -!- SIMILARITY: Belongs to the GMC oxidoreductase family. {ECO:0000305}.
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DR AlphaFoldDB; P0DO29; -.
DR SMR; P0DO29; -.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0016614; F:oxidoreductase activity, acting on CH-OH group of donors; IEA:InterPro.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR012132; GMC_OxRdtase.
DR InterPro; IPR000172; GMC_OxRdtase_N.
DR InterPro; IPR007867; GMC_OxRtase_C.
DR PANTHER; PTHR11552; PTHR11552; 1.
DR Pfam; PF05199; GMC_oxred_C; 1.
DR Pfam; PF00732; GMC_oxred_N; 1.
DR PIRSF; PIRSF000137; Alcohol_oxidase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR PROSITE; PS00623; GMC_OXRED_1; 1.
DR PROSITE; PS00624; GMC_OXRED_2; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Glycoprotein; Oxidoreductase; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..599
FT /note="Dehydrogenase eriK"
FT /id="PRO_0000452928"
FT BINDING 43..44
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 64..65
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 122..125
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 569
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 580..581
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 339
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 365
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 398
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 456
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 518
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 599 AA; 63976 MW; A2EC6C5A89A49D59 CRC64;
MAFLKARLAA LLSVAVSCSA VLYDDAKKLP STSYDYIVVG GGTAGSVLAN RLTEDAKTQV
LVLEGGPSGQ GVLELEIPFY NLYGPHDPLW NWNISVLPQD TAADRVLVYP AGRVLGGTSM
INGMYYSRGP SSDWDRMAAI TGDSGWSWDK IYPYFIKSEV LTPSVGGRNT TGELDPSIHG
KQGIVATSSP NWSYETDPLI ISALNELGGP YSPILDFNNG SPLGVAWFQY TMRNGSREDA
ATSYFADKFL GRSNLHVLVN ATVDRVVQSK SGGPVNGVEY HLSNGTGSTL HATANKEVIV
SAGTFGTPHL LLNSGIGDNS TLASYNVTPI AHVPDVGKNL TDYSTVILTW SVNSTTTLYD
LITKNETFAN DSLAQWTASH TGPFSNGVSN HMFNLRLNET DPEVQQMLKQ YGDPSSSDKA
PHITLQFVEG GLGSGNSISM ENFVVTPLSR GSVTLNTTDP SGPPVVDAGI LTSPFDVFVL
EQGILAARKF LSASAWDNYI IAPASGLDAG IPVDGSVNTT ALESYIRTQA TAGWRETGTA
KMSPKGARWG VVDPDFRVKN VQGLRVVDAS VFPEIPSLHT QIPIYAIAER AADLIKGSH
