EUPC_PHOSX
ID EUPC_PHOSX Reviewed; 313 AA.
AC A0A4P8GG75;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=2-oxoglutarate-dependent dioxygenase eupC {ECO:0000303|PubMed:30980906};
DE EC=1.14.11.- {ECO:0000305|PubMed:30980906};
DE AltName: Full=Eupenifeldin biosynthesis cluster protein C {ECO:0000303|PubMed:30980906};
GN Name=eupC {ECO:0000303|PubMed:30980906}; ORFNames=gme12628;
OS Phoma sp.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Didymellaceae; Phoma.
OX NCBI_TaxID=1707701;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RC STRAIN=XZ068 / CGMCC No. 10481;
RX PubMed=30980906; DOI=10.1016/j.fgb.2019.04.004;
RA Zhai Y., Li Y., Zhang J., Zhang Y., Ren F., Zhang X., Liu G., Liu X.,
RA Che Y.;
RT "Identification of the gene cluster for bistropolone-humulene meroterpenoid
RT biosynthesis in Phoma sp.";
RL Fungal Genet. Biol. 129:7-15(2019).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=8360103; DOI=10.7164/antibiotics.46.1082;
RA Mayerl F., Gao Q., Huang S., Klohr S.E., Matson J.A., Gustavson D.R.,
RA Pirnik D.M., Berry R.L., Fairchild C., Rose W.C.;
RT "Eupenifeldin, a novel cytotoxic bistropolone from Eupenicillium
RT brefeldianum.";
RL J. Antibiot. 46:1082-1088(1993).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=18095654; DOI=10.1021/np070513k;
RA Ayers S., Zink D.L., Powell J.S., Brown C.M., Grund A., Bills G.F.,
RA Platas G., Thompson D., Singh S.B.;
RT "Noreupenifeldin, a tropolone from an unidentified ascomycete.";
RL J. Nat. Prod. 71:457-459(2008).
RN [4]
RP BIOTECHNOLOGY.
RX DOI=10.1016/j.phytol.2008.09.008;
RA Bunyapaiboonsri T., Veeranondha S., Boonruangprapa T., Somrithipol S.;
RT "Ramiferin, a bisphenol-sesquiterpene from the fungus Kionochaeta ramifera
RT BCC 7585.";
RL Phytochem. Lett. 1:204-206(2008).
CC -!- FUNCTION: 2-oxoglutarate-dependent dioxygenase; part of the gene
CC cluster that mediates the biosynthesis of eupenifeldin, a bistropolone
CC meroterpenoid that acts as an antitumor agent (PubMed:30980906). The
CC first step of eupenifeldin biosynthesis is the biosynthesis of 3-
CC methylorcinaldehyde performed by the non-reducing polyketide synthase
CC eupA (PubMed:30980906). Oxidative dearomatization of 3-
CC methylorcinaldehyde likely catalyzed by the FAD-dependent monooxygenase
CC eupB is followed by oxidative ring expansion by the 2-oxoglutarate-
CC dependent dioxygenase eupC to provide the first tropolone metabolite,
CC tropolone stipitaldehyde (Probable). In parallel, generation of
CC sesquiterpene alpha-humulene from farnesylpyrophosphate (FPP) is
CC catalyzed by the terpene cyclase eupE (PubMed:30980906). The cytochrome
CC P450 monooxygenase eupD then hydroxylates humulene to humulenol
CC (PubMed:30980906). The putative Diels-Alderase eupF probably catalyzes
CC the formation of the tropolone-humulene skeleton by linking humulenol
CC and the polyketide moiety (Probable). The short-chain
CC dehydrogenase/reductase eupG and the flavin-dependent monooxygenase
CC eupH are also essential for eupenifeldin biosynthesis and are likely
CC the additional decorating enzymes of the tropolone-humulene skeleton to
CC produce final eupenifeldin or derivatives (Probable).
CC {ECO:0000269|PubMed:30980906, ECO:0000305|PubMed:30980906}.
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00805};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:30980906}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of eupenifeldin.
CC {ECO:0000269|PubMed:30980906}.
CC -!- BIOTECHNOLOGY: Eupenifeldin is a bistropolone-humulene meroterpenoid
CC first discovered as an antitumor and anti-leukemia agent
CC (PubMed:8360103). This metabolite shows also anthelmintic activity
CC against the parasitic worm Hemonchus contortus, anti-malarial activity
CC as well as antifungal activity (PubMed:18095654, Ref.4).
CC {ECO:0000269|PubMed:18095654, ECO:0000269|PubMed:8360103,
CC ECO:0000269|Ref.4}.
CC -!- SIMILARITY: Belongs to the iron/ascorbate-dependent oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; MK400120; QCO93106.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A4P8GG75; -.
DR SMR; A0A4P8GG75; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 2.60.120.330; -; 1.
DR InterPro; IPR026992; DIOX_N.
DR InterPro; IPR044861; IPNS-like_FE2OG_OXY.
DR InterPro; IPR027443; IPNS-like_sf.
DR Pfam; PF03171; 2OG-FeII_Oxy; 1.
DR Pfam; PF14226; DIOX_N; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase.
FT CHAIN 1..313
FT /note="2-oxoglutarate-dependent dioxygenase eupC"
FT /id="PRO_0000449154"
FT DOMAIN 187..284
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 212
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 214
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 263
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 274
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
SQ SEQUENCE 313 AA; 34976 MW; 661FEF93D1D3FE35 CRC64;
MEIANTQAAI PTIDISALLS PTASEQSRQT VINNMSDACH AYGFFNLVGH DIPPEAMRDA
LDCNKLFFAL PQDRKMEVSI DKSIGRSFRG YEPPGIQTHH EGLLPDTKET FMVGREVMEG
DPDCGSFSTG PNLWPSDLHK KGFQDRVMSY QARMLRLVET ILDCLALGLP KSWNCTSHVF
KPLLNKPSIP MRFLHYGPVE IHDDRQFGVA DHTDFGFVSI LLQEAGTSGL EVFYPPTKSW
VPVPVFEQGF VINMGDMMQK HRHSVAFFLN GDLKLNAKAL DGSGHETIVG EQIQQRLIET
MGMTGNLLRR ELV
