EUPD_PHOSX
ID EUPD_PHOSX Reviewed; 285 AA.
AC A0A4P8GEB4;
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=Cytochrome P450 monooxygenase eupD {ECO:0000303|PubMed:30980906};
DE EC=1.-.-.- {ECO:0000269|PubMed:30980906};
DE AltName: Full=Eupenifeldin biosynthesis cluster protein D {ECO:0000303|PubMed:30980906};
DE Flags: Precursor;
GN Name=eupD {ECO:0000303|PubMed:30980906}; ORFNames=gme12637;
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,
RP CATALYTIC ACTIVITY, AND 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: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of eupenifeldin, a bistropolone meroterpenoid
CC that acts as an antitumor agent (PubMed:30980906). The first step of
CC eupenifeldin biosynthesis is the biosynthesis of 3-methylorcinaldehyde
CC performed by the non-reducing polyketide synthase eupA
CC (PubMed:30980906). Oxidative dearomatization of 3-methylorcinaldehyde
CC likely catalyzed by the FAD-dependent monooxygenase eupB is followed by
CC oxidative ring expansion by the 2-oxoglutarate-dependent dioxygenase
CC eupC to provide the first tropolone metabolite, tropolone
CC stipitaldehyde (Probable). In parallel, generation of sesquiterpene
CC alpha-humulene from farnesylpyrophosphate (FPP) is catalyzed by the
CC terpene cyclase eupE (PubMed:30980906). The cytochrome P450
CC 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=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:30980906}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of eupenifeldin as well
CC as of the intermediate humulenol. {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 cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MK400120; QCO93115.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A4P8GEB4; -.
DR SMR; A0A4P8GEB4; -.
DR UniPathway; UPA00213; -.
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 GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
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.
PE 1: Evidence at protein level;
KW Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..285
FT /note="Cytochrome P450 monooxygenase eupD"
FT /id="PRO_5020416429"
FT BINDING 229
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"
SQ SEQUENCE 285 AA; 32710 MW; FE5BF584F5C65A62 CRC64;
MSIAGLVTTL PWLMNMLRAV PGATGRFERF AGWCYEQLLL KRESLAVERA TNHNHEPRDV
MTWLINSMDE GDRCAPPTES ALQEDARTLI SAGSDTVAIT FTNILYFLVK HPTIYQKLQR
LMDHEFPQGY SSWTYNKAKG VPYIDYIIHE TLRLRPAVPM GFLRQTPPQG LQIDEIFIPG
DVIVNVPTYT IHRDSRYFYD AAKFIPERWE ELSPDTAAYL AFQRGPFTCS GKNLATMQLR
MLISCLALRY RIHFAPGEDG VAFATQEKET LTMWIPPLQM VFRPR
