EUPF_PHOSX
ID EUPF_PHOSX Reviewed; 352 AA.
AC A0A4P8GEA3;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 25-MAY-2022, entry version 7.
DE RecName: Full=Putative hetero-Diels-Alderase {ECO:0000303|PubMed:30980906};
DE EC=5.5.-.- {ECO:0000305|PubMed:30980906};
DE AltName: Full=Eupenifeldin biosynthesis cluster protein F {ECO:0000303|PubMed:30980906};
DE Flags: Precursor;
GN Name=eupF {ECO:0000303|PubMed:30980906}; ORFNames=gme12633;
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: Putative hetero-Diels-Alderase; 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 -!- 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 eupF Diels-Alderase family. {ECO:0000305}.
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DR EMBL; MK400120; QCO93111.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A4P8GEA3; -.
DR SMR; A0A4P8GEA3; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 2.120.10.30; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
PE 1: Evidence at protein level;
KW Glycoprotein; Isomerase; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..352
FT /note="Putative hetero-Diels-Alderase"
FT /id="PRO_5020871144"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 211
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 352 AA; 39140 MW; 6CF7761B2D2527A6 CRC64;
MRYHLSALVL VFTAFRETLT APTPGNNTIP LPNRLLHQWP NGTWVENISV RPNGNLLVTT
STPDGSVWQV KEPWKENPEV ERVFNFDEWV DRLIGIGETQ DDKYVVVGSR FYSTDAQSSH
VARTFCAMEL DFSGNTTEPS ARLIAWMPES YLLQGVAALP WDRDTVLISD QYVLRPRAVQ
IDWTPSPGQI WVLDTRTGEY GLVMTDYAEL NTTYAKGPDV GIDGIKIRDH DLFWVNQDDS
GIYRVKIDDA GVPVAPVKPQ LVASYNTMWD DMAFDPFNEN VIWATGLNAV FAATLDGQIV
PVDGVGTSDN LTLPGPTACA FGRTEKDKSI LYVTGNLLTV PESLLDVKLG GW
