EUPE_PHOSX
ID EUPE_PHOSX Reviewed; 379 AA.
AC A0A4P8GFV8;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 25-MAY-2022, entry version 8.
DE RecName: Full=Alpha-humulene synthase eupE {ECO:0000303|PubMed:30980906};
DE EC=4.2.3.104 {ECO:0000269|PubMed:30980906};
DE AltName: Full=Eupenifeldin biosynthesis cluster protein E {ECO:0000303|PubMed:30980906};
GN Name=eupE {ECO:0000303|PubMed:30980906}; ORFNames=gme12634;
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: Alpha-humulene synthase; 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 -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate = alpha-humulene + diphosphate;
CC Xref=Rhea:RHEA:31895, ChEBI:CHEBI:5768, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:175763; EC=4.2.3.104;
CC Evidence={ECO:0000269|PubMed:30980906};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31896;
CC Evidence={ECO:0000269|PubMed:30980906};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A0A2U8U2L5};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:30980906}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of humulene.
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 terpene synthase family. Alpha-humulene
CC synthase eupE subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; MK400120; QCO93112.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A4P8GFV8; -.
DR SMR; A0A4P8GFV8; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0080017; F:alpha-humulene synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
PE 1: Evidence at protein level;
KW Lyase; Magnesium.
FT CHAIN 1..379
FT /note="Alpha-humulene synthase eupE"
FT /id="PRO_0000449160"
SQ SEQUENCE 379 AA; 43179 MW; 8EF9E6315AE369C4 CRC64;
MKEIWETLKQ YFGDGFVPGS APLRYEMHFC DMKEPLNKKQ SMRYGVEIPE DAMPLFSVLG
DTCAPPCSCQ DISGVIEHID RYLENAPIRH ADDYTITSGK DDEDINQVSL YIMRDTLSWW
VHWGGSLHPN NYWKLIYVAF AAIPDDVQVH PRDFIDGTYR FLGHSWNDCL NGLLAEGVPS
DQVKLAEMTL WRQMATQYIE KVDPGLRSLL VSKTTLMTQY RVMTANTLGC AVLLLASEGV
IVGDLDDGAL EMASIAQCLS MDMAKEALGV LEGEKTETVA GDRRQLKREL RWLYVRCMKY
LDAQPHAEFL RRFASSGLHY VPMMDRYLER VRGHIRFPIR ESVARILEPF IKREPTPNKS
GREADHIAQV VNEPITVAL
