EUPB_PHOSX
ID EUPB_PHOSX Reviewed; 446 AA.
AC A0A4V1E8I5;
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=FAD-dependent monooxygenase eupB {ECO:0000303|PubMed:30980906};
DE EC=1.-.-.- {ECO:0000305|PubMed:30980906};
DE AltName: Full=Eupenifeldin biosynthesis cluster protein B {ECO:0000303|PubMed:30980906};
GN Name=eupB {ECO:0000303|PubMed:30980906}; ORFNames=gme12631;
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: FAD-dependent 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=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A6T923};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:30980906}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
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 paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; MK400120; QCO93109.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A4V1E8I5; -.
DR SMR; A0A4V1E8I5; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Membrane; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..446
FT /note="FAD-dependent monooxygenase eupB"
FT /id="PRO_0000449151"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 40..41
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 248..250
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 322
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 332..336
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT CARBOHYD 33
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 243
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 446 AA; 49612 MW; E7B063DD8950E6D6 CRC64;
MTIYTFTSSE PHIAIVGGGI VGVILTLGLL RQNVSVRLYE QSAGFREIGA GIAFTASARR
CMELMDPAII DALRRCGAVS VSDKVADEDD HLRWIDGYNQ HSKAHPTYQK PLAEICGSGF
QGCRRDQLLE ELAKHIPSGT IMFHKRLDTI QQGKDHKMIL NFVDGSSNQA DAVIGCDGIK
SRVRQHLFGD NHPASFPQYT HKVAYRGLVP MDRAIEILGT WKAHNFHHHV GPGAHLTHYP
VANHTALNVV VFLSDETPWP DSTTMVSKGT RSEVEKALQG WHPTVLGIVN LLPDELSKWA
LFDQGEFPLP HYSKGRICLA GDAAHASSPH HGAGACLGVE DALCLSTLLS QVRTTLTQAD
EGSKDKSESS MGQLLEAAFE TFNLVRRTRT QWLVNSSRRV CDLYHQQEWA DPIRCPKAET
CFEEIRDRSY KIWHFDVDGM LEQTRT
