DPMPE_MACPH
ID DPMPE_MACPH Reviewed; 472 AA.
AC K2QVI4;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 02-DEC-2020, sequence version 2.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=FAD-dependent monooxygenase dpmpE {ECO:0000303|PubMed:32286350};
DE EC=1.-.-.- {ECO:0000305|PubMed:32286350};
DE AltName: Full=Diterpenoid pyrone biosynthesis cluster protein E {ECO:0000303|PubMed:32286350};
DE Flags: Precursor;
GN Name=dpmpE {ECO:0000303|PubMed:32286350}; ORFNames=MPH_09197;
OS Macrophomina phaseolina (strain MS6) (Charcoal rot fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Dothideomycetes incertae sedis; Botryosphaeriales; Botryosphaeriaceae;
OC Macrophomina.
OX NCBI_TaxID=1126212;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MS6;
RX PubMed=22992219; DOI=10.1186/1471-2164-13-493;
RA Islam M.S., Haque M.S., Islam M.M., Emdad E.M., Halim A., Hossen Q.M.M.,
RA Hossain M.Z., Ahmed B., Rahim S., Rahman M.S., Alam M.M., Hou S., Wan X.,
RA Saito J.A., Alam M.;
RT "Tools to kill: Genome of one of the most destructive plant pathogenic
RT fungi Macrophomina phaseolina.";
RL BMC Genomics 13:493-493(2012).
RN [2]
RP FUNCTION, PATHWAY, AND BIOTECHNOLOGY.
RX PubMed=32286350; DOI=10.1038/s41467-020-15664-4;
RA Tsukada K., Shinki S., Kaneko A., Murakami K., Irie K., Murai M.,
RA Miyoshi H., Dan S., Kawaji K., Hayashi H., Kodama E.N., Hori A., Salim E.,
RA Kuraishi T., Hirata N., Kanda Y., Asai T.;
RT "Synthetic biology based construction of biological activity-related
RT library of fungal decalin-containing diterpenoid pyrones.";
RL Nat. Commun. 11:1830-1830(2020).
CC -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of diterpenoid pyrones (PubMed:32286350). The
CC first step of the pathway is the synthesis of the alpha-pyrone moiety
CC by the polyketide synthase dpmpA via condensation of one acetyl-CoA
CC starter unit with 3 malonyl-CoA units and 2 methylations (Probable).
CC The alpha-pyrone is then combined with geranylgeranyl pyrophosphate
CC (GGPP) formed by the GGPP synthase dpmpD through the action of the
CC prenyltransferase dpmpC to yield a linear alpha-pyrone diterpenoid
CC (Probable). Subsequent steps in the diterpenoid pyrone biosynthetic
CC pathway involve the decalin core formation, which is initiated by the
CC epoxidation of the C10-C11 olefin by the FAD-dependent oxidoreductase
CC dpmpE, and is followed by a cyclization cascade catalyzed by the
CC terpene cyclase dpmpB (Probable). The short chain
CC dehydrogenase/reductase dpmpG then oxidizes the 8S hydroxy group to a
CC ketone and the short chain dehydrogenase/reductase dpmpH reduces the
CC ketone to the 8R hydroxy group to yield higginsianin B
CC (PubMed:32286350). Higginsianin B is further methylated by the
CC methyltransferase dpmpI to produce the intermediate named FDDP B
CC (PubMed:32286350). The cytochrome P450 monooxygenase dpmpJ then
CC oxidizes the C-26 methyl to primary alcohol, producing the final
CC diterpenoid pyrone with a C-26 primary alcohol on the gamma-pyrone
CC moiety named FDDP C (PubMed:32286350). {ECO:0000269|PubMed:32286350,
CC ECO:0000305|PubMed:32286350}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:32286350}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- BIOTECHNOLOGY: Diterpenoid pyrones display various biological
CC activities and FDDP C shows anti-cancer and anti-HIV activities
CC (PubMed:32286350). FDDP C shows also inhibitory activity of 42-mer-
CC amyloid beta aggregation that is involved in the pathogenesis of
CC Alzheimer's disease (PubMed:32286350). {ECO:0000269|PubMed:32286350}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EKG13731.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AHHD01000387; EKG13731.1; ALT_SEQ; Genomic_DNA.
DR AlphaFoldDB; K2QVI4; -.
DR SMR; K2QVI4; -.
DR EnsemblFungi; EKG13731; EKG13731; MPH_09197.
DR eggNOG; ENOG502SESR; Eukaryota.
DR HOGENOM; CLU_009665_12_1_1; -.
DR InParanoid; K2QVI4; -.
DR OrthoDB; 462247at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000007129; Unassembled WGS sequence.
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 Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..472
FT /note="FAD-dependent monooxygenase dpmpE"
FT /id="PRO_0000451546"
FT TRANSMEM 448..468
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 39..40
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 137
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 242..244
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 317
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 327..331
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 472 AA; 53143 MW; 2A43D2DDD7F9AE22 CRC64;
MESSSSKGGF KVLIIGGSVT GLTLAHSLDK MGVDYRLLEK RKEIAPQEGA SIGILPNGAR
ILDQLGLYNA IEQSAIALGT SDVYFPDGFH FTSSYPKRMH DRRSFAYPIA FMERRKLLEI
LYDLLPDKSR VEVDKAVSRI EEHPEHHGVL RAYTHDGDVY EGNLVVGADG VHSRTRREMW
RLSGSSPTGD VPVSERNSTS VEYACIFGIS DGIAELTPGR QVMRFGNGWT LAVIPSRQGQ
VFWFIVQKLD REYQYGSAPR FAPEDAAEQC SKLARLPIHG DVRFDDLWQR RKAVNMAALE
ENVFQTWSCG RLVCIGDSIH KMTVNLGQGA NCAIEDVAVL CNILHHALNE KANSELSDQD
VEALLRRFHK EHFPRVSRVY DMSWSVTRVH ARDGSMRKFV GRYVAPYFGE RLQGRLFNLM
ADAAKIDFLP LPRASRSGWE EYRSSERNAL LWASSLALLI VLIALFTGRS YW
