DPFGH_GIBZE
ID DPFGH_GIBZE Reviewed; 349 AA.
AC I1RL15;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 52.
DE RecName: Full=Short chain dehydrogenase/reductase dpfgH {ECO:0000303|PubMed:32286350};
DE EC=1.1.1.- {ECO:0000269|PubMed:32286350};
DE AltName: Full=Diterpenoid pyrone biosynthesis cluster protein H {ECO:0000303|PubMed:32286350};
GN Name=dpfgH {ECO:0000303|PubMed:32286350};
GN ORFNames=FG04592, FGRAMPH1_01T15655;
OS Gibberella zeae (strain ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084
OS / PH-1) (Wheat head blight fungus) (Fusarium graminearum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX NCBI_TaxID=229533;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=17823352; DOI=10.1126/science.1143708;
RA Cuomo C.A., Gueldener U., Xu J.-R., Trail F., Turgeon B.G., Di Pietro A.,
RA Walton J.D., Ma L.-J., Baker S.E., Rep M., Adam G., Antoniw J., Baldwin T.,
RA Calvo S.E., Chang Y.-L., DeCaprio D., Gale L.R., Gnerre S., Goswami R.S.,
RA Hammond-Kosack K., Harris L.J., Hilburn K., Kennell J.C., Kroken S.,
RA Magnuson J.K., Mannhaupt G., Mauceli E.W., Mewes H.-W., Mitterbauer R.,
RA Muehlbauer G., Muensterkoetter M., Nelson D., O'Donnell K., Ouellet T.,
RA Qi W., Quesneville H., Roncero M.I.G., Seong K.-Y., Tetko I.V., Urban M.,
RA Waalwijk C., Ward T.J., Yao J., Birren B.W., Kistler H.C.;
RT "The Fusarium graminearum genome reveals a link between localized
RT polymorphism and pathogen specialization.";
RL Science 317:1400-1402(2007).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=20237561; DOI=10.1038/nature08850;
RA Ma L.-J., van der Does H.C., Borkovich K.A., Coleman J.J., Daboussi M.-J.,
RA Di Pietro A., Dufresne M., Freitag M., Grabherr M., Henrissat B.,
RA Houterman P.M., Kang S., Shim W.-B., Woloshuk C., Xie X., Xu J.-R.,
RA Antoniw J., Baker S.E., Bluhm B.H., Breakspear A., Brown D.W.,
RA Butchko R.A.E., Chapman S., Coulson R., Coutinho P.M., Danchin E.G.J.,
RA Diener A., Gale L.R., Gardiner D.M., Goff S., Hammond-Kosack K.E.,
RA Hilburn K., Hua-Van A., Jonkers W., Kazan K., Kodira C.D., Koehrsen M.,
RA Kumar L., Lee Y.-H., Li L., Manners J.M., Miranda-Saavedra D.,
RA Mukherjee M., Park G., Park J., Park S.-Y., Proctor R.H., Regev A.,
RA Ruiz-Roldan M.C., Sain D., Sakthikumar S., Sykes S., Schwartz D.C.,
RA Turgeon B.G., Wapinski I., Yoder O., Young S., Zeng Q., Zhou S.,
RA Galagan J., Cuomo C.A., Kistler H.C., Rep M.;
RT "Comparative genomics reveals mobile pathogenicity chromosomes in
RT Fusarium.";
RL Nature 464:367-373(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=26198851; DOI=10.1186/s12864-015-1756-1;
RA King R., Urban M., Hammond-Kosack M.C.U., Hassani-Pak K.,
RA Hammond-Kosack K.E.;
RT "The completed genome sequence of the pathogenic ascomycete fungus Fusarium
RT graminearum.";
RL BMC Genomics 16:544-544(2015).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, 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: Short chain dehydrogenase/reductase; part of the gene cluster
CC that mediates the biosynthesis of diterpenoid pyrones
CC (PubMed:32286350). The first step of the pathway is the synthesis of
CC the alpha-pyrone moiety by the polyketide synthase dpfgA via
CC condensation of one acetyl-CoA starter unit with 3 malonyl-CoA units
CC and 2 methylations (Probable). The alpha-pyrone is then combined with
CC geranylgeranyl pyrophosphate (GGPP) formed by the GGPP synthase dpfgD
CC through the action of the prenyltransferase dpfgC to yield a linear
CC alpha-pyrone diterpenoid (Probable). Subsequent steps in the
CC diterpenoid pyrone biosynthetic pathway involve the decalin core
CC formation, which is initiated by the epoxidation of the C10-C11 olefin
CC by the FAD-dependent oxidoreductase dpfgE, and is followed by a
CC cyclization cascade catalyzed by the terpene cyclase dpfgB (Probable).
CC The short chain dehydrogenase/reductase dpfgG then oxidizes the 8S
CC hydroxy group to a ketone and the short chain dehydrogenase/reductase
CC dpfgH reduces the ketone to the 8R hydroxy group to yield higginsianin
CC B (PubMed:32286350). Higginsianin B is further methylated by the
CC methyltransferase dpfgI to produce the intermediate named FDDP B
CC (PubMed:32286350). The cytochrome P450 monooxygenase dfgpJ then
CC catalyzes a three-step oxidation at C-27 to generate a carboxylic acid
CC as well as C-26 hydroxylation (PubMed:32286350). Finally,
CC methyltransferase dpfgK methylates the carboxylic acid generated by
CC dpfgJ, yielding the final diterpenoid pyrones from the pathway which
CC were named FDDP D and FDDP E (PubMed:32286350).
CC {ECO:0000269|PubMed:32286350, ECO:0000305|PubMed:32286350}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|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 E shows anti-HIV activity (PubMed:32286350). FDDP D
CC and FDDP E show also inhibitory activity of 42-mer-amyloid beta
CC aggregation that is involved in the pathogenesis of Alzheimer's disease
CC (PubMed:32286350). {ECO:0000269|PubMed:32286350}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {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; HG970333; CEF79627.1; -; Genomic_DNA.
DR RefSeq; XP_011320989.1; XM_011322687.1.
DR AlphaFoldDB; I1RL15; -.
DR SMR; I1RL15; -.
DR STRING; 5518.FGSG_04592P0; -.
DR GeneID; 23551831; -.
DR KEGG; fgr:FGSG_04592; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G15655; -.
DR eggNOG; KOG1208; Eukaryota.
DR HOGENOM; CLU_010194_44_6_1; -.
DR InParanoid; I1RL15; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000070720; Chromosome 2.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Membrane; NAD; Oxidoreductase; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..349
FT /note="Short chain dehydrogenase/reductase dpfgH"
FT /id="PRO_0000451551"
FT TRANSMEM 9..31
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 223
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 32..40
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 59..60
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 78..80
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 223..227
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 256..258
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 349 AA; 38296 MW; 871BFCB6BF382D71 CRC64;
MSPLWVRRLC IRVVDSLYGS FLYLPLAILF LKRSVTGFGT GEWDESQIPK LDGKVAVVTG
GNAGIGYYTV KHLASRGAKV YLGARSESRA KAAIKRLLEE NPLIPQENVV WLRLDLANQS
QVVDAAVELQ SKEQRLDILV NNAGIDPYDY IRTADGFEMT MAVKYTNPAA AAQEESDVRV
ITVSSSGEAY SSPTNQFTSP KDLDDPCASP GWENSCLGQA MRYGTTKLAN VLFASELQRR
MDEEDANIIS LSLNPGTVRT DGAANVMPFM VRPLVRFLFT APERGADTSL FAATAEEIKE
NSERWKGRYL DGPGRIKVPS LRARDAVAGR NLWNITEAAV RGTGALDRL
