DPFGA_GIBZE
ID DPFGA_GIBZE Reviewed; 2172 AA.
AC I1RL11; A0A098DKZ3;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Non-reducing polyketide synthase dpfgA {ECO:0000303|PubMed:32286350};
DE EC=2.3.1.- {ECO:0000305|PubMed:32286350};
DE AltName: Full=Diterpenoid pyrone biosynthesis cluster protein A {ECO:0000303|PubMed:32286350};
GN Name=dpfgA {ECO:0000303|PubMed:32286350};
GN ORFNames=FG04588, FGRAMPH1_01T15647;
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, 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: Non-reducing polyketide synthase; 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:0000305|PubMed:32286350}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; a methyltransferase (CMeT) domain
CC responsible for methylations; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm. {ECO:0000305}.
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}.
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DR EMBL; HG970333; CEF79623.1; -; Genomic_DNA.
DR RefSeq; XP_011320993.1; XM_011322691.1.
DR AlphaFoldDB; I1RL11; -.
DR SMR; I1RL11; -.
DR STRING; 5518.FGSG_04588P0; -.
DR GeneID; 23551827; -.
DR KEGG; fgr:FGSG_04588; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G15647; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_3_1; -.
DR InParanoid; I1RL11; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000070720; Chromosome 2.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; 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; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR041068; HTH_51.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF18558; HTH_51; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2172
FT /note="Non-reducing polyketide synthase dpfgA"
FT /id="PRO_0000451524"
FT DOMAIN 1671..1747
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 74..181
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 392..786
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 895..1197
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1277..1575
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1608..1631
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1650..1672
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1751..1773
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1975..2155
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 1757..1773
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 529
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 981
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1707
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2172 AA; 238750 MW; 0A86C4496B80D70B CRC64;
MATDSPSLLI CGSVISDPDH AYLSRIRSSI IHNPHLAELQ DAVIELPELW SLLVEREKSL
QRVDAARVLR NLVEWIKCGN SSLPLEGRTS RNTQLAVLTV LAHFSEYMIY LNSHDMSEED
GRGNLDAHTS VLEGVRDGGI QGLCVGLLSA IALACSPTIT DVAKYGTVAV RLALCVGALV
DLDETELSEP TACIFARWPQ SEDDDREELL KAVLENYPSS YVGVRLDVCS VNITAPKGVA
MSLMRSLEET GAVAKQINLQ GRYHHPGHEA MFQKLTDLCA SLQMLQFPHH SHPLVPLRWN
DSGEVVTDQT PLHEVALQCI LVKRADWYTT ITKSVTDMAQ RTVASSADSK ARVLALGPVD
CIPRSILFIT PLQVVRPMAN AAFYHGYPDD SIAIIGVSCR FPGSETLPQF WEEIRAKRVN
SCLEAAGSLD CAFFRKPPRE AEHMDPQHRL GLHLAYEALQ SGGYFSPSSS VTDNVGCYIG
MSSCDYEENV NSHPPTAYSF TGTARAFSSG RISHFFGFTG PSMVIDTACS SSGVAIHTAC
KAIQSGECSM ALAGGINLMV PEARSHQNLA AASFLSPTGQ CRPFDARADG YRRSEGGGFV
LLKRLSAAVA DNDCILGVLA ASAVNNSKGS RSITLPSIES QSHLYRRVLQ AAGLHPHQVS
YVEAHGTGTQ KGDPIEWQSI QNVFGGRDRS GLPPLRLGSV KGNIGHCEAA SGVAALVKVI
LMLQNRQIPP QANFSVLNPA LPSLEEANMD IPVCLEPWEA PFRAAMVNNY GASGTNAAML
VCQPPLASPE RLMSTGQPHQ CPILIASHSE SSIRQYCRTL MSFVETQRCV LGDSLLPSIA
FHLGQRQNES CRHRVAFSAT SADELKVRLH SQARNNHDES KASKPQGRPK PVVLVFAGQT
GRQALLSREA YLSSSLLQHH LDRCDRILQT MGLHSLFPRI FETEPVDDLV DLHCMHFSLQ
YSVAASWIDT GLEIKAMVGH SLGQLTALCV SGVLSLRDAL KMISGRASLI QNKWGSERGC
MLSVEADAPT VETIAQSMPG AGKIEIACYN AALHQVIVGT EAAIAAFEEV ARSRNVSVKR
LLVSRGFHSE MMDCIVPEYQ QLIQQLTLHP SVIPFEPCCK LGDNWDNITP ELIARQSREP
VYFSDAIRRV EKRLGPCIWL EAGSGSAGVT MARRALTNPG TPSFPSHSFH SILLQGQNPI
KSLADTTINL WNEGIRVQFW LYHASERRRF MPLELPPSPF EKSEHWLPVL QKHKDSELAN
QNQDQKQEAP ELVSLAGPTD GETVEFFINQ HSNDYSTFVR GRTVFGQVLA PSSVYIEAVT
RAFTLLPMYL STPSSSPPSV EVKQVRMHAP FGLDLQKRLR LTLRKETMSS WRFVVESHPI
DDGDNKARKI QASGTINWQG QGCAYLEPSR PLLRRLYDRC DELRDDRSAS TVQGLFVKNI
LARVATYDNR YLGIQSITSK GLEAVADVAM PTIMSQACAG TVLSPPIFDN FLLIAELHAS
SLEDLAEDVY ICNGFDAVIP HAHPGDMVSK CEGPWMVLSY LNRENDKTVS CDIFVTSADR
DILLLEIIGA SLKRIPIRSL QKALESINGI QQIQGSTARG TASTVVIDSD SDLPDSEANS
PRVGSDLHAD FPDLHPTYVP RISRVTSSDY PMDSSSFSSA QPPSSASSVL SDHDQESTAL
LSLLSEHLNC SQGIPPDTRL GEIGLDSLVA IQLKSDVEKA FGKRLSLDTI DENLTFSDLY
RMVLNHDLPN DRGSTVLSDK APKSKSDSSL HGQSYHVTPI RETTVSFQDS TLFTTQARLE
FAQIKQETSS FAQMTGFAGF YTDVHQKQTS LVLAYILEAF STLGCDLSAL QAGDPLPPLR
YTSKYQKLVS RFHKILEGAG LISVCEGQSV RFRTAEPLPQ FGSSADTYRE LLNECPKYRP
DHQLLNVTGS RLSDCLSGRA DPLQLLFRDA AAVKLLEDVY VSSPMFATGN KMLGEFLHRV
LSRLGSTKRL RVLEVGAGTG ATTRNAMDQL LASNVDFTYT FTDVSIALVT SAKKKFGALY
NSQRRQSNME FTVLDIEKSP PANMLESYDL IISSNCIHAT RNLGQACANI EKLLRRDGGM
LCLLELTRPL SWLDCVFGLL DGWWRFDDDR TYALADEHKW KSTLLDAGFI HVDWTDDGYR
ESEQFRLITA WR
