ID GPY1_GIBF5 Reviewed; 2543 AA.
AC S0EMV0;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 27-NOV-2024, entry version 60.
DE RecName: Full=Highly reducing polyketide synthase GPY1 {ECO:0000303|PubMed:27856636};
DE Short=HR-PKS GPY1 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000305|PubMed:27856636};
DE AltName: Full=Gibepyrone A biosynthesis cluster protein 1 {ECO:0000303|PubMed:27856636};
GN Name=GPY1 {ECO:0000303|PubMed:27856636}; Synonyms=PKS13;
GN ORFNames=FFUJ_12020;
OS Gibberella fujikuroi (strain CBS 195.34 / IMI 58289 / NRRL A-6831) (Bakanae
OS and foot rot disease fungus) (Fusarium fujikuroi).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium fujikuroi species complex.
OX NCBI_TaxID=1279085;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 195.34 / IMI 58289 / NRRL A-6831;
RX PubMed=23825955; DOI=10.1371/journal.ppat.1003475;
RA Wiemann P., Sieber C.M.K., von Bargen K.W., Studt L., Niehaus E.-M.,
RA Espino J.J., Huss K., Michielse C.B., Albermann S., Wagner D.,
RA Bergner S.V., Connolly L.R., Fischer A., Reuter G., Kleigrewe K., Bald T.,
RA Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M., Brown D.W.,
RA Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U., Gueldener U.,
RA Tudzynski B.;
RT "Deciphering the cryptic genome: genome-wide analyses of the rice pathogen
RT Fusarium fujikuroi reveal complex regulation of secondary metabolism and
RT novel metabolites.";
RL PLoS Pathog. 9:E1003475-E1003475(2013).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION, AND MUTAGENESIS OF GLY-1443.
RX PubMed=27856636; DOI=10.1074/jbc.m116.753053;
RA Janevska S., Arndt B., Niehaus E.M., Burkhardt I., Roesler S.M.,
RA Brock N.L., Humpf H.U., Dickschat J.S., Tudzynski B.;
RT "Gibepyrone biosynthesis in the rice pathogen Fusarium fujikuroi is
RT facilitated by a small polyketide synthase gene cluster.";
RL J. Biol. Chem. 291:27403-27420(2016).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of gibepyrone A, a 2H-pyran-2-one
CC metabolite exhibiting a moderate antimicrobial activity against Gram-
CC positive bacteria and yeasts (PubMed:27856636). The highly reducing
CC polyketide synthase GPY1 is sufficient to produce gibepyrone A. GPY1
CC uses an acetyl-CoA starter unit, three malonyl-CoA extender units, and
CC two SAM-dependent methylations to establish the gibepyrone A carbon
CC backbone, followed by product release upon intramolecular cyclization
CC (PubMed:27856636). The gibepyrone A derivatives gibepyrones B and D are
CC produced by cluster-independent P450 monooxygenases, probably to
CC protect the fungus from the toxic product (PubMed:27856636). In
CC contrast, the formation of gibepyrones E and F from gibepyrone A is a
CC spontaneous process and independent of enzymatic activity
CC (PubMed:27856636). {ECO:0000269|PubMed:27856636}.
CC -!- INDUCTION: Expression is up-regulated by gibepyrone A which is able to
CC induce its own production by an elevated GPY1 gene expression in a
CC positive feedback loop (PubMed:27856636). Expression is down-regulated
CC by the cluster-specific ABC transporter GPY2 (PubMed:27856636). Members
CC of the velvet complex, VEL1, VEL2, and LAE1, negatively affect GPY1
CC gene expression and gibepyrone A product formation, whereas SGE1
CC represents a positive regulator of gibepyrone biosynthesis
CC (PubMed:27856636). {ECO:0000269|PubMed:27856636}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; an
CC enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and
CC an acyl-carrier protein (ACP) that serves as the tether of the growing
CC and completed polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:27856636}.
CC -!- DISRUPTION PHENOTYPE: Results in total loss of gibepyrone A
CC biosynthesis. {ECO:0000269|PubMed:27856636}.
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; HF679033; CCT75967.1; -; Genomic_DNA.
DR AlphaFoldDB; S0EMV0; -.
DR SMR; S0EMV0; -.
DR STRING; 1279085.S0EMV0; -.
DR EnsemblFungi; CCT75967; CCT75967; FFUJ_12020.
DR VEuPathDB; FungiDB:FFUJ_12020; -.
DR HOGENOM; CLU_000022_31_0_1; -.
DR OrthoDB; 2596010at2759; -.
DR Proteomes; UP000016800; Chromosome 11.
DR GO; GO:0004312; F:fatty acid synthase activity; IEA:TreeGrafter.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:TreeGrafter.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:TreeGrafter.
DR CDD; cd02440; AdoMet_MTases; 1.
DR CDD; cd05195; enoyl_red; 1.
DR CDD; cd00833; PKS; 1.
DR Gene3D; 3.30.70.3290; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 1.
DR Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase_dom.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013154; ADH-like_N.
DR InterPro; IPR011032; GroES-like_sf.
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; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020807; PKS_DH.
DR InterPro; IPR049551; PKS_DH_C.
DR InterPro; IPR049552; PKS_DH_N.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR049900; PKS_mFAS_DH.
DR InterPro; IPR050091; PKS_NRPS_Biosynth_Enz.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR43775:SF54; SYNTHASE, PUTATIVE (JCVI)-RELATED; 1.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF21089; PKS_DH_N; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00822; PKS_KR; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF50129; GroES-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 2.
DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR SUPFAM; SSF53901; Thiolase-like; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS52004; KS3_2; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2543
FT /note="Highly reducing polyketide synthase GPY1"
FT /id="PRO_0000445361"
FT DOMAIN 9..435
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348,
FT ECO:0000305|PubMed:27856636"
FT DOMAIN 953..1256
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 2464..2541
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 574..881
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27856636"
FT REGION 953..1253
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27856636"
FT REGION 953..1089
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1103..1256
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1399..1587
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27856636"
FT REGION 1830..2136
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27856636"
FT REGION 2161..2335
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27856636"
FT ACT_SITE 182
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 318
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 358
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 985
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1169
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT MOD_RES 2501
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 1443
FT /note="G->V: Blocks the methyltransferase activity of the
FT CMet domain and impairs the production of gibepyrone A."
FT /evidence="ECO:0000269|PubMed:27856636"
SQ SEQUENCE 2543 AA; 275977 MW; 4D959494D5F3AB13 CRC64;
MPSQIPQWRE PIAIVSMACR LPGGIDKPLD LWDHVRAGCS SATAIPKDRF NAENFLSMDP
NQKGAQAFRG AHFVKRDIKQ FDHKFFGISK DTATAMDPQQ KQLLEVVYEC LESANISMET
ISKSKIGCYC AMFVSDYHDM LMQDPEYLPT FIAIGTTRTM LANRVSHALD LGGPSVTIDT
ACSGALVALH LACQALQAGE CDGAVIGASN LFLSPDYALS LTRLGAIAAD GQCKTFDASA
NGYGRGEGTN AVYVKRLSDA IRDGDSIRAV IRGTSSNSSG ATPAITEPSG RAQADTILQA
YAQAGINDFS ETGYFECHGT GTPVGDCIEL GAVGSVFSES HKTQDALWVG STKPNVGHSE
AASGLSSLIK VVLALEKGEI PPNTNYKTPN PKIDFDGWRV RVPTVPQPWP SKSIRRASVN
SLGIGGSTAH AVVEFYEPPQ LTNGSTNGAN AVNGTNGING TNGINGINGV NGHHEDEEKT
NDPYFLLFTS GASKSSRETN EQNLLEFLKS HEECKSLTSP LVKALNARSQ INIRPWKSFA
VAQSVDGLVQ QLETNALKVG AGPTIGGSPR VLFTFTGQGA MWSQMGKRLL DAFPVARNSL
YNLEEVVREL QSSKTPTWSL IDKLTTELSQ EEIDSPAIAH PLCMAVQIAL TDVLSSWGVL
PDGVVGHSGG ETAAAYACGA LTAKEAITVA YYRGIACQNA PSGAMLVIRS APNAKELQDA
LERNDVQIAC FNGPQNLTLA GSAEGVKNVA AELSTHGIVS RAVAVTRAYH TRAMKTVVDE
YVGQLKGVIQ PKIGRVPMYS SVTGLELKGT EVDADYWGAN LVSPVLYTDA VTLALTSSNL
KFDLCIELGP HSLLSRPTSE IVKSLPDSPQ LPFFATMLRN ADSSQQLMNL AGDLVLNGKQ
LDLDQVNKIA GKVGRLPNHI QDNLPAYAWD YSSTPWTEPR NSQEWRFRKS PRHEILGSRC
RGVNPSAPTW RNKVSIEDAP WLVDHQVNGI VTFSFTTGIA MVIEAMMQVQ EENKEIDWAN
HSFELQDFVF SNSIILPDES HIDLFLTLIP DNDNAKSEET WYDFTISSLR GDVDIRHCHG
RAAVLETSKD NVALRRRTSW HHMPLKVPLK SYYKTLERVG YGYGPKFQLL TEVRVRPSLS
ACSAKIDMTS TAQSPVPGQR YLLHPAMMDA ALQTPALANR SGFFQEIDTL LLPSKMKRIS
IRMPAKNTDV ASCTTNTSPV GFSRIQGSVE CYDSLSRPFF VVEGLQMDRA TSDDNTTLPW
LRLTWKPDIG DISSSDPMLS PIKIQSLPAE KKLVNLENLV KELIPLIVEN GIEKGKDLAP
HLLSYHSWFL DQAELHKERL AARHKQQNGF ATVQDAIMNV VANSGISQTV DASIVSQLAI
NMSRIFQGDV EALAVWLEND LLYRFYEESI FTTSMNQKLL SVAELLAHKN PNMKILEIGA
GTGGATTELL HGFSKAGGKN AYQSFTFTDI SAGFFDKAKK KFAQWDRIEF KTLDVEKDIA
EQGFTEKYDL VVAANVLHAT ADLPFAMKNI RSLLRDDGYL LVGELSEDLT SANFLWGPLT
GWWLRPRSPG RSGPGLTLDE WRNELAADFD SVSEIEAKHD KTDTEQLSST IVMMARAKPM
EYTPTKPLSE EKVHIAGVGS DLSMQDHLQK YLGTRGISAS SSSLEDLASR EWAGEWLILV
DETEGSFLAS LQPEQLTALK SWLTKPIKCI WVTRKVYLDP QNTTGGLVTG FARTLRGENS
QCQLYTLDLS SDGDITANVI YHVLERAHYS HDDPISRLDY EIAEKDGQLW TCRLVNDTPL
ENAYGPARKM DASSTQVVKA PHHLVMGEVG ILESLTMAQD DAYTAIPDGH VLVDVKAAGL
DDRDGFIAQG SLPATSFGRE CSGVVTRCGA NVSSFSPGDR VAVIGQGTFA TQYLAPSDCC
SKIPDWLSFE DAAAIPTNFI TALYALTTPA RVSTGQKILI VNASSTQGIA LIKTATALKL
DVYAAISDAT TKPILTRVGL HSAKIFVNPT NTGRSSVSRS TTFQAYKLVL NTKSGQYADF
AHLVANRGTY IEVTSGESSG DVGHVVPNKN VMFASVDLAD AYQESKQDLG ELLGQVIDMV
EKREVDVDSS VSVNGLDSLQ SSFAALIEGT SNKQVVSLAN VDDQKLIKTR PKTSRFNPHK
TYIITGGLGG LGRAISVWMA SYGARHIILA TSSITRASES GDLLQQLSSY GCNARVEVCD
VGDSEAVERL VASIDTPVGG VIHSALKLSD CFFEDITLED FDAVFGPKVN GSLNLHNSLL
NQDLDFFVML SSGCGVLGNE GQSNYAASST FLDTFARYRQ SLGLPASSVD LGFVEDVGNI
SERPEIQASL LSRGLRPITV RDVLRVVEGA IATGSPKNLI TDSTYDSFVQ SQIVLSFGMI
DKATAEYQSW AQDAKFGLLR SRAADNAALD SDSDSGESAV QTAFKALRNT LGRLGDAPEG
KEAALQPFVC TALVAKLAQV LSIKVGDIQP SRSAIQYGMD SLIAIEVRSW ARYAFQIDLP
INDLTNPYSI QDLSARVSRM IAG
//
