GRA9_GIBZE
ID GRA9_GIBZE Reviewed; 1598 AA.
AC I1R9A6; A0A098CZ32;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 25-MAY-2022, entry version 62.
DE RecName: Full=Fatty acid synthase subunit alpha {ECO:0000303|PubMed:30395461};
DE EC=2.3.1.86 {ECO:0000305|PubMed:30395461};
DE AltName: Full=Gramillins biosynthesis cluster protein FGSG_00036 {ECO:0000303|PubMed:30395461};
DE Includes:
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] reductase {ECO:0000250|UniProtKB:P19097};
DE EC=1.1.1.100 {ECO:0000250|UniProtKB:P19097};
DE AltName: Full=Beta-ketoacyl reductase {ECO:0000250|UniProtKB:P19097};
DE Includes:
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] synthase {ECO:0000250|UniProtKB:P19097};
DE EC=2.3.1.41 {ECO:0000250|UniProtKB:P19097};
GN ORFNames=FG00036, FGRAMPH1_01T00127, FGSG_00036;
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, AND PATHWAY.
RX PubMed=30395461; DOI=10.1021/jacs.8b10017;
RA Bahadoor A., Brauer E.K., Bosnich W., Schneiderman D., Johnston A.,
RA Aubin Y., Blackwell B., Melanson J.E., Harris L.J.;
RT "Gramillin A and B: cyclic lipopeptides identified as the nonribosomal
RT biosynthetic products of Fusarium graminearum.";
RL J. Am. Chem. Soc. 140:16783-16791(2018).
CC -!- FUNCTION: Fatty acid synthase subunit alpha; part of the gene cluster
CC that mediates the biosynthesis of gramillins A and B, bicyclic
CC lipopeptides that induce cell death in maize leaves but not in wheat
CC leaves (PubMed:30395461). The nonribosomal peptide synthetase GRA1
CC incorporates respectively a glutamic adic (Glu), a leucine (Leu), a
CC serine (Ser), a hydroxyglutamine (HOGln), a 2-amino decanoic acid, and
CC 2 cysteins (CysB and CysA) (Probable). The biosynthesis of 2-amino
CC decanoic acid incorporated in gramillins could be initiated by a fatty
CC acid synthase composed of the alpha and beta subunits FGSG_00036 and
CC FGSG_11656 (Probable). The cytochrome P450 monooxygenase FGSG_15680
CC could hydroxylate the fatty acid chain (Probable). Subsequent oxidation
CC to the ketone by the oxidoreductase FGSG_00048 and transamination by
CC aminotransferase FGSG_00049 could form 2-amino-decanoic acid
CC (Probable). On the other hand, FGSG_15680 could also be responsible for
CC the HO-modified glutamine at the gamma-position (Probable). Whether
CC hydroxylation occurs on the fully assembled product or on the Gln
CC residue prior to assembly into the gramillins requires further proof
CC (Probable). The thioredoxin FGSG_00043 could also be required for the
CC disulfide-bond formation between CysA and CysB (Probable). The specific
CC involvement of the remaining proteins from the cluster is more
CC difficult to discern, but could have broader regulatory (FGSG_00040 and
CC FGSG_11657) or enzymatic functions (FGSG_00044 and FGSG_00045)
CC (Probable). The final C-domain of GRA1 does not possess the expected
CC sequence of a termination CT domain, often implicated in
CC macrocyclization and release of a cyclopeptidein fungal NRPs; and the
CC thioesterase FGSG_00047 may act in concert with the terminal C-domain
CC of GRA1 to catalyze the formation of the macrocyclic anhydride and
CC release of the products (Probable). {ECO:0000269|PubMed:30395461,
CC ECO:0000305|PubMed:30395461}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 2n H(+) + n malonyl-CoA + 2n NADPH = a long-chain
CC fatty acyl-CoA + n CO2 + n CoA + H2O + 2n NADP(+);
CC Xref=Rhea:RHEA:22896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:83139; EC=2.3.1.86;
CC Evidence={ECO:0000305|PubMed:30395461};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a fatty acyl-[ACP] + H(+) + malonyl-[ACP] = a 3-oxoacyl-[ACP]
CC + CO2 + holo-[ACP]; Xref=Rhea:RHEA:22836, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:9916, Rhea:RHEA-COMP:14125,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:78776, ChEBI:CHEBI:138651;
CC EC=2.3.1.41; Evidence={ECO:0000250|UniProtKB:P19097};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + H(+)
CC + NADPH; Xref=Rhea:RHEA:17397, Rhea:RHEA-COMP:9916, Rhea:RHEA-
CC COMP:9945, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78776, ChEBI:CHEBI:78827; EC=1.1.1.100;
CC Evidence={ECO:0000250|UniProtKB:P19097};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:30395461}.
CC -!- SUBUNIT: Fatty acid synthase is composed of alpha and beta subunits.
CC {ECO:0000250|UniProtKB:P19097}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Fungal fatty acid
CC synthetase subunit alpha family. {ECO:0000305}.
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DR EMBL; HG970332; CEF71863.1; -; Genomic_DNA.
DR RefSeq; XP_011315622.1; XM_011317320.1.
DR AlphaFoldDB; I1R9A6; -.
DR SMR; I1R9A6; -.
DR STRING; 5518.FGSG_00036P0; -.
DR GeneID; 23547555; -.
DR KEGG; fgr:FGSG_00036; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G00127; -.
DR eggNOG; ENOG502QQJX; Eukaryota.
DR HOGENOM; CLU_000114_0_0_1; -.
DR InParanoid; I1R9A6; -.
DR Proteomes; UP000070720; Chromosome 1.
DR GO; GO:0005835; C:fatty acid synthase complex; IEA:InterPro.
DR GO; GO:0004316; F:3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0004321; F:fatty-acyl-CoA synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0008897; F:holo-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IEA:InterPro.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR040899; Fas_alpha_ACP.
DR InterPro; IPR026025; FAS_alpha_yeast.
DR InterPro; IPR041550; FASI_helical.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF18325; Fas_alpha_ACP; 1.
DR Pfam; PF18314; FAS_I_H; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR PIRSF; PIRSF000454; FAS_yeast_alpha; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
PE 3: Inferred from homology;
KW Fatty acid biosynthesis; Fatty acid metabolism; Lipid biosynthesis;
KW Lipid metabolism; Magnesium; Metal-binding; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..1598
FT /note="Fatty acid synthase subunit alpha"
FT /id="PRO_0000450561"
FT DOMAIN 143..221
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 96..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 543..784
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000250|UniProtKB:Q8TGA2"
FT REGION 818..844
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 994..1513
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000250|UniProtKB:Q8TGA2"
FT REGION 1280..1301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 111..126
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1280..1297
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1175
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1175
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 181
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1598 AA; 176732 MW; 0FEF2079C1B374F8 CRC64;
MEAERETELS QLLLTELLSY QFANPVKWIE TQDVLLKEKE INHMIEIGPS STLTNMAKRT
ISKKYSEHDA ALREPRLLQS FDEHAAEIYC ETMQIRTQPH KSSAPQEPVP KAAPKAAPPV
PVATAPLPEP GRQVSTMPIN VEDVPIQSRD VIVATVAQKL RKHFLDIDCS KSIAQLCGGR
STMENELVGD LSLIFDPLPD RAEEMGISEL SQIVSGSTST TKLLTAHGKL TASIFTHKMP
GGFTITDARK HLEVQWRLGV GRQNAILLRM ATEVLPSRLK TREEATMLLD KIAEAYADEQ
GLKLQPMTEV PMSAPTTSSE TKVISGCSDV ELYTSNDISL PESEALVNAQ KMLNIVKTEN
DTLQEKMDLL TTELGDDFIQ GILPAWSPAK IRKYESCWNW ALQDLLLLLN SILRGETSLD
NSVTRSTCDM IVRRSNDRLI DVMRYMLSSN KLAGDELLVS MAKSVLAMLI EDSQNWLSCA
QTSRFFGHEL HNPIDAYAQG TPGSDSVEVK VKTRSQGTWK YDTSLIDLYK SSLACVREDG
LRLKGKTVLL TGAGPSSIGR ELLQHLLVSG ALVLVATSRF SPTACRELQN LYMKWGSSGS
QLVVCPFNQG SRGDCESLVQ YIFSAKAKGG LGWDLDFVIP FAAVSEEGQI DELDSKSEKA
HRIMLTNVLR LLGSIKQHKQ AGPRNTSPVK VLLPLSPNHG VFGRDGLYAE SKAGLEMLLN
KWYSEDWTSY LAICGVTIGW VRGTGLMAVN DAVAAEVEVR TGVKTFSQFE MAQRLAALLV
NPFAHEVEIQ PVKVDISGGM ADTTDLRSIL SDIRREIKQD STSTPTHQHL PSHHHVDEPE
IGKPLSSVSP MANLKLNFPQ LPDYEDDISP LNTLSGMVDL DRTVVITGIS EVGPWGNSRT
RWEMEAFGEF SLEGCIEMAW IMGLITHYNG KLGDDMGGEQ YTGWVDAKTK APVADVDVKA
RYEEQIIEHS GIRLVEPELD NGYDPRKKQL LHEIVLTRDL APFAAPPELA KQFMQEHGEK
VDAIPGSTEN EDWTVRLRKG AVILVPKALR FDRSAAGQIP QGWDARRYGV PDWAVDQIGR
ETLFALVATA ESLLSSGIVD PYELYQYMHV SEVGNCVGSG LGGQQALKKA FRYRYHDKPV
QSDVLQEVFS NTAAAWINML LLSSSGPIRT PVGACATAVE SLELGYELIT AGKAKIALVG
GHDDMTEEVA YEFAKMRATV NTDEEEARGR MYSEMSRPMT TTRDGFVESQ GSGIQVLASA
TMAIKMGLPI YGIVSWAGTA SDKTGRSVPS PGKGTLTNAR ETHGADKNLL LDIHFRKDRI
TRHQQQIQAD LEQDLKSLEQ RFAMSRSITK SEVDKMSLFL HKEAIERNKQ VLKSLGHTFW
TSHTDISPIR GALSAWGLSI DDLDFVSLHG TSTVLNDKNE TSVIQSQLSH LGRTRGNPAY
CITQKYLTGH SKGAAGAWMI NGALQALNTG LIPGNRNADD VAPELEGNDF LFFPHHSVQT
NGLRAFSITS FGFGQKGAQA IIVHPRYLYA ALSDAEEFHQ YRRRLNVRQR RATKFFQRGL
ATETLFIAKE EPPYTEKQES RVLLNPEARM EGQHYKDV
