FUSA1_GIBZE
ID FUSA1_GIBZE Reviewed; 2554 AA.
AC I1RVD8; A0A098DC30;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Highly reducing polyketide synthase PKS6 {ECO:0000303|PubMed:25412204};
DE Short=HR-PKS PKS6 {ECO:0000303|PubMed:25412204};
DE EC=2.3.1.- {ECO:0000305|PubMed:25412204};
DE AltName: Full=Fusaristatin A biosynthesis cluster protein PKS6 {ECO:0000303|PubMed:25412204};
GN Name=PKS6 {ECO:0000303|PubMed:25412204};
GN ORFNames=FGRAMPH1_01T09371, FGSG_08208 {ECO:0000303|PubMed:25412204};
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 IDENTIFICATION, FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=25412204; DOI=10.1021/np500436r;
RA Soerensen J.L., Sondergaard T.E., Covarelli L., Fuertes P.R., Hansen F.T.,
RA Frandsen R.J., Saei W., Lukassen M.B., Wimmer R., Nielsen K.F.,
RA Gardiner D.M., Giese H.;
RT "Identification of the biosynthetic gene clusters for the lipopeptides
RT fusaristatin A and W493 B in Fusarium graminearum and F.
RT pseudograminearum.";
RL J. Nat. Prod. 77:2619-2625(2014).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of the lipopeptide fusaristatin A
CC (PubMed:25412204). Fusaristatin A consists of a polyketide chain linked
CC to three amino acid residues glutamine (Gln), dehydroalanine (dehydro-
CC Ala), and beta-aminoisobutyric acid (PubMed:25412204). The biosynthesis
CC starts with formation of a linear polyketide chain by the highly
CC reducing polyketide synthase PKS6 (PubMed:25412204). The gene cluster
CC does not contain an acyl-CoA ligase or an acyl-transferase, and it is
CC therefore predicted that the polyketide is transferred directly to the
CC nonribosomal peptide synthetase NRPS7 (Probable). Modules 1-3 from
CC NRPS7 incorporate dehydro-Ala, Gln, and beta-aminoisobutyric acid in
CC the compound, which is released by cyclization (PubMed:25412204). The
CC beta-aminoisobutyric acid units are most likely not freely available to
CC the NRPS, but can be synthesized from thymine, which requires a
CC dehydrogenase, a monooxygenase, and an aminotransferase. The
CC fusaristatin A cluster contains a cytochrome P450 monooxygenase
CC (FGSG_08207) and an aminotransferase (FGSG_17085), which theoretically
CC can perform two of the enzymatic steps (Probable). The enzymes may
CC however also be involved in biosynthesis of dehydroalanine or
CC modification of the polyketide (Probable). The dehydro-Ala residue can
CC be a result of cyclization, where serine is dehydrated (Probable). The
CC last gene of the cluster encodes a protein with an A/B barrel domain
CC found in variable enzymes, which hampers functional prediction
CC (Probable). {ECO:0000269|PubMed:25412204, ECO:0000305|PubMed:25412204}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25412204}.
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:25412204}.
CC -!- DISRUPTION PHENOTYPE: impairs the production of fusaristatin A.
CC {ECO:0000269|PubMed:25412204}.
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DR EMBL; HG970333; CEF76488.1; -; Genomic_DNA.
DR RefSeq; XP_011320599.1; XM_011322297.1.
DR AlphaFoldDB; I1RVD8; -.
DR SMR; I1RVD8; -.
DR STRING; 5518.FGSG_08208P0; -.
DR GeneID; 23555233; -.
DR KEGG; fgr:FGSG_08208; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G09371; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_31_1_1; -.
DR InParanoid; I1RVD8; -.
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: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:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
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; IPR011032; GroES-like_sf.
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; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
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 Pfam; PF00698; Acyl_transf_1; 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; 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; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
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.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2554
FT /note="Highly reducing polyketide synthase PKS6"
FT /id="PRO_0000445363"
FT DOMAIN 2457..2534
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:25412204"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 59..484
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25412204"
FT REGION 595..913
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25412204"
FT REGION 981..1281
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25412204"
FT REGION 1451..1556
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25412204"
FT REGION 1840..2153
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25412204"
FT REGION 2177..2353
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25412204"
FT ACT_SITE 230
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2494
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2554 AA; 277961 MW; 9A5C35FA343E5F60 CRC64;
MGSLSAVPAT NGNHAALNGS ASTNGQHVNG STHVNGNHSL NGSAQVNGHS ATTANLEPIA
VVGMSCRLPG DATDTQKLWE LITKGRSAWS KVPTDRWNQE AFHDPAAEGK PGRTSTDGGH
FLKDDIKAFD ASFFGVNPIE ATAMDPQQRL VLEIAYEAFE NAGLTLQQLS GSNTGVYVGL
WASDYQEMLL RDIDFPPIYQ ASGVGAAIAS NRVSYCFNLH GPSLTLDTGC SASLVALHQA
VHSLRAGETD KCFVAGVNLQ LDPQRYGYQN KLSMFSKQGK SFTFDHRAKG ASGYGRGEGC
SGVVLMPLSK AQKQGFPIRA VIRNSVANQD GKTNGITVPS AAAQSAAIEK AYAQVGLTPY
ADYVEAHGTG TTVGDPIEAK AIAKVLGAGR QSDSPLPIGS LKANIGHTES AAGLTGLVKA
VLMLENNMIP PQVNYEKPNP EIDLDALNLR IPISLENKPL KRISVNSFGY GGTNAHVVVD
AADAIPIKPT NTDSQETKDT LRVREQLFVL SAASEKSSQD LVLNVAKYLE SKADAADTDA
LLSRLAYTLS RRTVMENRIG VVASDLADLV EQLTKLSSEG IPRADRQTSP RIGFVFSGQG
AQYPRMGQSL LGTWPTFTSS MKRAAECVKA CGSSWDLLEE LLKDASESRM EDPCIAQPMS
TAVQISLVDA LKDLGVIPTA VVGHSSGEIA AAYCAEAISF EDAMTVSYHR GRLTSELRLE
NKGKAGSMIA VGASAATVKQ SIDQLGTAAA NRITIACHNS PASVTVSGDA DVIESLKQRL
DEQDIWNRLL RTGGAAYHSP QMLQIAQKYH EAIKDVSGSV PASNVAMASS VTGEDQGDKP
ITRDYWVHNL VSPVRFTDAL KKTCVGENGT RKVDLLLELG SHFQLESPIK QTLRTFTGEA
AKVHYTGSLK RGEDAQLSML QMLRSLYLQK SPVAFWKVNA GFGATFQLLT DLPPYPFDHS
KTYWHEGRVS RAYKHRQNLP HELLGTLVHD NNPQEPRWRC LLNLKDVPWL SGHIIQGQTI
FPATAYLSMV FQAARQDMAA RNPQASINRF ILRNVTFSQA LVMENNKTDL EISLSLRPQA
ISARKSSQQW QEFRIFSTSA DDVWIEHVRG LVQVILKSEA VQEDSFVPTR ITLPPHAQHI
PANQFYHRAR DIGVNWSAPF DNLNDIKIAA GSCIADSSFV AGPSAGACEK DYVIHPGVMD
AILYHGMMGV LIFDENDKSP VVPTFIEKMI VAEQDQAKPI EEVTCHAART ESALTFDIGI
FEKNHEDNMV LQAWGVVATK LPDVSIGEGR KRDLCHVPDW ATYLPKTTQE YIDGLCKKSL
DDRSIIPEIK ALEAMTVHYV KQALASTPED EVAEGYQRNW YNWMKTLADQ EPDPEYLKAG
EEDDSVSAQV ARRLGPRLGD ILRGTTHSLS ILNEDSMLSG LYLEGGNVRC ISQIATYMGE
LGRLNPNMKI VEVGAGTGSA TLPVLQALQA PNRVLASQYD FTDISPGFFP AARELLADYE
GVVQYKILNA EKTAEENGFE PNSYDVLIAS NVLHATPCID AVLENVKTML RPGGKLILME
PTENLPHYGL VFGSLAGWWA GVDEGRTLSP MLSRSQWIET LSKNGFINNG PIFEDYPVAE
GGSIHVFVSE VPVPASTEAP LDVDIVSYSG EATYTDFAER LQKNLWDRSV QSCNVSSSMS
GDKLSVIMPD FVDRVAWDMD GPLFESLRSR VAGSKVIIFV MCTAKSKEKR PSGDWIYGFV
RSIRYEYASV RLVTLELESG LEAGVDALKT ILNSPTADLS LPLEDIELEY MEREGQIFVS
RVRSEPKFDN YVSRDLGRAG SEEALFLNER PMSAELGVPG VLDTIRWVDN PEITGPVDPD
CVRLQLCAAS INFKDVLVAS GQLEGITQMR NDCSGIVLDV GANMTDKFKV GDRVCSLYSQ
SFTNYPMVHG LCCHVIPDDM DFADAASIPL VWSTVYYCLI TIARLQKGES ILIHSAAGAV
GQASIMLAHH IGAEVFVTCG NDAKVELLNT EFGIPRDHIF SSRTTVFRDK IRAMTNGNGV
DVVLNSLGGE MFRESCNTLA AHGRFVEIGR KDLMENALMP MEFLLNNITF SYVDFAHILA
TRTALASQLL GDVMKLFASG AVQHVRQIKY PISEMASAFR LVQAGKHTGK VILTVEPDVK
VQVVPSKPSP VQLKPDATYL VVGGLGGLGK RLVDWTAEKG ARNIVIFSRT AQPDADAQSF
LDKLVSMGVT VRVEKCDVSS EESVIEALAR IQETMPPIRG LFQAAMVLHD ILLEHMTVEE
WCKVTAPKVQ GTWNLHKYLP EDMDFFVMLS SVVSMVGTVG AGNYASACAF QDGIARYRRR
LGLTAYAVNI GAIVEAGYVS ENPEVAVNLR KNGLGSVAIS EFLSHLGDVI QNKTEYSQSS
LGILPNGNER GLGEARWAND KRLAQIFGAE TQAGNKTVGG GADNVGFALQ SATTFQEAQD
IICDAIVKQL ATILAIQSDD IIPARSLDSY GLDSLVGVEL RNWIGAYLQV NLPLLVMWNT
SSINELAEIV TKGSRLVKVK VEDTEEEQVD VVKD
