W4931_FUSPC
ID W4931_FUSPC Reviewed; 2564 AA.
AC K3VA96;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=Highly reducing polyketide synthase 40 {ECO:0000303|PubMed:25412204};
DE Short=HR-PKS PKS40 {ECO:0000303|PubMed:25412204};
DE EC=2.3.1.- {ECO:0000305|PubMed:25412204};
DE AltName: Full=W493 A and B biosynthesis cluster protein PKS40 {ECO:0000303|PubMed:25412204};
GN Name=PKS40 {ECO:0000303|PubMed:25412204}; ORFNames=FPSE_09187;
OS Fusarium pseudograminearum (strain CS3096) (Wheat and barley crown-rot
OS fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX NCBI_TaxID=1028729;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CS3096;
RX PubMed=23028337; DOI=10.1371/journal.ppat.1002952;
RA Gardiner D.M., McDonald M.C., Covarelli L., Solomon P.S., Rusu A.G.,
RA Marshall M., Kazan K., Chakraborty S., McDonald B.A., Manners J.M.;
RT "Comparative pathogenomics reveals horizontally acquired novel virulence
RT genes in fungi infecting cereal hosts.";
RL PLoS Pathog. 8:E1002952-E1002952(2012).
RN [2]
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 lipopeptides W493 A and B
CC (PubMed:25412204). W493 A and B consist of six amino acid residues D-
CC allo-thr, L-Ala, D-Ala, L-Gln, D-Tyr, and L-Val/L-Ile linked to a 3-
CC hydroxy-4-methyltetradecanoic acid polyketide chain (PubMed:25412204).
CC The biosynthesis starts with formation of the linear polyketide chain
CC by the highly reducing polyketide synthase PKS40 (PubMed:25412204). The
CC gene cluster contains a putative acyl-CoA ligase (FPSE_09184) for
CC formation of a CoA thioester polyketide. The thiol bond could be
CC hydrolyzed by the putative thioesterase (FPSE_09186) and then accepted
CC by the first T domain in module 1 of NRPS32 (PubMed:25412204). The
CC second T domain is responsible for accepting a threonine, which is
CC adenylated by the A domain and epimerized to the D-allo-threonine
CC formed by the E domain. The five successive modules incorporate Ala,
CC Ala, Gln, Tyr, and Val/Ile into the final product, which is released by
CC cyclization (PubMed:25412204). {ECO:0000269|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 W493 A and B.
CC {ECO:0000269|PubMed:25412204}.
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DR EMBL; AFNW01000306; EKJ70677.1; -; Genomic_DNA.
DR RefSeq; XP_009260579.1; XM_009262304.1.
DR AlphaFoldDB; K3VA96; -.
DR SMR; K3VA96; -.
DR STRING; 101028.EKJ70677; -.
DR EnsemblFungi; EKJ70677; EKJ70677; FPSE_09187.
DR GeneID; 20367804; -.
DR KEGG; fpu:FPSE_09187; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_31_1_1; -.
DR InParanoid; K3VA96; -.
DR Proteomes; UP000007978; Chromosome 1.
DR Proteomes; UP000007978; Unassembled WGS sequence.
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;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2564
FT /note="Highly reducing polyketide synthase 40"
FT /id="PRO_0000445364"
FT DOMAIN 2472..2549
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 11..435
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25412204"
FT REGION 435..482
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 580..914
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25412204"
FT REGION 973..1280
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 1854..2167
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25412204"
FT REGION 2191..2370
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25412204"
FT COMPBIAS 439..478
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 181
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2509
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2564 AA; 279195 MW; 5F1B7ABE7B072C81 CRC64;
MAPNMTAPEP IAIIGMSCRF PGGASEPSRL WDTLSEGKSA WSEVPEDRFN MKAFYQRGDP
HASTTNTAGG HFLDEDLSKF DSNFFGVKPL EARAWDPQQR LTLELAYEAF ENAGLTIPQL
WGSNTGVYVG QWSSDYSEIL ARDPEYQELY HTLGAGPAIT SNRVSFFFNL RGPSFTVDTG
CSSSLVALHN AVQSLRNGES TMSLVGGVNV LLDPQRFTYQ SKLKMFSPDG RSFSFDHRAN
GYGRGEGCGC VVLKPLSLAV KDGDRIRAVI RNSALNQDGR TPQGISVPSM VAQEELIRRA
YAEVGLVPTE TDYVEAHGTG TAVGDPIEAQ AIAAVLAQTR KPGQEPLSLA SVKGNIGHTE
SAAGIAGLIK SVLMLENQAI PPQVNYEKPN PKIPLDKWNL QIPIRFEEKQ LRRISVNSFG
YGGTNAHVIV DRVDEHNHSN GTNGTNGTHH HNGTNGSNGN GTNGTNGTNG TDGFHDTESI
SDSISDRPRV FVLSGAEEQS CHQNAERLAQ YLTKLPASLL EDSDGFLDKL AVSVNKRTVH
DYSASVIAYD GEDLLAQLDV LQQTPVAIRA PVKGGARVGY VFGGQGAQYY SMGREMIKSW
TPFRQSLDRA NAHLKTMGCQ WDLLTELSHE KAQDSHVDEP EYGQTLSTAV QLALVDTLVA
TKMRPTSVVG HSSGEIAAAY AAGALSFEDA LTVAYHRGRL TSQLISTGIS GGMLAVGSSP
DAVQDYIEQV KATTKANVKI ACYNSPTSVT LSGDSEAINA ISELLQDDDV FNRKLKTQGA
AYHSQMMQAM EEEYRSAIAY IQPRPVDAPV TMMSSLLGKK LPAGFLLDGD YWARNLVSPV
LFAGALRGIM VGDEHDGSSQ HSPQVDLLLE IGPHATMQGA VKETLKGLGS SVRIQYLSCL
KRKTSAAENM LRTLADLFAL GASVDLHYAN AGFRTKLPPI LKDLPPYAFN HDQRLWHDGR
ISHEFTHRQF LPHELLGNLS ADVNHTEPRW RRFLRLKELP WLQHHIVQGQ VIFPAAGYLA
MAMEAMRRFT AFETENQSKA TAGYSFRNTS FSKALVLRED DADTEICLSL RPEARSARNS
WQDWKEFRVF SISPGKGWSE HCRGRIRAVV DQGILAEALK DTTGVKDRIA ASVPHHITSN
RLYATARQVG MEWYGPFDNV VNLQARTDLS VATNRMPTLL SSAHPFGLST YVVHPGMLDS
TLFHGLVASV LVEQEVKAPV VPTFLEQLTI STAIQVPEGE ELRTYSVSRE EGSCWSAQVE
LNGESVISFH GLRTAQLPSD VVNTRPHQLA HSPEWVCHYP SMTREQLIDT CINSVPAGSA
RQRNIVLYAD VRAHVERALS HVQPDQVASG HEQSWYNWMK SFLATEPDSS DVVSEAREAT
KSEKFVGFDA VKIIGENLEQ LLTGEVTSLS LLSTNDMLER LYSEERNQRC YTQISAYCKA
VGLYNPALKV LEVGGGTASA TLPFLQALSH QGHPLVAQYD FTDLSTAFFA AARERLGQYG
HNVNYEAFDL AQDPETQGFE PGSYDIIVAC NVVHATPSIA SSLEHIRQLL RPGGTLVLME
ITNGDPFYQL IFGSLSGWWS GVSEGRESTA ILSEYDWKNV LAEQGYQSDP IMVGDYATSE
GGTISVIFAK TPLESRRDHL SETSLHFATD LFADSSAGYL DNVAEHLGQK SELSLRQITT
GNLESIKDID STVVVIDPET IEALAGRMDA SLWEKFQKCA LSCKGLLLVS RGATGSSVVP
EGALAVGFAR SMRLEQHGIR YITLDLDPSV DRDANELSRV LAQLLTSETF DFDRTISDAD
YEFAERKGQL HVNRLFPNVK LEESVAHSTR RSKPEQTEFL DTSRPLKVEL GVDGLLETFR
WVDDHQHARS LAPDEVRIEC RAASINFRDV LIATGGLGGA GTMMNDCAGT VVEVGSNMAS
RYSVGDRVCS YYAQSYNNYP IVDGQHCAKI PDNVSFALGA SLPIVWATTY HSLVNVAKLK
AGESILIHAA AGAVGQAAVI LAQHLGAVVY ATCGSQEKRE RLESMGVNPS HIFTSRSPAF
GPALRAATNN KGVNVILNSL AGELFRESLE CLTSFGRFIE IGKKDFLDDA LMPTKFLLQN
ITFACVDLVQ MINEDKPLVH GLLNDVVELV ASGQLKDEVN LQLYKLGEIE SAFRLISAGK
HMGKVILTVD QGETVLALPA TPNIPKLLPD ATYLLVGGFG GLGVRLIRWL ASRGAKTIVT
MSRSGAKSPA AKTCIEEMDS LGVRIIAKSC DISSKEALQV VVKELEDVDG LAPVRGVINA
AMALEDAMFD QMTHQQWVSS LAPKVAGTRN LDEVLPNYMD FFVVLSSIAG IIGHQAQANY
AAACTFQDAF MHYRRSQGRA SFAIDVGVVS DAGFVSEAPA VFSNMKRQGF SFISVAELLA
TLDYALSNDG PDCQASIGVM AEASPNNAEW LEQRRISHLV KDSANGAAGL NEGSGSDADH
IGHIRSAKTA EEALDAVGQA VLAELSKLTV TPVDRILPHR TLDSYGVDSL VAVELRNWVV
AIVAADLSLL LIRESRSIEE LIHLVAGKSR LVPAKLQDAV SKLA
