ZEA2_GIBZE
ID ZEA2_GIBZE Reviewed; 2352 AA.
AC A0A098D8A0; A0A0E0RTV5; I1S5K5; Q2VLJ2;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 07-JAN-2015, sequence version 1.
DT 25-MAY-2022, entry version 42.
DE RecName: Full=Highly reducing polyketide synthase ZEA2 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000305|PubMed:16262793, ECO:0000305|PubMed:18427109};
DE AltName: Full=Polyketide synthase 4 {ECO:0000303|PubMed:16262793};
DE Short=PKS4 {ECO:0000303|PubMed:16262793};
DE AltName: Full=Zearalenone biosynthesis polyketide synthase 2 {ECO:0000303|PubMed:16517624};
GN Name=ZEA2 {ECO:0000303|PubMed:16517624};
GN Synonyms=PKS13 {ECO:0000303|PubMed:16262793};
GN ORFNames=FGRAMPH1_01T05751, FGSG_02396, FGSG_12126;
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 [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE,
RP INDUCTION, AND PATHWAY.
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=16262793; DOI=10.1111/j.1365-2958.2005.04884.x;
RA Kim Y.T., Lee Y.R., Jin J., Han K.H., Kim H., Kim J.C., Lee T., Yun S.H.,
RA Lee Y.W.;
RT "Two different polyketide synthase genes are required for synthesis of
RT zearalenone in Gibberella zeae.";
RL Mol. Microbiol. 58:1102-1113(2005).
RN [2]
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 [3]
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 [4]
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 [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16517624; DOI=10.1128/aem.72.3.1793-1799.2006;
RA Gaffoor I., Trail F.;
RT "Characterization of two polyketide synthase genes involved in zearalenone
RT biosynthesis in Gibberella zeae.";
RL Appl. Environ. Microbiol. 72:1793-1799(2006).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16751498; DOI=10.1128/aem.00963-05;
RA Lysoee E., Klemsdal S.S., Bone K.R., Frandsen R.J., Johansen T., Thrane U.,
RA Giese H.;
RT "The PKS4 gene of Fusarium graminearum is essential for zearalenone
RT production.";
RL Appl. Environ. Microbiol. 72:3924-3932(2006).
RN [7]
RP FUNCTION.
RX PubMed=18427109; DOI=10.1073/pnas.0800657105;
RA Zhou H., Zhan J., Watanabe K., Xie X., Tang Y.;
RT "A polyketide macrolactone synthase from the filamentous fungus Gibberella
RT zeae.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:6249-6254(2008).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of zearalenone (ZEA), a nonsteroid
CC estrogen that is a contaminant of cereal grains and causes estrogenic
CC disorders in humans and animals (PubMed:16262793, PubMed:16517624,
CC PubMed:18427109). The ZEA backbone is synthesized from a single acetyl-
CC CoA molecule and eight malonyl-CoA molecules (PubMed:16262793,
CC PubMed:16517624, PubMed:18427109). The reducing polyketide synthase
CC ZEA2 is proposed to synthesize a reduced hexaketide intermediate by
CC using different combinations of its reductive domains during each round
CC of condensation (PubMed:16262793, PubMed:16517624, PubMed:16751498,
CC PubMed:18427109). The hexaketide thioester is then transacylated to the
CC non-reducing polyketide synthase ZEA1 and is further condensed with
CC three malonyl-CoAs without reductive tailoring to yield a mixed
CC reduced/unreduced nonaketide (PubMed:16262793, PubMed:16517624,
CC PubMed:18427109). ZEA1 must be able to interact with ZEA2 to facilitate
CC starter-unit acyltransfer and initiate polyketide biosynthesis
CC (PubMed:18427109). ZEA1 also mediates the required C2-C7 cyclization to
CC form the resorcylate core and catalyzes the formation of the
CC macrolactone (PubMed:18427109). ZEB1 is then responsible for the
CC chemical conversion of beta-zearalenonol (beta-ZOL) to ZEA in the
CC biosynthetic pathway (PubMed:16262793). {ECO:0000269|PubMed:16262793,
CC ECO:0000269|PubMed:16751498, ECO:0000269|PubMed:17823352,
CC ECO:0000269|PubMed:18427109}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:16262793}.
CC -!- INDUCTION: Expression is positively regulated by the zearalenone
CC biosynthesis specific transcription factor ZEB2 (PubMed:16262793).
CC Conditions for carbon-, nitrogen-, or phosphorus-starvations lead to
CC very low expression (PubMed:16262793). Increase in pH results in
CC gradual reduction of the gene expression (PubMed:16262793).
CC {ECO:0000269|PubMed:16262793}.
CC -!- DISRUPTION PHENOTYPE: Results in the loss of zearalenone production but
CC still produces beta-zearalenonol (PubMed:16262793, PubMed:16517624,
CC PubMed:16751498). {ECO:0000269|PubMed:16262793,
CC ECO:0000269|PubMed:16517624, ECO:0000269|PubMed:16751498}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABB90283.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=ESU07825.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; DQ019316; ABB90283.1; ALT_SEQ; Genomic_DNA.
DR EMBL; DS231663; ESU07825.1; ALT_SEQ; Genomic_DNA.
DR EMBL; HG970332; CEF74680.1; -; Genomic_DNA.
DR RefSeq; XP_011318310.1; XM_011320008.1.
DR AlphaFoldDB; A0A098D8A0; -.
DR SMR; A0A098D8A0; -.
DR STRING; 5518.FGSG_12126P0; -.
DR EnsemblFungi; ESU07825; ESU07825; FGSG_12126.
DR GeneID; 23558941; -.
DR KEGG; fgr:FGSG_12126; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G05751; -.
DR eggNOG; KOG1202; Eukaryota.
DR PHI-base; PHI:714; -.
DR Proteomes; UP000070720; Chromosome 1.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
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:0106150; P:zearalenone biosynthetic process; IMP:GO_Central.
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 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; 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; 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; 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; 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 2: Evidence at transcript level;
KW Multifunctional enzyme; Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..2352
FT /note="Highly reducing polyketide synthase ZEA2"
FT /id="PRO_0000438785"
FT DOMAIN 2269..2346
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:18427109"
FT REGION 12..436
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18427109"
FT REGION 544..875
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18427109"
FT REGION 925..1237
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18427109"
FT REGION 1643..1955
FT /note="Enoylreductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18427109"
FT REGION 1979..2159
FT /note="Catalytic ketoreductase (KRc) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18427109"
FT ACT_SITE 181
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 181
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 634
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 955
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2306
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2352 AA; 255283 MW; 9000ACBFFB173B2C CRC64;
MSVDNKQVPG PVAIVGLACR FPGDATSPSK FWDLLKSGKD AYSETTDRYN AQAFYHPNSK
RQNVLPVTGG HFLKQDPHVF DAAFFNITAA EAISLDPKQR IALEVAYEAF ENAGKPLKQV
AGTTTACFVG SSMSDYRDAV VRDFAHNPKY HVLGTCEEMI ANRISHFFDI HGPSATVHTA
CSSSLVAIHL ACQSLLSGDA EMALAGGVGM ILTPDGTMQL NNLGFLNPEG HSRSFDKDAG
GYGRGEGCGI LVLKKLDKAI QDGDNIRAVI RASGVNSDGW TQGVTMPSSE AQAALIKHVY
ETRGLDYGAT QYVEAHGTGT KAGDPVETGA IHRTIGQGAS KNRKLWVGSV KPNIGHLEAA
AGVASVIKGV LAMENSLIPP NIHFASPNPE IPLDEWNMAV PTKLTPWPAA RTKRMSVSGF
GMGGTNGHVV LEAFNSTPQS ILYGDAQYQP AHNGKRLFTF SSHDQAGLDR VSKSLVDHLD
SLGPAGARPE YLADLGYSLS VGKSGLSWKT AHLAESLTEL REKLSSPQSE HAVREPRSQP
KIGFVFTGQG AQWARMGVEM LHRPVFKESV QRSTDYLQQL GCDWTPIVEL SRAQKESRLT
LPEISQPICS VLQIALVDEL RSWGVAPVSV VGHSSGEIAA AYCIEALSHK DAIAVAYFRG
KVSAGLNHLN GGMMAVGCSR AEAETLIDES DLQGGHVTVA CVNSPSNVTL SGDVAPLDQL
KGILEKRGIF ARRLRVEVAY HSTHMNSVFA DYTASIADIE PQSCPSHQPI MVSSVTNNQV
DPALLGSYYW GRNLISPVLF SDTIKEMVSP ADGNGQKAVD LLVEIGPHGA LGGPIEQILS
HFDIENVGYQ SMLTRGQNAV ETSLELATSL FLQGVAIDIQ KVNGDSGCRL LTNLPPYPWN
HSKKFRAESR LQRELIAQST PTRSIIGAPV PKMNESQRVW RGFIRLDDEP WIRGHTVGTT
VLFPGAGMVS IVLEAAQQMV DPGKVARAFR LRDVSFSAAM ALPEDQATEV IIQMKPQLVA
TSGSTPATWW EFTVSSCAGT DQLRDNCRGL ITIDYEGNTS QQMAHEDSQV VSGRISDYHQ
ILEECPATYA KDRFYKHMMK AAWRYGETFQ GVENCHPGDG KTVFDVKLID IGETFSKGQL
DRPFLIHGAT LDAVFQGWLG STYKNGTFEF DKPFVPTKIG EMEISFNVPS EAGYMMPGLC
RSHRSGFNEL SADTIMFDKD LSRVILSVID FRTSELEMDG AATEETTVEV DPADITSKVL
WDYSLSLMEP CDLKQVMGSI VAQNSLTDFV RMLLHDNPAA NIVEFISRSD GLPNTYASKL
PPGTILPTQI RYAVVDETED VGDENAASSM LTIDALVDSV SASGATADIV VIPQGFQFQD
NYAKILEPLA KVSKPNTTIV VAVDTPDTTV PLKAKGFQLL HSIQGTPSLE VFAGLTGEQE
KPTNGIHKEE VVLLLPSMLS TVTKEFAEEV QLDLEGQGFS VSTESLAESI DDSTFDGKTC
VSLLEVERPL LDSLSESDFQ LIRKVVLTSQ RILWVTHGES PSLALVDGFS RCIMSEIEGV
KFQVLHLSEP TGLQHGPRLA AKVIASKASD NEFRDKDGLL QVARIFKGLT ENENIRHHLH
DDVRVTRLSN QEHPLRLTIG KPGLLDTLYF VDDERVLAPL ADHEVEIQVK ATGLNFRDVM
ASMALVPVKG LGQEASGIVL RTGRDATHLK PGDRVSTLDM GTHATVMRAD HRVTVKIPDA
MSFEEAAAVP VVHTTAYYAL VRLAKLQRGQ SVLIHAAAGG VGQAALQLAN HLGLVVYATV
GSDDKRKLLT DTYQVSEDHI FNSRDASFAK GIMRVTGGRG VDCVLNSLSG ELLRVSWSCL
ATFGTFVEIG LRDITNNMLL DMRPFSKSTT FSFINMYTLF EEDPSALGDI LEEVFKLLGG
GILQTPSPMT VYPINQVEDA FRIMQQGKHR GKIVLSFPDD AQAPVLHVAK NSMKLDSQAT
YLFVGGLGGL GRSLAKEFVS CGAKNIAFIS RSGDSTSEAK ATIKEITSRG ANVKAYAADI
SNETAFLNAM KECSREFPPI KGVVQMAMVL RDVVFEKMTY EEWKLPLKPK VQGSWNLHKY
FDHERPLDFM VICSSSSGIY GYPSQAQYAA GNTYQDALAH YRRAQGLRAV SVNLGIMRDV
GVLAEQGTSG NIKLWEEVLG IREPAFHALM KSLIKGQTDN NSEFPAQICT GLGTADIMAT
HGLAKPTYFQ DPRFGPLAVT SLSSDASGDK QSTAMSISSQ LSEASSKAKA TEIITNALIG
KVADILQMPQ SEVDPGQPLY RYGVDSLVAL EVRNWITREM KVNVALLEIL AAVPMESFAG
KLASTSKLVT VS
