ID ZEA1_GIBZE Reviewed; 2038 AA.
AC A0A098D6U0; A0A0E0RTV4; I1RFC4; Q2VLJ3;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 07-JAN-2015, sequence version 1.
DT 27-MAR-2024, entry version 51.
DE RecName: Full=Non-reducing polyketide synthase ZEA1 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:18427109};
DE AltName: Full=Macrolactone megasynthetase {ECO:0000303|PubMed:18427109};
DE AltName: Full=Polyketide synthase 13 {ECO:0000303|PubMed:16262793};
DE Short=PKS13 {ECO:0000303|PubMed:16262793};
DE AltName: Full=Zearalenone biosynthesis polyketide synthase 1 {ECO:0000303|PubMed:16517624};
GN Name=ZEA1 {ECO:0000303|PubMed:16517624};
GN Synonyms=PKS13 {ECO:0000303|PubMed:16262793};
GN ORFNames=FGRAMPH1_01T05749, FGSG_02395;
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.
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, AND CATALYTIC ACTIVITY.
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: Non-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). ZEA1 exhibits broad starter-unit
CC specificities toward fatty acyl-CoAs ranging in sizes between C6 and
CC C16 and displays the highest activity toward decanoyl-CoA
CC (PubMed:18427109). ZEB1 is then responsible for the chemical conversion
CC of beta-zearalenonol (beta-ZOL) to ZEA in the biosynthetic pathway
CC (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 -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm (By similarity).
CC {ECO:0000250|UniProtKB:Q5B0D0}.
CC -!- DOMAIN: The release of the polyketide chain from the non-reducing
CC polyketide synthase is mediated by the thioesterase (TE) domain
CC localized at the C-ter of the protein (By similarity).
CC {ECO:0000250|UniProtKB:Q5ATJ7}.
CC -!- DISRUPTION PHENOTYPE: Results in the loss of zearalenone production but
CC still produces beta-zearalenonol (PubMed:16262793, PubMed:16517624).
CC {ECO:0000269|PubMed:16262793, ECO:0000269|PubMed:16517624}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABB90282.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=ESU07824.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; DQ019316; ABB90282.1; ALT_SEQ; Genomic_DNA.
DR EMBL; DS231663; ESU07824.1; ALT_SEQ; Genomic_DNA.
DR EMBL; HG970332; CEF74679.1; -; Genomic_DNA.
DR RefSeq; XP_011318309.1; XM_011320007.1.
DR AlphaFoldDB; A0A098D6U0; -.
DR SMR; A0A098D6U0; -.
DR STRING; 229533.A0A098D6U0; -.
DR ESTHER; gibze-q2vlj3; Thioesterase.
DR GeneID; 23549774; -.
DR KEGG; fgr:FGSG_02395; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G05749; -.
DR eggNOG; KOG1202; Eukaryota.
DR InParanoid; A0A098D6U0; -.
DR OrthoDB; 5396558at2759; -.
DR PHI-base; PHI:713; -.
DR Proteomes; UP000070720; Chromosome 1.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0016218; F:polyketide synthase activity; IDA:UniProt.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0106150; P:zearalenone biosynthetic process; IDA:UniProt.
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; 3.40.50.1820; alpha/beta hydrolase; 1.
DR Gene3D; 3.30.70.250; Malonyl-CoA ACP transacylase, ACP-binding; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 1.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR InterPro; IPR029058; AB_hydrolase.
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; 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; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR049551; PKS_DH_C.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR001031; Thioesterase.
DR InterPro; IPR016039; Thiolase-like.
DR NCBIfam; TIGR04532; PT_fungal_PKS; 1.
DR PANTHER; PTHR43775:SF53; ATROCHRYSONE CARBOXYLIC ACID SYNTHASE-RELATED; 1.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1.
DR SUPFAM; SSF53901; Thiolase-like; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00606; KS3_1; 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 Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..2038
FT /note="Non-reducing polyketide synthase ZEA1"
FT /id="PRO_0000438784"
FT DOMAIN 364..794
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348,
FT ECO:0000305|PubMed:18427109"
FT DOMAIN 1254..1573
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 1616..1693
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:18427109"
FT REGION 9..246
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18427109"
FT REGION 888..1172
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18427109"
FT REGION 1221..1572
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18427109"
FT REGION 1254..1405
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1425..1573
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1700..1738
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1778..1882
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:18427109"
FT ACT_SITE 537
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 672
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 711
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 979
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2021
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT MOD_RES 1653
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2038 AA; 222411 MW; 843ED0E45BFFCEA9 CRC64;
MAPNKKTILL FGDQTDSWVD GIDRLYQDAA SIPWLQSFLD DLTHTFKTHT VGMDAVLRNS
LGDFANLQEL AEKYRYTTDD VGMAQAFLIY AVRAGILLKW AKYEPSLLST DENQPEWVGI
SGGLISLSVL AVAETFEKLY EACLEVAGLL ARLCRFTSVK SRSMEDRSGA WGWTVLGIGA
NELRNALDQY QQSMGIPPIK RAQVAVTGHR WNTIVGPPSI LQLIVKECPA IRSLPKNELN
IHALQHTVVT SRADLDYIVG DSTLLSQPLS LTFTLWGMDD PRAHYTTWGD MLRAICSQAL
SRPLDITHVV DQLSSKLRSF PQLDVKSIGP CSHLSYLTNV LKSAGRTVSV ADDHPPSTPP
KQLPGRIAIV GMAGRGPGSD NVEEFWNVIM SKLDLCEEIP EDRFNLSEFY RSKHDSGCTT
TTKFGCFMDK PGHFDNRFFH ISPREALLMD PGHRQFLMTT YEALEMAGYS DGATRAVDPA
RIATFFGQCN DDWHDVSHHT LGCDAYTLQG VQRAFGAGRI AFQFKWEGPT YSLDSACAST
ASSIHLACTS LLAKETDMAV AGAANVVGYP HSWTSLSKSG VLSDTGNCKT FRDDADGYCR
ADFVGTVVLK RLEDAIAHND NILAVVAASG RNHSGNSSSI TTSDAKAQEK LYRKMMHNAR
VSPNDISYVE MHGTGTKVGD PAEMGALASL FSHRRTPKPV VVGGVKANVG HSESKQAAGV
ASLLKCIMMF QKNILPPQAG MPHALNPNFP PLSEINIEIP SEPSTFESPV SQPRRILLNN
FDAAGGNACI LLEDFGNNMV KKSDPRVHHT VVTSSRTQAS YHGNKAKLLQ WLRQNPGARI
EDVAYTTTAR RTHHPIRFAV TASSTQELIS KLEADTADSP AAKESPVVFV FTGQGSHYAG
MGSELYETSP VFRETVNLCA TICEEQNFPP FLDLITQSDS EMSDKTTLEV QLAVLTLEIG
LAALWRSIGI QPSVVIGHSL GEYAALHVSG VLSLADVLYL VGQRALLILQ RCEVNTSAML
SVAMPVTDTH AFLEAQADPS CEIACVNSTN ASVISGSIEN ITELQAGLKA RSKMLSVPYG
FHSSQMDPIL ADYAALAGGV TFSEPKIPVA STLLASLVDT SGTFHAGYMA RQCRQPVNFV
GALEAIQSNY SDPIWLEIGP SQVCSSFVRA TLSPPPSKIL STLDKGTNAW LSLGKCMSSL
YKHGATIDWL ALHQPYVDNL SLLNLPTYAW DLKEFWIRYT ETKDQLPTST TNGHETFKAN
ISTCAQQVVE HISPPNMKVT FRASLSDPGF KALIDGHRLR DRSVCPGSVF SEAGLAAVTY
VLQLHHSKSL KLPALVLRNL SLKRPLTYDL VGPDGELITV VAPGGSSNDT FKVAWKASKG
NVSYSLGDCM VAACDGQLIQ ARWDKVSYFI RSRVDEIVAS SKSGISHRLQ PQILYGLFAN
TVKYDAAFKC IQEAYISSDF QEAAAVIVLN SDPVGTKFVA SPYWGESLVH LAGFVVNSNP
SRQSHDTTFM MDGFESFEQT VIPEPGKPYH TYVRVTGNES ASVVCDVYIF DDDKLIMHCA
GLHFHEVENA VLDQLLGGTN TSNTTRDQPA PIMSRKEVPK PVDTTEKVEA VSNDSQSDAH
VLDSILKIIS KETGSDLADF QDDTLIADLG VDSIMAIEIA SQVTEETGMD LLPSFIIDYP
AIGDLRRVFA PKSTHISLDN DLSRPSLVDD TSQALQSSGS ESFDQPPTSV TSTSDSGSIV
KIDLGPDVDS PAPKIKITLL QGRPGNGRTP FYLIADGTGT IATYIHLPQF KSQIPIYGID
SPFLRCPTRF TTDVGITGAA RFITEALMKA QPEGTFVLGG FSGGAMLAYE VCRQLAAANR
KVDSLMLIDM CSPRSKTVED KNDIGWAIFE SISRQNGLWR STDMTRQHLQ AIFAAVATYH
PQPLKASERP KRTAIIWAEK GMIDRCAGDS ELMQKLAKRG IPTEPYPKFM EDSELGPVAW
GLPHKTKNDL GPNGWERYVG DALCLSMPAD HLEMPMPGHV HLLHEKMTRA FEFFNEAG
//
