ID EQXS_GIBF5 Reviewed; 3914 AA. AC S0DS59; DT 25-APR-2018, integrated into UniProtKB/Swiss-Prot. DT 18-SEP-2013, sequence version 1. DT 14-DEC-2022, entry version 53. DE RecName: Full=Trichosetin synthetase PKS-NRPS1 {ECO:0000303|PubMed:28379186}; DE EC=2.3.1.- {ECO:0000305|PubMed:28379186}; DE EC=6.3.2.- {ECO:0000305|PubMed:28379186}; DE AltName: Full=Hybrid PKS-NRPS synthetase 1 {ECO:0000303|PubMed:28379186}; DE AltName: Full=Trichosetin biosynthesis cluster protein PKS-NRPS1 {ECO:0000303|PubMed:28379186}; GN Name=PKS-NRPS1 {ECO:0000303|PubMed:28379186}; ORFNames=FFUJ_02219; OS Gibberella fujikuroi (strain CBS 195.34 / IMI 58289 / NRRL A-6831) (Bakanae OS and foot rot disease fungus) (Fusarium fujikuroi). OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes; OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium; OC Fusarium fujikuroi species complex. OX NCBI_TaxID=1279085; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=CBS 195.34 / IMI 58289 / NRRL A-6831; RX PubMed=23825955; DOI=10.1371/journal.ppat.1003475; RA Wiemann P., Sieber C.M.K., von Bargen K.W., Studt L., Niehaus E.-M., RA Espino J.J., Huss K., Michielse C.B., Albermann S., Wagner D., RA Bergner S.V., Connolly L.R., Fischer A., Reuter G., Kleigrewe K., Bald T., RA Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M., Brown D.W., RA Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U., Gueldener U., RA Tudzynski B.; RT "Deciphering the cryptic genome: genome-wide analyses of the rice pathogen RT Fusarium fujikuroi reveal complex regulation of secondary metabolism and RT novel metabolites."; RL PLoS Pathog. 9:E1003475-E1003475(2013). RN [2] RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE. RX PubMed=28379186; DOI=10.3390/toxins9040126; RA Janevska S., Arndt B., Baumann L., Apken L.H., Mauriz Marques L.M., RA Humpf H.U., Tudzynski B.; RT "Establishment of the inducible Tet-On system for the activation of the RT silent trichosetin gene cluster in Fusarium fujikuroi."; RL Toxins 9:0-0(2017). CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that CC mediates the biosynthesis of trichosetin, a trans-fused decalin- CC containing tetramic acid with antimicrobial activity (PubMed:28379186). CC The PKS module of PKS-NRPS1 together with the enoylreductase (ER) CC catalyze the formation of the polyketide unit which is then conjugated CC to L-serine by the condensation domain of the PKS-NRPS1 NRPS module (By CC similarity). Activity of the Dieckmann cyclase domain (RED) results in CC release of the Dieckmann product intermediate (By similarity). Diels- CC Alderase (DA) is involved in endo-selective Diels-Alder cycloaddition CC to form the decalin ring, leading to the production of N- CC desmethylequisetin also called trichosetin (By similarity). The cluster CC does not contain the equisetin N-methyltransferase and consequently, CC trichosetin is isolated as final product (PubMed:28379186). CC {ECO:0000250|UniProtKB:A0A0E4AZP0, ECO:0000269|PubMed:28379186}. CC -!- CATALYTIC ACTIVITY: CC Reaction=acetyl-CoA + ATP + 11 H(+) + L-serine + 7 malonyl-CoA + 8 CC NADPH + 2 S-adenosyl-L-methionine = (5S)-3-[(2E,6R,8E,10E,12E)-2,6- CC dimethyltetradeca-2,8,10,12-tetraenoyl]-5-(hydroxymethyl)pyrrolidine- CC 2,4-dione + AMP + 7 CO2 + 8 CoA + diphosphate + 6 H2O + 8 NADP(+) + 2 CC S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:67324, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:33384, ChEBI:CHEBI:57287, CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:58349, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:169938, ChEBI:CHEBI:456215; CC Evidence={ECO:0000250|UniProtKB:A0A0E4AZP0}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67325; CC Evidence={ECO:0000250|UniProtKB:A0A0E4AZP0}; CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:28379186}. CC -!- INDUCTION: Expression is positively regulated by the trichosetin CC cluster-specific transcription activator TF22 (PubMed:28379186). CC {ECO:0000269|PubMed:28379186}. CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation CC (C) domains) which when grouped together are referred to as a single CC module. Each module is responsible for the recognition (via the A CC domain) and incorporation of a single amino acid into the growing CC peptide product (By similarity). Thus, an NRP synthetase is generally CC composed of one or more modules and can terminate in a thioesterase CC domain (TE) that releases the newly synthesized peptide from the enzyme CC (By similarity). Occasionally, epimerase (E) domains (responsible for CC l- to d-amino acid conversion) are present within the NRP synthetase CC (By similarity). EqxS contains also a polyketide synthase module (PKS) CC consisting of several catalytic domains including a ketoacyl synthase CC domain (KS), an acyl transferase domain (AT), a dehydratase domain CC (DH), a methyltransferase domain (MT), and a ketoreductase domain (KR) CC (PubMed:28379186). Instead of a thioesterase domain (TE), eqxS finishes CC with a reductase-like domain (R) for peptide release (PubMed:28379186). CC EqxS has the following architecture: KS-AT-DH-KR-PCP-C-A-T-R CC (PubMed:28379186). {ECO:0000250|UniProtKB:Q4WAZ9, CC ECO:0000305|PubMed:28379186}. CC -!- DISRUPTION PHENOTYPE: Completely abolishes trichosetin production CC (PubMed:28379186). {ECO:0000269|PubMed:28379186}. CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase CC family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; HF679025; CCT65286.1; -; Genomic_DNA. DR SMR; S0DS59; -. DR STRING; 5127.CCT65286; -. DR EnsemblFungi; CCT65286; CCT65286; FFUJ_02219. DR VEuPathDB; FungiDB:FFUJ_02219; -. DR HOGENOM; CLU_000022_37_4_1; -. DR Proteomes; UP000016800; Chromosome 3. DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro. DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW. 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 Gene3D; 1.10.1200.10; -; 1. DR Gene3D; 3.10.129.110; -; 1. DR Gene3D; 3.30.300.30; -; 1. DR Gene3D; 3.30.559.10; -; 1. DR Gene3D; 3.40.366.10; -; 1. DR Gene3D; 3.40.47.10; -; 1. DR Gene3D; 3.40.50.12780; -; 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; IPR045851; AMP-bd_C_sf. DR InterPro; IPR020845; AMP-binding_CS. DR InterPro; IPR000873; AMP-dep_Synth/Lig. DR InterPro; IPR042099; ANL_N_sf. DR InterPro; IPR023213; CAT-like_dom_sf. DR InterPro; IPR001242; Condensatn. DR InterPro; IPR013120; Far_NAD-bd. 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; IPR042104; PKS_dehydratase_sf. DR InterPro; IPR020807; PKS_DH. DR InterPro; IPR013968; PKS_KR. DR InterPro; IPR020806; PKS_PP-bd. DR InterPro; IPR009081; PP-bd_ACP. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR InterPro; IPR016039; Thiolase-like. DR Pfam; PF00698; Acyl_transf_1; 1. DR Pfam; PF00501; AMP-binding; 1. DR Pfam; PF00668; Condensation; 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; PF07993; NAD_binding_4; 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; SM00825; PKS_KS; 1. DR SMART; SM00823; PKS_PP; 2. DR SUPFAM; SSF47336; ACP-like; 2. DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 2. DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR SUPFAM; SSF53901; Thiolase-like; 1. DR PROSITE; PS00455; AMP_BINDING; 1. DR PROSITE; PS50075; CARRIER; 2. DR PROSITE; PS00606; KS3_1; 1. DR PROSITE; PS52004; KS3_2; 1. PE 2: Evidence at transcript level; KW Ligase; Methyltransferase; Multifunctional enzyme; Oxidoreductase; KW Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat; KW Transferase. FT CHAIN 1..3914 FT /note="Trichosetin synthetase PKS-NRPS1" FT /id="PRO_0000443987" FT DOMAIN 4..420 FT /note="Ketosynthase family 3 (KS3)" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" FT DOMAIN 2356..2436 FT /note="Carrier 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258" FT DOMAIN 3502..3579 FT /note="Carrier 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258" FT REGION 525..847 FT /note="Malonyl-CoA:ACP transacylase (MAT) domain" FT /evidence="ECO:0000250|UniProtKB:S4W172, ECO:0000255" FT REGION 913..1214 FT /note="Dehydratase (DH) domain" FT /evidence="ECO:0000250|UniProtKB:S4W172, ECO:0000255" FT REGION 1364..1593 FT /note="Methyltransferase (MT) domain" FT /evidence="ECO:0000250|UniProtKB:S4W172, ECO:0000255" FT REGION 2083..2255 FT /note="Ketoreductase (KR) domain" FT /evidence="ECO:0000250|UniProtKB:S4W172, ECO:0000255" FT REGION 2447..2518 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2529..2956 FT /note="Condensation (C) domain" FT /evidence="ECO:0000250|UniProtKB:S4W172, ECO:0000255" FT REGION 2991..3388 FT /note="Adenylation (A) (KR) domain" FT /evidence="ECO:0000250|UniProtKB:S4W172, ECO:0000255" FT REGION 3615..3831 FT /note="Reductase (RED) domain" FT /evidence="ECO:0000250|UniProtKB:S4W172, ECO:0000255" FT COMPBIAS 2447..2497 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 177 FT /note="For beta-ketoacyl synthase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" FT ACT_SITE 301 FT /note="For beta-ketoacyl synthase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" FT ACT_SITE 340 FT /note="For beta-ketoacyl synthase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348" FT MOD_RES 2396 FT /note="O-(pantetheine 4'-phosphoryl)serine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258" FT MOD_RES 3539 FT /note="O-(pantetheine 4'-phosphoryl)serine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258" SQ SEQUENCE 3914 AA; 431704 MW; F792FA1A3D555151 CRC64; MSDNEPIAII GSACRFPGDS SSPSKLWDLL KSPRDLLTKV PPNRYNADAF YHADSKHHGT TNVRHSYFLN EDPARFDNNF FNIQPGEAEA IDPQQRLLME VVYQGLCASG QTIEGLRGSP TAVYVGVMCD DWSGIITRDL EVFPQYGATG MARSIMSNRI SYFFDWHGPS MTIDTACSSS LVAVHQAIQT LRSGESEVAI AAGANLILTP GRSKMWDQDV NGYARGEGIA AVVLKPLSAA IRDNDHIDCI IRATGVNQDG RTPGLTMPSA TAQADLIRST YARAGLDINK PEDRPQFFHA HGTGTPAGDP REAEAIYRAF YSDVKDDKLY VGSIKTVLGH TEGTAGLASL IGTALAIQNK TIPPNMHFDV LNPKIKPFYD NLEVPTKAIA WPETHKGQPR RASINSFGFG GTNAHAIIEA YEPATTDSAP GPLFSPLTFS ASSEPSLRSL LSSYSDHLKS NPDLSLKDLA YTLQTRRSTL AYRVAITASD VEDAYTQLDT IGNGEQSSTI GVRQVTKASP KIMGVLTGQG AQWPRMGARL VEESAFASQR LFELDEALSS LPKDDRPSWT LREMILADSK SSRIAEAAIS QPLCTAVQVV LVDLLRQAGV ELSSVVGHSS GEIGAAYAAG LLTARDAIRV AYYRGLYAKL AQSPNGRKGA MMAVGTTFDD ASEFCELDAF QGRIQVAARN SSSSITLSGD EDAIVEAIET FKDEGKFARQ LKVDTAYHSA HVLPCAKPYL DAMERCQIES ANPTSTKWYS SVHDGQAMTA ELLTPQYWVD NMTSAVLFSP AVEHAWREGG PYDVIIEVGP HPVLKTPCLD TLEDMTGDRP PYSGVLGREK DDIQQFASGL GFIWTQLGAG SATFERFEKV ASDSKSIPSF IHDLPNYPFD HARQFMSMSR VSGWYNSMQE APHPILGRRC HDRETSQTIQ WRNVLNPKEI PWLHGHQIQG QIIFPATGYI SMAIEAVNII AGSDLGLVTI EDLRIGRALA FSDDDASVES MFDLRIISRS EKEIEAEFSC YSGLPQNHTT SMVLNATAHV KASLSVPTAQ KLPNLKIDDF NLRKVEVDRF YDFLGRLGYN YSWPFHGTTS IRRKANYATG TLEDQSGSEW EDQLLVHPGM LDTSLQTTFA AFCCPGDERM WALHLPTSFR SIVVNPYFTS AGIGKQKSFQ YQSVAIQERK ASKVIVELNL LSEETGDTFL QIEGMELVPF SPATPENDAV LFSRFDYRLA SPDGELTAAE YSFRDEDYKM ALDSERIAFY YLRRLVETIT PEDKANTLPH YRHLVEWAAH VVPQVIDGRN PHIPSSAQKD THEDIQNILK KHYERVDVRL LESVGENLPQ VIRENGNILE HMTKDGMLDD VYEEGFGLDL VNKYIAHMTA QIAHRYPRMN ILEIGAGTGG STREILPRLG SAFSTYTYTD VSGGFFDTAQ DRFKDYAERM IFKTFDMNIS PGSQGFTEGT YDLVIASNVL HATLELEDMM KHVRSFLKPG GFLIILETVN NDCLRVGLPM GSLPGWWLGA EHGRRWGPTL TLPQWDSLLW KCGFGGIDTT TPPVHKILPG HVFCAQALDD RVEILRSPLS HLSDLPETKS TELVIVGGET LKVHRMCEQI SRRLKPKYAS IARFNSIEEL NTSGLADSCA VVSLTELDEP LFANMTSDKL DALKTLWKQG GSILWVTSGA RDENPYSYMT TGVGRCMRFE YPNITLQALD IKAMTDRTPG LVAEHLLRLE LLDKWSKELR PEELLWSLEP EIYVDDDTTI VPRLYPYESG NARYNAERRN IVEDADLQTD RVIFVENEGK WEVQHASPLH IPQELPFASK MKTIRITHFS PATINFAPGV SLMVCAGIDA ASGERLLAVT HVAESPISVP ADWCIPLGEL DGVDTLANVS AFLIASSILK HVATEETLVV HGAPSRLASA LEGLAKESSI TVFLTTSERA NKNGWQYIDS HLPERVIKAS IPRSATKFIN LSQDANMGET GRAISACLPR YCEVINTERL FIWGKLIRES VSKEDISIVF NRAFYETKSL SSTATDARLI SLQDVSGVSA AEVRFAVVDC IDSSVKASIR PIDDGRIFQA DKTFLLIGLS GELGQSLGKW MVEQGARNIV LTSRRPNVSQ HFLDEMATMG ATVKALPMDV TNRDSLHACV DTIQKTLPPI AGVVNGAMVL RDALFENMPY EDFMKVLSPK VLGSQLLDEL FYDTPLDFFI FFSSTTAVMG NSGQSNYIAG NMFMNALAAQ RKKRGVAASS IDISSIIGLG YVERAEDLSE DTFIKMGYKP MSEQDLQKLF AEAIVLGRPE CDEVCELVTG VTPIYTDAQA SDQYLKDVKF GHFLMERLDT QAYTGKTSTV PVRVQLADVK TKADAVAIIK GMFSLLTPVI IADLERFLHF EQGVDSLMAV EVRSWFIKEL DIDIPVLKIL GGMSVPDLIE ESLNLISDSI LDVSSLEAGS TPTTQPPKPT LQIARVTPPE SSHGTSDDSK QQTGSDSSRS PIDTPLTSME IQEPAKAEDS TDNSTPLKTF PNELSSIMSY GQAGFWFLND YLVNKRAFNM AVMLKLTGQV RVQALEKAVN LVAERHEVLR TRFFWGDDGD ERTPLQGINP ADLKLTTKKV ADESEAGMEL KKLHDEEWDL SRGEGVKITL LSLSDNVHFL LLGMHHIYID GYSFSVFFKD LEVAYTKNTL PSLPVESQYR SFALQQRQMY ANGNLTKSIE YYRRSFPKEF SPIQLFPFAL TPARQFANDY SQHEAKMSID PELAPKVRQL ARVNRSTSFH VYLAALELLL FTLLPNIEEV FIGIADANRG DKKFMGSLGF FLNLLPLRFR RKRRGTQLSS IIQTARDTAY GALQHSQLPF DVLLRELNVP RSDKYTPIFQ VFMDYRQVVQ ERSSWGGCKL HGEKWHNAGT GYDIALEVNE NITTDTLLGL RLQKQLYSEE HTALLLRSYL SVLEYMVQGT NKAADTVPPW SKDDIQVALD AGKAPEFQPK WQSTISHHID QTIQANSTKV ALKDGNGTVL TYEQMGNRVN SITQALIDAG TTQGTVVGVF QEPSSDWICS LLAIFKAGAV YVPLDLRNSI PRLASIVKAS RPSLIITDHT TDDKVELIGA KYITQLQLSK VVDQEFKEPN RAKVGSLAVI LFTSGSTGEP KGLMMTHTNL MSYAEVSSKT FSKPDESLMV LQQSPFSFDF SLDQTVAALA NGGCLCIVPA SKRGDPDEIS KIMVKEGVTY TTATPSEYDL WLRYSTSTLR QCTSWKYAFS GGEAMSHKLA REFGTLSLKN LHVFNGYGPA ETTILSHRID LQYTDPDLPD PLPAGCPMPG FSVCIVDEKM RPVPLGVQGE IVLGGPCIVS GYLSMPDATK DKFLPDTFFG TSGKVYRSGD RGRLCHDGLL FCDGRLEDSN MIKLRGFRVE LDEVEKTIIS HSAGTLSHAV VTLRGTEEGR YLAAHVVFAP EFPEQNRESI MKTLRQTLPL PPYMRPSVFQ ILADIPRTAH LKVDRKAIQE MPVQISASHD SGTLTVAEQR LSELWRRVLP LDPGSLSPES DFFLIGGNSI LLVKLQALLR QTFKTAPKLV ALMGASTLGT MAVVLESCGS VGVIDWDQET ALPNGLQGAV ALRPVNKITD ITVLLTGSAG YLGRHLVPAL VEDPRVTRVH CLVRSVNNEK LSTSSSSKVR VIESDLSKPG LGLSASTYSR LAEETDVIIH SAANRSFWDR YEVLKPDNLD SVKELVRFAA SSGRSIPLHF LSSGAVKIYD GDVVTPPTDG SDGYVATKWA SETFLRNAAG SIGLPVYAHR PTVSSKAQTK TDQASIVDEL FSIVKFLGVR PSFEGVTGSV DVLPTGDIVK AIQDSVLSSS AGGEGYNVLQ HEAHQRAFVE DFAGVVRADD SLNKLPSISI LDWFGKAKKA GFSYFLASQN LVMGEGEGHL VSRR //