EQXS_GIBF5
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 03-AUG-2022, entry version 52.
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}.
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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 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; 3.30.300.30; -; 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; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
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; SSF47336; 2.
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; PS00455; AMP_BINDING; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
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 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 7..423
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000250|UniProtKB:S4W172, ECO:0000255"
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
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
