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   20-JUN-2018, entry version 38.
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)
OS   (Bakanae and foot rot disease fungus) (Fusarium fujikuroi).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina;
OC   Sordariomycetes; Hypocreomycetidae; Hypocreales; Nectriaceae;
OC   Fusarium; 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.,
RA   Bald T., Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M.,
RA   Brown D.W., Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U.,
RA   Gueldener U., Tudzynski B.;
RT   "Deciphering the cryptic genome: genome-wide analyses of the rice
RT   pathogen Fusarium fujikuroi reveal complex regulation of secondary
RT   metabolism and 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
RT   the silent trichosetin gene cluster in Fusarium fujikuroi.";
RL   Toxins 9:0-0(2017).
CC   -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster
CC       that mediates the biosynthesis of trichosetin, a trans-fused
CC       decalin-containing tetramic acid with antimicrobial activity
CC       (PubMed:28379186). The PKS module of PKS-NRPS1 together with the
CC       enoylreductase (ER) catalyze the formation of the polyketide unit
CC       which is then conjugated to L-serine by the condensation domain of
CC       the PKS-NRPS1 NRPS module (By similarity). Activity of the
CC       Dieckmann cyclase domain (RED) results in release of the
CC       intermediate N-desmethylequisetin also called trichosetin (By
CC       similarity). Diels-Alderase (DA) is involved in endo-selective
CC       Diels-Alder cycloaddition to form the decalin ring (By
CC       similarity). The cluster does not contain the equisetin N-
CC       methyltransferase and consequently, trichosetin is isolated as
CC       final product (PubMed:28379186).
CC       {ECO:0000250|UniProtKB:A0A0E4AZP0, ECO:0000269|PubMed:28379186}.
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
CC       (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP)
CC       and condensation (C) domains) which when grouped together are
CC       referred to as a single module. Each module is responsible for the
CC       recognition (via the A domain) and incorporation of a single amino
CC       acid into the growing peptide product (By similarity). Thus, an
CC       NRP synthetase is generally composed of one or more modules and
CC       can terminate in a thioesterase domain (TE) that releases the
CC       newly synthesized peptide from the enzyme (By similarity).
CC       Occasionally, epimerase (E) domains (responsible for l- to d-amino
CC       acid conversion) are present within the NRP synthetase (By
CC       similarity). EqxS contains also a polyketide synthase module (PKS)
CC       consisting of several catalytic domains including a ketoacyl
CC       synthase domain (KS), an acyl transferase domain (AT), a
CC       dehydratase domain (DH), a methyltransferase domain (MT), and a
CC       ketoreductase domain (KR) (PubMed:28379186). Instead of a
CC       thioesterase domain (TE), eqxS finishes with a reductase-like
CC       domain (R) for peptide release (PubMed:28379186). EqxS has the
CC       following architecture: KS-AT-DH-KR-PCP-C-A-T-R (PubMed:28379186).
CC       {ECO:0000250|UniProtKB:Q4WAZ9, ECO:0000305|PubMed:28379186}.
CC   -!- DISRUPTION PHENOTYPE: Completely abolishes trichosetin production
CC       (PubMed:28379186). {ECO:0000269|PubMed:28379186}.
CC   -!- SIMILARITY: Belongs to the NRP synthase family. {ECO:0000305}.
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DR   EMBL; HF679025; CCT65286.1; -; Genomic_DNA.
DR   ProteinModelPortal; S0DS59; -.
DR   EnsemblFungi; CCT65286; CCT65286; FFUJ_02219.
DR   OrthoDB; EOG092C004L; -.
DR   Proteomes; UP000016800; Chromosome 3.
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   Gene3D; 1.10.1200.10; -; 1.
DR   Gene3D; 3.30.559.10; -; 2.
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; IPR020845; AMP-binding_CS.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig.
DR   InterPro; IPR023213; CAT-like_dom_sf.
DR   InterPro; IPR001242; Condensatn.
DR   InterPro; IPR032821; KAsynt_C_assoc.
DR   InterPro; IPR018201; Ketoacyl_synth_AS.
DR   InterPro; IPR014031; Ketoacyl_synth_C.
DR   InterPro; IPR014030; Ketoacyl_synth_N.
DR   InterPro; IPR013120; Male_sterile_NAD-bd.
DR   InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR   InterPro; IPR013217; Methyltransf_12.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020801; PKS_acyl_transferase.
DR   InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR   InterPro; IPR020807; PKS_dehydratase.
DR   InterPro; IPR013968; PKS_KR.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR029063; SAM-dependent_MTases.
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; 2.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   SUPFAM; SSF53901; SSF53901; 2.
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   Complete proteome; Ligase; Methyltransferase; Multifunctional enzyme;
KW   Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW   Reference proteome; Repeat; Transferase.
FT   CHAIN         1   3914       Trichosetin synthetase PKS-NRPS1.
FT                                /FTId=PRO_0000443987.
FT   DOMAIN     2356   2436       Carrier 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00258}.
FT   DOMAIN     3502   3579       Carrier 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00258}.
FT   REGION        7    423       Ketosynthase (KS) domain.
FT                                {ECO:0000250|UniProtKB:S4W172,
FT                                ECO:0000255}.
FT   REGION      525    847       Malonyl-CoA:ACP transacylase (MAT)
FT                                domain. {ECO:0000250|UniProtKB:S4W172,
FT                                ECO:0000255}.
FT   REGION      913   1214       Dehydratase (DH) domain.
FT                                {ECO:0000250|UniProtKB:S4W172,
FT                                ECO:0000255}.
FT   REGION     1364   1593       Methyltransferase (MT) domain.
FT                                {ECO:0000250|UniProtKB:S4W172,
FT                                ECO:0000255}.
FT   REGION     2083   2255       Ketoreductase (KR) domain.
FT                                {ECO:0000250|UniProtKB:S4W172,
FT                                ECO:0000255}.
FT   REGION     2529   2956       Condensation (C) domain.
FT                                {ECO:0000250|UniProtKB:S4W172,
FT                                ECO:0000255}.
FT   REGION     2991   3388       Adenylation (A) (KR) domain.
FT                                {ECO:0000250|UniProtKB:S4W172,
FT                                ECO:0000255}.
FT   REGION     3615   3831       Reductase (RED) domain.
FT                                {ECO:0000250|UniProtKB:S4W172,
FT                                ECO:0000255}.
FT   ACT_SITE    177    177       {ECO:0000255|PROSITE-ProRule:PRU10022}.
FT   MOD_RES    2396   2396       O-(pantetheine 4'-phosphoryl)serine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00258}.
FT   MOD_RES    3539   3539       O-(pantetheine 4'-phosphoryl)serine.
FT                                {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
//