EQXS_FUSHE
ID EQXS_FUSHE Reviewed; 3948 AA.
AC S4W172;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2013, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Equisetin synthetase eqxS {ECO:0000303|PubMed:23614392};
DE EC=2.3.1.- {ECO:0000269|PubMed:18652469};
DE EC=6.3.2.- {ECO:0000269|PubMed:18652469};
DE AltName: Full=Equisetin biosynthesis protein S {ECO:0000303|PubMed:23614392};
DE AltName: Full=Hybrid PKS-NRPS synthetase eqxS {ECO:0000303|PubMed:23614392};
GN Name=eqxS {ECO:0000303|PubMed:23614392};
GN Synonyms=eqiS {ECO:0000303|PubMed:18652469};
OS Fusarium heterosporum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium heterosporum species complex.
OX NCBI_TaxID=42747;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DOMAIN, AND PATHWAY.
RC STRAIN=ATCC 74349 / MF6069;
RX PubMed=23614392; DOI=10.1021/cb400159f;
RA Kakule T.B., Sardar D., Lin Z., Schmidt E.W.;
RT "Two related pyrrolidinedione synthetase loci in Fusarium heterosporum ATCC
RT 74349 produce divergent metabolites.";
RL ACS Chem. Biol. 8:1549-1557(2013).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND DOMAIN.
RX PubMed=18652469; DOI=10.1021/ja803078z;
RA Sims J.W., Schmidt E.W.;
RT "Thioesterase-like role for fungal PKS-NRPS hybrid reductive domains.";
RL J. Am. Chem. Soc. 130:11149-11155(2008).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of equisetin, a trans-fused decalin-
CC containing tetramic acid with antimicrobial activity (PubMed:23614392).
CC The PKS module of eqxS together with the enoylreductase eqxC catalyze
CC the formation of the polyketide unit which is then conjugated to L-
CC serine by the condensation domain of the eqxS NRPS module
CC (PubMed:23614392). Activity of the Dieckmann cyclase domain (RED)
CC results in release of the Dieckmann product intermediate
CC (PubMed:23614392, PubMed:18652469). Diels-Alderase eqx3 is involved in
CC endo-selective Diels-Alder cycloaddition to form the decalin ring,
CC leading to the production of N-desmethylequisetin also called
CC trichosetin (By similarity). Subsequent N-methylation is carried out by
CC eqxD to give equisetin (PubMed:23614392).
CC {ECO:0000250|UniProtKB:A0A0E4AZP0, ECO:0000269|PubMed:18652469,
CC ECO:0000269|PubMed:23614392}.
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:0000269|PubMed:18652469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67325;
CC Evidence={ECO:0000269|PubMed:18652469};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:23614392}.
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:23614392). Instead of a thioesterase domain (TE), eqxS finishes
CC with a reductase-like domain (R) for peptide release (PubMed:23614392).
CC EqxS has the following architecture: KS-AT-DH-KR-PCP-C-A-T-R
CC (PubMed:23614392). {ECO:0000250|UniProtKB:Q4WAZ9,
CC ECO:0000305|PubMed:23614392}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; KC439347; AGO86662.1; -; Genomic_DNA.
DR SMR; S4W172; -.
DR BioCyc; MetaCyc:MON-19331; -.
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; -; 2.
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; IPR025110; AMP-bd_C.
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; PF13193; AMP-binding_C; 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; 2.
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; 1.
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 1: Evidence at protein level;
KW Ligase; Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT CHAIN 1..3948
FT /note="Equisetin synthetase eqxS"
FT /id="PRO_0000441289"
FT DOMAIN 2389..2464
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3540..3617
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 7..441
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23614392"
FT REGION 543..847
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23614392"
FT REGION 931..1233
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23614392"
FT REGION 1376..1574
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23614392"
FT REGION 2105..2277
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23614392"
FT REGION 2480..2553
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2564..2991
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23614392"
FT REGION 3026..3424
FT /note="Adenylation (A) (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23614392"
FT REGION 3653..3870
FT /note="Reductase (RED) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:23614392"
FT COMPBIAS 2480..2532
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 2424
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3577
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3948 AA; 435334 MW; AB825042AEC50CF6 CRC64;
MDASEPIAVI GSACRFPGGS DSPSKLWELL KEPRDLLSKV PPERYNADAF YHADATHHGT
ANVRHSYFLS EDPSSFDNNF FNIQPGEAEA IDPQQRLLME VVYQGLCSAG QTIEGLRGSP
TAVYVGVMCD DWSGIITRDL EVFPRYGATG MARSIMSNRI SYFFDWHGPS MTIDTACSSS
LVAVHQAIQT LRSGESEVAI AAGANLILTP GMYVAESKLS MLSPSGRSKM WDQDVDGYAR
GEGIAAVVLK PLSAAIRDND HIDCIIRATG VNQDGRTPGL TMPSATAQAD LIRSTYARAG
LDINKAEDRP QFFHAHGTGT PAGDPREAEA ISRAFYSPDN LSKDDKLYVG SIKTIIGHTE
GTAGLASLIG TSLAIQSKVI PPNMHLDVLN PKVAPFYNNL EVPTSALEWP ETRSGQPRRA
SINSFGFGGT NAHAIIEAYE PNAAARASGT LFSPLTFSAS SEPSLRFLLM SYSEHLKLNP
QIPLKDLAYS LQTRRSTLAY RVAITATTAE NASKQLDAIV DGEQSSSINT RQLSKSSPKI
LGIFTGQGTQ WPRMGARLLE ESPFASKRLA ELDDALSSLP ADDRPTWTLR EMILANADRS
RVAEAAISQP LCTAVQVVLV DLLSQAGIQL SAVVGHSSGE IGAAYAAGLL TARDAIRVAY
YRGLYAKLAQ SPNGHKGAMM AVGTTFGDAA DFCELEAFQG RIQIAAKNSP SSITLSGDKD
AIIEAIEIFK DEGKFARQLK VDTAYHSSHV IPCAQPYLEA MNKCGIETAT ATKTQWYSSV
HGGQIMHADS LTTSYWVDNM TSAVLFSPAV AQAWEEGGPY DLAIEVGPHP ALKTPALDTI
EAISEGRPPY TGVIARGKDD VQQFSTALGF IWTHLGPGSV AFEKFESVVS GSKDRPSFIQ
DLPNYPFDHA KQFMSMSRVS GWFNSIQEAP HPLLGRRCHD RETSHSVQWR NVLSHKEIPW
LQGHQLQGQI IFPATGYISM AVEAIKILAE PSSLGLITIE DLNITRALAF VDEDASVETL
FELRILSRSE NEINAEFCCY SGIPHTHTAT MSLNATAQIK ASLGAPTSDK LSKTAVNDFD
LRPVSVDRFY DFLARLGYNY SWPFRGTTSI RRKANFATGT LEDQSGSNWE DQLMVHPGML
DSSLQTTFAA FCCPGDERLW ALHLPTSFRS ITINPYFTSA GIGKQNSFTY QSVAIEERKA
SKVLVELNLL SEEAGDTFLQ IEGMELVPFS PATPANDAVL FSRFDYRLAG PDGELTAAEY
SFKPEDYKMA LDCERIAFYY LRRLVETITP EERANTLLHY RHLVDWAAYV VPQVSNGGNP
HIPASAQNDT HDDIQQLLKK HYERVDIRLL ESVGENLPQV IRDSGNILEH MTKDGMLQDV
YEQGFGLNLV NQYIAHMTAQ IAHRYPRMNI LEIGAGTGGS TREILPRLGS AFSTYTYTDV
SGGFFDMAQD RFKDCADRMI FKTFDMNISP ASQGFTEGAY DLVIASNVLH ATLELEDMMK
HVRSFLKPGG FLIILETVNN DCLRVGLPMG SLPGWWLGAE HGRQWGPTLT LPQWDSLLSK
CGFGGIDTTT PPVHKILPGH VFCAQALDER IEILRSPMDH LATLPETKST QLAIIGGQTL
KVHRMCDQIS RRLSSRYTSI SRFHSIEEIN ETGLPESCTV LSLTELDEPL FTNMTSGKLD
ALKILWKQGG CILWITSGSR AENPHSYMTT GVGRCMRFEY PNITLQALDI KQISDRCPEL
IVDHLLRLEI LDKWSKELRS DELLWSLEPE IYIEEDTTII PRLYPYEAGN ARYNAERRKV
IKQADTKTDR VIFAECEGKW EIQHASPLHV ARELPFSSDV STRTIRITHL SPAIVNIVPG
VSVMACAGVD TASNEPVIAV THIAESPVSI PTGWCIHLDK LDPVKTLTAV SAVLIASSIL
ERLAKGETLV VHDTPPHVRV ALDKLAKTAS VAIFYTSSDE AMSKLGARYI DRRSPLRVIK
ASLPKSASKF IDLSQDSDKN ETSKVISMCL PWDYETIDTA HLFGLRNVAQ QSAFEKDVSS
SLKKAFEAFN SQLNTTASTN SVSLKETSNP IVDQVRFAIL DCTDTPIQAS VHPIDDGRIF
RADKTFLLVG LTGELGQSLC KWMVEQGARN IVLTSRRPNV SEHFLDSFTE TGATVKALPM
DATNRSSIEA CLETIKKTSP PIAGVVNGAM VLRDALFENM PYEDFIKVLN PKVLGSQLLD
EMFYDTPLDF FIFFSSTTAV MGNSGQSNYI AGNMYMNALA AQRKKRGVAA SSIDISSIIG
LGYVERAEDL SEDTFIKMGY KPMSEQDLQK LFAEAIVLGR PDCHEVCELV TGVTPIYTDA
QASDQYLKDV KFGHFLMERL DTQAYTGKTS TVPVRVQLAD VKIRADAVAI IKESFIVRLR
RVLAVGPDEV INEKVTLVEQ GVDSLMAVEV RSWFIKELDV DIPVLKILGG MSVPDLVDEC
LDLLSPSILD VSSLEAGNAQ AAKPTTVIPQ TPTRVTPPES SQGTSDQDKP YTGSDSSHSP
IGTPLTSWDR QDSSPPDKSD DAPNSTDILA PPRTFPNELS SIMSYGQAGF WFLNDYLVNK
KAFNMAVMLK LTGPIRTQPL EKAVKLVAER HEILRTRFFW SEDGDERTPM QGINPPEMKL
TVKTIADEEE AETELEHLHE ENWELSSGEG VKVILLRLSD QVHFLLSGMH HIYLDGYSFS
VFFKDLESAY INHRLPPLPV ESQYRTFALQ QRKAYEDGDL LKSIEYYRQN FPQEFAPIRP
FPFASTGSRQ LANEYSQHEA KLSIAPDVSA KIRQLARANR STSFHVYLAA LKILLFSLLP
DAEELFIGIA DANRGDKKFM GSLGFFLNVL PLRFQRGKPR SRVSSAIQSA RDAVYGALQH
SHLPFDVLLR ELNVPRSDKH TPIFQVFMDY RQVVQERSSW GGCKLSDEKW CNAGTGYDIA
LEVTENINTD TLLSLRLQKQ LYSEEHTQVL LRSYLNVLEY MIRGSDKTVD AAPAWSDHDL
QVAVDAGKAP DYESKWQPTV SHQIDQVIQD NPDNIALKDG NGNVLTYVQM GNRIDAISKA
LIDAGTVQGT VVGVFQEPST DWICSLLAIF KAGAVYVPLD LRNSIPRLAS IVKASRPSVI
ITDSTTDEKV ESIGAKFVTK LQLDGLNPMI HHDSIEINHA KAGYLAVILF TSGSTGEPKG
LMMTHTNLLA YAEVSSKTFA RADEDLVVLQ QSPFSFDFSL DQTMAALTNG GCLYVVPASK
RGDPDEISKI MVEESVTYTT ATPSEYDLWL RYSAETLRQC TSWKYAFSGG EAMSYKLARE
FGTLKLRNLH VFNGYGPAET TILSHRIDLK YTDPDLPDPL PAGYPLPGFA VCIVDNKMRP
VPPGVQGEIV LGGPCIVSGY LNMPESTRDK FLPDTFFGTS GTVYRSGDRG RLCQDGLLFC
DGRLEGNRMI KLRGFRVELD EVEKTIVSHS AGALSHAVVT VRGAEEGRYL VAHVVFAPDF
PEKDREGTMR SLRQTLPLPP YMRPSAFQVL TDIPRTAHLK IDRKAIQDIP VQTTQSEVSE
ILTPSEQRLS ELWRRVLPLD PGTLTHESDF FLIGGNSILL VKLQTLLRQV SWTAPKLVTL
MGSSTLGAMA GVLEDCGPVN IIHWDEETKF PQDLQLTTPL RAAGKSTDIT VLLTGSSGYL
GRHLLSSLLN DHRVAQVHCL CRNLNDHQVV ENPSSKVRVL QSDLAQHKLG LPDSTYSQLA
TEVDVIIHCA ANRSFWDRYE ALKADNLEST KELVKLVVSS GRAIPLHFLS SGAVIKYNSG
LAPPADGGDG YVATKWASEA FLRQAVDSIN LPVFSHRPVA CESVQQSEEE DISILNELIQ
IVKLLGCRPS FDGVGGFVDV MPVNEVVEAI HKTGLNSQTE EGFCILEHKA HQRAYVKSFA
AAVESDSDLS KIPCIPILEW FGRTKKAGFS YFLASQDLIL GSQLFSRR
