TAS1_MAGO7
ID TAS1_MAGO7 Reviewed; 1728 AA.
AC G4N137;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Hybrid PKS-NRPS synthetase TAS1 {ECO:0000303|PubMed:26503170};
DE EC=6.3.2.50 {ECO:0000269|PubMed:26503170, ECO:0000269|PubMed:32565425};
DE AltName: Full=Tenuazonic acid biosynthesis cluster protein 1 {ECO:0000303|PubMed:28820236};
DE AltName: Full=Tenuazonic acid synthetase 1 {ECO:0000303|PubMed:26503170};
GN Name=TAS1 {ECO:0000303|PubMed:26503170}; ORFNames=MGG_07803;
OS Magnaporthe oryzae (strain 70-15 / ATCC MYA-4617 / FGSC 8958) (Rice blast
OS fungus) (Pyricularia oryzae).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Magnaporthales; Pyriculariaceae; Pyricularia.
OX NCBI_TaxID=242507;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=70-15 / ATCC MYA-4617 / FGSC 8958;
RX PubMed=15846337; DOI=10.1038/nature03449;
RA Dean R.A., Talbot N.J., Ebbole D.J., Farman M.L., Mitchell T.K.,
RA Orbach M.J., Thon M.R., Kulkarni R., Xu J.-R., Pan H., Read N.D.,
RA Lee Y.-H., Carbone I., Brown D., Oh Y.Y., Donofrio N., Jeong J.S.,
RA Soanes D.M., Djonovic S., Kolomiets E., Rehmeyer C., Li W., Harding M.,
RA Kim S., Lebrun M.-H., Bohnert H., Coughlan S., Butler J., Calvo S.E.,
RA Ma L.-J., Nicol R., Purcell S., Nusbaum C., Galagan J.E., Birren B.W.;
RT "The genome sequence of the rice blast fungus Magnaporthe grisea.";
RL Nature 434:980-986(2005).
RN [2]
RP FUNCTION, DOMAIN, INDUCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=26503170; DOI=10.1038/ncomms9758;
RA Yun C.S., Motoyama T., Osada H.;
RT "Biosynthesis of the mycotoxin tenuazonic acid by a fungal NRPS-PKS hybrid
RT enzyme.";
RL Nat. Commun. 6:8758-8758(2015).
RN [3]
RP FUNCTION, AND INDUCTION.
RX PubMed=28820236; DOI=10.1021/acschembio.7b00353;
RA Yun C.S., Motoyama T., Osada H.;
RT "Regulatory mechanism of mycotoxin tenuazonic acid production in
RT Pyricularia oryzae.";
RL ACS Chem. Biol. 12:2270-2274(2017).
RN [4]
RP FUNCTION, AND INDUCTION.
RX PubMed=32765467; DOI=10.3389/fmicb.2020.01641;
RA Ninomiya A., Urayama S.I., Suo R., Itoi S., Fuji S.I., Moriyama H.,
RA Hagiwara D.;
RT "Mycovirus-induced tenuazonic acid production in a rice blast fungus
RT Magnaporthe oryzae.";
RL Front. Microbiol. 11:1641-1641(2020).
RN [5] {ECO:0007744|PDB:6KOG}
RP X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) OF 1258-1690, FUNCTION, DOMAIN,
RP ACTIVE SITE, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF CYS-1436;
RP HIS-1579; SER-1581; ASN-1633 AND GLU-1635.
RX PubMed=32565425; DOI=10.1074/jbc.ra120.013105;
RA Yun C.S., Nishimoto K., Motoyama T., Shimizu T., Hino T., Dohmae N.,
RA Nagano S., Osada H.;
RT "Unique features of the ketosynthase domain in a nonribosomal peptide
RT synthetase-polyketide synthase hybrid enzyme, tenuazonic acid synthetase
RT 1.";
RL J. Biol. Chem. 295:11602-11612(2020).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of the toxin tenuazonic acid (TeA), an
CC inhibitor of protein biosynthesis on ribosomes by suppressing the
CC release of new protein (PubMed:26503170, PubMed:28820236,
CC PubMed:32765467, PubMed:32565425). TAS1 alone is sufficient for TeA
CC synthesis via the condensation of isoleucine (Ile) with acetoacetyl-CoA
CC by the N-termainal NRPS module and subsequent cyclization conducted by
CC the C-terminal KS domain (PubMed:26503170, PubMed:32565425).
CC {ECO:0000269|PubMed:26503170, ECO:0000269|PubMed:28820236,
CC ECO:0000269|PubMed:32565425, ECO:0000269|PubMed:32765467}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetoacetyl-CoA + ATP + L-isoleucine = AMP + CoA + diphosphate
CC + 2 H(+) + tenuazonic acid; Xref=Rhea:RHEA:52800, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57286,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:58045, ChEBI:CHEBI:136842,
CC ChEBI:CHEBI:456215; EC=6.3.2.50;
CC Evidence={ECO:0000269|PubMed:26503170};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52801;
CC Evidence={ECO:0000269|PubMed:28820236, ECO:0000269|PubMed:32565425};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=44.3 mM for isoleucine {ECO:0000269|PubMed:26503170};
CC KM=1.2 mM for acetoacetyl-CoA {ECO:0000269|PubMed:26503170};
CC KM=8.1 mM for ATP {ECO:0000269|PubMed:26503170};
CC KM=0.34 mM for N-acetoacetyl-L-Ile-SNAC (for the KS domain)
CC {ECO:0000269|PubMed:32565425};
CC -!- INDUCTION: Expression is induced by the presence of dimethylsulphoxide
CC (DMSO) or by the deletion of OSM1, a HOG1-related mitogen-activated
CC protein kinase (PubMed:26503170). Expression is directly induced by the
CC TeA-specific transcription factor TAS2 which is itself regulated by the
CC secondary metabolism regulator LAE1 (PubMed:28820236). Infection by the
CC totivirus activates the expression of TAS1 by up-regulating the
CC transcription of the gene transcription factor TAS2 (PubMed:32765467).
CC {ECO:0000269|PubMed:26503170, ECO:0000269|PubMed:28820236,
CC ECO:0000269|PubMed:32765467}.
CC -!- DOMAIN: The PKS portion of TAS1 has only a ketosynthase (KS) domain and
CC this domain is indispensable for TAS1 activity by conducting the final
CC cyclization step for tenuazonic acid release (PubMed:26503170,
CC PubMed:32565425). The KS domain has intrinsic tolerance for a broad
CC range of substrates since it is able to accept also TeA analogs
CC containing leucine (Leu), phenylalanine (Phe) and valine (Val) instead
CC of isoleucine (Ile) (PubMed:32565425). {ECO:0000269|PubMed:26503170,
CC ECO:0000269|PubMed:32565425}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of tenuazonic acid
CC (PubMed:26503170). {ECO:0000269|PubMed:26503170}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; CM001233; EHA53213.1; -; Genomic_DNA.
DR RefSeq; XP_003713020.1; XM_003712972.1.
DR PDB; 6KOG; X-ray; 1.68 A; A/B=1258-1690.
DR PDBsum; 6KOG; -.
DR AlphaFoldDB; G4N137; -.
DR SMR; G4N137; -.
DR STRING; 318829.MGG_07803T0; -.
DR TCDB; 4.C.1.1.19; the fatty acid group translocation (fat) family.
DR EnsemblFungi; MGG_07803T0; MGG_07803T0; MGG_07803.
DR GeneID; 2683730; -.
DR KEGG; mgr:MGG_07803; -.
DR VEuPathDB; FungiDB:MGG_07803; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_003656_0_0_1; -.
DR InParanoid; G4N137; -.
DR OMA; WDLFFCF; -.
DR OrthoDB; 42354at2759; -.
DR BioCyc; MetaCyc:MON-20082; -.
DR Proteomes; UP000009058; 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:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
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; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Ligase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1728
FT /note="Hybrid PKS-NRPS synthetase TAS1"
FT /id="PRO_0000438986"
FT DOMAIN 1141..1219
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 153..499
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26503170"
FT REGION 608..1002
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26503170"
FT REGION 1225..1256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1266..1676
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26503170"
FT COMPBIAS 1227..1256
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1436
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022,
FT ECO:0000269|PubMed:32565425"
FT ACT_SITE 1579
FT /evidence="ECO:0000269|PubMed:32565425"
FT ACT_SITE 1633
FT /evidence="ECO:0000269|PubMed:32565425"
FT MOD_RES 1177
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 1436
FT /note="C->A: Impairs TeA-producing activity."
FT /evidence="ECO:0000269|PubMed:32565425"
FT MUTAGEN 1579
FT /note="H->A: Decreases TeA-producing activity to 6%."
FT /evidence="ECO:0000269|PubMed:32565425"
FT MUTAGEN 1579
FT /note="H->F: Impairs TeA-producing activity."
FT /evidence="ECO:0000269|PubMed:32565425"
FT MUTAGEN 1581
FT /note="S->A: Decreases TeA-producing activity to 4%."
FT /evidence="ECO:0000269|PubMed:32565425"
FT MUTAGEN 1581
FT /note="S->T: Decreases TeA-producing activity to 67%."
FT /evidence="ECO:0000269|PubMed:32565425"
FT MUTAGEN 1633
FT /note="N->A: Decreases TeA-producing activity to 9%."
FT /evidence="ECO:0000269|PubMed:32565425"
FT MUTAGEN 1633
FT /note="N->H: Decreases TeA-producing activity to 31%."
FT /evidence="ECO:0000269|PubMed:32565425"
FT MUTAGEN 1635
FT /note="E->A: Increases by 2-fold TeA-producing activity."
FT /evidence="ECO:0000269|PubMed:32565425"
FT MUTAGEN 1635
FT /note="E->F,L,Q: Does not affect TeA-producing activity."
FT /evidence="ECO:0000269|PubMed:32565425"
FT MUTAGEN 1635
FT /note="E->G: Increases by 3-fold TeA-producing activity."
FT /evidence="ECO:0000269|PubMed:32565425"
FT STRAND 1265..1274
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1277..1279
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1280..1288
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1311..1314
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1316..1318
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1322..1325
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1328..1331
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1335..1338
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1343..1360
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1371..1378
FT /evidence="ECO:0007829|PDB:6KOG"
FT TURN 1383..1385
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1403..1406
FT /evidence="ECO:0007829|PDB:6KOG"
FT TURN 1408..1411
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1415..1423
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1429..1433
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1435..1437
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1438..1451
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1456..1464
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1471..1476
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1507..1515
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1516..1522
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1526..1537
FT /evidence="ECO:0007829|PDB:6KOG"
FT TURN 1539..1542
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1551..1565
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1567..1571
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1573..1577
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1584..1602
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1622..1625
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1628..1631
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1635..1637
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1638..1652
FT /evidence="ECO:0007829|PDB:6KOG"
FT HELIX 1666..1668
FT /evidence="ECO:0007829|PDB:6KOG"
FT STRAND 1673..1677
FT /evidence="ECO:0007829|PDB:6KOG"
SQ SEQUENCE 1728 AA; 187803 MW; C482FBB54504D9FE CRC64;
MYNRCCRKVW IQGRVAYRPA YIRQSPPQQT LYRGIDLLPF TTIVMDHQSG FQNPSPSGGL
MFSASAKRFI SRIVGFVGRG AEVQQKAVGL CPLKTERRRA AAGGLLLPTG LRMGRSIIMS
VRPLPFLTGP APSPDTAAGF KPSPPTGNLV SVSPLSKAQM ALWFDYLQHP TSTHYFLTLK
VELDKQPLSL DKIIQVIRGL GKQHAMLRTT FHVDTDTDDM SKSYMAVHDD SWDQEIHVLM
NDAQLYEALR KPFQLSSESP VRWVVQMKLQ PGSARSTYTV YAAGHHIGVD GASMSVLSNQ
LLEAVASEVE DQPDHSGPHY GDYIQRQARY LRSSAGAAAG RFWLSQLRHT QPFRWRMEPP
EEINTPNYRQ LDTWNFFPTA EIQEWGNLYK TSWFRVATSI VGLVTAAMAE PQAHHDHALM
VAFGARPRGF ENNVSHMANT MPVKFPLSSL LRDDATFSDA VKAMGRNVST AKKHENFPFM
SLMEQANRHM DPTLLDFKVA ITYSPKLANK SCELFPVEGI WDLFFCFLEQ EDGVALGVIS
NPRVFGAEAL GQLQSLFNEV FALSKARPSF KLSDLAFLQN RTPARFISGP ALDDVESISK
SRVYRLIKAR AASQPDLVAL MSAEKGVQMT YRELAAQSSQ VAHFLQKQRL CKGDAVLVHL
ERGFAQIVWI LGVMEAGACY VALDKTWPAA RKEAILRTAN GKLLVTDDEQ MDFEKQDTTV
VFLAPSAAEI ASMPQSTCEC EVADDDLAYV VFTSGSTGQP KGVMVEHSNL SHYVSATRSL
VKTGPHSRML QLASFAFDAI VLEYAVTLAH GGTLCFANHP EVLVGEYLAD VIDSNQVNFF
HCTPSVLSTL PAGRRLPSLR IVSVGGEASP PGLLDHWRKR VELLHAYGPT ECTVICTLES
LTQDESTQTA IDATVIGKAL PNLDIRICEE GKLEPLAPNQ VGEICVVGPQ VSRGYMGQEE
LTASKFHNIT LADGHPSRLY RTGDKGFIDD DGKLHIQGRI GNREIKVRGY RLDLYEVEKN
VMAFDPEVTQ VSIQQVGESL VALVVPASID CDRIRSKLLK DMPRYAVPTR FIRVASLPLN
TNGKIDHTQA SSLAAELVMH DTVLPTVDAT PTPTAAVRAV GVTEENLRLK TKENGMERQE
MLRRHLTAEV TALWAKLLGS SRQFDPEVGF FDAGGHSLLL TQLHKLIKER FGTGSRPSLL
DIFSMSSIRK QVDCLMGIVD QDAMLGSEPT GGSSSRSQSR RSAETSSSST SAPSSVPVDA
ERNLYAIVGI SCRFPGANTA EQLWNVLMEQ RDAITTFCPA ENLGFALEEN SVFVPRYGMI
DALKDFEPSA YSMSDAEAQT IDPQKRVFLD VAADALADAG TSASPGNPLD PVGVFVGAAT
NTFLSSRDNP GSKPPGDEEP QSFANHYQQL LDCPIGTFAS FKLNLTGPVV TLNTACSSAL
AALHLACASL SHGDCNAAVV GGVSMAYPQE GGYVTARPGG DSSAVFSPSG VCHPLDSRAD
GCVPADGAAA LVIKRLADAR ADGCRVYAVI EGVAVSADGS DDKAGLGVPS SSGQSRTVEA
ALRRAGPQAL SRLRYVEMHG SGTPWGDALE VQGLKMAFDR LSKTGAAEQS GTGRAQPEAD
RIYLGSNKGN CGNTEAASGL LSLIKASMAL NLGVVPPLPN LAEPNPKCEF EETKFEPLGK
QLALAPGDRV MNKRQRIVRS PNWISDATWF VISTVDNLLP KLTPAAVA
