THAH_BURTA
ID THAH_BURTA Reviewed; 3925 AA.
AC Q2T4N2;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Polyketide synthase ThaH {ECO:0000305};
GN Name=thaH {ECO:0000303|PubMed:20853892}; OrderedLocusNames=BTH_II1673;
OS Burkholderia thailandensis (strain ATCC 700388 / DSM 13276 / CIP 106301 /
OS E264).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Burkholderiaceae; Burkholderia; pseudomallei group.
OX NCBI_TaxID=271848;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700388 / DSM 13276 / CIP 106301 / E264;
RX PubMed=16336651; DOI=10.1186/1471-2164-6-174;
RA Kim H.S., Schell M.A., Yu Y., Ulrich R.L., Sarria S.H., Nierman W.C.,
RA DeShazer D.;
RT "Bacterial genome adaptation to niches: divergence of the potential
RT virulence genes in three Burkholderia species of different survival
RT strategies.";
RL BMC Genomics 6:174-174(2005).
RN [2]
RP NOMENCLATURE.
RC STRAIN=ATCC 700388 / DSM 13276 / CIP 106301 / E264;
RX PubMed=20853892; DOI=10.1021/ja105003g;
RA Ishida K., Lincke T., Behnken S., Hertweck C.;
RT "Induced biosynthesis of cryptic polyketide metabolites in a Burkholderia
RT thailandensis quorum sensing mutant.";
RL J. Am. Chem. Soc. 132:13966-13968(2010).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700388 / DSM 13276 / CIP 106301 / E264;
RX PubMed=29914944; DOI=10.1128/aac.00463-18;
RA Wozniak C.E., Lin Z., Schmidt E.W., Hughes K.T., Liou T.G.;
RT "Thailandamide, a Fatty Acid Synthesis Antibiotic That Is Coexpressed with
RT a Resistant Target Gene.";
RL Antimicrob. Agents Chemother. 62:0-0(2018).
CC -!- FUNCTION: Involved in production of the polyketide antibiotic
CC thailandamide. {ECO:0000305|PubMed:29914944}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00258};
CC Note=Binds 4 phosphopantetheines covalently. {ECO:0000255|PROSITE-
CC ProRule:PRU00258};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000305|PubMed:20853892}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: No longer inhibits growth of Salmonella in an
CC overlay assay, suggesting it does not produce thailandamide.
CC {ECO:0000269|PubMed:29914944}.
CC -!- MISCELLANEOUS: Thailandamide is a polyketide that is toxic to human
CC cell lines but also has antibacterial activity on E.coli, S.typhimurium
CC and S.aureus. It probably acts on acetyl-CoA carboxylase in the fatty
CC acid synthesis pathway, which is rarely found to be an antibiotic
CC target. These data suggest it might be a good starting point for
CC engineering of novel antibiotics. {ECO:0000305|PubMed:29914944}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; CP000085; ABC35522.1; -; Genomic_DNA.
DR SMR; Q2T4N2; -.
DR PRIDE; Q2T4N2; -.
DR EnsemblBacteria; ABC35522; ABC35522; BTH_II1673.
DR KEGG; bte:BTH_II1673; -.
DR HOGENOM; CLU_000022_58_5_4; -.
DR OMA; VHEAHEA; -.
DR Proteomes; UP000001930; Chromosome II.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016746; F:acyltransferase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:1901576; P:organic substance biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 4.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.47.10; -; 2.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
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; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
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; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 2.
DR Pfam; PF00109; ketoacyl-synt; 2.
DR Pfam; PF02801; Ketoacyl-synt_C; 2.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF00550; PP-binding; 4.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 2.
DR SMART; SM00823; PKS_PP; 4.
DR SUPFAM; SSF47336; SSF47336; 4.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 4.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 3.
PE 3: Inferred from homology;
KW Antibiotic biosynthesis; Cytoplasm; Metal-binding; Multifunctional enzyme;
KW Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT CHAIN 1..3925
FT /note="Polyketide synthase ThaH"
FT /id="PRO_0000452507"
FT DOMAIN 1073..1148
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2664..2737
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3622..3699
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3762..3839
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1166..1233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1679..1698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2594..2613
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2619..2657
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2753..2841
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3512..3531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3578..3619
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3734..3754
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..50
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2781..2805
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3512..3527
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1108
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2698
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3659
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3799
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3925 AA; 410741 MW; BA87903C1425E779 CRC64;
MPRWRPTWLK RLSCPKQPRH PTHPKHPTHP KHPKHPKHPR HPKHPRISRR CSSASARGKW
ISTTSSTWFD GDHVNKKDIL LAYREGLLDT GSAQRVLDAL RERSASAPLS SVEQGIWATQ
RAAPGSTAYH VPVVLHVARA LDIDALRRAC LDLALAFPIL TSTIVERDGE PRRAAFSSAP
AQLRHERVGA LSDDALAARL ADAKREPFDL RAGPLWRLFA FERGRADFVL MLVVHHLSYD
GASTLPLVDT LLAMHDARAA GATPAIEPFA PAHDAYVADE ARWLASADAA ATLDYWRRAL
DGAPPALELP LDRPRPAQQT FNGKVVQRAL PEVLGERAAA FAAQGGLTRA ALFLAVFKLL
LSRYAAQDDI VVGVPVSRRP LAARGAVGNF VNLLPLRSRV DARLTFAAFA AQVQGTLNAG
RDHAAYPFPE LVKRLNVPRD AALAPVFQAL FAYQNFAGAD AEAAFCARHR ARFLQIEHQA
GESEIGVEVF ERASASVVHL KFNPDLFDDA SAARMLDHFV HLLDATLADP RRPLADYPLV
TPAERERIVS RWNATAAPYP DDRCLHELVD EHARTRADAR AVSDARDALG FGELKRRSDA
IAAALVDAGA APRALVGVCM TRSVDLLAAL IGVMKAGAAY VPLDPRYPDA RLRAIVDDAQ
LEHVLTDAES APVAAPLCAD GARVMLDAAR CAAGGSRAPL PRATPDDLAY VIYTSGSTGK
PKGVMVPHRA VVNLLCSMAR APGMAAGERM LALATYAFDM SVPELFLPLA VGGECMLAQA
DAARDPRVLM EAIAERRPTI MQITPTACAM LFEAGWRNAE RVALLCGAEP LTETVRRRLA
ETGTRAWNMY GPTETTVWST MAPIAADRPI TLGAPLANTR VYIVDGQDRL LPPGLYGEMV
IAGDGVARGY LGRPELSAER FVRDPFVNAG RGANAYRTGD IARWRDDGSL EFAGRSDAQV
KLRGFRIELG DIEAHLKRHP AIEDAVAVVN EAHGLKRLVG YVVVRGGAAA PSWSALRSWL
LAALPAHMVP ACYEALPAVP LTPNGKIDRR GLAARPLAAA AGAQAADGLE AGGLVGGLEG
EVLALWRETL KVGDIGPTDG FFDAGGDSIL AVALAARIEQ RFGVTFSATT LFKYACVRDI
AGYIASAEAR PRAGGANARA GVEAGAAVAT PPGRPAGEAA GAQRDRAPRA ADERADAPPA
APSDAHASKA AAIDSRGGAA GGDGEPARAA SHGDAPADGL AIIGIALRVP GAADARAFWR
NLREGRSALE RLDARRLMAH GVASALAGAR QTVGVRATIA DKHRFDAEFF GVSMRDAALM
DPQARQLLQH AWLAFEDAGY VPADAPDTAV FVSASHSRYA AKQADGARAA AEAVLDDPAD
YVGWILEQGG TIPALISYKL GLTGPSLYVH TNCSSSLAAL YAAWQTIRAG DAKQALVAAA
TLFADERLGY VHQPGLNFSS DGRIKTFDRN ADGMVPGEGV VAVLVKRVAE ALADGDRIYA
IVRDVALNND GAAKAGFYAP SVRGQAQVID ALLRRTGVRA ADIVYVEAHG TGTQIGDPIE
VAALTDAYRA HGAGTGHCGL GSVKTNVGHL DTAAGLVGLV KVALSLEQRM LPPSLNFDAP
NPALDLASSP FYVVERATPI APRAGRTFAA VSAFGVGGTN AHALVEAHRD ARDAAIATGA
TGAPDVPDAP DAPDAPDAQT VVPLSAKTPA QLTQRAAQLL DALRGDDARR PALADVAFTL
QRGRQPMGSR AAFVVDSIDM LCEQLAAYVA AGGAHAPRGA ARADATHAHA GDAHRLAERW
VAGDDVDWRA LSRGGRRIGL PGYPFGGDVY GGARDAHDPS RRLHPLLHRN VSTLSQVAFT
STFDGGEPFL RDHLLHGRRV LPGAAYLEMI HAAAERALAP AAGAGAGVAL ANVVWVRPVE
VVDASVTVRL AFAPADDDGL VAFEIRSETA GGGGALHCRG HVQRIAEPAP GQIDLHALRE
RCAAPRLSAA RCYETYARLG LDYGPSHRGV VDVRGEREHL LARIVLAGLP DADARPMHAG
LVDSAFQATL AAVAETPDEL ERLDAAPVPF ALGRLDVLAP CAPQMWASIR VRRIGGAHAD
GGRTASDDAL LAKIDIDLVD DAGNVCVRVR DLAARRFVRE PARAPSRTLA VRARWRGARA
SGVPGASGGV PREVVLVGVD ARAAEPIRAA LGASGVACEV WPIPADADPA GQFAALAARV
LERLQAAVRA RPTSPRLLQL VSLDDAPWFA AALAAMLKTA ALEQPCVLGQ QIALPSRLSP
ARIAAALADC AAMPDARRLR FGANDADADA DGALEVETFA ELDAWPEQAA PPWKAGGVYL
VTGGGGRIAR RLIDAIAAHA ANATVVVASR TQPGAARADA RHATDASDTP HAPGVTVDRI
ALDVTDGARV RDAVRSIVSR HGRLDGVLHG AGVLDDDFIL NKDARALHAV IAPKAQGAWH
LDAATASLDL DCFVLFSSVA GALGNAGQVD YSGANAFMDA FAHWRRARVA AGERRGRTVS
IGWPLWAEGG MRIDDASLAA LERSLGMRPM PTPAAIGALY AALACGESHV VLFHGDPAPL
RRAAWLAASA PTQDDPAAAS IEPAASSTEL PEMNVQATAP ADAGARPRDD APAAAVAHAA
PDASDAPDAR PADAAPADDA RLTEHALALL KRLLSTALHT PASRLDAHAP LERYGIDSIV
VVSMNGELEK AFGSLSKTLF FEYRTLHELA CYFVAHHRER LARLLPAGHG ARLAPAPAQP
LAPRAPSAEP ARDAARSLEP EQGQGQGQGQ EPEPASQTAA ASESARAPAQ ASAHARRERA
APETRTQAPA QAHAPAQASA PDAARDAFDI AIVGLAGRYP GADSVDAFWA NLRDGRDCVT
EVPAERWDHA RYFHPDKAHP GTTYAKWGGF VDGVDRFDAA FFNMSPREAA IVDPQERLFL
ETVYEAIEDA GYTPRTLAGG AGRDAAVGVY VGVMYQEYQL YGAQASALGE PCALPSSPSS
IANRVSFFCD FDGPSIAVDT MCSSSLTAIH LACQSLRSGE CAAAVAGGVN LTLHPNKYLL
LSFGRFASSK GRCESFGAGG DGYVPAEGVG AVVLKPLARA RADGDHVYGV IKGSALNHGG
RTNGFTVPNP ASQRRVILRA LREAGVDPRR LGYVEAHGTG TSLGDPIEID ALSRAFAEFT
QDKQFCPIGS VKSNIGHAES AAGVAALTKV LMQLKHDTLA PSLHADVLNP NIDFAATPFY
VQRERADWPP AVDAGEAGGV ARRRPRVCAV SSFGAGGSNA HLIVEEYVAS DGERAVRSAS
DQLVVLSARS PEQLRERARR LRARLLADAG GTPLDALAYT LQVGREAMAY RFATIVATRD
ALAARLDALA NDALFDGQAL PGDADGFARR AERDETLVSL ARDDAFRDAV GRWVAEGQLA
RLAQLWVRGV DLDWTLLHRS PPARISLPTY PFKRDRHWGV PNLAGLPGAA GVANVAGVAG
AAGPAGVEHA ASGAGAASVA SAAGAASAAS TASTASRAGT PSPAVAASTG ETVAAPASHD
AFATAGAKPG VVLAPATAAG YVATPRPKPT VMLDTDAAAA ARARPGAASS PSPSSPSPLP
SSPPRMSSRQ HASPAAAPDP RAALLDIEAF LAGSLAAALM ATTDEIDREQ TFNALGVDSI
VGVEWVRAIN DRYGTALPAT VIYDHPSVRA MARHVSSNAT PGVAGVARGD ASAPQAAPSA
FAAAASSASG AVSPAPFASA APPEPPASPA RADGALDAAG ATSLDAIRAH LVDSLAQALY
VEPAEIGVDQ PFAELGLDSI VGVEWITAVN RRFGTALPAV AIYDHPSVVA LARFVGTQLG
ARLPAAQAAR AGAFAGVEPG EPDARALPAA ARAAAPPAHT DAAAHTDTDA LLRAIERGEL
DAGDADAIWR RMQSRAARPE PLAQP
