STHA_PHANO
ID STHA_PHANO Reviewed; 2851 AA.
AC Q0UK48;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Highly reducing polyketide synthase sthA {ECO:0000303|PubMed:31553484};
DE Short=HS-PKS sthA {ECO:0000303|PubMed:31553484};
DE EC=2.3.1.- {ECO:0000305|PubMed:31553484};
DE AltName: Full=Stemphyloxin II biosynthesis cluster protein A {ECO:0000303|PubMed:31553484};
GN Name=sthA {ECO:0000303|PubMed:31553484}; ORFNames=SNOG_07866;
OS Phaeosphaeria nodorum (strain SN15 / ATCC MYA-4574 / FGSC 10173) (Glume
OS blotch fungus) (Parastagonospora nodorum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Phaeosphaeriaceae;
OC Parastagonospora.
OX NCBI_TaxID=321614;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SN15 / ATCC MYA-4574 / FGSC 10173;
RX PubMed=18024570; DOI=10.1105/tpc.107.052829;
RA Hane J.K., Lowe R.G.T., Solomon P.S., Tan K.-C., Schoch C.L.,
RA Spatafora J.W., Crous P.W., Kodira C.D., Birren B.W., Galagan J.E.,
RA Torriani S.F.F., McDonald B.A., Oliver R.P.;
RT "Dothideomycete-plant interactions illuminated by genome sequencing and EST
RT analysis of the wheat pathogen Stagonospora nodorum.";
RL Plant Cell 19:3347-3368(2007).
RN [2]
RP INDUCTION, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=31553484; DOI=10.1002/chem.201904360;
RA Li H., Hu J., Wei H., Solomon P.S., Stubbs K.A., Chooi Y.H.;
RT "Biosynthesis of a Tricyclo[6.2.2.02,7]dodecane System by a Berberine
RT Bridge Enzyme-like Intramolecular Aldolase.";
RL Chemistry 25:15062-15066(2019).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of the phytotoxin stemphyloxin II
CC (PubMed:31553484). The first step of the pathway is the synthesis of
CC dehydroprobetaenone I by the polyketide synthase sthA and the enoyl
CC reductase sthE via condensation of one acetyl-CoA starter unit with 7
CC malonyl-CoA units and 5 methylations (PubMed:31553484). The C-terminal
CC reductase (R) domain of sthA catalyzes the reductive release of the
CC polyketide chain (PubMed:31553484). Because sthA lacks a designated
CC enoylreductase (ER) domain, the required activity is provided the enoyl
CC reductase sthE (PubMed:31553484). The short-chain
CC dehydrogenase/reductase sthC then catalyzes reduction of
CC dehydroprobetaenone I to probetaenone I (PubMed:31553484). The
CC cytochrome P450 monooxygenase sthF catalyzes successive epoxidation,
CC oxidation (resulting from epoxide opening) and hydroxylation to install
CC a tertiary alcohol in the decaline ring to yield betaenone C from
CC dehydroprobetaenone I and betaenone B from probetaenone I
CC (PubMed:31553484). The FAD-linked oxidoreductase sthB is responsible
CC for the conversion of betaenone C to betaenone A via an intramolecular
CC aldol reaction between C-1 and C-17 to form the bridged tricyclic
CC system in betaenone A (PubMed:31553484). Finally, the cytochrome P450
CC monooxygenase sthD catalyzes the hydroxylation of C-15 to afford the
CC final metabolite stemphyloxin II (PubMed:31553484).
CC {ECO:0000269|PubMed:31553484}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 10 AH2 + 2 H(+) + 7 malonyl-CoA + 5 S-adenosyl-L-
CC methionine = 10 A + 7 CO2 + 8 CoA + dehydroprobetaenone I + 6 H2O + 5
CC S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:51348, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:145061; Evidence={ECO:0000269|PubMed:31553484};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51349;
CC Evidence={ECO:0000269|PubMed:31553484};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:Q9Y8A5};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000250|UniProtKB:Q9Y8A5};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:31553484}.
CC -!- INDUCTION: Expression is highly up-regulated during plant infection.
CC {ECO:0000269|PubMed:31553484}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; an
CC acyl-carrier protein (ACP) that serves as the tether of the growing and
CC completed polyketide via its phosphopantetheinyl arm; and a C-terminal
CC reductase (R) domain that catalyzes the reductive release of the
CC polyketide chain. {ECO:0000269|PubMed:31553484}.
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DR EMBL; CH445335; EAT85332.2; -; Genomic_DNA.
DR RefSeq; XP_001798193.1; XM_001798141.1.
DR SMR; Q0UK48; -.
DR STRING; 13684.SNOT_07866; -.
DR EnsemblFungi; SNOT_07866; SNOT_07866; SNOG_07866.
DR GeneID; 5975086; -.
DR KEGG; pno:SNOG_07866; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_31_0_1; -.
DR InParanoid; Q0UK48; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000001055; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
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; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 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; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
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; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2851
FT /note="Highly reducing polyketide synthase sthA"
FT /id="PRO_0000448648"
FT DOMAIN 2360..2443
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 9..418
FT /note="Ketoacyl synthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 304..324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 529..851
FT /note="Acyl transferase (AT) domain"
FT /evidence="ECO:0000255"
FT REGION 949..1242
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1390..1577
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255"
FT REGION 2079..2252
FT /note="Ketoreductase (KR)domain"
FT /evidence="ECO:0000255"
FT REGION 2447..2496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2535..2767
FT /note="Reductase (R) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 2447..2489
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 180
FT /note="For ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2399
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2851 AA; 312742 MW; 7ECBB8AD64DDBF0F CRC64;
MSHNKPVNEP IVIIGSGCRF AGGANSPSKL WDLLRNPKDL RSDVTSRFNS QGYYHKDGTH
HGHMNVLQSY LIGEDTRLFD AEFFGVNPVE AKAMDPQQRL LLEVVYEAIE SAGLSMERMR
GSDTAVFAGL MCGDYEAMML RDLDQAPTHF AIGTSRAILS NRVSYFFDWH GPSITIDTAC
SSSLVAVHHA VQALRSGDSH AAIACGSNLI LGPEMYVIES KLKMLSPDGL SRMWDKDANG
YARGEGVTAV VLKTLSQALA DNDRIEAVIR ETGVNQDGAT PGITMPSASA QRALIHSVYR
KAGLDPESPN DRPQYIESHG TGTPAGGSIK TVLGHTEGSA GIAALLKVTK AIQNATVPPN
LWFQQLNHKL EPFYGNIQIP TQPVTWPATE KRRRKRASIN NFGFGGTNAH AIVEGYEPKE
EIPPPSFHHV DATVSTPFVF SAASKESLRA NLAAYALHLD AHPQISTRDL AYTLRERRSV
LPFRIAFPES NTKDLKLSIA ARLSESDGEG LGVRTWAANN GGSSKLLGIF TGQGAQYARM
GTELLAQTNM ARKTLEELEG YLAELPEEDR PSWSLQSELL ADPSVSRVGE AAISQPLCTA
VQIILVKLLC SAKVRFDTVI GHSSGEIAAA YAAGYLSARD ALLVAYYRGL HCKLAASPNG
NVKGAMLAAG TSLEDATELC EDEEFSGRIN VAASNSSSSV TISGDEDAID ELATVFDDEK
KFNRRLKVDT AYHSKHMLPC FEPYVASLRR VGITVLPGND QCTWISSVHE GRAINPATDE
LADVYWAQNM TKPVLFSQAV QAAVAPVRGG EPFAAALEVG PHAALAGPAK QTIQEVAQKE
IPYHGSLVRG ENATKAFATC LGFLWERLDA ASLDLGSCEA ALSSSGGVQQ YTVLADLPTY
QWKHETVYWA ESRRSRRMRL REGPFHQLLG NVSPDSAPHI LRWKNVLKPK EMTWLEGHQV
QNQVVLPAAT YICTAIEAAR SLAQGKNIQL IELSNFCIHN AITFDQNDVG VEVLVELSRI
NVKENHVNAT FTYTAGLGDE TNDLALAANG ELNILLVDDD PSLALFPERQ EPPPHMIPVQ
PSRLYDFMKG LEYDFSGPFQ SLAKLERKLG TATCLAKKAR KSVPDADDLL VHPVDLDAAF
QSVMLAYSYP GDDQLRLLHL PTSIERLRVN PAALSSQKYV ENDTTILDST CTTADRAEPG
NGFSGSVNMY AAGFDHAAIQ VEQVKFKPVG SDAKDDRNVF YKMHWVPSKP DGLLAAASVP
ITERDRKLMF VLSRIAAYYL RKFDEMIAED DPARLESPLC HYMRYARHMM GLLRAGEHKW
AYKEWLQDTE QDVFDDIASK GFQDNSDVRI MLLVGSTMPR VFRRETTMLE HFRTSGLLDE
YYSNGFGTKQ CTLWVAGVLK QLADCNPHLN LLEIGAGTGS ATKTILKSVG HDFASYTFTD
ISSSFFENAA ETFSDYGSRM VFKVCNAEND PVEQGFEAGT YDVVIAFMVI HACAKLDEAV
ANLRKLLKPG GLLVLGEGAS DGAMQAGAGF IFGTLPGWWR GVDEGRTLSP LVSASEWQVI
LRDAGFSGID TMSPPELFDA FGITLFVSTA VDERIEFVRN PRAKASRAVY NKVVVIGGIT
STIAKLAEEI QTVLTPLAIQ VLLCTSLEDL QENVLDDETV IISLVDLEAP VFKDITSERW
YKFRLLFETK REILWLTSGR LEDEPYSNMT VGFGRSAMHE EETLRVQYLD VADVSQLNAV
MVMQYLLRFT SSELDKSDIL YTKEPEVIID ANGRELVPRL FTIQAANNRL NSVTRPIYED
VDTSQSVVEL RYAKEEPSFR KLSRYEVSAK LEPSHDTTIK LRVAYSVISA LRCPAGYQYL
IMGFDESGAR RVALVNSLTS VLCVPLKSTI LCELYDMSEP SYLTLLAAEI IAMTIVDPLF
TGQKLAILNA SKLIIQAIAS YATAKGVETT FIVDAGGEFV PKDVAVQSHL PLYPSRSDMS
FILPTNLACF VSFSALNKAD SEDAMKSLLP FYCQKMNTST LFSTHGVDTG ALGATAQHVL
SRAISSRKGR VIDWTPPSTS LSVRITRFEM TQLFKADKTY WLVGLSGALG ISLCDWMIER
GVKYLVLTSR NPKIDERWIE NHEKHGVMIK ILLCDVTDEA AIKDVHQTIV RTLPPIAGLL
NGAMVLRDVS VRNMEYAQVT DVIRPKVLGS IHLDRIFHDI DLDFFVLLSS INCVIGNVGQ
ANYAAANMGM IGVAGHRRKR GLRSSVVNVG AIIGVGYITQ SDRQLDVTVA KTAMMHLSEQ
DFHQIFAECM EAGHLDNDSG PEISTGLLEI TPDTIDIPPW YSDPKFKRFQ VHQAAAGAGK
AEVANSASTQ ELLLACRSQA DITKVVQQAY CAQLRRILQV STADEDLMMM RGVDLGFDSL
LSVDVRSWFL KNFRVSIPVL KIMANDVRMS TLVDLAAESI PAELIPHVQQ QQQQAGRQDA
SSNTSSDDET ASTLPTSPES ASPGTSTPVP EKDISPVDTF NSVDWYFETT PPSISTFSEL
TSAPAPRSDP KVVVLTGCSG LLGHHLLSTL IAQPSIRKII CLAVRSLPSR LSSGELPLPG
DKIEYHAGDL TAPQLGLSTS TWISIFKQAD AVIHNGSDTS HLKYYSALKL ANVDSTKQLV
STCLQRMIPF HYVSSAGVAL FAERDAFPPV SCTTTGKTPP ADGSHGYMCG KWVCEKMLER
VYEQYHLPIV IQRPSTIIRS GEDAAVERAG FDWVNSLLHF AHQTQTVPRV DHNAGAFDLV
SVDTCCSDVA RKLTRATKER ITYVNNVGDV VIPMASMADV GLDRIGKRYN VLTMDEWTKT
VVEAGMHPAV AALIETFDEP GVEKYPMLLR E
