PHMA_PHANO
ID PHMA_PHANO Reviewed; 4042 AA.
AC Q0V6Q6;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Polyketide synthase-nonribosomal peptide synthetase phmA {ECO:0000303|PubMed:31815421};
DE Short=PKS-NRPS phmA {ECO:0000303|PubMed:31815421};
DE EC=2.3.1.- {ECO:0000305|PubMed:31815421};
DE EC=6.3.2.- {ECO:0000305|PubMed:31815421};
DE AltName: Full=Phomacin biosynthesis cluster protein A {ECO:0000303|PubMed:31815421};
GN Name=phmA {ECO:0000303|PubMed:31815421}; ORFNames=SNOG_00308;
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 FUNCTION, INDUCTION, DOMAIN, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RX PubMed=31815421; DOI=10.1021/acschembio.9b00791;
RA Li H., Wei H., Hu J., Lacey E., Sobolev A.N., Stubbs K.A., Solomon P.S.,
RA Chooi Y.H.;
RT "Genomics-driven discovery of phytotoxic cytochalasans involved in the
RT virulence of the wheat pathogen Parastagonospora nodorum.";
RL ACS Chem. Biol. 15:226-233(2020).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of the mycotoxins phomacins, leucine-derived
CC cytochalasans with potent actin polymerization-inhibitory activities
CC and monocot-specific antigerminative activities (PubMed:31815421). The
CC first step in the pathway is catalyzed by the hybrid PKS-NRPS phmA,
CC assisted by the enoyl reductase phmE, that are responsible for fusion
CC of the leucine precursor and the polyketide backbone to produce a 2-
CC pyrrolidone intermediate (PubMed:31815421). The polyketide synthase
CC module (PKS) of phmA is responsible for the synthesis of the polyketide
CC backbone and the downstream nonribosomal peptide synthetase (NRPS)
CC amidates the carboxyl end of the polyketide with the leucine precursor
CC (PubMed:31815421). Because phmA lacks a designated enoylreductase (ER)
CC domain, the required activity is provided the enoyl reductase phmE
CC (PubMed:31815421). Reduction by the hydrolyase phmG, followed by
CC dehydration and intra-molecular Diels-Alder cyclization by the Diels-
CC Alderase phmD then yield the required isoindolone-fused macrocycle
CC (Probable). A number of oxidative steps catalyzed by the tailoring
CC cytochrome P450 monooxygenase phmB, the FAD-linked oxidoreductase phmC
CC and the short-chain dehydrogenase/reductase phmF, are further required
CC to afford the final products, phomacin D and phomacin E
CC (PubMed:31815421). {ECO:0000269|PubMed:31815421,
CC ECO:0000305|PubMed:31815421}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:31815421}.
CC -!- INDUCTION: Expression increases over time in planta on wheat (Avena
CC sativum) and peaks at 10 days post inoculation when the plant tissue is
CC heavily necrotic and P.nodorum is undergoing asexual sporulation.
CC {ECO:0000269|PubMed:31815421}.
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. Thus, an NRP synthetase is generally composed of one
CC or more modules and can terminate in a thioesterase domain (TE) that
CC releases the newly synthesized peptide from the enzyme. Occasionally,
CC epimerase (E) domains (responsible for L- to D- amino acid conversion)
CC are present within the NRP synthetase. CcsA contains also a polyketide
CC synthase module (PKS) consisting of several catalytic domains including
CC a ketoacyl synthase domain (KS), an acyl transferase domain (AT), a
CC dehydratase domain (DH), a methyltransferase domain (MT), and a
CC ketoreductase domain (KR). Instead of a thioesterase domain (TE), phmA
CC finishes with a reductase-like domain (R) for peptide release. PhmA has
CC the following architecture: KS-AT-DH-MT-KR-PCP-C-A-T-R.
CC {ECO:0000250|UniProtKB:Q4WAZ9, ECO:0000305|PubMed:31815421}.
CC -!- DISRUPTION PHENOTYPE: Leads to significant reduced virulence in wheat
CC seedling infection assays. {ECO:0000269|PubMed:31815421}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; CH445325; EAT91803.2; -; Genomic_DNA.
DR RefSeq; XP_001790998.1; XM_001790946.1.
DR SMR; Q0V6Q6; -.
DR STRING; 13684.SNOT_00308; -.
DR EnsemblFungi; SNOT_00308; SNOT_00308; SNOG_00308.
DR GeneID; 5967890; -.
DR KEGG; pno:SNOG_00308; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_37_8_1; -.
DR InParanoid; Q0V6Q6; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000001055; Unassembled WGS sequence.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
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; 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; 1.10.1200.10; -; 1.
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; -; 2.
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; 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; 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; 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; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 2.
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; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Isomerase; Ligase; Methyltransferase;
KW Multifunctional enzyme; NADP; Oxidoreductase; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Repeat; S-adenosyl-L-methionine;
KW Transferase; Virulence.
FT CHAIN 1..4042
FT /note="Polyketide synthase-nonribosomal peptide synthetase
FT phmA"
FT /id="PRO_0000449441"
FT DOMAIN 2351..2433
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3562..3642
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 13..414
FT /note="Ketoacyl synthase (KS) domain"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 519..837
FT /note="Acyl transferase"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 909..1208
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 1349..1572
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 2073..2246
FT /note="Ketoreductase (KR)domain"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 2460..2504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2535..2554
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2584..3019
FT /note="Condensation"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 3047..3443
FT /note="Adenylation"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 3703..3924
FT /note="Reductase-like"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT MOD_RES 2393
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3602
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 4042 AA; 445626 MW; 5D4078DF88432223 CRC64;
MGSSSKDYTN EPIAIVGSAC RFPGGASEPS KLWDLLEHPT DVLKEIPESR FSVDGFYHPN
GLHHGTTNVR HSYILDDDIR LFDAQFFGIK PIEANSIDPQ QRLLMETVYE GLEAAGQSIQ
RLQGSQTAVY VGLMSSDYKD LLGNDQESYP TLVALHQAVQ LLRSGDGTNV ALAAGTNLLL
NPDQYIAESK LKMLSPDGRS RMWDEKANGY ARGDGIAVVV LKRLSQALED GDHIECLIRE
TQINQDGKTK GITMPSATAQ TALIRATYAK AGLDLSKPSD RPQYFEAHGT GTPAGDPIEA
EAIHTAFFGG DLGEAGHDKL FVGSIKTVIG HTEGTAGLAA VLKASLALQN RAVPPNRLFD
RLNSKIRPFY GDLEILTKAQ EWPVLVPGSV ARASVNSFGF GGANAHAILE AYEPPSLVSD
DVLVTPLAPV QFSAASETAL RGTLRKYAEF LEKNQDVNLR DLAWTLNTRR SVLAARTAVF
GANALDLAHE LQKRAEADVA TLIPVASRSL PAKPRILGVF TGQGAQWARM GAELLDASPA
VDRIISELEK SLSTLPDGPE WSVKGEILAT GGASRVAEAA ISQPLCTAVQ IVLVDLLKSA
GINFEAVVGH SSGEMGAAYA AGYLSAQDAI RVAYYRGRHL HLAGGLGGEQ GGMMAVGTSF
EDAEELCSLP EFQGRIGVAA INSGASVTLS GDLDTIEAAK EILDDEKKFA RLLKVDKAYH
SHHMIACSDA YRKSLADCSI KVLRPSRGSA TWLSSVYGED IVDYRKELTS EYWINNMVRP
VLFSQAVEFA AAEKGPFDCA IEVGPHPALK GPALQVLQEF LGNSIPYTGL LSRDRDDKKA
FAEGLGYLWQ AFGENAIDHK SFDTFVAGAS APLPQITSNL PTYAWDHDRR FWHESRQYAA
NRTKPDPTHE LLGTKCPDGT EQQCRWRNML RPQEIPWLAG HQIQGQMVFP AAGYVSAAVE
AVKFSNEGLP ITTIEIEDFV IGQAIIFNDD YASVETQFTL TNIVSDHMSW SASFAFYSAS
QKHSLGMDLN ASGRISALFG PPKDDVLPPS TGRELNMIDV DPEQFYNSLS KLGFGYTGAF
KALRNLYRKM DVAMGEIQNP RSTDPAYNLL LHPATFDNAI QSIILAYCYP GDGRLWSVHL
PTSIKKIRIN PSLCENSAGQ EAVLHFKSTI TSGRSTEIQG DVELYDTNGV NSIMQLEGLH
TKPLGHATPE NDRTLFLETI WDTAEPTKEL ALLAQPDISK KAQLGLDIER VAFYYIRNLG
HVTTKADREQ AEDYHKHFFN YIDHTVVSVN NGTSLFAKKE WMHDTHEQVL DIIKSYPESI
DMKLMYAVGE HLLPVIRHET TMLEYMREDD MLNDFYVKAL GFDEYTETMA DQVCQLAHRY
PHMNVLEIGA GTGGATKRIF KKLGKRFSSY TYTDISTGFF EKAREVFSEV ESKMTFKALN
IEKDPIAQGY TEGSYDLIVA SLVLHATHVM EDTMRNVRRL LKPGGYLIML ELGDYVDMRT
GLMFGPLPGW WMGYDDGRKL SPTMSEDDWD KCMKKVGFSG VDAIVPRQEH VPISLAIMTA
QAVDEHVEFI RNPFASDGMF LLGHHLTLIG GSTDKTAKLL EAALPYLRSF YKHVTTVKSL
ASLSTIELPF MGSVICLEDL DVAVFENLST ETLQGVQHLF TKSKSCLWVT QGRKDDNPYQ
NMTVGLGRVA TLEMTHLRLQ SLDFDVIDSS TAVIMAKSLL RFEATEAWEQ QGLAKNLLWS
VEPEMSYEKG SFRVPRLIPN HARNNRYNSS RRLITQNKDP RTSTIGLRWT SKGYEIHNES
PASSGLAFDG RVELQVSHSS LEAIRITKAD YAYLVLGTNL RTKEQAFAIT PDRHSIVRVF
DSWTVPYTMT TEEALRLLPL VQDHLMALAT MSDFSSGEAL ILIEPRWRFA RLLSNLAQEK
GVKLILLTTR LDIKDQDWIT LHPNAPRRII QSHMPKTASR LISCTDDLEF EANVKACLPP
NCKMQRTEIF SSRVSKLDSF SSMAFIPSSL RSAFVRAHHE SSPGDKESIA SVSDIVSRGK
PAKATFFSWD SSPTIPVQIT PVDLEPLFSS DKTYWLVGLT GGLGLSLCEW MIQRGAKYVV
LTSRNPQVDA KWEAHMKAHD AVVRIYANDV TDRDSVRSVY KQIRDELPPI GGVAQGAMVL
SDAMFVDMGL ERVCKVVEPK VKGAIHLEEL FSEADLEFFV FFSSMAYVTG NQGQSIYAAA
NAYMAALAAQ RKKRGLAGSV INIGAIVGNG YVTRQLTDEQ RDYLAHMGNV FMSEQDFHQI
FAEGVVAGRP GNDDIPEIMT GLGLAHMDDS DKVTWFNNPK FSHCVLWPDD QGAAVGMSKQ
NVTVKSRLLL ATTADEVNEA IQESFTMKLR SSLQIEDSVA ILKMNAEELG LDSLVAVDLR
SWFVKELNVE MPVLKILGGF TVAELVSAAQ EQLPASLTPN FGKEIDPALK AAAMLEKAAK
TETVPRITNE ANTAAYREEV DEEEQEEDEA DNRPNFFSSA SKDATQSSER FAIDASHISK
SREVAFKATL LAPPATRSKT SSSSSSFTSD PENDFMMKSQ MSAATPLSSY NDEYITAEDI
KFERVSPMSF GQARFWFLKF YLQDQTTFNI TTSIRLSGRL NVETFANAVQ AVGRRHEGLR
TAFFTDRHNQ PMQGILHQSV LHLEHLRVSS QEAIDIEYAK TKNHVYNIGG GETMKIILLS
LADDLYQIII GYHHINMDGM SLEVILSDLQ KVYNQQQLAR VVPQYLDFSE SQRREHSTGK
WGKEISFWKG EFADIPAPLP ILPMSKKSNR SPLTKYASNT VKFKIDAATS AQIQIACKRA
KASPFNFYLA AFKTLLYRTA GEEQNDICIG IADGGRNSEH VEESVGFFLN ILPLRFKQDS
AQTFLEALRD ARSKVVAALA NSRVPFDVIL NEVNAPRAAT HNPLFQAFIN YRQGVQERRQ
FCGCDSEATQ FDGSQTAYDI SIDILANPGA DSTVYISGQS DLYSEENVKL LAHSYLALIK
SFAKNPASRL GRPPLYDPQD THRALDVGVG PELTDTWPNT LVDRVDEMAS RFGSQIALKG
PRNQLTYSQM TDRIHSIASS LKSNKIGNCS RVGVLQDPST DFFCSLLAIL RIGAIFVPLE
LRLTSPRLAV IVEDSNIDAI IYDKANQKDL LTLGSGFQKV NVSLIPAKST STVVNEAQPG
SPAVILYTSG STGKPKGILL SHASWRNQIQ SSTQAFRIPQ GTGVHLQQSS WSFDIAISQT
FVALANGASL LIVSKELRGD SIAMARMIVS DRITHVQATP SEMVSWLHDA DANALRSSSW
KFAMSGGEKM NSALIGEFKA LGKSDLALVN AYGPAETTLA VGSAEIDILD PGALDTAFRL
FPNYSVYILD SKKQPVPLGI SGEVYIGGAG VATGYLNNDN LTKERFLPDD FAPERYLQND
WTIMHRSGDR GRLTADGLVL EGRVDGDTQI KLRGIRIDLQ DIESTIVQHS KGAVRDAVVS
LRKSGETQIL AAHIVLSAAF SGNAKTILDS IQTSLPLPQY MRPATTLVVK TLPTNYSGKL
DRKAVSELPL RPVSKTSVPV TKENKSPESE LRTIWKQVLG DDITSSHEID YETDFFHVGG
NSLALVRVQG MLKAAFNVEP PVAQLFDNST LGAMLNLISP ASQTMSTEHS SLLPNVVEYS
PQAAASSGTI DWEKETALTD DLYDAEINPT PRDQGLAFKT VAITGASGFL GKEILKRMVD
DVHIDKIHAI AIRRHISDLP AIFSNAKVQV HRGDLNAPRL GLSETRAKEI FDETDTVIHN
GADVSFLKTY KTLSKTNVGS TRELVKLCLP SRIPIHFISS ASVAHLSGRA SFGEESVSEY
EPPQDGSDGY TATKWASERF LELVSEKFSI PVWIHRPSSI TGAEAPALDL MTNLLQFSKT
MSKVPYSPTW SGTLDFVSVE SVAHDIVEEV KNDSAHSSGM VRFMYESGDL EIAVQDMQGS
LAKQTGEEFD KVDVETWTRE AVSEGLDELV AAYLSTAANL PIMFPRLIRD NKRRRIEQKV
QEQPSRGSSL REVVGRWLWS RQ
