HPS1_DOTSN
ID HPS1_DOTSN Reviewed; 3974 AA.
AC M2YKT6;
DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Hybrid PKS-NRPS synthetase 1 {ECO:0000303|PubMed:31053329};
DE EC=2.3.1.- {ECO:0000305|PubMed:31053329};
DE EC=6.3.2.- {ECO:0000305|PubMed:31053329};
GN Name=hps1 {ECO:0000303|PubMed:31053329}; ORFNames=DOTSEDRAFT_180045;
OS Dothistroma septosporum (strain NZE10 / CBS 128990) (Red band needle blight
OS fungus) (Mycosphaerella pini).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Dothideomycetidae; Mycosphaerellales; Mycosphaerellaceae; Dothistroma.
OX NCBI_TaxID=675120;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NZE10 / CBS 128990;
RX PubMed=23209441; DOI=10.1371/journal.pgen.1003088;
RA de Wit P.J.G.M., van der Burgt A., Oekmen B., Stergiopoulos I.,
RA Abd-Elsalam K.A., Aerts A.L., Bahkali A.H., Beenen H.G., Chettri P.,
RA Cox M.P., Datema E., de Vries R.P., Dhillon B., Ganley A.R.,
RA Griffiths S.A., Guo Y., Hamelin R.C., Henrissat B., Kabir M.S.,
RA Jashni M.K., Kema G., Klaubauf S., Lapidus A., Levasseur A., Lindquist E.,
RA Mehrabi R., Ohm R.A., Owen T.J., Salamov A., Schwelm A., Schijlen E.,
RA Sun H., van den Burg H.A., van Ham R.C.H.J., Zhang S., Goodwin S.B.,
RA Grigoriev I.V., Collemare J., Bradshaw R.E.;
RT "The genomes of the fungal plant pathogens Cladosporium fulvum and
RT Dothistroma septosporum reveal adaptation to different hosts and lifestyles
RT but also signatures of common ancestry.";
RL PLoS Genet. 8:E1003088-E1003088(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NZE10 / CBS 128990;
RX PubMed=23236275; DOI=10.1371/journal.ppat.1003037;
RA Ohm R.A., Feau N., Henrissat B., Schoch C.L., Horwitz B.A., Barry K.W.,
RA Condon B.J., Copeland A.C., Dhillon B., Glaser F., Hesse C.N., Kosti I.,
RA LaButti K., Lindquist E.A., Lucas S., Salamov A.A., Bradshaw R.E.,
RA Ciuffetti L., Hamelin R.C., Kema G.H.J., Lawrence C., Scott J.A.,
RA Spatafora J.W., Turgeon B.G., de Wit P.J.G.M., Zhong S., Goodwin S.B.,
RA Grigoriev I.V.;
RT "Diverse lifestyles and strategies of plant pathogenesis encoded in the
RT genomes of eighteen Dothideomycetes fungi.";
RL PLoS Pathog. 8:E1003037-E1003037(2012).
RN [3]
RP FUNCTION, INDUCTION, DOMAIN, AND PATHWAY.
RX PubMed=31053329; DOI=10.1016/j.funbio.2019.02.006;
RA Ozturk I.K., Dupont P.Y., Chettri P., McDougal R., Boehl O.J., Cox R.J.,
RA Bradshaw R.E.;
RT "Evolutionary relics dominate the small number of secondary metabolism
RT genes in the hemibiotrophic fungus Dothistroma septosporum.";
RL Fungal Biol. 123:397-407(2019).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the hps1-dma1 gene
CC cluster that probably mediates the biosynthesis a derivative of
CC cyclopiazonic acid (CPA) (Probable). The hybrid polyketide synthase-
CC nonribosomal peptide synthetase (PKS-NRPS) nps1 might incorporates
CC acetyl-CoA, malonyl-CoA, and tryptophan (Trp) and utilizes a C-terminal
CC redox-incompetent reductase domain to make and release the tryptophan
CC tetramic acid, cyclo-acetoacetyl-L-tryptophan (c-AATrp), as the first
CC intermediate in the pathway (By similarity). In addition, the cluster
CC also includes the tryptophan dimethylallyltransferase dma1, the FAD-
CC dependent oxidoreductase toxD, the cytochrome P450 monooxygenase cyp3.1
CC and the methyltransferase DOTSEDRAFT_139328; the latter 2 being not
CC present in all CPA-producing fungi but involved in additional
CC modifications that occur in biosynthesis the of a range of CPA and CPA-
CC like products (Probable). Further studies are required to clarify
CC whether the CPA-like hps1-dma1 cluster is functional or a non-
CC functional relic reflecting evolution of D.septosporum (Probable).
CC {ECO:0000250|UniProtKB:B6F209, ECO:0000305|PubMed:31053329}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:31053329}.
CC -!- INDUCTION: Barely expressed under any of the conditions tested.
CC {ECO:0000269|PubMed:31053329}.
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. Hps1 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), hps1
CC finishes with a reductase-like domain (RED) for peptide release. Hps2
CC has the following architecture: KS-AT-DH-MT-KR-C-A-T-RED.
CC {ECO:0000305|PubMed:31053329}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; KB446545; EME39480.1; -; Genomic_DNA.
DR SMR; M2YKT6; -.
DR STRING; 675120.M2YKT6; -.
DR EnsemblFungi; EME39480; EME39480; DOTSEDRAFT_180045.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_37_4_1; -.
DR OMA; MNSDGRT; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000016933; Unassembled WGS sequence.
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; -; 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; -; 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; 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; 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; 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; 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; 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; PS00455; AMP_BINDING; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 2: Evidence at transcript level;
KW Ligase; Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..3974
FT /note="Hybrid PKS-NRPS synthetase 1"
FT /id="PRO_0000447726"
FT DOMAIN 3537..3613
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:31053329"
FT REGION 8..445
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31053329"
FT REGION 561..883
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31053329"
FT REGION 954..1251
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31053329"
FT REGION 1398..1529
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31053329"
FT REGION 2108..2282
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31053329"
FT REGION 2492..2516
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2560..2994
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31053329"
FT REGION 3021..3423
FT /note="Adenylation (A) (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31053329"
FT REGION 3657..3940
FT /note="Reductase (RED) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31053329"
FT COMPBIAS 2499..2516
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 3573
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3974 AA; 431061 MW; 5B02176572779AB3 CRC64;
MKEQSQKIAI IGSACRFPGG ATSPSKLWQQ LVQPQDLLRP VPRDRFALST YHNHDGTKPG
ATNVTNKAYL LDEDPMEFDA SFFSISPAEA QGMDPQQRQL LEVTYEALES AGYGLSKVSG
SSTGVYVGSS GADYRDIQNR DLDTLGRWHA TGTASSILAN RISHFYGLCG PSLTLDTACS
SSLVGLHLAV QAIRNGDCEQ ALVAGSNLIL DPTPYISGSR LKLFSPDAQC RMWDESGKGY
GRGEGVAVVL LKPLVNALLD GDHVEAVIRE TGVNQDGHTP GITMPSAEAQ TNLIRHVYAK
AGLDPRVTAP QFFEAHGTGT AAGDPVEARA IYESFFGDGK TVTNQAGAPK LNVGSIKTVI
GHLEGAAGIA GLLKATLALQ HAHIPPNLLF KKPNPALVPY LDALEVPVTA KQWPAVEEGT
PRLASVNSFG FGGTNAHCLI ESFPQDDSHP TGKRGLGRQE SEETCIGPVV LSAQSGRSLM
SAMKVLASYI ESNPGARLRD LLHTLGRRRS KLSVRTFFVA TSRQELISQL RHSAENVKDA
TGFGFRPPAR LVGGSQGVLG IFTGQGAQWA TMGRVLYQRC GQFRASIERC QAALDALPDG
PQWSIAEEML KTKQASRLSE AAVSQPLCTA LQIALVDLIE LAGLRFDAVV GHSSGEIAAC
YYMGLITSRD AICIAYYRGV HSSLAEGTNG QKGAMMAVSM THNESNEFCS RPDFQGRIHI
AAHNAPSSVT LSGDADAIFR AQKELAGAGI FARVLKVDTA YHSDQMLPCV APYLQSLESL
NIPIREPRSD CIWVSSVRPD SFDSSSSLNL EEMRSQYWLD NMVQPVLFAP AIAKALRQHG
SSFDMAVEIG PHPALAAPAK DTIMEFSGTV PLYTGILERG LDDVHASSTA IALIWQQMTD
DNIDVATYAE AFDVTGDPPA KLLKGLPSYE WDHKPYWRES RISRTIRRRE NDSHPLLGSR
LSADARNEFR WRNILRLVDV PWLSGHVFQD KTMLPLAAQV SMVIDACSLA FPQSSVESID
ITDLEISRDI LVEAEGPETE LLSTLRVVDR NTTADGTTSI SAAWSCHVSH DSELGIPESV
CICQVQFSFG SGLAASLPRR VSDPSTTTPI SSAKIYESFD HDGLQYSGLF NRLSSVSQAL
GFASASASWT CDELQDHKLH PAVLDVGFQL LMPATFSQKA ENACGPYLPR SVACISLRRG
FASLKTGEGL SLAIDAFSAV EESSNVLGDV AFYSASGECV IQVESVKLVP VITPDASNDR
RIFTKDVWIE DTFDLSPYAC DQDLEDDTGH LAGLVDRLCL YYCRQALDNM CGAVTLLSPL
RLLHEELQAV IEAVKSGNHI SLAAEYAEDS YDSLMEECLP YHDHKALKRV HELGQNLVKI
MQGTTSSPRL RGARLDYPWN TELRNAIAIL GHRITQKHPN MNILEIGNGD SGMTAHILQS
IGTAYLSYTC ASPRSMLSQS SPVDVLGNVE LKSMNILQEP ERQGFDRHKY DLLISSAPIH
GDAAFQTALS NMRTLLRPGG YLLLVAKTGT NLLTTLTLGT SVVSGLESIE ESNTPAGKSP
SELDSLLLAC EFSGLEQIVQ DSPHVLTNAY SLIASHAASH MFNLVHNPRP SMAQIIDERA
RILLIGGRSL ATARLVRDVR KMLSEVTPHI VFVDSIEKLE ALPIEDDFDC LCFNDLDQPL
FAGRRNAKTL EYLQKLYGNV RNLLWYTSGR IHKPEASMSI GVGRSLCGDA PWHNSQFIDV
SSAAKVTAHS VVEAYCRLAL APTIASSNEN LLWSVEPELV IQGDRTLISR VVENRSINDR
FNATRRPILR EAKYSEIEVC LKQDPQGQVQ LAQYIPVQTI AHNAGLCRIR VKYTAALVAA
DAAKAALCFG HRVGTETPVF AITKQAGSLV VTPEAATLVC ENETIDPVHN LSSMALYIQA
AICASRAAQE GRTLLFGVRE DVIGAVQTSP LWKDKPVIIV VIDSDDRQCA DGVIFLHPMS
TRRAIRKKLS QQIDMALDCS SFGHDQLWSR VISTLQCRHE KLTAVDFFAE SSLSSLQGWL
QEAHVAAPQM WHPQPEARAF DILPIQSIGQ EGSSSQISSA IVAWQATENF TYRVAGLESE
KLFSDSKTYF LAGMTDSLGL SISAWMIRSG AKHLVLAGRD PTIPPQWLEE MSSLGANIKV
LTVDICQKVM LTKAVKEIQA HMPPIAGVCN ATLVLSDGLL ADETFESFDR TLKAKIDGSR
NLDQVFSEPS LAFFVLFGSM VSVTGNSGQA DYHAANLYMS SLVNHRRSRG LAASIMDTGV
VTDVGLVQQG GDAVATMARR QYVEPISEAT LHHWVGEAVL ASPVSSGEES RIVVGPKRVP
RTLDPDLRPA WYSNPRFSHF LIDDASPTSS DSQGSASLLE RLQLAASEDH MLAILMEAAQ
AKLEALLGME HGAVAAGGAG SLLSFGVDSG VALQASNWLA QEVHVRMPVM KLLTTPNLKQ
LCLDVMRNMA TDLPRCSAKE TAIGGTVMSV RAGRSASPGA SCSDRSLSTR SDETRSIRTP
ALASSLQDSF VHTGASTPID TLTSADSLHS ATASGSAKGA PLSPGQAQLW AATIQSGNDT
RYNFTLQFDV EGAIDVDRLR SALVSLIAQQ EMLRCSFVEV SAGEVQQRVW PGKDLSRCFK
HLPPGDLRRA EEEYERLSQH CWQLSEGDTF MLVLTNGPAD KHVITLAAHH IIMDGMSIAM
FFRLLALAYE GQHLPVLQRA YTAYAEEHVA ELAADRLDDK LEFWKTCLSP LVPTMPVFPM
AISGVRKALD DGDTGILTVK SSISAPVVDR IKSMGRKLRC TPFHFMTTAL IVLCAKMLHL
KDICIGVTDA GRLDERDGET VGHFADILPL RTRVEPGTSM ADLVPIVLHN IAQAAENAGV
PFSSIVRATK TPRSATHSPI FQVGFNFLPG DARTQFGAST MQWRTGNLAQ SLNDVSWWVH
ARDDGSYTMQ VDGRSDLYSL DGLDLLMQTY KDLAETLCTE PNTNLERLRT SSDQAIKAAD
EAGLGQAKDF GWETTLPDRF DAMAEKYFDQ RAAVDSAGGV TYEELRHRVH DIAAALQDSG
SAPGAAVAVI TGPSVNTLAS MLAIIRIRCV YVPLDLSLPH ARHTAMIKDC GARVLLFEDS
TAERASALRM DGMEVVNVFE LLTVGRTQRE VSNLSDPHEP AILLYTSGST SVPKGVVLSQ
AGFLNYVAAK TAFLGLEREM VLQQSSISFD MGLAQMLHSF CNGGTLVIVP QHARGDPVAT
AQIMLAHHIT FTVATPTEYT AWLSTSSHTI DQYDQWRHVC YGGEFVTDRL SAMFRQLQRQ
KPLLNNSYGP TETSCATTLC VMSEKGSPAM IGYVGKPLAN SRIRIVDQDG QPLPLGHAGE
ICIGGPGLAV RYVNPDDTRN RFIMQQEVSS SSQASTQAPR RLYRTGDRGK LLVDGSLILL
GRMEGDTQVK MHGLRIDVTE VEHALLNAIP DFLAEAIVTM RGAADNAFLV AHVVMSAGIT
ASKGELQLLT RLLRLPRYML PKSIIAVDGL PTTTSGKIDR RAISQLPLEA PGSKKTSADQ
LVEAEVLRIW REVLGEEAHL DSESDFFSVG GDSLLVIKLQ AGIKALMGLS ISLAELYETS
TLREMAEKMA SVRRTQPKPS LIDWDAEVQV PTPIAKLAAA ARPDDHAESA ATSGTEVVLT
GAADLLGYEI LVALLNEPSV RVIHCVAIAE GHGARLPSDA RVVVYPGSLR HPTLSLSDEE
RSNLQDRAHA IIHAGAEGHC LNNYATLRSA NLLSTQFLAQ IALPRCLPVH FVSGTRVTLL
SGTSSLPPLS VASYRPAQHG HDGYTATKWA SEVFFEALTR LSPALPVTIH RPCALTGMNA
APDNVMNALV RCSAAIKAVP RNDEAEGYVD FKDARTVAHD MVEQVLAGLG HDPQRACSAG
VRFIHHSSGH KVPARDLGRR MEMLYGGTFR KLEMGEWIAL AKASAGLHYL AATFLEAMMD
KHVTSVYPYM GEEI
