ASC7_DIDFA
ID ASC7_DIDFA Reviewed; 1886 AA.
AC A0A5C1RDA3;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2019, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Highly reducing polyketide synthase {ECO:0000303|PubMed:31554725};
DE EC=2.3.1.- {ECO:0000305|PubMed:31554725};
DE AltName: Full=Ascochitine biosynthesis cluster protein 7 {ECO:0000303|PubMed:31554725};
GN ORFNames=orf7 {ECO:0000303|PubMed:31554725};
OS Didymella fabae (Leaf and pod spot disease fungus) (Ascochyta fabae).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Didymellaceae; Ascochyta.
OX NCBI_TaxID=372025;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=AF247/15;
RX PubMed=31554725; DOI=10.1128/msphere.00622-19;
RA Kim W., Lichtenzveig J., Syme R.A., Williams A.H., Peever T.L., Chen W.;
RT "Identification of a polyketide synthase gene responsible for ascochitine
RT biosynthesis in Ascochyta fabae and its abrogation in sister taxa.";
RL MSphere 4:0-0(2019).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of the selective antifungal agent
CC ascochitine, an o-quinone methide that plays a possible protective role
CC against other microbial competitors in nature and is considered to be
CC important for pathogenicity of legume-associated Didymella species
CC (PubMed:31554725). The pathway probably begins with the synthesis of a
CC keto-aldehyde intermediate by the ascochitine non-reducing polyketide
CC synthase pksAC from successive condensations of 4 malonyl-CoA units,
CC presumably with a simple acetyl-CoA starter unit (Probable). Release of
CC the keto-aldehyde intermediate is consistent with the presence of the
CC C-terminal reductive release domain (Probable). The HR-PKS (orf7)
CC probably makes a diketide starter unit which is passed to the non-
CC reducing polyketide synthase pksAC for further extension, producing
CC ascochital and ascochitine (Probable). The aldehyde dehydrogenase
CC (orf1), the 2-oxoglutarate-dependent dioxygenase (orf3) and the
CC dehydrogenase (orf9) are probably involved in subsequent oxidations of
CC methyl groups to the carboxylic acid of the heterocyclic ring
CC (Probable). The ascochitine gene cluster also includes a gene encoding
CC a short peptide with a cupin domain (orf2) that is often found in
CC secondary metabolite gene clusters and which function has still to be
CC determined (Probable). {ECO:0000269|PubMed:31554725,
CC ECO:0000305|PubMed:31554725}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:31554725}.
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; an enoylreductase (ER)
CC domain that reduces enoyl groups to alkyl groups; a ketoreductase (KR)
CC domain that catalyzes beta-ketoreduction steps; and an acyl-carrier
CC protein (ACP) that serves as the tether of the growing and completed
CC polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:31554725}.
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DR EMBL; MN052628; QEN17975.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A5C1RDA3; -.
DR SMR; A0A5C1RDA3; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
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; 3.40.47.10; -; 1.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR002328; ADH_Zn_CS.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
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; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 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; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF53901; SSF53901; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 3: Inferred from homology;
KW Multifunctional enzyme; Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW Transferase; Virulence.
FT CHAIN 1..1886
FT /note="Highly reducing polyketide synthase"
FT /id="PRO_0000448991"
FT DOMAIN 1802..1879
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 14..437
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000250|UniProtKB:A0A098D8A0, ECO:0000255"
FT REGION 483..568
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000250|UniProtKB:A0A098D8A0, ECO:0000255"
FT REGION 618..924
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000250|UniProtKB:A0A098D8A0, ECO:0000255"
FT REGION 1169..1480
FT /note="Enoylreductase (ER) domain"
FT /evidence="ECO:0000250|UniProtKB:A0A098D8A0, ECO:0000255"
FT REGION 1503..1681
FT /note="Catalytic ketoreductase (KRc) domain"
FT /evidence="ECO:0000250|UniProtKB:A0A098D8A0, ECO:0000255"
FT ACT_SITE 182
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 182
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 648
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1839
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1886 AA; 206316 MW; 414DB1DE4328229D CRC64;
MPSTDSSTKG TQDVAIVGLS CRFSGSATSA NKFWDMLCNG ESGHSETPRF NPKGFSDPGF
RKQNQSATAY GHFLQQDVGA FDSRFFGITP EEALAMDPQQ RMMLEVAYEA FENAGMTIEQ
LAGSRTSCFI GSFTSDYREM LFRDADAAPR YTVTGTGVSM LANRVSWFFD LRGPSVALNT
ACSSSLVALH LARRSLQSGE ADIAIVGGTN LMLGSEMFTF FSNLNFLSRD GLSRSFDASG
EGYGRGEGVA AVILKRVDDA IQDNDNIRAV VRGTSTNQDG KTKAITLPSL DAQIDLIRSA
YKEGGLSFND TTYFEAHGTG TRRGDPVELE AISKTLCVDR PTNSKIIVGS VKSNVGHTEA
TAGLAGIIKA IYMLEKGIIP ATINYSRPLP EFDLNSSLLT IPVETKPWPG TSVRRISINS
FGFGGANAHA VLDDAPSYLA SKSLGNGTKD ANSNAPVLRT NGSLVNGNGA NEDVQTSTEQ
LSFLFSGQDQ QSLDRNFETM VQHIQTKSFS DSRSELQYLV DLAYTLSERR SRFKVRAEVV
ASSVTQLVSK IQERSFARVN NDLANTKKSI PAEERTCELK RRVLVDLPAY SWDHSSTYWA
ESRVSKEFRL RKHPQRSLIG APQPSYGENE HIWRGYLRLS EEPWVKDHQV LGAIVYPAAG
YIAMAIEAAQ DIADKGRKVS RYNLRDVQFQ AAAVIKEDVP LELIIQMRPH RSATRSTATS
WLEFSISSCH NEKNLRDNCF GLLSIEYESS QDSSMALEQE REDALVLDKH RRTAEVCHTT
QSPKALYQEL ASVGLNYGEA FQQISEISKT DGLSSCRVLS YVPDRFSTPN VIHPATLDCM
IQTIFPALSG NHTPIHAAMV PTLLEEMSVA SRTPNAAASF FRGSASARYS GAREMLAEFA
MVDQDNKLSV TARGLHCTAI SEATNPRTEQ DEDGRRNICS QLMWVPATGV DSVEQVQNKA
TAPTQTFPPH DQDILILEGD HAYATALSDA LMSLDQGKGS YIPIPKSFLR ASLQDLEGKT
CIATLEMGTS FLANAATDGF DTLKEIVRRC SRIIWVSSST EPIGSVITGL ARTMRNENAG
LVFRTLQVPS QDMYDSENLA EVVSQLAASP TMDSEFRLEG GVLRVSRVLR DTKTDNMVAS
MARNGGPEIR LSTLSQVGTA QKLALPRLGM LDEIYFEADE TANGLLRDEE VEIEVKASGV
NFRDVLVVMG NVSDDLIGHE ASGIISRVGS KVTSFRVGDR VCAIGHGCHR SVYRSTADLV
HKIPDGMSFE EAATVPLVYT TAYTAIIDLA RAQKGQSILI HAAAGGVGLA AIQIAIHLGL
EIFATVSSEP KRQLLHDHGV MEDHIFNSRD ISFAKGIMRT TTGRGVDIVL NSLAGEQLRQ
SWHCLAPFGN FVEIGIKDII TNSSLDMSPF AKDATFTAFE VINIMHKDPK RMANILRNVF
QLLGNRSVKP VKPLLSKPIS EVGEALRLLQ AGKHMGKVAL TWDRGQTIPM ATTVVKPVLS
DTATYVLVGG FGGLGQSIAR MFADRGARHL CILSRSGARS REAVETINKL ENQGVQVQSL
ACDVSDEGSL RTAFETCKIE MPPIRGVIQG AMVLRDISFE KMSHNQWHEA LKPKVDGTWN
LHKLMLRDLD FFIILSSFMG IFGSRTQGNY AAAGAYQDAL AHHRRSQGLK AVSLDLGLMR
DVSAFSKKEA LSGPFKDWQE PFGLREVDVH GLLDHVIASE MTAPSTIPAQ ILTGFGTARE
AEEAGIEPPY YLEDPRFSLL HTTIVEAQQD TATQQQPAAT PPDLVAKHTT GDLLRQATST
EDVTDLVLEI LIVKVAKHLE QNVANIDPEE PLYTYGVDSL VAIEFRNWIM KEFAADIALL
DITAEEPMFD LVDKIVAKSK FLSVPS
