ASC5_DIDFA
ID ASC5_DIDFA Reviewed; 2645 AA.
AC A0A5C1RD96;
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=Non-reducing polyketide synthase AC {ECO:0000303|PubMed:31554725};
DE Short=pksAC {ECO:0000303|PubMed:31554725};
DE EC=2.3.1.- {ECO:0000269|PubMed:31554725};
DE AltName: Full=Ascochitine biosynthesis cluster protein 5 {ECO:0000303|PubMed:31554725};
GN Name=pksAC {ECO:0000303|PubMed:31554725};
GN ORFNames=orf5 {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], FUNCTION, DOMAIN, DISRUPTION PHENOTYPE,
RP AND PATHWAY.
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: Non-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 (orf2) that is often found in secondary metabolite gene
CC clusters and which function has still to be determined (Probable).
CC {ECO:0000269|PubMed:31554725, ECO:0000305|PubMed:31554725}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:31554725}.
CC -!- DOMAIN: Multidomain protein; including an N-terminal starter unit:ACP
CC transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a
CC malonyl-CoA:ACP transacylase (MAT) domain, a product template domain, a
CC acyl carrier protein (ACP) domain, a methyltransferase domain (CMeT)
CC and a reductive NADPH-binding domain that is required for NADPH-
CC dependent product release (Probable). The CMet adds methyl groups as
CC check-point tags, which are recognized by KS, such that a lack of
CC methylation causes release of immature products at the triketide stage
CC (By similarity). {ECO:0000250|UniProtKB:Q65Z23,
CC ECO:0000305|PubMed:31554725}.
CC -!- DISRUPTION PHENOTYPE: Blocks the production of ascochitine and its
CC derivatives. {ECO:0000269|PubMed:31554725}.
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DR EMBL; MN052626; QEN17973.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A5C1RD96; -.
DR SMR; A0A5C1RD96; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
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; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 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; IPR013120; Far_NAD-bd.
DR InterPro; IPR041068; HTH_51.
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; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF18558; HTH_51; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
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 3: Inferred from homology;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Phosphopantetheine; Phosphoprotein; Transferase; Virulence.
FT CHAIN 1..2645
FT /note="Non-reducing polyketide synthase AC"
FT /id="PRO_0000448990"
FT DOMAIN 1711..1788
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:31554725"
FT REGION 73..2366
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31554725"
FT REGION 419..837
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31554725"
FT REGION 943..1252
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31554725"
FT REGION 1330..1641
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31554725"
FT REGION 1684..1716
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1794..1816
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2023..2197
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31554725"
FT REGION 2269..2573
FT /note="NADPH-binding (R) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31554725"
FT COMPBIAS 1684..1699
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 260
FT /note="Proton donor/acceptor; for transacylase activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0K0MCJ4"
FT ACT_SITE 583
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2009
FT /note="For methyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:Q65Z23"
FT MOD_RES 1748
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2645 AA; 291898 MW; 1BD9BD0CF83AE88C CRC64;
MPHRLPSHGA SLGLIFGPQA MNFDSNTFTT LRAKLVKDRH SQWAIDAIAA LPAEWSAVSG
NVAIFKQYDA GKALQNLNEW LKTGHVPPAD IPFCNVLLAP MVVIDHVISY LEFLQSAFPD
LDDDEELPAS AKESLETLGL SLGTLSAFAV SSSSTLSEVK KHGATAIRLA MLVGAVGDAE
DLAREPEEGA LSFSAFWKST ELHDLLHTSL DAIPEAYISV AVDEKRSTIT TSRSKASSHM
QDLRSSGLYI AEVSIRGRFH WDGHESTLQE LIQYCDRNLQ FQFPDTSRIV LPSHSVTGGE
YITQEDGSLH AIALRAILVD LSQWLETITG AYGSESSKGI KSVVCFGPER CVPSALVRRL
GSKLTHVLDV DLPTSALPKQ LLQSADVSST NGVKIPASIK GQSPARQHPI DIDANDDKIA
VIGMACNVPG GEDMDEFWKI LVAGKSQHEE LPRGTGRFEF ETPWREPYTK TKWYGNFIKD
YDVFDHKFFK KGPREMLNTE PQHRLLLHAA YQTLEQSGYF SKPDYDKHIA CFLGPGHVDY
ASSVNCYAPN AYTATGNLKS MCAGKISHHF GWTGPILTLD TACSSSCVAI HYACRSILSG
EVSAALAGGS NVLSSVEWYE NLSGAQFLSP TGQCKPFDAK ADGYCRGDGI GLVFLKKLST
ALADGDQVYG VIAGSKVYQN VGSTTITVPN ADSLATLFKD ITKQARIDPA KVSVVEAHGT
GTPVGDPAEY EAICRIFGGS QRTDVLSLSS VKGLFGHTEG ASGVCSLLKV LLMMHENAIP
PQASFGSMNP GLKATTQDNI EVPTRLTPWK PNTQIALINN YGASGSNSSL VVTEPPAFET
FDHEALQYRA FPFWIPGLDD KSIQRYATRL RAWFQRHHSS SKDLSMRNMS FQLAFQSNRT
LPQALVFKAA SVSDLESKLK AFENGTLNSI SSAATSQRPV ILCFGGQIST YIGLDREVYE
NVAVLRQFLD QCDETSVSLG FPSVFPHIFQ KEPIYDLIKL QLALFAMQYS CAQAWIACGV
EVAAVVGHSF GELTASCVSG TVSLQDAITM IAGRARLIQK KWGTDSGAMI AVDTELSGVN
DLLAKTREGS GADDNPSIAC YNGHRSFTLA GTTKSIEQAE SILKQDATFS STRWKRLNVT
NAFHSVLVDS LHHDLQSLGK RIVFNEPKLH FERSTKERMS GKPNSDYIAH HMRNPVYFDH
AVQRLAKDFP AAIWLEAGSN STITSMANRA LSSSAASSTS SFHAVSITTD KSFDLLVDST
LKLWKEQLNV SFWAHHRSQT HQYTPMILPP YQFEKSRHWL ETKPPPKPEP IPVEKSTTQA
VETSKGFTSF AGYIDGNQRS LRYRINSNHE TFQRHVNGHI CAKLAAVWPS SIQIDMVLDA
LMNLRAEFKD LSYQPQISNI VHHRPLLLDN SKDYWLELVA KDDKGLTWDW NFSSSSGLGS
KSTICTSGVC SFCSATDPNR LAEFQTLERL SSRRRCVELL EARDVENIMQ GTANIYRAFS
EVIEYTDDYR YVKKLVGHNN ESAARVVKKH YGKTWLDYLL FDGLGQTAGM YVNLMADKAN
VSEKGIFMCE TINRWLRSPT IRSHESLPTD WEVYAVHHPI SDKKYVSDIF SFDARDGSLV
EVVLGASYNK VPLPVMRGIL GSQSSTTRLD AITANAEIPS QAGIGSQQPH LNFKPLSALP
ALSNGTTGTE NPQIKSKTNK VKKVPTRKSG GSDLETPAKT RNILENLTGV EASSINDDSN
LIDLGLDSLL SMELIRDVED IFKVDLDAEQ MLDLTDFASL VKYIREIRGV LEEQNVDDSE
SESEELQQQA TPIDSATRQN HEKLTMNGTG LLTNGESVPE VPLDSTLVLD AFRYIKEASD
DFIVKNKFET YCAEFMPRSE EVSIAIFCNA FEELGCPIRT ATAGTRLERV QHLPKHKKVV
DYIYKALEKN AGLIEISGEE IIRTSVPCPS EQTEAMLESL LHDRPAQDAE IQLMRITGAA
FGKCLAGKAD VLPLLFGSIE GRALLTKLYA TSTLSNTILQ QLEVFVEKIG SSWPKDGGPL
RILEVGAGTG GTTTKIVPVL ARLGIPVEYT MTDVSSFFTA TGRTKFKEYP FMKFKTVDIE
KEPDAKLLKT QHIVLGSNVI HATRVLSVSL SNIHKMLRPD GLIIYHELTS QLLWADIIFG
LVEGWWLFED GRDHALQSPQ HWEKILRSVG YGHVDWTDGT RPEAKIQNLI FAMASDPTYD
REPLPTASIM TDVADQVATV NAYVCQYSSN FQFRRNSASR ATGLSSGRCV LITGATGSLG
AHLVAYCAER LDVSKVICFN RTSQTAGVAR QAKAFKSKGI SLEVNTNPKL EVIETDASKD
QLGLSPSEYA ALVDSVTDIV HNAWPMSINR GVRSYEGQFR VMRNLVDLAR DATMQRPEPF
KFGFQFISSI GVVGMYPLLT NNFLVPEHRM PVESVVPSGY GYAKLVCERM LDETLHLYPQ
AFHPSAVRIN QIAGSTRSGY WNRNEHLVFL IKSSQTLNAL PDLQGHLTWC PVDTVAATLG
ELLLDNANSV ASAHPIYHIE NPSRQSYSEM IRVLADSLFI DHANIIPFYD WVQRVRDFEG
PVTENPAKQV VDFFDEHFLR MSCGDLVLDT VKSREISATL RARGVITSDL VNKYVEAWRR
AGVLR
