PATK_ASPCL
ID PATK_ASPCL Reviewed; 1720 AA.
AC A1CFL8;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=6-methylcalicylic acide synthase {ECO:0000303|PubMed:19383676};
DE Short=6MSAS {ECO:0000303|PubMed:19383676};
DE EC=2.3.1.165 {ECO:0000305|PubMed:19383676};
DE AltName: Full=Non-reducing polyketide synthase patK {ECO:0000305};
DE AltName: Full=Patulin synthesis protein K {ECO:0000303|PubMed:19383676};
GN Name=patK {ECO:0000303|PubMed:19383676}; ORFNames=ACLA_093660;
OS Aspergillus clavatus (strain ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 /
OS NRRL 1 / QM 1276 / 107).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=344612;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 1007 / CBS 513.65 / DSM 816 / NCTC 3887 / NRRL 1;
RX PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT fumigatus.";
RL PLoS Genet. 4:E1000046-E1000046(2008).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=15082620; DOI=10.1093/ije/dyh028;
RG Patulin Clinical Trials Committee, Medical Research Council;
RT "Clinical trial of patulin in the common cold. 1944.";
RL Int. J. Epidemiol. 33:243-246(2004).
RN [3]
RP FUNCTION.
RX PubMed=19383676; DOI=10.1099/mic.0.024836-0;
RA Artigot M.P., Loiseau N., Laffitte J., Mas-Reguieg L., Tadrist S.,
RA Oswald I.P., Puel O.;
RT "Molecular cloning and functional characterization of two CYP619 cytochrome
RT P450s involved in biosynthesis of patulin in Aspergillus clavatus.";
RL Microbiology 155:1738-1747(2009).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=22222931; DOI=10.1016/j.fct.2011.12.022;
RA de Melo F.T., de Oliveira I.M., Greggio S., Dacosta J.C., Guecheva T.N.,
RA Saffi J., Henriques J.A., Rosa R.M.;
RT "DNA damage in organs of mice treated acutely with patulin, a known
RT mycotoxin.";
RL Food Chem. Toxicol. 50:3548-3555(2012).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=26619846; DOI=10.1007/s13277-015-4474-z;
RA Boussabbeh M., Ben Salem I., Rjiba-Touati K., Bouyahya C., Neffati F.,
RA Najjar M.F., Bacha H., Abid-Essefi S.;
RT "The potential effect of patulin on mice bearing melanoma cells: an anti-
RT tumour or carcinogenic effect?";
RL Tumor Biol. 37:6285-6295(2016).
CC -!- FUNCTION: 6-methylsalicylic acid synthase; part of the gene cluster
CC that mediates the biosynthesis of patulin, an acetate-derived
CC tetraketide mycotoxin produced by several fungal species that shows
CC antimicrobial properties against several bacteria (By similarity). PatK
CC catalyzes the first step of the pathway which is the synthesis of 6-
CC methylsalicylic acid via condensation of 1 acetate and 3 malonate units
CC (By similarity). The pathway begins with the synthesis of 6-
CC methylsalicylic acid by the polyketide synthase (PKS) patK via
CC condensation of acetate and malonate units. The 6-methylsalicylic acid
CC decarboxylase patG then catalyzes the decarboxylation of 6-
CC methylsalicylic acid to yield m-cresol (also known as 3-methylphenol).
CC These first reactions occur in the cytosol. The intermediate m-cresol
CC is then transported into the endoplasmic reticulum where the cytochrome
CC P450 monooxygenase patH converts it to m-hydroxybenzyl alcohol, which
CC is further converted to gentisyl alcohol by the cytochrome P450
CC monooxygenase patI. The oxidoreductases patJ and patO further convert
CC gentisyl alcohol to isoepoxydon in the vacuole. PatN catalyzes then the
CC transformation of isoepoxydon into phyllostine. The cluster protein
CC patF is responsible for the conversion from phyllostine to neopatulin
CC whereas the alcohol dehydrogenase patD converts neopatulin to E-
CC ascladiol. The steps between isoepoxydon and E-ascladiol occur in the
CC cytosol, and E-ascladiol is probably secreted to the extracellular
CC space by one of the cluster-specific transporters patC or patM.
CC Finally, the secreted patulin synthase patE catalyzes the conversion of
CC E-ascladiol to patulin (PubMed:19383676) (Probable).
CC {ECO:0000250|UniProtKB:A0A075TRC0, ECO:0000305|PubMed:19383676}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 3 H(+) + 3 malonyl-CoA + NADPH = 6-
CC methylsalicylate + 3 CO2 + 4 CoA + H2O + NADP(+);
CC Xref=Rhea:RHEA:12240, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:36658, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=2.3.1.165;
CC Evidence={ECO:0000305|PubMed:19383676};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12241;
CC Evidence={ECO:0000305|PubMed:19383676};
CC -!- PATHWAY: Mycotoxin biosynthesis; patulin biosynthesis.
CC {ECO:0000305|PubMed:19383676}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:A0A075TRC0}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm (By similarity).
CC {ECO:0000250|UniProtKB:Q5B0D0}.
CC -!- BIOTECHNOLOGY: Patulin was originally used as an antibiotic and
CC specifically trialed to be used against the common cold, but it is no
CC longer used for that purpose since it has been shown to induce
CC immunological, neurological and gastrointestinal effects
CC (PubMed:15082620). Genotoxic effects of patulin with dose-dependent
CC increase in DNA strand breaks in brain, liver and kidneys have been
CC detected in mice (PubMed:22222931). However, more recently, it has been
CC proposed that patulin might also have anti-tumor properties
CC (PubMed:26619846). {ECO:0000269|PubMed:15082620,
CC ECO:0000269|PubMed:22222931, ECO:0000269|PubMed:26619846}.
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DR EMBL; DS027052; EAW11667.1; -; Genomic_DNA.
DR RefSeq; XP_001273093.1; XM_001273092.1.
DR AlphaFoldDB; A1CFL8; -.
DR SMR; A1CFL8; -.
DR STRING; 5057.CADACLAP00008433; -.
DR EnsemblFungi; EAW11667; EAW11667; ACLA_093660.
DR GeneID; 4704855; -.
DR KEGG; act:ACLA_093660; -.
DR VEuPathDB; FungiDB:ACLA_093660; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_35_3_1; -.
DR OMA; HRRFWRT; -.
DR OrthoDB; 19161at2759; -.
DR UniPathway; UPA00918; -.
DR Proteomes; UP000006701; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; ISS:GO_Central.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0050641; F:6-methylsalicylic acid synthase activity; ISS:GO_Central.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0140723; P:patulin biosynthetic process; ISS:GO_Central.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 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; 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; 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; 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; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Multifunctional enzyme; NADP; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1720
FT /note="6-methylcalicylic acide synthase"
FT /id="PRO_0000437111"
FT DOMAIN 1644..1718
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..402
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 509..823
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 868..1139
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1148..1545
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 14..29
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 146
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1678
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1720 AA; 185005 MW; 828565A00E61ADB3 CRC64;
MDKQSASGEI PAMRWEPYHR RDPRNAKELS KTTSRGYFLD HLEDFDSQFF GISPKEAEQM
DPQQRISLEV AWEALEDAGI PAKGLSGSDT AVFWGVNSDD YSKLVLEDLP NIEAWMGIGT
AYCGIPNRIS YHLNLMGPST AVDAACASSL VAIHHGVQAI QLGESKIAIV GGVNALCGPG
LTRVLDKAGA ISSEGFCRSF DDEAKGYGRG EGAAAIILKN LSRAINDKDR ILAVIKGSAV
AQDGKTNGIM APNAKAQQLV AQNALAVGNI DPLTVRYVEA HATSTPLGDP TEISAIAAVY
GVGRDSQDPC FIGSIKPNIG HLEAGAGAMG FIKATLAIRK GILPPQANLN KLNSRIDWDK
AGVKVVQEAT KWPETDTIRR ASICSYGYGG TVSHAVIEQF LPLSGLESLQ TQSPDGPGVL
LLSGPQQKRL SVQAETLRKW IAQDGRNHDL SSVLTTLATR RDHHDYRAAM VVESHDDAET
ALEALAKGAD HPLVAQGRVL GTDIRKDVVW VFSGHGAQWT DMGKELLNNP VFYRAIQPLD
ELVQAEIGLS PIEMLLTGDF DSSDRVQILT YIMQIGISAV LKSNGVFPQA IIGHSVGEIA
ASVVAGALTP AEGALIVTRR AALYRRVMGQ GGMILVNLPA SQVEQELGQR EDLVVAIESS
PSSCVVAGDR DVVAQAAESF KERGVKTFTV KTDIAFHSPT LNGLIDPMLE ALAEDLAPST
PTVRLFSTSL VDPRGQDLRD IHYWTNNMVN RVRLTSAVNA AVEEGYRIFL EVSSHPVVTH
SINETLMDGG LEDFAVIPTL LRQKPTEKHI LYSIAQLHCR GAEVDWKAQL PGPWADGLPT
TTWMHKPIWR KIESAPLHTG LTHDVEKHTL LGQRIGIAGT NTTVYTTRLD NDTKPFPGSH
PLHGTEIVPA AGLINTFMKG TGGRRLQNVV LRVPVAINAP RSVQVVVQED QVKIMSRLLS
DTPQATEDDS SWATHTTAYW ARDIQEAVDP IDIAAVKKRL GTRIRDDFSI NYLDQVGVSA
MGFPWAITEH YHKDKEMIAR VDVNPAVTGD APLPWDSSSW APILDAATSV GSTVFGTPAL
RMPAQIDRVD IFTSQDPPKI GWLYVEDASD AAPTSHVSVL NEAGEVVAKF TAMRFSEIEG
TPGVSGSMES LVHQLAWPPA TPAEEPLSID TVLLVSSDAA TMRQYANTIP RGVRSFEFSS
VQDLISQDKS GLRLDKGTAV AYIPGEVQSL EEIPAASESF TWEVLELVKY IVKGGLPLKA
FILTSNVGSG ETPTALAQAP LFGLARIIAS EHPDLGCLID SENPVFPLTA MRYIQGADVI
RINDDVARTA RLRSLPRNKL HPASQPPRLL PRSEGTYLIT GGLGVLGLET ADFLVENGAR
RLILISRRAL PPRRTWDAAP SDLQPTLAKI RNLESRGATV HILPLDISHP AAATQLSTAL
DTLSLPPVLG VVHAAGVLDN QLILETTRDA FTRVLAPKIA GALALHAVFP PNTLDFFLLF
SSCGNLFGFP GQASYGAGNA FLDTLATHRA RLGDAAVAVQ WTSWRGMGMG ASTEFINAEL
ESKGITDVTR DEAFGAWLHL ARYDIDHGVV LRSLAFDEGE PLPVSILTDI AVRRVGVAAA
GDVPGTAAAG GADAIPSSGP ELKVYLDEKI RGCVAKVLQM GAEDVDSKAA LADLGVDSVM
TVSLRRQLQQ TLKVKVPSTL TWSHPTVSHL VGWFAEKVGK
