ID   MSAS_PENPA              Reviewed;        1774 AA.
AC   P22367;
DT   01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1991, sequence version 1.
DT   03-AUG-2022, entry version 119.
DE   RecName: Full=6-methylsalicylic acid synthase;
DE            Short=6-MSAS;
DE            EC=2.3.1.165;
OS   Penicillium patulum (Penicillium griseofulvum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=5078;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RC   STRAIN=DSM 62862 / 11829;
RX   PubMed=2209605; DOI=10.1111/j.1432-1033.1990.tb19252.x;
RA   Beck J., Ripka S., Siegner A., Schiltz E., Schweizer E.;
RT   "The multifunctional 6-methylsalicylic acid synthase gene of Penicillium
RT   patulum. Its gene structure relative to that of other polyketide
RT   synthases.";
RL   Eur. J. Biochem. 192:487-498(1990).
CC   -!- FUNCTION: This multifunctional enzyme is a polyketide synthase. It
CC       catalyzes a total of 11 steps by seven different component enzymes, in
CC       the biosynthesis of the antibiotic patulin.
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   -!- PATHWAY: Mycotoxin biosynthesis; patulin biosynthesis.
CC   -!- SUBUNIT: Homomultimer.
CC   -!- INDUCTION: In the late logarithmic growth phase.
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DR   EMBL; X55776; CAA39295.1; -; Genomic_DNA.
DR   PIR; S13178; S13178.
DR   AlphaFoldDB; P22367; -.
DR   SMR; P22367; -.
DR   KEGG; ag:CAA39295; -.
DR   OMA; HRRFWRT; -.
DR   BioCyc; MetaCyc:MON-9061; -.
DR   BRENDA; 2.3.1.165; 4632.
DR   UniPathway; UPA00918; -.
DR   GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR   GO; GO:0050641; F:6-methylsalicylic acid synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
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; 3.40.366.10; -; 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; IPR006162; Ppantetheine_attach_site.
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.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   1: Evidence at protein level;
KW   Antibiotic biosynthesis; Direct protein sequencing; Multifunctional enzyme;
KW   NADP; Phosphopantetheine; Phosphoprotein; Transferase.
FT   CHAIN           1..1774
FT                   /note="6-methylsalicylic acid synthase"
FT                   /id="PRO_0000180292"
FT   DOMAIN          1698..1772
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          1..21
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          186..238
FT                   /note="Acyltransferase"
FT   REGION          642..676
FT                   /note="Acetyl/malonyl transferases"
FT   REGION          1403..1450
FT                   /note="2-oxoacyl reductase"
FT   ACT_SITE        204
FT                   /note="For beta-ketoacyl synthase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT   ACT_SITE        653
FT                   /note="For malonyltransferase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT   BINDING         1419..1424
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         1732
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1774 AA;  190733 MW;  05ED5DD10863F938 CRC64;
     MHSAATSTYP SGKTSPAPVG TPGTEYSEYE FSNDVAVVGM ACRVAGGNHN PELLWQSLLS
     QKSAMGEIPP MRWEPYYRRD ARNEKFLKNT TSRGYFLDRL EDFDCQFFGI SPKEAEQMDP
     QQRVSLEVAS EALEDAGIPA KSLSGSDTAV FWGVNSDDYS KLVLEDLPNV EAWMGIGTAY
     CGVPNRISYH LNLMGPSTAV DAACASSLVA IHHGVQAIRL GESKVAIVGG VNALCGPGLT
     RVLDKAGAIS SDGSCKSFDD DAHGYARGEG AGALVLKSLH RALLDHDNVL AVIKGSAVCQ
     DGKTNGIMAP NSVAQQLAAN NALSAANIDP HTVRYVEAHA TSTPLGDPTE ISAIASVYGA
     DRPADDPCYI GSIKPNIGHL EAGAGVMGFI KAVLAIQKGV LPPQANLTKL NSRIDWKTAG
     VKVVQEATPW PESDPIRRAG VCSYGYGGTV SHAVIEEFSP ILQPDPLGNG AVSGPGLLLL
     SGPQEKRLAL QAKTLRDWMT AEGKDHNLSD ILTTLATRRD HHDYRAALVV DDYRDAEQVL
     QSLANGVDHT FTTQSRVLGS DISKDVVWVF SGHGAQWPDM GKQLIHNPVF FAAIQPLDEL
     IQAEIGLSPI ELLRTGDFES SDRVQILTYV MQIGLSALLQ SNGITPQAVI GHSVGEIAAS
     VVAGALSPAE GALIVTRRAL LYRQVMGKGG MILVNLPSAE TEEILGSRSD LVVAIDSSPS
     SCVVAGDKEL VAETAEALKA RGVKTFTVKS DIAFHSPTLN GLVDPLRDVL AETLSPVSPN
     VKLYSTALAD PRGQDLRDVE YWAGNMVNRV RLTSAVKAAV EDGYRLFLEV STHPVVSHSI
     NETLMDAGME DFAVIPTLLR KKPTEKHILH SIAQLHCRGA EVNWAAQMPG RWATGVPTTT
     WMHKPIWRKI ETAPLHTGLT HDVEKHTLLG QRIPVPGTDT YVYTTRLDND TKPFPGSHPL
     HGTEIVPAAG LINTFLKGTG GQMLQNVVLR VPVAINAPRS VQVVVQQDQV KVVSRLIPSE
     PSQLDDDASW VTHTTAYWDR KVAGSEDRID FAAVKSRLVT KLADNFSIDY LDKVGVSAMG
     FPWAVTEHYR NDKEMLARVD VNPAISGDAP LPWDSSSWAP VLDAATSVGS TIFPTPALRM
     PAQIERVEVF TSQDPPKISW LYVQEASDSV PTSHVSVVSE AGEVLAKFTA MRFSEIEGTP
     GVSGSMESLV HQIAWPPATP AEEPLSIETV ILVSPDATTR ALYAASLPTR VNSFQFSSTQ
     EFFSNASSLP LEKGTVVTYI PGEVASLAEV PAASESFTWN LLELIKFTVN GSLPIKVFTL
     TANIGEGQTP TALAQSPLYG LARVIASEHP DLGTLIDVEE PVIPLSTMRY IQGADIIRIN
     DGIARTSRFR SLPRNKLLPA SEGPRLLPRP EGTYLITGGL GVLGLEVADF LVEKGARRLL
     LISRRALPPR RTWDQVSEDL QPTIAKIRLL ESRGASVHVL PLDITKPDAV EQLTTALDRL
     SLPSVQGVVH AAGVLDNELV MQTTRDAFNR VLAPKIAGAL ALHEVFPPKS VDFFVMFSSC
     GNLVGFTGQA SYGSGNAFLD TLATHRARLG DAAVSFQWTS WRGLGMGAST DFINAELESK
     GITDVTRDEA FAAWQHLAKY DMDHGVVLRS RAFEDGEPIP VSILNDIAVR RVGTVSNTSP
     AAAGSSDAVP TSGPELKAYL DEKIRGCVAK VLQMTAEDVD SKAALADLGV DSVMTVTLRR
     QLQLTLKIAV PPTLTWSHPT VSHLAVWFAE KLAK