ID   NSCA_TRIEC              Reviewed;        1777 AA.
AC   F2PWS5;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   31-MAY-2011, sequence version 1.
DT   03-AUG-2022, entry version 53.
DE   RecName: Full=Non-reducing polyketide synthase nscA {ECO:0000303|PubMed:23758576};
DE            EC=2.3.1.- {ECO:0000305|PubMed:23758576};
DE   AltName: Full=Conidial yellow pigment biosynthesis polyketide synthase nscA {ECO:0000303|PubMed:23758576};
DE   AltName: Full=Neosartoricin B biosynthesis protein A {ECO:0000303|PubMed:23758576};
GN   Name=nscA {ECO:0000305|PubMed:23758576}; ORFNames=TEQG_05346;
OS   Trichophyton equinum (strain ATCC MYA-4606 / CBS 127.97) (Horse ringworm
OS   fungus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Onygenales; Arthrodermataceae; Trichophyton.
OX   NCBI_TaxID=559882;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC MYA-4606 / CBS 127.97;
RX   PubMed=22951933; DOI=10.1128/mbio.00259-12;
RA   Martinez D.A., Oliver B.G., Graeser Y., Goldberg J.M., Li W.,
RA   Martinez-Rossi N.M., Monod M., Shelest E., Barton R.C., Birch E.,
RA   Brakhage A.A., Chen Z., Gurr S.J., Heiman D., Heitman J., Kosti I.,
RA   Rossi A., Saif S., Samalova M., Saunders C.W., Shea T., Summerbell R.C.,
RA   Xu J., Young S., Zeng Q., Birren B.W., Cuomo C.A., White T.C.;
RT   "Comparative genome analysis of Trichophyton rubrum and related
RT   dermatophytes reveals candidate genes involved in infection.";
RL   MBio 3:E259-E259(2012).
RN   [2]
RP   FUNCTION.
RX   PubMed=23758576; DOI=10.1021/sb400048b;
RA   Yin W.B., Chooi Y.H., Smith A.R., Cacho R.A., Hu Y., White T.C., Tang Y.;
RT   "Discovery of cryptic polyketide metabolites from dermatophytes using
RT   heterologous expression in Aspergillus nidulans.";
RL   ACS Synth. Biol. 2:629-634(2013).
CC   -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC       that mediates the biosynthesis of neosartoricin B, a prenylated
CC       anthracenone that probably exhibits T-cell antiproliferative activity,
CC       suggestive of a physiological role as an immunosuppressive agent
CC       (PubMed:23758576). The non-reducing polyketide synthase nscA probably
CC       synthesizes and cyclizes the decaketide backbone (By similarity). The
CC       hydrolase nscB then mediates the product release through hydrolysis
CC       followed by spontaneous decarboxylation (By similarity). The
CC       prenyltransferase nscD catalyzes the addition of the dimethylallyl
CC       group to the aromatic C5 (By similarity). The FAD-dependent
CC       monooxygenase nscC is then responsible for the stereospecific
CC       hydroxylation at C2 (By similarity). Neosartoricin B can be converted
CC       into two additional compounds neosartoricins C and D (By similarity).
CC       Neosartoricin C is a spirocyclic compound that is cyclized through the
CC       attack of C3 hydroxyl on C14, followed by dehydration (By similarity).
CC       On the other hand, neosartoricin D is a further cyclized compound in
CC       which attack of C2 on C14 in neosartoricin C results in the formation
CC       of the acetal-containing dioxabicyclo-octanone ring (By similarity).
CC       Both of these compounds are novel and possibly represent related
CC       metabolites of the gene cluster (By similarity).
CC       {ECO:0000250|UniProtKB:A1D8I9, ECO:0000250|UniProtKB:F2S6Z9,
CC       ECO:0000305|PubMed:23758576}.
CC   -!- COFACTOR:
CC       Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC         Evidence={ECO:0000250|UniProtKB:A0A0K0MCJ4};
CC       Note=Binds 1 phosphopantetheine covalently. {ECO:0000255};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:23758576}.
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}.
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DR   EMBL; DS995747; EGE06343.1; -; Genomic_DNA.
DR   AlphaFoldDB; F2PWS5; -.
DR   SMR; F2PWS5; -.
DR   STRING; 63418.F2PWS5; -.
DR   EnsemblFungi; EGE06343; EGE06343; TEQG_05346.
DR   eggNOG; KOG1202; Eukaryota.
DR   HOGENOM; CLU_000022_6_4_1; -.
DR   Proteomes; UP000009169; Unassembled WGS sequence.
DR   GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR   GO; GO:0031177; F:phosphopantetheine 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; 3.40.366.10; -; 3.
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; IPR032821; PKS_assoc.
DR   InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR   InterPro; IPR020807; PKS_dehydratase.
DR   InterPro; IPR042104; PKS_dehydratase_sf.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR030918; PT_fungal_PKS.
DR   InterPro; IPR032088; SAT.
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; PF00550; PP-binding; 1.
DR   Pfam; PF14765; PS-DH; 1.
DR   Pfam; PF16073; SAT; 1.
DR   SMART; SM00827; PKS_AT; 1.
DR   SMART; SM00825; PKS_KS; 1.
DR   SMART; SM00823; PKS_PP; 1.
DR   SUPFAM; SSF47336; SSF47336; 1.
DR   SUPFAM; SSF52151; SSF52151; 1.
DR   SUPFAM; SSF53901; SSF53901; 1.
DR   TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR   PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR   PROSITE; PS50075; CARRIER; 1.
PE   3: Inferred from homology;
KW   Acyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW   Phosphoprotein; Transferase.
FT   CHAIN           1..1777
FT                   /note="Non-reducing polyketide synthase nscA"
FT                   /id="PRO_0000437891"
FT   DOMAIN          1700..1777
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          27..261
FT                   /note="N-terminal acylcarrier protein transacylase domain
FT                   (SAT)"
FT                   /evidence="ECO:0000255"
FT   REGION          399..832
FT                   /note="Ketosynthase (KS) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          934..1212
FT                   /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          1297..1616
FT                   /note="Product template (PT) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          1674..1704
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1674..1689
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        569
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT   MOD_RES         1737
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1777 AA;  194437 MW;  0A83A2F714C48D5E CRC64;
     MDNSMMDSTL RRILFFSNEF PSDDLKDLFR RLDQHSKDRR FRLLSIFLEE STAILKDEVS
     KLPRPLKELV PPFNSVLSLV DVDFRQGPLG AAMESSMLTI LELGLFIGHY ESEDTEWDLV
     PGQSVLAGLS IGILAAAAVA LSSSLADVAK TGAEAVRVSF RLGVYVADIS TKLEAPQSDG
     TLSSWAHVVT EMTEASVQDE LKQFNTGTHS PELTKVFVSA ADKTSVSVSG PPSRIKAAFQ
     HSPVLRYSKS LPLPVYDGLC HASHLYTRSD IDSIINSSES VILPDRSVRL ALLSSQTGKP
     FVAKTASDLF LEIGTELLTG TIYLDNVTAG IVQHLQPQSK ETSSCQIDSF RTSLVLRGIH
     SAVEAELSRD RQLTRRDLVS WISRDFGPRR PRSQASSKLA IVGMACRLPG GANDLDLFWK
     LLEEGRDTLT TVPPDRFDLN THYDPTGKTE NATQTPYGNF IDRPGFFDAG FFNMSPREAE
     QTDPMQRLAL VTAYEALEMA GVVPGRTPST HPSRIGTFYG QASDDWRELN ASQNISTYAV
     PGGERSFGNG RINYFFKFSG PSFNLDTACS SGLAAVQAAC SALWAGEVDT AIAGGLNVIT
     DPDNYCGLGN AHFLSKTGQC KVWDKDADGY CRADGIGSVV IKRLEDAEAD NDNILAVVLG
     ASTNHSAEAI SITHPHAGAQ KANYRQVLNQ AGVNPIDVSY IELHGTGTQA GDAVESESVS
     DIFAPVTPRR RPDQRLYLGA VKSNIGHGEA AAGIASLLKA LLVYQKNLIP MHIGIKSEIN
     PTIPKDLERR NVGLAMQNTP WPRPAGKKRL AVVNSFGAHG GNTTLLLEDA PERVKIQGTE
     DRITHSILLS AKSKTSLQAN MESLLSYLDQ HPETSLADLA YTTSSRRMHH NMRFGTLVSS
     ISGLQKMLRS QLDNPNFASE IRPVPNEAPS VILAFTGQGA YYHGMGSELF AEFPYFRAQV
     QQLDRLAQRL GFPSVVPPWR RFWSLLGVSI SAVIGHSLGE YAALAVAGVI SAADAIYLVG
     RRAQLVEERC AQASHSMLSV RASEDAIQEM LAVELETASI TYEVSCCNTN QDTVIGGPKG
     EINDIRRALE AKSIKCTILD VPYAFHTAQM NPILDDLETL AKAVPFKAPS IPVISPLLAT
     VIYDVKSLDA NYLRRATRET VDFAAAIEAA QDMGLVDSKT IWIDVGPHPI CAGLVRSMIP
     SASAIPSCRR NEDSIATISK GLVTLYLAGL TPSWVEFFKP REREYSLLYL PKYRWNETDY
     WIPYIGTWTL DKAHLKHGTK PKTPFSGSMS RPSALRTSLV HQITAETVEA TTATLHTISD
     MQHPDFLEAI HGHTMNKCGV ATSSIWSDMA FTVGEYLYRR LVPNTKDVHM NLTDVEVLHA
     QVASKTKGSV QPLVLRAHLD LSTNSMSLAW FNADGETGEC AAESFATATI RFEDPEAWRK
     DWARLAHLVR GRIEVLEQRA TEGKASRLSK PLAYALFKNV VDYADRYRGM DSVVLDELEA
     MAEVTLVPER YGTWHTPPHW IDSVSHLAGL VMNGSDASNT RDYFFVTPGC DSFRLLKKLE
     PGARYRSYVR MFPLPEDPNM HSGDVYILQG EEIVGMVGMI RFRRVPRLLM DRFFSPPTTT
     SVAVPVPPLT GATMKCKDIT QTAPALPTPA PPIVVSSPVV SSTMACNIPE PAPLLATSSK
     SSTPKESPIV TPAESERAEP VDNSMTSQCL RLMARETGLE VEALTADASF VQLGVDSLMS
     LVLSEKFRAE LGVEIKSSLF LECPTIGEMT AWIEEYC