ID NSCA_TRIVH Reviewed; 1819 AA.
AC D4CZZ2;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 1.
DT 27-MAR-2024, entry version 66.
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:0000303|PubMed:23758576}; ORFNames=TRV_00386;
OS Trichophyton verrucosum (strain HKI 0517).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Arthrodermataceae; Trichophyton.
OX NCBI_TaxID=663202;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=HKI 0517;
RX PubMed=21247460; DOI=10.1186/gb-2011-12-1-r7;
RA Burmester A., Shelest E., Gloeckner G., Heddergott C., Schindler S.,
RA Staib P., Heidel A., Felder M., Petzold A., Szafranski K., Feuermann M.,
RA Pedruzzi I., Priebe S., Groth M., Winkler R., Li W., Kniemeyer O.,
RA Schroeckh V., Hertweck C., Hube B., White T.C., Platzer M., Guthke R.,
RA Heitman J., Woestemeyer J., Zipfel P.F., Monod M., Brakhage A.A.;
RT "Comparative and functional genomics provide insights into the
RT pathogenicity of dermatophytic fungi.";
RL Genome Biol. 12:R7.1-R7.16(2011).
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; ACYE01000020; EFE44835.1; -; Genomic_DNA.
DR RefSeq; XP_003025446.1; XM_003025400.1.
DR AlphaFoldDB; D4CZZ2; -.
DR SMR; D4CZZ2; -.
DR GeneID; 9581672; -.
DR KEGG; tve:TRV_00386; -.
DR HOGENOM; CLU_000022_6_1_1; -.
DR OrthoDB; 5396558at2759; -.
DR Proteomes; UP000008383; 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 CDD; cd00833; PKS; 1.
DR Gene3D; 3.30.70.3290; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 2.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 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; 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 NCBIfam; TIGR04532; PT_fungal_PKS; 1.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR43775:SF24; NON-REDUCING POLYKETIDE SYNTHASE APTA-RELATED; 1.
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; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF53901; Thiolase-like; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00606; KS3_1; 1.
DR PROSITE; PS52004; KS3_2; 1.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 3: Inferred from homology;
KW Acyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Transferase.
FT CHAIN 1..1819
FT /note="Non-reducing polyketide synthase nscA"
FT /id="PRO_0000437893"
FT DOMAIN 413..846
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT DOMAIN 1343..1653
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 1742..1819
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 25..277
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 952..1249
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1339..1658
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1343..1479
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1507..1653
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1703..1742
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1717..1731
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 586
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 721
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 764
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 1375
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1564
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT MOD_RES 1779
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1819 AA; 198944 MW; 08373DB37ACB387F CRC64;
MDSTSRRVVF FSNEFPNDDL KELFRRLDQH SKDRRFRLLS IFLEESTAVL KDEVSKLPRP
LKELVPPFDS VLGLVDVDFR QGPLGAAMES SMLTILELGL FIGYVSLLCL LDQVKMLTSL
VYTSHYESED TEWDLVPGES VLAGLSIGIL AAAAVALSSS LADVAKTGAE AVRVSFRLGV
YVADISTKLE TPQSDGTLSS WAHVVTEMTE AGVQDELRQF NTDTHSPELT KVFISAADKT
SVSVSGPPSR IKAAFQHSPV LRYSKSLPLP VYDGLCHASH LYTQSDIDSI INSAESVIVA
DRSVRLALLS SQTGKPFIAK TASELFLEIG TELLTGTIYL DNVTAGIVQH LQPQSKEISS
WQIDSFRTSL VLRGIHSAVE AKLSGEQRQL IRRDLVNWVN KDFGPRQPRS HASSKLAIVG
MACRLPGGAN DLDLFWKLLE EGRDTLTTVP PDRFDLNTHY DPTGKTENAT QTPYGNFIDR
PGFFDAGFFN MSPREAEQTD PMQRLALVTA YEALEMAGVV PGRTPSTHPS RIGTFYGQAS
DDWRELNASQ NISTYAVPGG ERAFGNGRIN YFFKFSGPSF NLDTACSSGL AAVQAACSAL
WAGEVDTAIA GGLNVITDPD NYCGLGNAHF LSKTGQCKVW DKDADGYCRA DGIGSVVIKR
LEDAEADNDN ILAVVLGAST NHSAEAISIT HPHAGAQKAN YRQVLNQAGV NPIDVSYIEL
HGTGTQAGDA VESESVSDIF APVTPRRRPD QRLYLGAVKS NIGHGEAAAG IASLLKALLV
YQKNLIPMHI GIKSVINPTI PKDLERRNVG LAMQNTPWPR PAGKKRLAVV NSFGAHGGNT
TLLLEDAPER VKIQGTEDRI THSILLSAKS KKSLQANMES LLSYLDQHPE TSLADLAYTT
SSRRMHHNMR FGTSVSCISG LQKVLRSQLD NVNFASEVRP VPNEAPSVIL AFTSQGAYYH
GMGRELFAEF PYFRAQVQQL DRLAQRLGFP SVVPVIENSI EDTPSSPILT QLSVVILEIA
LARFWSLLGV SISAVIGHSL GEYAALAVAG VISATDAIYL VGRRAQLVEE RCAQGSHSML
SVRAPEDEIQ KMLAAEPETA SIAYEVSCCN TNQDTVIGGL TGEINDIRRT LEAKSIKCTI
LDVPYAFHTA QVNPILDDLE TLAKAVPFKA PSIPVISPLL ATVIYDVKSL NANYLRRATR
ETVDFAAAIE AAQDMGLVDS KTIWIDVGPH PICAGLVRSM IPSAPAMSSC RRNEDSIATI
SKSLVTLYLA GINPCWAEFF KPREREYSLL HLPKYRWNEI DYWIPYLGTW TLDKAHLKHG
TKPTTPFSVS MSRPSALRTS LVHQITAETV EATTATLHTI SDMQHPDFLE AIHGHTMNKC
GVATSSIWSD MAFTVGEYLY RRLVPNTKDV HMNLTDVEVL HAQVASKTKG SVQPLVLRAH
LDLSTSSMSL SWFNANGETG ECAAESFATA MIRFEDPMAW RKEWARLAHL VRGRIEVLEQ
RASEGKASRL SKPLAYALFK NVVDYADRYR GMDSVVLDEL EAMAEVTLVP ERYGTWHTPP
HWIDSVSHLA GLVMNGSDAS NTRDYFFVTP GCDSFRLLKK LEPGAQYRSY VRMFPLPEDP
NMHGGDVYIL QGEEIVGMVG MIRIRRVPRL LMDRFFSPPT TTSVAGPVPP LSGETTKYHD
IAQTAPALPA PTLPIVVPNP VASSTMASKA PEPAPLLATS SESSTPKESP IVTPAESERE
DPVDNNMISQ CLRLMARETG LEVEALTADA SFVQLGVDSL MSLVLSEKFR AELGVEIKSS
LFLECPTIGE MTAWIEEYC
//
