NSCA_TRIT1
ID NSCA_TRIT1 Reviewed; 1802 AA.
AC F2S6Z9;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 51.
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=TESG_06702;
OS Trichophyton tonsurans (strain CBS 112818) (Scalp ringworm fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Arthrodermataceae; Trichophyton.
OX NCBI_TaxID=647933;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 112818;
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).
RN [3]
RP FUNCTION.
RX PubMed=23368997; DOI=10.1021/ol303435y;
RA Chooi Y.H., Fang J., Liu H., Filler S.G., Wang P., Tang Y.;
RT "Genome mining of a prenylated and immunosuppressive polyketide from
RT pathogenic fungi.";
RL Org. Lett. 15:780-783(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, PubMed:23368997). The non-reducing polyketide
CC synthase nscA probably synthesizes and cyclizes the decaketide backbone
CC (By similarity). The hydrolase nscB then mediates the product release
CC through hydrolysis followed by spontaneous decarboxylation (By
CC similarity). The prenyltransferase nscD catalyzes the addition of the
CC dimethylallyl group to the aromatic C5 (By similarity). The FAD-
CC dependent 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 (PubMed:23758576).
CC Neosartoricin C is a spirocyclic compound that is cyclized through the
CC attack of C3 hydroxyl on C14, followed by dehydration
CC (PubMed:23758576). On the other hand, neosartoricin D is a further
CC cyclized compound in which attack of C2 on C14 in neosartoricin C
CC results in the formation of the acetal-containing dioxabicyclo-octanone
CC ring (PubMed:23758576). Both of these compounds are novel and possibly
CC represent related metabolites of the gene cluster (PubMed:23758576).
CC {ECO:0000250|UniProtKB:A1D8I9, ECO:0000269|PubMed:23758576,
CC ECO:0000305|PubMed:23368997}.
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:0000269|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; GG698521; EGD99348.1; -; Genomic_DNA.
DR AlphaFoldDB; F2S6Z9; -.
DR SMR; F2S6Z9; -.
DR EnsemblFungi; EGD99348; EGD99348; TESG_06702.
DR HOGENOM; CLU_000022_6_1_1; -.
DR OrthoDB; 68112at2759; -.
DR Proteomes; UP000009172; 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; -; 2.
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..1802
FT /note="Non-reducing polyketide synthase nscA"
FT /id="PRO_0000437890"
FT DOMAIN 1725..1802
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 935..1235
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1322..1641
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1699..1729
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1699..1714
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 1762
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1802 AA; 196921 MW; B74638CD169D8B7F 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 KHIGIKSEIN
PTIPKDLERR NVGLAMQNTP WPRPAGKKRL AVVNSFGAHG GNTTLLLEDA PERVKIQGTE
DRITHSILLS AKSKTSLQAN MESLLSYLDQ HPETSLADLA YTTSSRRMHH NMRFGTLVSS
ISGLQKMLRS QLDNPNFASE IRPVPNEAPS VILAFTGQGA YYHGMGSELF AEFPYFRAQV
QQLDRLAQRL GFPSVVPVIE NRIEDAPSSP ILTQLSVVIL EIALARFWSL LGVSISAVIG
HSLGEYAALA VAGVISAADA IYLVGRRAQL VEERCAQASH SMLSVRASED AIQEMLAVEL
ETASITYEVS CCNTNQDTVI GGPKGEINDI RRALEAKSIK CTILDVPYAF HTAQMNPILD
DLETLAKAVP FKAPSIPVIS PLLATVIYDV KSLDANYLRR ATRETVDFAA AIEAAQDMGL
VDSKTIWIDV GPHPICAGLV RSMIPSASAI PSCRRNEDSI ATISKGLVTL YLAGLTPSWV
EFFKPREREY SLLYLPKYRW NETDYWIPYI GTWTLDKAHL KHGTKPKTPF SGSMSRPSAL
RTSLVHQITA ETVEATTATL HTISDMQHPD FLEAIHGHTM NKCGVATSSI WSDMAFTVGE
YLYRRLVPNT KDVHMNLTDV EVLHAQVASK TKGSVQPLVL RAHLDLSTNS MSLAWFNADG
ETGECAAESF ATATIRFEDP EAWRKDWARL AHLVRGRIEV LEQRATEGKA SRLSKPLAYA
LFKNVVDYAD RYRGMDSVVL DELEAMAEVT LVPERYGTWH TPPHWIDSVS HLAGLVMNGS
DASNTRDYFF VTPGCDSFRL LKKLEPGARY RSYVRMSPLP EDPNMHSGDV YILQGEEIVG
MVGMIRFRRV PRLLMDRFFS PPTTTSVAVP VPPLTGATMK CKDITQTAPA LPTPAPPIVV
SSPVVSSTMA CNIPEPAPLL ATSSKSSTPK ESPIVTPAES ERAEPVDNSM TSQCLRLMAR
ETGLEVEALT ADASFVQLGV DSLMSLVLSE KFRAELGVEI KSSLFLECPT IGEMTAWIEE
YC
