NSCA_ARTBC
ID NSCA_ARTBC Reviewed; 1798 AA.
AC D4AWH3;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 1.
DT 03-AUG-2022, entry version 63.
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=ARB_00538;
OS Arthroderma benhamiae (strain ATCC MYA-4681 / CBS 112371) (Trichophyton
OS mentagrophytes).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Arthrodermataceae; Trichophyton.
OX NCBI_TaxID=663331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4681 / CBS 112371;
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; ABSU01000014; EFE32713.1; -; Genomic_DNA.
DR RefSeq; XP_003013353.1; XM_003013307.1.
DR AlphaFoldDB; D4AWH3; -.
DR SMR; D4AWH3; -.
DR STRING; 663331.D4AWH3; -.
DR EnsemblFungi; EFE32713; EFE32713; ARB_00538.
DR GeneID; 9519388; -.
DR KEGG; abe:ARB_00538; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_1_1; -.
DR OMA; LNTHYDP; -.
DR Proteomes; UP000008866; 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; Reference proteome; Transferase.
FT CHAIN 1..1798
FT /note="Non-reducing polyketide synthase nscA"
FT /id="PRO_0000437892"
FT DOMAIN 1721..1798
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 25..256
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 395..828
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 436..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 931..1230
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1390..1628
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1685..1719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 440..455
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1696..1710
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 565
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1758
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1798 AA; 196677 MW; D33FECFBE73033EE CRC64;
MDSTFRRVVF FSNEFPSDDL KELFRRLDQH SKDRRFRLLS IFLEESTAIL KDEVSKLPRP
LKELVPPFGS VLGLVDVDFR QGPLGAAMES SMLTILELGL FIGHYESEDT EWDLVPGESV
LAGLSIGILA AAAVALSSGL SDVAKAGAEA VRVSFRLGVY VADISAKLEA PQSDGTLSSW
AHVVTEMTEA SVQDELKQFN TDTHSPELTK VFISAADKTS VSVSGPPSRI KAAFQHSPVL
RYSKSLPLPV YDGLCHASHL YTQSDIDSII NSAESVILPD RSVRLALLSS KTGKPFIAKT
ASELFLEIGT ELLTGTIYLD NVTAGIVRHL QPQSKEMSSW QIDSFRTSLV LRSIHSAVEA
KISGEQRQLT RRDLVNWVNK DFGPRRPRSH ASSKLAIVGM ACRLPGGAND LDLFWKLLEE
GRDTLTTVPP DRFDLNTHYD PTGKTENTTQ TPYGNFIDRP GFFDAGFFNM SPREAEQTDP
MQRLALVTAY EALEMAGVVP GRTPSTHPSR IGTFYGQASD DWRELNASQN ISTYAVPGGE
RAFGNGRINY FFKFSGPSFN LDTACSSGLA AVQAACSALW AGEVDTAIAG GLNVITDPDN
YCGLGNAHFL SKTGQCKVWD KDADGYCRAD GIGSVVIKRL EDAEADNDNI LAVVLGACTN
HSAEAISITH PHAGAQKANY RQVLNQAGVN PIDVSYIELH GTGTQAGDAV ESESVSDIFA
PVTPRRRPDQ RLYLGAVKSN IGHGEAAAGI ASLLKALLVY QKNLIPMHIG IKSEINPTIP
KDLERRNVGL AMQNTPWPRP AGKKRLAVVN SFGAHGGNTT LLLEDAPERV KIQGTEDRIT
HSVLLSAKSK KSLQANMESL LSYLDQYPET SLADLAYTTS SRRMHHNMRF GTSVSCISGL
QKVLRSQLDN PNFASEVRPV PNEVPSVILA FTGQGAYYHG MGRELFAEFP YFRAQVQQLD
RLAQRLGFPS VVPVIENSIE DTPSSPILTQ LSVVILEIAL ARFWSLLGVS ISAVIGHSLG
EYAALAVAGV ISATDAIYLV GRRAQLIEER CAQGSHSMLS VRAPEDAIQK MLAAEPETAS
IAYEVSCCNT NQDTVIGGLN GEINDIRRAL EAKSIKCTIL DVPYAFHTAQ MNPILDDLEA
LAKAVPFKAP SIPVISPLLA TVIYDVKSLN ADYLRRATRE TVDFAAAIEA AQDMGLVDSK
TIWIDVGPHP ICAGLVRSMI PSASAMSSCR RNEDSISTIS KSLVALYLAG INPCWAEFFK
PREGEYSLLH LPKYRWNEID YWIPYIGTWT LDKAHLKHGT KPTTPFSVSM SRPSALRTSL
VHQITAETVE ATTAMLHTIS DMQHPDFLEA IHGHTMNKCG VATSSIWSDM AFTVGEYLYR
RLVPNTKDVH MNLTDVEVLH AQVASKTKGS VQPLVLRAHL NLSTNSMSLS WFNADGETGE
CAAESFASAM IRFEDPVAWR KEWARLAHLV RGRIEVLEQR ASEGKASRLS KPLAYALFKN
VVDYADRYRG MDSVVLDELE AMAEVTLVPE RYGTWHTPPH WIDSVSHLAG LVMNGSDASN
TRDYFFVTPG CDSFRLLKKL EPGARYRSYV RMFPLPEDPN MHGGDVYILQ GEEIVGMVGM
IRFRRVPRLL MDRFFSPPTT TSVPGPVPPL AGVTMKYHDI AQTAPVRPTP TPPIVLPNPV
VSSTMASKAP EPAPLLATSS ESSTPKESPI VTPAESERAD PVDNNMISQC LRLMARETGL
EVEALTADAS FVQLGVDSLM SLVLSEKFRT ELGVEIKSSL FLECPTIGEM TAWIEEYC
