NSCA_NEOFI
ID NSCA_NEOFI Reviewed; 1794 AA.
AC A1D8I9;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Non-reducing polyketide synthase nscA {ECO:0000303|PubMed:23368997};
DE EC=2.3.1.- {ECO:0000305|PubMed:23368997};
DE AltName: Full=Conidial yellow pigment biosynthesis polyketide synthase nscA {ECO:0000303|PubMed:23368997};
DE AltName: Full=Neosartoricin biosynthesis protein A {ECO:0000303|PubMed:23758576};
GN Name=nscA {ECO:0000303|PubMed:23368997}; ORFNames=NFIA_112240;
OS Neosartorya fischeri (strain ATCC 1020 / DSM 3700 / CBS 544.65 / FGSC A1164
OS / JCM 1740 / NRRL 181 / WB 181) (Aspergillus fischerianus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=331117;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 1020 / DSM 3700 / CBS 544.65 / FGSC A1164 / JCM 1740 / NRRL 181
RC / WB 181;
RX PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT fumigatus.";
RL PLoS Genet. 4:E1000046-E1000046(2008).
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, a prenylated
CC anthracenone that 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 (PubMed:23368997). The hydrolase nscB then mediates the product release
CC through hydrolysis followed by spontaneous decarboxylation
CC (PubMed:23368997). The prenyltransferase nscD catalyzes the addition of
CC the dimethylallyl group to the aromatic C5 (PubMed:23368997). The FAD-
CC dependent monooxygenase nscC is then responsible for the stereospecific
CC hydroxylation at C2 (PubMed:23368997). There is no gene encoding O-
CC acetyltransferase in the nsc gene cluster; thus, the last step of 2-O-
CC acetylation leading to neosartoricin may be catalyzed by an
CC unidentified O-acetyltransferase (PubMed:23368997).
CC {ECO:0000269|PubMed:23368997, 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:0000269|PubMed:23368997}.
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; DS027692; EAW20700.1; -; Genomic_DNA.
DR RefSeq; XP_001262597.1; XM_001262596.1.
DR AlphaFoldDB; A1D8I9; -.
DR SMR; A1D8I9; -.
DR STRING; 36630.CADNFIAP00010391; -.
DR PRIDE; A1D8I9; -.
DR EnsemblFungi; EAW20700; EAW20700; NFIA_112240.
DR GeneID; 4589233; -.
DR KEGG; nfi:NFIA_112240; -.
DR VEuPathDB; FungiDB:NFIA_112240; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_1_1; -.
DR OMA; LNTHYDP; -.
DR OrthoDB; 68112at2759; -.
DR Proteomes; UP000006702; 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; IPR016036; Malonyl_transacylase_ACP-bd.
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 SUPFAM; SSF55048; SSF55048; 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..1794
FT /note="Non-reducing polyketide synthase nscA"
FT /id="PRO_0000437888"
FT DOMAIN 1717..1794
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 19..256
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 392..825
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 427..448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 928..1249
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1314..1633
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1637..1665
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1682..1718
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1642..1656
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1686..1707
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 562
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1754
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1794 AA; 195269 MW; B7A561B466D86FB3 CRC64;
MATPRGQTVW FGNEFPNDDL KDLFRRLHQH SKDRRFRLLS VFLDESTAIL KEEVANLPQQ
LQELVPHFDT ACTLPEVDFR QGPLGAAMES ALLTILELGM LIGNYEAEDI EWDLDPSQTI
LAGLSIGIIA GAAVALSSSL ADVAKVGAES VRVSFRLGVY VADISTKLEA PQSDGTLQSW
AHVVTGMSHE AVQEELSQFN AVTQNPEITK VFVSAADKTS VSVTGPPSRI KAAFQHSPSL
RYSKSLPLPV YDGLCHAPHL YSQDDIEIVI NSAKSVIPTS RPVRLPLISS QTGKPFEAKT
AGELFLEIGT ELLTGTIYLD NVTAGILEHV KLKEPTGNYQ IISFRMSQVL NGIQAAIETD
FPALGRARRD LVSWVHGDYG ARRPSSYAAS KLAIVGMACR LPGGANDPEL FWELLEQGRD
TLTTVPPDRF DLNTHYDPTG KTENATQTPF GNFIDRPGYF DAGFFNMSPR EAEQTDPMHR
LALVTAYEAM EMAGLVPGRT PSTRPNRIGT FYGQASDDWR ELNASQNIST YAVPGGERAF
ANGRINYFFK FSGPSYNIDT ACSSGLAAVQ AACSALWAGE ADTVIAGGLN IITDPDNYAG
LGNGHFLSKT GQCKVWDKDA DGYCRADGIG SVVIKRLEDA EADNDNILAV VLGARTNHSA
EAVSITHPHA GAQKANYRQV LHQAGVNPLD VSYVELHGTG TQAGDAVESE SVSDVFAPSM
PRRRPDQRLY LGAVKSNIGH GEAAAGIASL LKALLVYQKN MIPKHIGIKT EINPIIPKDL
DRRHVGLAMS NTPWPRPAGK KRLAVVNSFG AHGGNTTVLL EDAPERVKVS TQDDRTTHPV
VISAKSKKSL QANIEKLLSW LDQNPDADLA DLSYTLCARR MHHSMRFGAA ASDIAALQKT
LRSWLDSPKA STELRAIPND APSVVLTFTG QGAYYSGMGR ELFAEFSYFR TQVLQLDQIA
QRLGFPSVVP VIDGSIDDGP ASPILTQLSV VVLEIALARF WSHLGIRISA VVGHSLGEYA
AFAVAGVISA ADALYLVGRR AQLTEERCTQ GSHSMLSVRA SEDDIEELIA GSPDTAEIAY
EVCCRNTPQD TVIGGTKESI DRIRQALEAN SIKCTQLDVP FAFHTAQMDP ILDSLETLAT
PIAFKAPSIP VLSPLLGSVV FDRKSIHAQY LRRATREAVD FVAAIEAAQD FGLVDAKTIW
IDVGPHPICA GLVRGIDSSA SVISSCRRNE DNLATMSKSL VTLHLAGLTP CWAEYFRPRE
REYSLLKLPT YSWNETDYWI PYIGTWTLDK ALLKYGEKKA PLSLAMSRPS ALRTSLVHQI
TAETVEATTA TLHVLSDMQH PDFLEALHGH RMNNCGVATS SIWSDMAFTV GEYLYRRLVP
QVKDVHMNLS DFEVLHAQVA LEKKGSVQPL VLKAHLDLST SSMSLTWFNA SAETGECAAE
SFATGVVRFE DPAAWTREWD RLSHLVLGRI EALEQRAAEG KASKLSKPLA YALFKNVVDY
ADRYRGMDQV VLHEHEAVAE VTLVAERHGT WHTPPHWIDS VSHLAGLVMN GSDASNTRDY
FYVTPGCSSF RLLNPLKAGG KYRSYVRMFP LLEEANMYAG DVYILQGEQI VGMVGQIRFR
RVPRLLMDRF FSPAAASHAE KQLQETAPSA TSVKKSTPPA AEAPASVPAL LSNPVAIPFP
AASKSEVSTP PLTPPSQQES PGESAVITPA TSDRGDPVDA GVVGQCLQVM ARETGLEVDA
LTPDASFVQL GIDSLMSLVL SEKFRAELGI EIKSSLFLEC PTIGEMTAWL EEYC
