NSCA_ASPFU
ID NSCA_ASPFU Reviewed; 1794 AA.
AC Q4WA61;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 105.
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:23368997};
GN Name=nscA {ECO:0000303|PubMed:23368997}; ORFNames=AFUA_7G00160;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
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:0000305|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:0000305|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; AAHF01000015; EAL84875.1; -; Genomic_DNA.
DR RefSeq; XP_746913.1; XM_741820.1.
DR AlphaFoldDB; Q4WA61; -.
DR SMR; Q4WA61; -.
DR STRING; 746128.CADAFUBP00008428; -.
DR PRIDE; Q4WA61; -.
DR EnsemblFungi; EAL84875; EAL84875; AFUA_7G00160.
DR GeneID; 3504088; -.
DR KEGG; afm:AFUA_7G00160; -.
DR VEuPathDB; FungiDB:Afu7g00160; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_1_1; -.
DR InParanoid; Q4WA61; -.
DR OMA; LNTHYDP; -.
DR OrthoDB; 68112at2759; -.
DR Proteomes; UP000002530; Chromosome 7.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0019748; P:secondary metabolic process; NAS:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IMP:AspGD.
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; 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; 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_0000437887"
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 428..448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 927..1230
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..1719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1637..1656
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1661..1675
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1679..1715
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; 195538 MW; 3823A246F4646E83 CRC64;
MATPRGQTVW FGNEFPNDDL KDLFRRLHQH SKDRRFRLLS VFLEESTAIL KEEVANLPQQ
LQELVPHFDT ACTLPEVDFR QGPLGAAMES ALLTILELGM LIGHYEAEDI EWDLDPSRTI
LAGLSIGILA GAAVALSSSL ADVAKVGAES VRVSFRLGVY VADISTKLEA PQSDGTLQSW
AHVVTGMSHE AVQEELSQYN AVTQNPEITK VFVSAADKTS VSVTGPPSRI KAAFQHSPSL
RYSKSLPLPV YDGLCHAAHL YSQDDIEIVI NSAKSVIPTS RPVRLPLISS QTGKPFAAKT
AGELFLEIGT ELLTGTIFLD TVTAGILEHV KLQEPTGNYE IVSFRMSQVL NGILTAIETD
FPELGRARRD MVSWVHGDYG ARRPSSYAAS KLAIVGMACR LPGGANDPEL FWELLEQGRD
TLTTVPPDRF DLNTHYDPTG KTENATQTPF GNFIDRPGYF DAGFFNMSPR EAEQTDPMHR
LALVTAYEAM EMAGMVPGRT PSTRPNRIGT FYGQASDDWR ELNASQNIST YAVPGGERAF
ANGRINYFFK FSGPSYNIDT ACSSGLAAVQ AACSALWAGE ADTVIAGGLN VITDPDNYAG
LGNGHFLSKT GQCKVWDKDA DGYCRADGIG SVVIKRLEDA EADNDNILAV ILGARTNHSA
EAVSITHPHA GAQKANYRQV LHQAGVNPLD VSYVELHGTG TQAGDAVESE SVSDVFAPST
PRRRPDQRLY LGAVKSNIGH GEAAAGITSL LKALLVFQKN MIPKHIGIKT EINPIIPKDL
ERRHVGLAME NTPWPRPAGK KRLAVVNSFG AHGGNTTVLL EDAPERVKVS TQDDRTTHPV
VISAKSKKSL QANIEKLLSW LDQNPDANLG DLSYTLCARR MHHSMRFGAA ASGIAALQKT
LRSWLDNPKA SAELRAIPND TPSVVLTFTG QGAYYSGMGR ELLAEFSYFR TEVFQLDQIA
QRLGFPSVVP VIDGSIDDGP ASPVLTQLSV TVLEIALARF WSHLGIRISA VIGHSLGEYA
AFAVAGVISA TEALYLVGRR AQLTEERCTQ GSHSMLSVRA SEDDIEELIA GSPDTAELAY
EVCCRNTPQD TVIGGTQESI DSIRQALEKN TIKCTQLDVP FAFHTAQMDP ILDSLETLAT
PITFKAPSIP VLSPLLGSVV FDRKSIHAQY LRRATRETVD FVAAIEAAQD FGLVDAKTIW
IDVGPHPICA SLVRGIDSSA SVISSCRRNE DNLATMSKSL VTLHLAGLTP CWAEYFRPRE
QEYSLLKLPT YSWNETDYWI PYIGTWTLDK ALLKYGEKKA PLSLSMSRPS ALRTSLVHQI
TTETVEATTA TLHVLSDMQH PDFLEALHGH RMNNCGVATS SIWSDMAFTV GEYLYRRLVP
QAKDVHMNLS DLEVLHAQVA LEKKGSVQPL VLKAHLNLST SSMSLAWFNA SAETGECAAE
SFATCVVRFE DPAAWTREWD RLSHLVLGRI EALEQRAVEG KASKLSKPLA YTLFKNVVDY
ADRYRGMDQV VLYEHEAVAE VTLVAERHGT WHTPPHWIDS VSHLAGLVMN GSNASNTRDY
FYVTPGCSSF RLLNPLKAGG KYRSYVRMFP LPEEANMYAG DVYILEGEQI VGMVGHIRFR
RVPRLLMDRF FSPAAASHTE KQLQETAPSA TNVKKSTPPP AEAPISVPVA PGNPVAIPLP
TASKSQVATP PLTPPSQEDS PGESAVITPA TSDRGDSTDA GVVGQCLKVM ARETGLEVDA
LTPDASFVQL GIDSLMSLVL SEKFRAELGI EIKSSLFLEC PTIGEMTAWL EEYC
