NSCA_TRIRC
ID NSCA_TRIRC Reviewed; 1798 AA.
AC F2T0M0;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 53.
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=TERG_08357;
OS Trichophyton rubrum (strain ATCC MYA-4607 / CBS 118892) (Athlete's foot
OS fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Arthrodermataceae; Trichophyton.
OX NCBI_TaxID=559305;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4607 / CBS 118892;
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).
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; GG700661; EGD92142.1; -; Genomic_DNA.
DR RefSeq; XP_003231059.1; XM_003231011.1.
DR AlphaFoldDB; F2T0M0; -.
DR SMR; F2T0M0; -.
DR STRING; 559305.F2T0M0; -.
DR PRIDE; F2T0M0; -.
DR EnsemblFungi; EGD92142; EGD92142; TERG_08357.
DR GeneID; 10377341; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_1_1; -.
DR InParanoid; F2T0M0; -.
DR Proteomes; UP000008864; 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_0000437895"
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 931..1224
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 1695..1721
FT /note="Disordered"
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; 196450 MW; 10A617C749D0DF58 CRC64;
MDSTLRRVVF FSNEFPSDDL KELFRRLDQH SKDRRFRLLS IFLEESTAVL KDEVSKFPRP
LKELVPPFDS VLGLVDVDFR QGPLGAAMES SILTILELGL FIGHYESEDT EWDLVPGESV
LAGLSIGILA AAAVALSSSL ADVAKTGAEA VRVSFRLGVY VADISTKLEA PQSDGTLSSW
AHVVTEMTEA SVQDELKQFN TDTHSPELTK VFISAADKTS ISVSGPPSRI KAAFQHSPVL
RYSKSLPLPV YDGLCHASHL YTQSDIDFII NSAESVILPD RSVRLALLSS QTGKPFIAKT
ASELFLEIGT ELLTGTIYLD NVTAGIVQHL QPQSKETSSW QIDSFRTSLV LRGIHSAVEA
NLSGEQRQLI RRDLVSWVNR DFGPRRPRSY ASSKLAIVGM ACRLPGGADD LDLFWKLLEE
GRDTLTTVPP DRFDLNTHYD PTGKTENATQ TPYGNFIDRP GFFDAGFFNM SPREAEQTDP
MQRLALVTAY EALEMAGVVP GRTPSTHPSR IGTFYGQASD DWRELNASQN ISTYAVPGGE
RAFGNGRINY FFKFSGPSFN LDTACSSGLA AVQVACSALW AGEVDTAIAG GLNVITDPDN
YCGLGNAHFL SKTGQCKVWD KDADGYCRAD GIGSVVIKRL EDAEADNDNI LAVVLGASTN
HSAEAISITH PHAGAQKANY RQVLNQAGVN PIDVSYIELH GTGTQAGDAV ESESVSDIFA
PVTPRRRPDQ RLYLGAVKSN IGHGEAAAGI ASLLKALLVY QKNLIPMHIG IKSEINPTIP
KDLERRNVGL AMQNTPWPRP AGKKRLAVVN SFGAHGGNTT LLLEDAPERV KIQGTEDRIT
HAILLSAKSK KSLQANMESL LSYLDQHPET SLADLAYTTS SRRMHHNMRF GTSVSCISGL
QKALRSQLDN PNFASEVRPV PNEAPSVILA FTGQGAYYHG MGRGLFTEFP YFRAQVQQLD
RLAQRLGFPS VVPVIENSIE DTPSSPILTQ LSVVILEIAL ARFWSLLGVS ISAVIGHSLG
EYAALAVSGV ISTADAIYLV GRRAQLVEER CAQGSHSMLS VRASEDAIQE MLAAEPETAL
IAYEVSCCNT NQDTVIGGFQ GEIDDIRRAL EAKSIKCTIL DVPYAFHTAQ MNPILEDLET
LAKAIPFKAP SIPVISPLLA TVIYDVKSLN ASYLRRATRE TVDFAAAIEA TQDMGLVDSK
TMWIDVGPHP ICAGLVRSMI PSAPVMSSCR RNEDSIATIS KSLVTLYLAG LNPCWAEFFK
PREREYSLLH LPKYRWNETD YWIPYIGTWT LDKAHLKHGT KPTTPFSVSM SRPSALRTSL
VHQITAETVR TTTATLHTIS DMQHPDFLEA IHGHTMNKCG VATSSIWSDM AFTVGEYLYR
RLVPNTKDVH MNLTDVEVLH AQVASKTKGS VQPLVLRAHL DLSTSSMSLS WFNADGETGE
CAAESFATAT ILFEDPGAWR KEWARLAHLV LGRIEVLEQR ATEGKASRLS KPLAYTLFKN
VVDYADRYRG MDSVVLDELE AMAEVTLVPE RYGTWHTPPH WIDSVSHLAG LVMNGSEASN
TRDYFFVTPG CDSFRLLEKL EPGARYRSYV RMFPLPEDPN MHGGDVYILQ GEEIVGVVGM
IRFRRVPRLL MDRFFSPPTT TSVAGPVPPL AGATTKCHDI AQTAPALPTP TPPIVVSNPI
VSSTLASKAL EPAPLLATSS GDSTPKEPPI VTPAESERAG PVDNNMISQC LRLMARETGL
EVEALTADAS FVQLGVDSLM SLVLSEKFRA ELGVEVKSSL FLECPTIGEM TAWIEEYC
