NSCA_ARTOC
ID NSCA_ARTOC Reviewed; 1796 AA.
AC C5FM57;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 1.
DT 03-AUG-2022, entry version 66.
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=MCYG_03598;
OS Arthroderma otae (strain ATCC MYA-4605 / CBS 113480) (Microsporum canis).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Arthrodermataceae; Microsporum.
OX NCBI_TaxID=554155;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4605 / CBS 113480;
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 (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: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:0000250|UniProtKB:Q5B0D0}.
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; DS995703; EEQ30779.1; -; Genomic_DNA.
DR RefSeq; XP_002848092.1; XM_002848046.1.
DR AlphaFoldDB; C5FM57; -.
DR SMR; C5FM57; -.
DR STRING; 63405.XP_002848092.1; -.
DR EnsemblFungi; EEQ30779; EEQ30779; MCYG_03598.
DR GeneID; 9229414; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_1_1; -.
DR OMA; LNTHYDP; -.
DR OrthoDB; 68112at2759; -.
DR Proteomes; UP000002035; 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..1796
FT /note="Non-reducing polyketide synthase nscA"
FT /id="PRO_0000437889"
FT DOMAIN 1719..1796
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 18..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..1251
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1317..1636
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1688..1720
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1688..1709
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 1756
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1796 AA; 195859 MW; A92733146947CBEF CRC64;
MDPTFPRVVF FSNEFPSDDL KDLFRRLHQQ SKDRRFKLLS IFLEESTAIL KDEVAKLPRP
LKELVPPFDS VLALANVDFR QGPLGAAMES SMLTILELGM FIGHYEAEDA EWDLVPSRTV
LAGLSIGILA AAAVALSSSL ADVAKNGAEG VRVSFRLGVY VADISTKLES PQPDGTLSSW
AHVVTETTQA GVQDELDQFN ADTQSPELTK VFVSAADKTS VSVSGPPSRI KAAFQHSPAL
RYSKSLPLPV YDGLCHASHL YTQNDIDAVI NSAESVIQPN RSVRLALLSS QTGKPFAART
ARELFLEIGT ELLTGTIYLD NVTAGIVEHF QLDSETSGKC QIDSFRTSLV LRGIYSTVEA
KFTKEQQQLI RRDLVCWVHK DFGPRRPHSH ASSKLAIVGM ACRLPGGAND LDLFWKLLEE
GRDTHTTVPP DRFDLNTHYD PTGKTENATQ TPFGNFIDRP GYFDAGFFNM SPREAEQTDP
MQRLALVTAY EAMEMAGVVP GRTPSTHPSR IGTFYGQASD DWRELNASQN ISTYAVPGGE
RAFANGRINY FFKFSGPSFN LDTACSSGLA AVQAACSALW AGEADTVIAG GLNVITDPDN
YCGLGNAHFL SKTGQCKVWD KDADGYCRAD GIGSVVIKRL EDAEADNDNI LAVVLGARTN
HSAEAISITH PHAGAQRANY RQVLHQAGVN PVDVSYIELH GTGTQAGDAV ESESVSDVFA
PVTPRRRPDQ RLYLGAVKSN IGHGEAAAGI ASLLKALLVY QKNMIPMHIG IKSEINPTIP
KDLERRNVGL AMENTPWPRP AGKKRLAVVN SFGAHGGNTT LLLEDAPERV KAQSTEDRIT
HPVLISAKSK KSLQANMESL LSYLDQHPET SLADLAYTTS SRRMHHSMRF GTAVSCIPAL
QKALRSQLCN PNFASEMRPI PNEAPSVVLA FTGQGAYYSG MGRELFIEFP YFRAQVQQLD
RLAQRLGFPS VVPVIDGSIE DSPASPILTQ LSVVILEIAL ARFWSLLGVS ISAVIGHSLG
EYAALAVAGV ISAADALYLV GRRAQLVEER CTPGSHSMLS VRASEDAIQE MLASEPETAA
IAYEVSCCNT YQDTVIGGLK DEINNIRMAL EAKSIKCTLL DVPYAFHTAQ MDSILDGLEA
LAMPVPFKAP SIPVLSPLLA TAVFDVKSFN ANYLRRATRE TVDFAAAIEA AQDMGLVDTK
TIWVDVGPHP ICAGLVRGMI PSASVVSSCR RNEDSIATIS KSLVTLHLAG LTPFWAEFFR
PRECEYSLLH LPKYRWNETD YWIPYIGTWT LDKAHLKHGT KPTPFSLSMS RPSALRTSLV
HQITAETVEA TTATLHTISD MQHPDFLEAI HGHTMNKCGV ATSSIWSDMA FTVGEYLYRR
LVPNVKDVHM NLADVEVLHA QVAGKTKGSV QPLVLQAHLD LSTNSMSLAW FNADGETGEC
AAESFATATV RFEDPVAWKK EWARLTHLVR GRIEALEQRA AEGKASRLSK PLAYALFKNV
VDYADRYRGM DSVVLDELEA MAEVTLVPER HGTWHTPPHW IDSVSHLAGL VMNGSDASNT
RDYFFVTPGC DSFRLLNKLE PGVRYRSYVR MFPLPEDPNM HGGDVYILQG EEIVGMVGMI
RFRRVPRLLM DRFFSPPTTT SVAGPAPPVA AATAKGHNVI PTTPAVPTPA PAIATSNPIV
NSAIAYKTPE STPPLAPSSE SSTPKESPIA TPPESERADP MDNMVSQCLR LMARETGLEV
EALTGDASFV QLGVDSLMSL VLSEKFRAEL GVEIKSSLFL ECPTIGEMTA WIEEYC
