KTNS_ASPNC
ID KTNS_ASPNC Reviewed; 1663 AA.
AC A2QK66;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 25-MAY-2022, entry version 86.
DE RecName: Full=Kotanin synthase {ECO:0000303|PubMed:22945023};
DE EC=2.3.1.- {ECO:0000269|PubMed:22945023};
DE AltName: Full=Kotanin biosynthesis cluster protein S {ECO:0000303|PubMed:22945023};
DE AltName: Full=Non-reducing polyketide synthase ktnS {ECO:0000303|PubMed:22945023};
GN Name=ktnS {ECO:0000303|PubMed:22945023}; ORFNames=An04g09530;
OS Aspergillus niger (strain CBS 513.88 / FGSC A1513).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=425011;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 513.88 / FGSC A1513 / ATCC MYA-4892;
RX PubMed=17259976; DOI=10.1038/nbt1282;
RA Pel H.J., de Winde J.H., Archer D.B., Dyer P.S., Hofmann G., Schaap P.J.,
RA Turner G., de Vries R.P., Albang R., Albermann K., Andersen M.R.,
RA Bendtsen J.D., Benen J.A.E., van den Berg M., Breestraat S., Caddick M.X.,
RA Contreras R., Cornell M., Coutinho P.M., Danchin E.G.J., Debets A.J.M.,
RA Dekker P., van Dijck P.W.M., van Dijk A., Dijkhuizen L., Driessen A.J.M.,
RA d'Enfert C., Geysens S., Goosen C., Groot G.S.P., de Groot P.W.J.,
RA Guillemette T., Henrissat B., Herweijer M., van den Hombergh J.P.T.W.,
RA van den Hondel C.A.M.J.J., van der Heijden R.T.J.M., van der Kaaij R.M.,
RA Klis F.M., Kools H.J., Kubicek C.P., van Kuyk P.A., Lauber J., Lu X.,
RA van der Maarel M.J.E.C., Meulenberg R., Menke H., Mortimer M.A.,
RA Nielsen J., Oliver S.G., Olsthoorn M., Pal K., van Peij N.N.M.E.,
RA Ram A.F.J., Rinas U., Roubos J.A., Sagt C.M.J., Schmoll M., Sun J.,
RA Ussery D., Varga J., Vervecken W., van de Vondervoort P.J.J., Wedler H.,
RA Woesten H.A.B., Zeng A.-P., van Ooyen A.J.J., Visser J., Stam H.;
RT "Genome sequencing and analysis of the versatile cell factory Aspergillus
RT niger CBS 513.88.";
RL Nat. Biotechnol. 25:221-231(2007).
RN [2]
RP FUNCTION.
RX PubMed=17315249; DOI=10.1002/cbic.200600434;
RA Huettel W., Mueller M.;
RT "Regio- and stereoselective intermolecular oxidative phenol coupling in
RT kotanin biosynthesis by Aspergillus niger.";
RL ChemBioChem 8:521-529(2007).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22945023; DOI=10.1002/anie.201203603;
RA Gil Girol C., Fisch K.M., Heinekamp T., Guenther S., Huettel W., Piel J.,
RA Brakhage A.A., Mueller M.;
RT "Regio- and stereoselective oxidative phenol coupling in Aspergillus
RT niger.";
RL Angew. Chem. Int. Ed. 51:9788-9791(2012).
RN [4]
RP FUNCTION.
RX PubMed=26389790; DOI=10.1021/jacs.5b06776;
RA Mazzaferro L.S., Huettel W., Fries A., Mueller M.;
RT "Cytochrome P450-catalyzed regio- and stereoselective phenol coupling of
RT fungal natural products.";
RL J. Am. Chem. Soc. 137:12289-12295(2015).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of the bicoumarin kotanin
CC (PubMed:22945023, PubMed:26389790). The non-reducing polyketide
CC synthase ktnS first catalyzes the formation of the pentaketidic 4,7-
CC dihydroxy-5-methylcoumarin from acetyl coenzyme A and 4 malonyl
CC coenzyme A molecules (PubMed:17315249, PubMed:22945023). Further O-
CC methylation by ktnB leads to the formation of 7-demethylsiderin
CC (PubMed:17315249, PubMed:22945023, PubMed:26389790). Then, an oxidative
CC phenol coupling catalyzed by the cytochrome P450 monooxygenase ktnC
CC forms the 8,8'-dimer P-orlandin via dimerization the monomeric
CC precursor, 7-demethylsiderin (PubMed:26389790). P-orlandin is
CC subsequently O-methylated in a stepwise fashion to demethylkotanin and
CC kotanin (PubMed:22945023). {ECO:0000269|PubMed:17315249,
CC ECO:0000269|PubMed:22945023, ECO:0000269|PubMed:26389790}.
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:22945023}.
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}.
CC -!- DISRUPTION PHENOTYPE: Leads to complete loss in coumarin biosynthesis
CC (PubMed:22945023). {ECO:0000269|PubMed:22945023}.
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DR EMBL; AM270096; CAK47960.1; -; Genomic_DNA.
DR AlphaFoldDB; A2QK66; -.
DR SMR; A2QK66; -.
DR PaxDb; A2QK66; -.
DR EnsemblFungi; CAK47960; CAK47960; An04g09530.
DR VEuPathDB; FungiDB:An04g09530; -.
DR HOGENOM; CLU_000022_6_0_1; -.
DR Proteomes; UP000006706; Chromosome 6L.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:1900596; P:(+)-kotanin biosynthetic process; IMP:GO_Central.
DR GO; GO:0019748; P:secondary metabolic process; NAS:AspGD.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
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; 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; PS50075; CARRIER; 1.
PE 3: Inferred from homology;
KW Acyltransferase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..1663
FT /note="Kotanin synthase"
FT /id="PRO_0000442165"
FT DOMAIN 1586..1663
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 19..168
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 304..734
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 830..1149
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1209..1527
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1544..1580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1544..1558
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 474
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1623
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1663 AA; 182776 MW; 52BD5136C1085FBD CRC64;
MLADMCVGVY KAAMNYEIRP HEFSFNTQES LFTGLGLGFL AATAVVASPS LLDLPITAAE
VVRIAMRAGI LLYQKSQDLE QLSLDSSLES WTTVVRGLDE SIVRGELEKF NKSMETPPSS
RIYISVVEPD GSVFISGPPS GLREFFNKSG KVQSAPRAPL PVYGGPCHAA HLYDRTHTEW
VVSKVNPEIA SRRLSGHPLV LSMGDGQPLA GENARDLFES ATYVLLTSII RWDSVLAAVK
KLPHWKQDTK LQLETFRPSS PAVHGLISAV QSEYPDCTVS VDDLGDWIID NSLEPPTIPI
DSRIAVVGMS CRLPGGSDDL QRFWELLEDG RDVHQKVPGN RYDVESHTDM TGRRLNTSHT
PFGCFIDSPG LFDASFFDMS PREAGQTDPT HRLALLTAYE ALEYSGYVPN RTRSTTRDRV
GTVYGQCSDD YREANAGQNI DMYFIPGNYR AFAPGRISYF FKFSGPSFNC DTACSASLAA
VQIACSALIR GEADMVVAGG LNILTGSDSF AGLSRGFFLS KTGNCKVFDD GADGYCRADG
IGSIVLKRLS DAQQDNDNIL GVILGTATNH SSHAISITHP HAPTQEHLYR SVLSQAGIGP
HDVDLVEMHG TGTQAGDAAE IESVTRVFSP PVPRRSHPLY ISSVKANLGH GEAAAGITAL
MKALLIFQHN AIPRHVGIKT ALNSKFPDLE RLNVHIPKET IPWPYRSNRK RYVMINNFSA
AGGNTSLLLE EPPVRPDPQG PPQTRFVVAL SAKSTTSLRR NLESLITWLE GNRSARLASL
AYTTTARRMH HKHRIAVHGA SVAEIIQALH QRGSRAELGL LVSKPPSVAF IFSGQGSFYA
GVGSQLFKEY PPYREQLQRL DEICQQNGFG SILPAITDTD ADVSQLSALV TQLTTVCVQI
ALCRLWRTLG VKPAVVIGAS LGEYAALYAA GALSASDAIF LVGQRTLLMQ KLCTANSYGM
LAVQGSVDDI RRCVQDRTYE VACINAPRSI TICASIKDIV DIQQSLVSQG YRSVKLNVPF
AFHSSQMDPI LDRYEEIAKA VSFRSLQIPL ISSTLADAAV QSRSLVASLF LRENTRAPAR
FAEAVAKAQD MGLVNSHTVW VEIGVHSTYS GAVRATVADL QAIVPSLRSD ETNWHTLAVS
MCTLQETGVP LDWNEWYRPF EPEVRLLDLP SYRWDLKNHW IQYNGDWLLV KDKRPRTDQI
SAATPSLRTA LVHQIMEESF RPDGGEIVVQ SDVMDKEFFA VASGHKMSGR PLVSVFSYPD
IAFTLARYMY SRLKPESPLP AMDFGQVRVL QGLLPRKDRS KPQWVRMRMR ADPQCAALQL
SISGLSDESS RHVEEKLASG VVRCGDRQSW QDEWADYAHL LTTRIVTLQQ MAENGQASRV
SRDLVYTLFK NIVDYADHYR GIQSAVLHGL EAVADVILAP SNDSRWTAPP HHIDPITHVG
GLVLNAGHAT DHHNTIYVME GWKSMRFAEE LVAGELYRSY VKMNPARDGS GFFVGDVYVM
REDHIVGKVR GMTLRPLPRI LMNRFFDPPD DGDGLATQHI QPHDLPQVQH QPSPTTDSGP
DDDPKDPNTG PLTPEVDLPV APSVEKANTK LVRGALALLA AETGVEPDGL TDETEVSALG
IDSLLSLVLV EKFATELQVN IQSSFFLESP TIRELKEYLT ASW
