KTNC_ASPNC
ID KTNC_ASPNC Reviewed; 420 AA.
AC A2QK67;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Bicoumarin synthase ktnC {ECO:0000303|PubMed:26389790};
DE EC=1.14.-.- {ECO:0000269|PubMed:26389790};
DE AltName: Full=Cytochrome P450 monooxygenase ktnC {ECO:0000303|PubMed:22945023};
DE AltName: Full=Kotanin biosynthesis cluster protein C {ECO:0000303|PubMed:22945023};
GN Name=ktnC {ECO:0000303|PubMed:22945023}; ORFNames=An04g09540;
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, DISRUPTION PHENOTYPE, AND PATHWAY.
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, CATALYTIC ACTIVITY, AND PATHWAY.
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 -!- CATALYTIC ACTIVITY:
CC Reaction=2 7-demethylsiderin + NADPH + O2 = 2 H2O + NADP(+) + orlandin;
CC Xref=Rhea:RHEA:62800, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:145991,
CC ChEBI:CHEBI:145992; Evidence={ECO:0000269|PubMed:26389790};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62801;
CC Evidence={ECO:0000269|PubMed:26389790};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:22945023, ECO:0000269|PubMed:26389790}.
CC -!- DISRUPTION PHENOTYPE: Leads to complete loss in kotanin biosynthesis,
CC but accumulates the monomeric intermediate 7-demethylsiderin
CC (PubMed:22945023). {ECO:0000269|PubMed:22945023}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AM270096; CAK47961.1; -; Genomic_DNA.
DR AlphaFoldDB; A2QK67; -.
DR SMR; A2QK67; -.
DR PaxDb; A2QK67; -.
DR EnsemblFungi; CAK47961; CAK47961; An04g09540.
DR VEuPathDB; FungiDB:An04g09540; -.
DR HOGENOM; CLU_022195_8_0_1; -.
DR Proteomes; UP000006706; Chromosome 6L.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:1900596; P:(+)-kotanin biosynthetic process; IDA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..420
FT /note="Bicoumarin synthase ktnC"
FT /id="PRO_0000442170"
FT BINDING 362
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
SQ SEQUENCE 420 AA; 47380 MW; EAF5DFC30AF63B03 CRC64;
MHKSAALSLR DAQFADMNMY CDVTDRTPIE AVHSCNNAES LNILNKLLAR ETDTALSQIF
EQPTGKDWKE LNTLQTILSL CSTVTMALLL GPDTAPDPVL HHHSTSFGEA IMSSCYRRTG
YPRILRPFVW RFSSECRNLR KHFSLVRERL VPEVARRVAA ARAADKTKDV RPSSLLDALI
AAAFDNGSLS PDDQGRNDAA QVQLLADDLI FYHFELCKPT AFNIIFQLYA IMDHPEYKAP
LREEALQALK LTNGDWTVET LKHAPKLESF TKETFRLYDI SGFVSFRRVM KPLTLNSIGL
SLRPGTILLS PCRNVHLDPE IYEDPTTFNG YRFYDSSREV CSPRVATTSL TFLTFSHGAG
SCPARVLATQ ICRTIFIKFL LQYDVEPVQK EILPYGFTSG PVYMPNPSVM MRIRPRSDGK
