PYND_ASPNC
ID PYND_ASPNC Reviewed; 482 AA.
AC A5ABG2;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Cytochrome P450 monooxygenase pynD {ECO:0000303|PubMed:24106156};
DE EC=1.14.14.- {ECO:0000269|PubMed:26414728};
DE AltName: Full=Pyranonigrin biosynthesis cluster protein D {ECO:0000303|PubMed:24106156};
DE Flags: Precursor;
GN Name=pynD {ECO:0000303|PubMed:24106156}; ORFNames=An11g00270;
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, AND INDUCTION.
RX PubMed=24106156; DOI=10.1002/cbic.201300430;
RA Awakawa T., Yang X.L., Wakimoto T., Abe I.;
RT "Pyranonigrin E: a PKS-NRPS hybrid metabolite from Aspergillus niger
RT identified by genome mining.";
RL ChemBioChem 14:2095-2099(2013).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26414728; DOI=10.1021/acs.orglett.5b02435;
RA Yamamoto T., Tsunematsu Y., Noguchi H., Hotta K., Watanabe K.;
RT "Elucidation of pyranonigrin biosynthetic pathway reveals a mode of
RT tetramic acid, fused gamma-pyrone, and exo-methylene formation.";
RL Org. Lett. 17:4992-4995(2015).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of pyranonigrins, a family of antioxidative
CC compounds (PubMed:24106156, PubMed:26414728). The first step of
CC pyranonigrins biosynthesis is performed by the hybrid PKS-NRPS
CC synthetase that condenses 6 malonyl-CoA units to an acetyl starter
CC unit, to form a 1,3,5-trioxotetradecane-6,8-dienyl-ACP
CC (PubMed:24106156). The enoyl reducrase (ER) domain of pynA is likely to
CC be functional during the first two rounds of polyketide chain
CC extension, to generate the saturated C-C bonds of the alkyl side chain
CC (Probable). PynA subsequently forms the amide bond between the acyl
CC chain and L-serine (PubMed:24106156, PubMed:26414728). Although pynA
CC has a terminal reductase domain, it appears to require the thioesterase
CC pynI for the release of the straight-chain intermediate from pynA via
CC the formation of a tetramic acid pyranonigrin J (PubMed:26414728). The
CC methyltransferase pynC then coverts pyranonigrin J to pyranonigrin I
CC via N-methylation (PubMed:26414728). The FAD-dependent monooxygenase
CC pynG catalyzes an epoxidation-mediated cyclization to form the dihydro-
CC gamma-pyrone moiety, followed by pynD-catalyzed oxidation of the
CC alcohol to the ketone and enolization to yield the characteristic
CC tetramic acid-fused gamma-pyrone core of pyranonigrin H
CC (PubMed:26414728). Pyranonigrin H is substrate of pynH for dehydration-
CC mediated exo-methylene formation from the serine side chain to produce
CC pyranonigrin E, before the oxidase pynE reduces the exo-methylene of
CC pyranonigrin E into a pendant methyl to form pyranonigrin G
CC (PubMed:26414728). The FAD-linked oxidoreductase pynB performs the
CC reverse reaction and converts pyranonigrin G back to pyranonigrin E
CC (PubMed:26414728). {ECO:0000269|PubMed:24106156,
CC ECO:0000269|PubMed:26414728, ECO:0000305|PubMed:24106156}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26414728}.
CC -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC transcription factor pynR. {ECO:0000269|PubMed:24106156}.
CC -!- DISRUPTION PHENOTYPE: Leads to the accumulation of pyranonigrin J.
CC {ECO:0000269|PubMed:26414728}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AM270218; CAK48260.1; -; Genomic_DNA.
DR RefSeq; XP_001394031.1; XM_001393994.1.
DR AlphaFoldDB; A5ABG2; -.
DR SMR; A5ABG2; -.
DR PaxDb; A5ABG2; -.
DR EnsemblFungi; CAK48260; CAK48260; An11g00270.
DR GeneID; 4984247; -.
DR KEGG; ang:ANI_1_1532094; -.
DR VEuPathDB; FungiDB:An11g00270; -.
DR HOGENOM; CLU_045283_0_0_1; -.
DR Proteomes; UP000006706; Chromosome 7R.
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:0019748; P:secondary metabolic process; IGC:AspGD.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
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.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..482
FT /note="Cytochrome P450 monooxygenase pynD"
FT /id="PRO_5002677566"
FT BINDING 417
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"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 482 AA; 54997 MW; FA1E05D3A922F735 CRC64;
MWRIPVIVAL VAGLLYWVRK QGSQPSRKIP QPRIGLPVVG DAHAFGKSPI SYIRQATARC
GPVFQINLLL TKIVMLRGAQ LNRFYLDTRE EVWSFGDGMG LFLEKVVVPG YLSHLKEMVS
SLNRGVIRSI ALEHYTRIAG EEARKIATNW AEKPDIEVFE QMSRYTHRVI VRCLMGQDFY
DHHLDELLDL LHRMEADIGH PFHFLLPNWV PHGPARRLHH ARDRMAAIFN ERLQAREQNP
EKWQDSLDYI AYTLKDSRTA HLRQYFAAHH TLLMFAAHTS TVASIAWTVL ELLRNPTHLE
ALKTALATDA DIHRSPTLIA TLKETSRRYS GVNMIRWARQ PHQLPADAAP GKGNIVVPEN
CIVSISPYLT HHDPETYADP HIWDPTRWLE GGRLSETQKS NRSEVTYFPF GAGCHRCPGE
QMAGMIAREM VAHMVKTYDV RWSSTGPPED FEQLDFSRVG SAWLKGDARV TVKRDKQGME
EA
