PYNG_ASPNC
ID PYNG_ASPNC Reviewed; 432 AA.
AC A5ABG5;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=FAD-dependent monooxygenase pynG {ECO:0000303|PubMed:26414728};
DE EC=1.-.-.- {ECO:0000269|PubMed:26414728};
DE AltName: Full=Pyranonigrin biosynthesis cluster protein G {ECO:0000303|PubMed:26414728};
GN Name=pynG {ECO:0000303|PubMed:26414728}; ORFNames=An11g00300;
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=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: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of pyranonigrins, a family of antioxidative
CC compounds (PubMed:24106156). The first step of pyranonigrins
CC biosynthesis is performed by the hybrid PKS-NRPS synthetase that
CC condenses 6 malonyl-CoA units to an acetyl starter unit, to form a
CC 1,3,5-trioxotetradecane-6,8-dienyl-ACP (PubMed:24106156). The enoyl
CC reducrase (ER) domain of pynA is likely to be functional during the
CC first two rounds of polyketide chain extension, to generate the
CC saturated C-C bonds of the alkyl side chain (Probable). PynA
CC subsequently forms the amide bond between the acyl chain and L-serine
CC (PubMed:24106156, PubMed:26414728). Although pynA has a terminal
CC reductase domain, it appears to require the thioesterase pynI for the
CC release of the straight-chain intermediate from pynA via the formation
CC 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=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A6T923};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26414728}.
CC -!- DISRUPTION PHENOTYPE: Leads to the accumulation of pyranonigrin I.
CC {ECO:0000269|PubMed:26414728}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; AM270218; CAK48263.1; -; Genomic_DNA.
DR RefSeq; XP_001394034.1; XM_001393997.1.
DR AlphaFoldDB; A5ABG5; -.
DR SMR; A5ABG5; -.
DR PaxDb; A5ABG5; -.
DR EnsemblFungi; CAK48263; CAK48263; An11g00300.
DR GeneID; 4984253; -.
DR KEGG; ang:ANI_1_1538094; -.
DR VEuPathDB; FungiDB:An11g00300; -.
DR HOGENOM; CLU_009665_19_5_1; -.
DR Proteomes; UP000006706; Chromosome 7R.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0019748; P:secondary metabolic process; IGC:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase; Reference proteome.
FT CHAIN 1..432
FT /note="FAD-dependent monooxygenase pynG"
FT /id="PRO_0000450060"
FT BINDING 13
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 32..33
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 126
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 240..242
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 315
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 325..329
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 432 AA; 48166 MW; 18E3C39358C611F5 CRC64;
MSTQVLIVGG GIGGLTLAAM CRRIGVSCRV LERSAALEPV GAGISLAPNA LRALDQIGLY
DYVRQEGQPV RKIRVYRNQT QWSEIDFQWL ERTFGYPVYS IERHGFHRRL YDAAGGSETV
NLGAEVAKVI PPQEEAEGVS VVLKDGRRYT GNVLVGADGV RSVVRRALMA TINSPPGQSG
AVGEDEDAAD VIQFTGRVHL SGYTHPLDHL GPADEGIAYW MLYDRSILTT WPCRDHRQWF
VGAVPSKLKD PNRSVWKHAD HNTINQVYGS EYHPFAPDFH FRDVVKHAER VVASDVFHQT
TFPPMAAGRI AMLGDASHAM TSFFGQGACQ AIEDATELAS ALGMIDVRPT DAETILQGYR
HSRERRGRDL VVFSDRFALL HTGRLLGSWG PFVRQMVYTW MPLWGWKWAL QWLYGHQPTL
VEQRNEAAKK TA
