PYNB_ASPNC
ID PYNB_ASPNC Reviewed; 541 AA.
AC A5ABH0;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 25-MAY-2022, entry version 73.
DE RecName: Full=FAD-linked oxidoreductase pynB {ECO:0000303|PubMed:24106156};
DE EC=1.1.1.- {ECO:0000269|PubMed:26414728};
DE AltName: Full=Pyranonigrin biosynthesis cluster protein B {ECO:0000303|PubMed:24106156};
DE Flags: Precursor;
GN Name=pynB {ECO:0000303|PubMed:24106156}; ORFNames=An11g00350;
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: FAD-linked oxidoreductase; 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=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
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 G.
CC {ECO:0000269|PubMed:26414728}.
CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; AM270218; CAK48268.1; -; Genomic_DNA.
DR RefSeq; XP_001394039.1; XM_001394002.1.
DR AlphaFoldDB; A5ABH0; -.
DR SMR; A5ABH0; -.
DR PaxDb; A5ABH0; -.
DR EnsemblFungi; CAK48268; CAK48268; An11g00350.
DR GeneID; 4984244; -.
DR KEGG; ang:ANI_1_1546094; -.
DR VEuPathDB; FungiDB:An11g00350; -.
DR HOGENOM; CLU_018354_10_2_1; -.
DR Proteomes; UP000006706; Chromosome 7R.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0019748; P:secondary metabolic process; IGC:AspGD.
DR Gene3D; 3.30.465.10; -; 2.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Oxidoreductase; Reference proteome;
KW Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..541
FT /note="FAD-linked oxidoreductase pynB"
FT /id="PRO_5002678902"
FT DOMAIN 71..242
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT CARBOHYD 30
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 430
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 461
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 541 AA; 59245 MW; CABE2901651C542E CRC64;
MRLSARGFVW SALLACTASA LSEAAATASN SSQTLRTCVS QALVAGDVNT RIIDPSNDTY
TDARLGEKIQ FNEFPALIAY AKKAEEVASL VRCAQRSGFK AVPRSGGHHF EAWSALNGTL
VIDLSHINHV NVSADTTTAN VGAGIRQGAL YLALDEHNVT FPGGICPTVA LGGLVSSGGF
SLQMRALGLA AEYVQSARVV LADGSLVTAS SSSHEDLFWA IRGGGGGTYG IIVDFDLQLM
QFPTSAMVAI SWNASSDRYP VAQRFFDWAP VQIPAFTSQV NVYKSSINFL GQYLGGTENE
LRKLINESGL LNIGTPTVYI SGNCDTDNSR LFGYTSYECV PANETNRQIM NVLPEPFSQY
SDYPQYQYEN EPEDPSIPIA EPWARFNRIS KSFFMQKDNI LPAADLKTVI DMMGQLDTDS
EIWGEWHAWN ISSATKADYA FPWREQAYAH LEFQVHGSLT NSTKQATYEK WFADLETYLR
PKIGVASYSG EMDAHISTNP FESYYGDSVC RLVEVKKAYD PDNFFTNPDA ITPTVPEGIS
C
