EPAD_ASPNC
ID EPAD_ASPNC Reviewed; 443 AA.
AC A2QTE7;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=FAD-dependent monooxygenase orf3 {ECO:0000303|PubMed:30384904};
DE EC=1.-.-.- {ECO:0000305|PubMed:30384904};
DE AltName: Full=Pestalamide A biosynthesis cluster protein orf3 {ECO:0000303|PubMed:30384904};
GN Name=orf3 {ECO:0000303|PubMed:30384904}; ORFNames=An09g01840;
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 IDENTIFICATION, FUNCTION, AND PATHWAY.
RX PubMed=30384904; DOI=10.1016/j.micres.2018.10.004;
RA Wang B., Li X., Yu D., Chen X., Tabudravu J., Deng H., Pan L.;
RT "Deletion of the epigenetic regulator GcnE in Aspergillus niger FGSC A1279
RT activates the production of multiple polyketide metabolites.";
RL Microbiol. Res. 217:101-107(2018).
CC -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of nigerpyrone and its derivatives
CC carbonarone A and pestalamide A (PubMed:30384904). The biosynthesis
CC pathway begins with the polyketide assembly by epaA to form
CC phenylacetyl triketide precursor from successive condensation of two
CC malonyl-CoA, presumably with one phenylacetyl-CoA starter unit produced
CC by the phenylacetyl-CoA ligase epaB (PubMed:30384904). For the
CC nigerpyrone biosynthesis, the reactive polyketide chain is released as
CC an aldehyde through the R-domain. A nonenzymatic cyclization and
CC dehydration may create nigerpyrone (PubMed:30384904). For the
CC biosynthesis of carbonarone A and pestalamide A, an extra methyl group
CC is added through the C-methyltransferase domain. Several further steps
CC involving the dehydrogenase orf1, the cytochrome P450 monooxygenase
CC orf2 and the FAD-dependent monooxygenase orf3 are required to form a
CC carbonarone A precursor which is converted to carbonarone A via
CC cyclization (PubMed:30384904). The O-acetyltransferase epaC could
CC catalyze the transfer of 2-methylsuccinyl-CoA, a common intermediate in
CC the ethylmalonyl-CoA pathway, to generate the final product pestalamide
CC A (Probable). {ECO:0000269|PubMed:30384904,
CC ECO:0000305|PubMed:30384904}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A6T923};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:30384904}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; AM270194; CAK40122.1; -; Genomic_DNA.
DR AlphaFoldDB; A2QTE7; -.
DR SMR; A2QTE7; -.
DR PaxDb; A2QTE7; -.
DR EnsemblFungi; CAK40122; CAK40122; An09g01840.
DR VEuPathDB; FungiDB:An09g01840; -.
DR HOGENOM; CLU_009665_6_3_1; -.
DR Proteomes; UP000006706; Chromosome 1L.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
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 3: Inferred from homology;
KW FAD; Flavoprotein; Glycoprotein; Membrane; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..443
FT /note="FAD-dependent monooxygenase orf3"
FT /id="PRO_0000446157"
FT TRANSMEM 5..25
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 35..36
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"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 443 AA; 48506 MW; 50B26763A8F90410 CRC64;
MSTDSIEVAI IGAGITGITL ALGLLSRGIP VRVYERARDF HEIGAGIGFT PNAEWAMKVV
DPRIQAAFKR VATPNASDWF QWVDGFNESG TDPRETEEQL LFKIYLGERG FEGCHRADFL
GELARLLPEG VVTFQKALDT VEPAADNSLG QLLRFQDGTT ATAHAVIGCD GIRSRVRQIL
LGEDHPAASA HYSHKYAARG LIPMDRAREA LGEDKVATRF MHLGPDAHAL TFPVSHGSLL
NVVAFVTDPN PWPYADRWTA QGPKEDVTAA FSRFGPTMRT IIDLLPDPID QWAVFDTYDH
PPNTYSRGAV CIAGDAAHAA APHHGAGAGC GVEDAAVLCA VLDMAAKRVD TAKDGTEGKA
ALITTAFETY DAVRRERAQW LVESSRVIGN LYEWQDKEVG SDASRCHDEV YWRSHRIWDY
DIDAMMRETA EVFEARVAGV AKN
