ID   LEPD_ASPFN              Reviewed;         508 AA.
AC   B8NJG8;
DT   30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   03-MAR-2009, sequence version 1.
DT   03-AUG-2022, entry version 57.
DE   RecName: Full=Cytochrome P450 monooxygenase lepD {ECO:0000303|PubMed:26051490};
DE            EC=1.-.-.- {ECO:0000305|PubMed:26051490};
DE   AltName: Full=Leporins biosynthesis protein D {ECO:0000303|PubMed:26051490};
GN   Name=lepD {ECO:0000303|PubMed:26051490}; ORFNames=AFLA_066890;
OS   Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS   / JCM 12722 / SRRC 167).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=332952;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC   167;
RX   PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA   Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA   Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT   "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT   aflatoxin contamination of food and feed.";
RL   Genome Announc. 3:E0016815-E0016815(2015).
RN   [2]
RP   IDENTIFICATION OF THE GENE CLUSTER 23, AND FUNCTION.
RX   PubMed=20447271; DOI=10.1111/j.1364-3703.2009.00594.x;
RA   Georgianna D.R., Fedorova N.D., Burroughs J.L., Dolezal A.L., Bok J.W.,
RA   Horowitz-Brown S., Woloshuk C.P., Yu J., Keller N.P., Payne G.A.;
RT   "Beyond aflatoxin: four distinct expression patterns and functional roles
RT   associated with Aspergillus flavus secondary metabolism gene clusters.";
RL   Mol. Plant Pathol. 11:213-226(2010).
RN   [3]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=26051490; DOI=10.1016/j.fgb.2015.05.010;
RA   Cary J.W., Uka V., Han Z., Buyst D., Harris-Coward P.Y., Ehrlich K.C.,
RA   Wei Q., Bhatnagar D., Dowd P.F., Martens S.L., Calvo A.M., Martins J.C.,
RA   Vanhaecke L., Coenye T., De Saeger S., Di Mavungu J.D.;
RT   "An Aspergillus flavus secondary metabolic gene cluster containing a hybrid
RT   PKS-NRPS is necessary for synthesis of the 2-pyridones, leporins.";
RL   Fungal Genet. Biol. 81:88-97(2015).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster 23
CC       that mediates the biosynthesis of a family of 2-pyridones known as
CC       leporins (PubMed:20447271, PubMed:26051490). The hybrid PKS-NRPS
CC       synthetase lepA and the enoyl reductase lepG are responsible for fusion
CC       of phenylalanine with a hexaketide and subsequent release of the stable
CC       tetramic acid precursor, pre-leporin C (PubMed:26051490). Because lepA
CC       lacks a designated enoylreductase (ER) domain, the required activity is
CC       provided the enoyl reductase lepG (PubMed:26051490). It is possible
CC       that the dehydrogenase lepF also participates in production of pre-
CC       leporin C (PubMed:26051490). Cytochrome P450 monooxygenase lepH is then
CC       required for the ring expansion step to yield leporin C
CC       (PubMed:26051490). Leporin C is then presumably further oxidized by the
CC       N-hydroxylase lepD to form leporin B (PubMed:26051490). LepI may
CC       possess a function in biosynthesis upstream of lepA (PubMed:26051490).
CC       Leporin B is further oxidized in the presence of ferric ion to give the
CC       leporin B trimer-iron chelate, but whether or not this reaction is
CC       catalyzed by an enzyme in the pathway or by ferric ion is not
CC       determined yet (PubMed:26051490). {ECO:0000269|PubMed:26051490,
CC       ECO:0000305|PubMed:20447271}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Leads to normal accumulation of leporin C
CC       accumulated but to 30-fold reduced production of leporin B
CC       (PubMed:26051490). {ECO:0000269|PubMed:26051490}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; EQ963479; EED49867.1; -; Genomic_DNA.
DR   RefSeq; XP_002380248.1; XM_002380207.1.
DR   AlphaFoldDB; B8NJG8; -.
DR   SMR; B8NJG8; -.
DR   EnsemblFungi; EED49867; EED49867; AFLA_066890.
DR   VEuPathDB; FungiDB:AFLA_066890; -.
DR   eggNOG; KOG0157; Eukaryota.
DR   HOGENOM; CLU_042557_0_0_1; -.
DR   OMA; AFLRFGF; -.
DR   Proteomes; UP000001875; Unassembled WGS sequence.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   SUPFAM; SSF48264; SSF48264; 1.
PE   3: Inferred from homology;
KW   Glycoprotein; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..508
FT                   /note="Cytochrome P450 monooxygenase lepD"
FT                   /id="PRO_0000438449"
FT   TRANSMEM        22..42
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         454
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        53
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        416
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   508 AA;  57547 MW;  916198A6206FCDA4 CRC64;
     MASPMKSDFL AGSHMKLPKI GIAAAVAVVA SIVIYLALSS FFVGTDEFKN DENQSIKEYP
     DNTRFMRFTH GKQLSKAGED LAGSEPYLVR NGKSKELVIF APEHLQEFHR KDANSHYKPE
     NMNMGDYAGQ LLGQCVGQLG GTKWKLARSH MDPEFSYRAS RSMMKRFSQE IDSWVSHLSE
     NPTRRSTQKD VFVQDVKKRC KDLSLRSIAI SIYGETFSEE NYAFLSTMNE LHEKIIFVAF
     LNKRVMSKWY NKLPTAEKRL MDSFQTQWKA FNLAQIKLAR EKKLSCPAEK IYVGVEAGDM
     SLPEFLQSLD EMLFTNIDIT GSILALIFQH LAKDQAMQKK LRAEISAHRA QPGYTVGDYI
     SKQNTLLHFS LLESIRVTPA MYFTLPECNA SPKRIGGFHI PAHTPTIVDV NRLNKNESIW
     GTEADAFRPE RFFGLDPARY RFGFVRWGIG RDKCLGKNMA EVILKLAILA VTDKYTLHVP
     PALPGQGEKS EAGFTINRDV EVEFRPAI