ID   LEPH_ASPFN              Reviewed;         507 AA.
AC   B8NJH2;
DT   30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   03-MAR-2009, sequence version 1.
DT   03-AUG-2022, entry version 58.
DE   RecName: Full=Cytochrome P450 monooxygenase lepH {ECO:0000303|PubMed:26051490};
DE            EC=1.-.-.- {ECO:0000305|PubMed:26051490};
DE   AltName: Full=Leporins biosynthesis protein H {ECO:0000303|PubMed:26051490};
DE   Flags: Precursor;
GN   Name=lepH {ECO:0000303|PubMed:26051490}; ORFNames=AFLA_066930;
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   -!- DISRUPTION PHENOTYPE: Leads to the accumulation of pre-leporin C at the
CC       expense of leporins B and C (PubMed:26051490).
CC       {ECO:0000269|PubMed:26051490}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; EQ963479; EED49871.1; -; Genomic_DNA.
DR   RefSeq; XP_002380252.1; XM_002380211.1.
DR   AlphaFoldDB; B8NJH2; -.
DR   SMR; B8NJH2; -.
DR   STRING; 5059.CADAFLAP00008117; -.
DR   PRIDE; B8NJH2; -.
DR   EnsemblFungi; EED49871; EED49871; AFLA_066930.
DR   VEuPathDB; FungiDB:AFLA_066930; -.
DR   eggNOG; KOG0158; Eukaryota.
DR   HOGENOM; CLU_001570_27_0_1; -.
DR   OMA; AFKEHRW; -.
DR   Proteomes; UP000001875; Unassembled WGS sequence.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IEA:InterPro.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002974; Cyt_P450_E_CYP52.
DR   InterPro; IPR002402; Cyt_P450_E_grp-II.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00464; EP450II.
DR   PRINTS; PR01239; EP450IICYP52.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   3: Inferred from homology;
KW   Glycoprotein; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..507
FT                   /note="Cytochrome P450 monooxygenase lepH"
FT                   /id="PRO_0000438450"
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        315
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        367
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   507 AA;  58357 MW;  55E27BC1C5277A89 CRC64;
     MFTLTEYFIA ACVWLVLYKV GNLLWNRHHY FKQQKARGCG EIKHYRHRDP ILGLDFVYTL
     SKAFKEHRWL PWQQELFAAQ GVKTFQANFL GSRAIYTSES ENMKAMSTTY WREFGLEPLR
     RGSGAADPVA GPGVSTVDGP MWDFSRNIIK PYFTRDGYSN LARLEVFVNR LLDLVPTDGS
     TFDMQPLLQR WFLDTSSEFL FGKTVDSLTH PENVKVAKAM VDTMRGIRVR LTMSKLMFLH
     RDPVWMENVK IVRDFVDERI DASLTQLQDV KSGKGTSCTE NQPDGRTDLL WDMVQQLQDK
     EALRGQIMAV FIPSNDTTSI LISNAIYALA RHPHVYQTLR EEVLALGDQE ITFEKLRGLR
     YLRYVINETH RLYPNGIQMV RIALEDTTLP VGGGPDQSQP IFIQKGDIVH ANRYLMHRDP
     DNWGPDAEVF RPERWGDVRP LWKFVPFGGG PRICPAHVLV DTEASYVLLR FVQRFRTLEP
     RDERPYKAIM RIGPSNLHGV NVAVKTA