LEPI_ASPFN
ID LEPI_ASPFN Reviewed; 387 AA.
AC B8NJH3;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=O-methyltransferase lepI {ECO:0000303|PubMed:26051490};
DE EC=2.1.1.- {ECO:0000305|PubMed:26051490};
DE AltName: Full=Leporins biosynthesis protein I {ECO:0000303|PubMed:26051490};
GN Name=lepI {ECO:0000303|PubMed:26051490}; ORFNames=AFLA_066940;
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: O-methyltransferase; part of the gene cluster 23 that
CC mediates the biosynthesis of a family of 2-pyridones known as leporins
CC (PubMed:20447271, PubMed:26051490). The hybrid PKS-NRPS synthetase lepA
CC and the enoyl reductase lepG are responsible for fusion of
CC 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 -!- DISRUPTION PHENOTYPE: Resulted in about a 5-fold reduction in leporin C
CC accumulation while leporin B is not detected (PubMed:26051490).
CC {ECO:0000269|PubMed:26051490}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000305}.
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DR EMBL; EQ963479; EED49872.1; -; Genomic_DNA.
DR RefSeq; XP_002380253.1; XM_002380212.1.
DR PDB; 5ZZD; X-ray; 1.85 A; A/B=1-387.
DR PDB; 6INW; X-ray; 1.80 A; A/B=1-387.
DR PDB; 6IV7; X-ray; 1.94 A; A/B=2-387.
DR PDB; 6IX3; X-ray; 2.13 A; A/B=2-387.
DR PDB; 6IX5; X-ray; 1.70 A; A/B=2-387.
DR PDB; 6IX7; X-ray; 1.83 A; A/B=2-387.
DR PDB; 6IX8; X-ray; 1.66 A; A/B=2-387.
DR PDB; 6IX9; X-ray; 1.78 A; A/B=2-387.
DR PDB; 6J1O; X-ray; 1.70 A; A/B=1-387.
DR PDB; 6J24; X-ray; 2.24 A; A/B=1-387.
DR PDB; 6J46; X-ray; 2.62 A; A/B=1-387.
DR PDBsum; 5ZZD; -.
DR PDBsum; 6INW; -.
DR PDBsum; 6IV7; -.
DR PDBsum; 6IX3; -.
DR PDBsum; 6IX5; -.
DR PDBsum; 6IX7; -.
DR PDBsum; 6IX8; -.
DR PDBsum; 6IX9; -.
DR PDBsum; 6J1O; -.
DR PDBsum; 6J24; -.
DR PDBsum; 6J46; -.
DR AlphaFoldDB; B8NJH3; -.
DR SMR; B8NJH3; -.
DR EnsemblFungi; EED49872; EED49872; AFLA_066940.
DR VEuPathDB; FungiDB:AFLA_066940; -.
DR eggNOG; KOG3178; Eukaryota.
DR HOGENOM; CLU_005533_5_0_1; -.
DR OMA; GGIGHQC; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00891; Methyltransf_2; 1.
DR PIRSF; PIRSF005739; O-mtase; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..387
FT /note="O-methyltransferase lepI"
FT /id="PRO_0000438455"
FT REGION 175..195
FT /note="Substrate binding"
FT /evidence="ECO:0000250"
FT BINDING 135..148
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 227..228
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 252
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 275..276
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 291
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT HELIX 2..16
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 20..37
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 40..49
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 52..63
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 65..71
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 78..85
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 89..101
FT /evidence="ECO:0007829|PDB:6IX8"
FT STRAND 104..107
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 117..123
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 125..136
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 138..151
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 164..169
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 175..179
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 183..192
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 207..211
FT /evidence="ECO:0007829|PDB:6IX8"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:6IX8"
FT STRAND 221..226
FT /evidence="ECO:0007829|PDB:6IX8"
FT TURN 229..231
FT /evidence="ECO:0007829|PDB:6IX5"
FT HELIX 232..240
FT /evidence="ECO:0007829|PDB:6IX8"
FT STRAND 246..252
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 254..261
FT /evidence="ECO:0007829|PDB:6IX8"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:6IX8"
FT STRAND 270..273
FT /evidence="ECO:0007829|PDB:6IX8"
FT STRAND 286..292
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 299..309
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 310..312
FT /evidence="ECO:0007829|PDB:6IX8"
FT STRAND 318..324
FT /evidence="ECO:0007829|PDB:6IX8"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 333..346
FT /evidence="ECO:0007829|PDB:6IX8"
FT HELIX 353..362
FT /evidence="ECO:0007829|PDB:6IX8"
FT STRAND 365..372
FT /evidence="ECO:0007829|PDB:6IX8"
FT STRAND 374..377
FT /evidence="ECO:0007829|PDB:6IX8"
FT STRAND 379..386
FT /evidence="ECO:0007829|PDB:6IX8"
SQ SEQUENCE 387 AA; 43322 MW; D818F5CC33C98CF4 CRC64;
METVAAIKTL IQQLAQSTDQ FGRAEINDAL RELQYSLETP FDTVMRMSLD TCQVAVARIG
SDLGLFKHLS QCASPQSAEE LADHLGCGRE LMSRLLRYMA SVRMVQQTDD IKYISSNITQ
TLAVPGLEAG MRHAFENLWP VLMALPDFLA ERKYPDIVDA KDTAFQKAFN TDQDCFHWLA
TQPTRIANFK VLLTDERTPN FLSTFPLEKE LGSWSAEPEK ALFVDIGGGM GHACIRLREK
YPNQPGRVIL QDLPPVLQAA QATLPLSGIE SMPHNFHTPQ PVQGAKFYFL RLILRDFPDH
QALEILQNIV PAMDAESRIV IDDGVPPEKG ARWAETGTDI CIMSALGSKE RTQRQWEELA
AKAGLQLQAL YQYTWPVVNA AMVFSLQ
