LEPA_ASPFN
ID LEPA_ASPFN Reviewed; 3946 AA.
AC B8NJG3;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Hybrid PKS-NRPS synthetase lepA {ECO:0000303|PubMed:26051490};
DE EC=2.3.1.- {ECO:0000305|PubMed:26051490};
DE EC=6.3.2.- {ECO:0000305|PubMed:26051490};
DE AltName: Full=Leporins biosynthesis protein A {ECO:0000303|PubMed:26051490};
GN Name=lepA {ECO:0000303|PubMed:26051490}; ORFNames=AFLA_066840;
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: Hybrid PKS-NRPS synthetase; 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: Impairs the production od leporins B and C or any
CC other potential open ring 2-pyridone (PubMed:26051490).
CC {ECO:0000269|PubMed:26051490}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; EQ963479; EED49862.1; -; Genomic_DNA.
DR RefSeq; XP_002380243.1; XM_002380202.1.
DR SMR; B8NJG3; -.
DR STRING; 5059.CADAFLAP00008108; -.
DR EnsemblFungi; EED49862; EED49862; AFLA_066840.
DR VEuPathDB; FungiDB:AFLA_066840; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_37_4_1; -.
DR OMA; MNSDGRT; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0016746; F:acyltransferase activity; IEA:InterPro.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Ligase; Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT CHAIN 1..3946
FT /note="Hybrid PKS-NRPS synthetase lepA"
FT /id="PRO_0000438442"
FT DOMAIN 2378..2455
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3515..3594
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 12..443
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26051490"
FT REGION 553..871
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26051490"
FT REGION 945..1238
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26051490"
FT REGION 1380..1580
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26051490"
FT REGION 2093..2266
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26051490"
FT REGION 2352..2372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2474..2531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2547..2976
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26051490"
FT REGION 3000..3402
FT /note="Adenylation (A) (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26051490"
FT REGION 3492..3511
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3633..3833
FT /note="Reductase (RED) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26051490"
FT COMPBIAS 2492..2531
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2415
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3554
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3946 AA; 432583 MW; FA76D79C2D9E90C8 CRC64;
MGSLSDVRVE PIAIVGSACR FPGGANSPSK LWDLLHSPRD VLMDFPPSRL RLSNFYHKDG
EHHGSTNVIN KSYLLAEDPN VFDAAFFNIN GLEAQAMDPQ HRILLETVYE ALERGGCSLD
DIQGTKTSVF VGVMNADYYD IQLRDSETMA RYNATGTARS IISNRISYFF DLKGASMTID
TACSSSLVAL HQAVLSLQNR EAEASIVAGA NLLLDPTMYI AESNLHMLSP EARSRMWDKD
ANGYARGEGF AAVYLKPLSA ALRDGDEIEC IIRGTGVNSD GRTKGITMPS SVAQTELIRD
TYRRAGLDPS VDRPQFVECH GTGTAAGDPV EARAVHDAFF PPSSKRDNER PLYAGSIKTI
IGHLEGCAGL AGVLKASLAL QNRIIPPNMH FNDLSPSVKP FYGMIQIPKQ PMPWPESTTF
RASVNSFGFG GTNAHVILEG YYKGGECLNG GCQQARLDSF VGPMLFSGNT QTTLRAMIKE
YFDYLSANPS LDLEGLARAL ADRRSMFPVR AFFSGSNREA LLKYMGQALI SSEGSDIGTR
SLASSDTPGL LGIFTGQGAQ WATMGKALIH SCLLFRVSIE NCEESLSTLP DPPSWSLMQE
LLADDKESRI GQAAFSQPLC TALQIALVDL CSASAITFDA VVGHSSGEIA AAYAAGILSA
KDAIRIAYYR GLYAKLASGP DGQPGAMMAV GLSMEGAMSF IAECGLYGKV CLAASNSPSS
VTLSGDKDAI LQAKGFLDER KVFARQLQVD TAYHSHHMLS CADAYLKSLE ACNIKPSLPR
AGCVWVSSVR GDIEILEKGD FTSLNSQYWV DNMVKPVLFS QAVECSLWAG GPFDMVLELG
PHPALKGPAT QTLKSALGTS LPYAGIMRRA TNEVEAFSGA IGYVWSHLTD YHIDFASYRE
SFFKEADRAP ATLKDLPSYP WQHDKAYWKE SRISRQFRLR HSPLHELLGR RAPDDSDSEM
RWRNVLRLSE LEWIRGHEFQ GQALFPAMGY IAMALEAVTI ATKGQQISLV DIEDFHVLQA
VVLEEEHPGV EIVFSLKQTG DCKWDFNCYT CSDEWKDLTK TSTGRLILFK GEGSASELPS
RPKKRANLSP LDREMFYRKL SSLGLSYHGL FKPQSSFQRS QSYATGSASW PLDQLGQEYV
VHPAVMDVAL HSIFVAFASP VSHELWATYL PVAIDRLSFN PNISLYGTDG ALTIEIDTFI
TESSSSTMKG DVYLLSPDAT PSILIEGVRL QSFTEAKALN DRLLFSKIVW GADIAHGFSS
HAVECANKDQ FELCDAMERT SLFFLQRAFA ELAPCEIEQS EPQFRHLHTA FLKVIEQIKG
GLHKSIHSEW LGDSWNDVNS LRRSFESSID LEMMHAIGQS LPDVIRGRRP LLEVMMRDNL
LNRFYTDGRL FVPLNLYVAK TVKAMIHKNP HMKILEIGAG TGATTKAILD TIGDTFDSYT
YTDISPGFFA QAQERFALHR QQMRFQTLDI ERDTVEQGFE RHSYDLVVAA NVLHATSHLQ
ETMGHVRSLL RPGGYLLIVE VTGETLQLMY VMGGFPGWWL GVDDGRTDGP GIPAVQWEGL
LQMTGFSGIE ATVSDLPSDG KHSCSALVSQ AIDDKLELFR DPLPRVGDVP IRDPILILGG
GTLPVAKLVT GVRKLLRPFR WNIQHAPSVD HLTVPLEGSR SVICLSELDN PLLSEPLTDT
RLSKLQAVLG SATNVLWITR DRLTDYPHSN MINGLGRTLQ FELPDINIQF LDIRSGISIG
ADQVVTKFLQ LCLVNSPEYL QDDVPWKIEP ELSFDGEEWQ IPRIIPYKAL NDRYNATRRQ
IMKPLDASRQ PVELACFDGR IIIREGKRVT GTSTGSVRLR TILTTRLVSS RLASFFLCMG
VEADNGRTAV AITTRMGSLM DIPSTDAWFL PQRSQCDPAL LYFIAGQVLA VALSFASPRS
GSVILYEPTE ALAEAIILSR SWVQEQPYFI TSRSGTLQKG WTYIHPRVSH NIARDVLPGD
TAALIDCSDD CPHWAVPTTV GKLIPLASCV VEYLTRTPST FSSIIEHAYS ESLLAALPST
AQLSASILSV EDSAGQSSSL LSYPNIVNFD CNNAVLATVA PLDCTGLFSS AKTYWMIGLN
SELGLSICRW MIVQGARHIA ITSRSGKVDA PWLDEIQSMN GNIKVYPMDV ADREAVHSVH
QEILRTMPPI AGVCNGAMVL SDKLFMNMKA EDMNKVLKPK VDGSIYLDEL FCTTQLDFFI
LFSSLASVVG NGGQCNYHAA NMFMTSLVSQ RRSRGLAASV IDIGLVVDVG YVARAGQSLI
DHLVNLFYTP LSESDIHKLF AEAVMASPVD SGLCPDIIMG VEPVHDISAS LKKPPWYNNP
IFSHLRLGTE ASSQDSDQSN STSASIRDQV SSASSVEEGT DVLLRCFAAK LEAMLSLATN
SVNVNMPLLD IGVDSLLAVE IRQWFLTKLY VDIPVLKVLS GDTVVEICAE AIQKFAQMSP
SAFQGTSSAA SKIKQATASP PEIGREEAQS TSRAGILPTD QDNDNSSDSE SQRKSGASSS
SGSGTRTPTS IDEYFETNVN MLSRSGPMSY AQSRLWFQQQ LVKDPTALNI VVRFDVKGYL
DVDRLAAAVT ATVNRHDALH SAYFAHLDTQ EPLQGVIEAP GDIFQHVKVH DDNAASAIFL
EMQNRHWDLE RGDVFKVTLL TFPTNVQSLI IAYHHIVLDG FSWHVYLRDL SMSYQQQALP
PVGPQALDFA LIEAQETKNE EYNAQLEFWR EELSPVPETF PLLPFSSSKV RQGMQSFQST
TATRELHFDI LARAKAASQR LRVTPFHFHL AIAQVLLYKL TNIGDLCIGV TDVNRTNRKF
AETVGFFLNL VPLRLRVKPT DSFTEVLHRT SKKALSAMEH SGVPIDVVLR ELNIRRSSGH
SPLFQVVFNY RVGDMLQVPF GGGRLELHSS IEARSPYDVV FNVTQCPSGA SYLQVTSRDA
LYAPEVSGVI CDMYIRLLED FAGDTSMQIQ DGLLNDKSEP GIGLGPRLEF GWPRTMSELF
SQRAATDANS IAVKDCRGAV SYAELQQRVA DITQDILGCN PPPNARVAVC IHPSRDTIAA
MLATLAAGCV YVPIDITLPE ARRRAILDSC RPSVILCDST SADSIDQFAP QECRKVDLGY
SPTRATTTAM PEPVADDPAF LLYSSGSTGI PKGILLPQKG YMNYLASKGH HLCLGREVVL
QQSSVGFDMS IAQIGNALAH GGTVVVVPQS VRGDPVATAQ LMLQEKVTFM IGTPSEYLML
LQHGGDYLRQ YRDWRHACLG GESVTEPLKR EFRRLSPNCP NVTDCYGPTE ISAATSFNTL
DLHRGAANEY STVGRPIPNS TIYILGANGD IVPPGLVGEI CIGGVGVALG YWNLPDLEKQ
KFIHDPFASS ADRRRGWTRL YKTGDRGRLG PDGGLIFMGR LDGDTQIKLR GLRIDLEEVA
NSLLQVAAGL LSETVVSVRG DPEFLVAHAV PARGQKVTNS DLESFKRSLP LPQYMCPAAI
VLLDRLPTTP NGKVDRKALQ DKPLPTEPDS SFPTEALSLA EGELRLVWQD VLQQTAQTGR
IDSRTDFFMA GGNSLLLVKL QGAIKNAYGL SIALKDLYRC STLGRMATLI DAEKKNQPIF
EKIDWEDETR VPGSLARGQR SREPKKTDLH IALTGSTGFL GMEILKALLE QPTVSKVHCL
AVDAQHGQSL PKSHKIVIYP GSLNVSALGL STREVDFLKS TVDALIHAGA NGHCLNNYFS
LRMPNLGSTR FLTELALSRG VPLHYVSSNR VTLLSGDVAL PPGSMSAFPP PETGSDGFTA
SKWASERYLE NVAEATGLDV CIHRPCALTG DQAPSEDALN AILRFSVLMK VVPQFPNVRG
FFDFEKVGVV ATNIVKKALQ SVQVTRVHAT SVASFAHHSS GVKVPIDKIQ DRMQDLYGGV
FGRLALADWV QRARTLGIEP LVASYLEAME SRGEEMAFPF LGMPSD
