AFLE_ASPPU
ID AFLE_ASPPU Reviewed; 388 AA.
AC Q00258; A0A0F0I463; Q6UEG4;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Norsolorinic acid reductase A {ECO:0000303|PubMed:8593042};
DE EC=1.1.1.- {ECO:0000305|PubMed:8593042};
DE AltName: Full=Aflatoxin biosynthesis protein E {ECO:0000303|PubMed:15006741};
GN Name=aflE {ECO:0000303|PubMed:15006741};
GN Synonyms=norA {ECO:0000303|PubMed:8593042}; ORFNames=P875_00052990;
OS Aspergillus parasiticus (strain ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=1403190;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1;
RX PubMed=8593042; DOI=10.1128/aem.62.2.360-366.1996;
RA Cary J.W., Wright M., Bhatnagar D., Lee R., Chu F.;
RT "Molecular characterization of an Aspergillus parasiticus dehydrogenase
RT gene, norA, located on the aflatoxin biosynthesis gene cluster.";
RL Appl. Environ. Microbiol. 62:360-366(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PATHWAY.
RC STRAIN=ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1;
RX PubMed=15094053; DOI=10.1016/s0014-5793(04)00327-8;
RA Yu J., Bhatnagar D., Cleveland T.E.;
RT "Completed sequence of aflatoxin pathway gene cluster in Aspergillus
RT parasiticus.";
RL FEBS Lett. 564:126-130(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1;
RA Yu J., Fedorova N., Yin Y., Losada L., Zafar N., Taujale R., Ehrlich K.C.,
RA Bhatnagar D., Cleveland T.E., Bennett J.W., Nierman W.C.;
RT "Draft genome sequence of Aspergillus parasiticus SU-1.";
RL Submitted (FEB-2015) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RX PubMed=1339261; DOI=10.1128/aem.58.11.3527-3537.1992;
RA Skory C.D., Chang P.K., Cary J., Linz J.E.;
RT "Isolation and characterization of a gene from Aspergillus parasiticus
RT associated with the conversion of versicolorin A to sterigmatocystin in
RT aflatoxin biosynthesis.";
RL Appl. Environ. Microbiol. 58:3527-3537(1992).
RN [5]
RP FUNCTION.
RX PubMed=8434913; DOI=10.1128/aem.59.2.479-484.1993;
RA Keller N.P., Dischinger H.C. Jr., Bhatnager D., Cleveland T.E.,
RA Ullah A.H.J.;
RT "Purification of a 40-kilodalton methyltransferase active in the aflatoxin
RT biosynthetic pathway.";
RL Appl. Environ. Microbiol. 59:479-484(1993).
RN [6]
RP FUNCTION.
RX PubMed=8368836; DOI=10.1128/aem.59.8.2486-2492.1993;
RA Yabe K., Matsuyama Y., Ando Y., Nakajima H., Hamasaki T.;
RT "Stereochemistry during aflatoxin biosynthesis: conversion of norsolorinic
RT acid to averufin.";
RL Appl. Environ. Microbiol. 59:2486-2492(1993).
RN [7]
RP FUNCTION.
RX PubMed=8368837; DOI=10.1128/aem.59.8.2493-2500.1993;
RA Yabe K., Hamasaki T.;
RT "Stereochemistry during aflatoxin biosynthesis: cyclase reaction in the
RT conversion of versiconal to versicolorin B and racemization of versiconal
RT hemiacetal acetate.";
RL Appl. Environ. Microbiol. 59:2493-2500(1993).
RN [8]
RP FUNCTION.
RX PubMed=10543813; DOI=10.1128/aem.65.11.4987-4994.1999;
RA Motomura M., Chihaya N., Shinozawa T., Hamasaki T., Yabe K.;
RT "Cloning and characterization of the O-methyltransferase I gene (dmtA) from
RT Aspergillus parasiticus associated with the conversions of
RT demethylsterigmatocystin to sterigmatocystin and
RT dihydrodemethylsterigmatocystin to dihydrosterigmatocystin in aflatoxin
RT biosynthesis.";
RL Appl. Environ. Microbiol. 65:4987-4994(1999).
RN [9]
RP FUNCTION.
RX PubMed=10584035; DOI=10.1128/aem.65.12.5639-5641.1999;
RA Zhou R., Linz J.E.;
RT "Enzymatic function of the nor-1 protein in aflatoxin biosynthesis in
RT Aspergillus parasiticus.";
RL Appl. Environ. Microbiol. 65:5639-5641(1999).
RN [10]
RP FUNCTION.
RX PubMed=11055914; DOI=10.1128/aem.66.11.4715-4719.2000;
RA Chang P.K., Yu J., Ehrlich K.C., Boue S.M., Montalbano B.G., Bhatnagar D.,
RA Cleveland T.E.;
RT "adhA in Aspergillus parasiticus is involved in conversion of 5'-
RT hydroxyaverantin to averufin.";
RL Appl. Environ. Microbiol. 66:4715-4719(2000).
RN [11]
RP FUNCTION.
RX PubMed=16256699; DOI=10.1006/bioo.2001.1216;
RA Hitchman T.S., Schmidt E.W., Trail F., Rarick M.D., Linz J.E.,
RA Townsend C.A.;
RT "Hexanoate synthase, a specialized type I fatty acid synthase in aflatoxin
RT B1 biosynthesis.";
RL Bioorg. Chem. 29:293-307(2001).
RN [12]
RP FUNCTION.
RX PubMed=11996570; DOI=10.1021/ja012185v;
RA Udwary D.W., Casillas L.K., Townsend C.A.;
RT "Synthesis of 11-hydroxyl O-methylsterigmatocystin and the role of a
RT cytochrome P-450 in the final step of aflatoxin biosynthesis.";
RL J. Am. Chem. Soc. 124:5294-5303(2002).
RN [13]
RP REVIEW, FUNCTION, PATHWAY, AND NOMENCLATURE.
RX PubMed=15006741; DOI=10.1128/aem.70.3.1253-1262.2004;
RA Yu J., Chang P.K., Ehrlich K.C., Cary J.W., Bhatnagar D., Cleveland T.E.,
RA Payne G.A., Linz J.E., Woloshuk C.P., Bennett J.W.;
RT "Clustered pathway genes in aflatoxin biosynthesis.";
RL Appl. Environ. Microbiol. 70:1253-1262(2004).
RN [14]
RP FUNCTION.
RX PubMed=15528514; DOI=10.1128/aem.70.11.6518-6524.2004;
RA Ehrlich K.C., Chang P.K., Yu J., Cotty P.J.;
RT "Aflatoxin biosynthesis cluster gene cypA is required for G aflatoxin
RT formation.";
RL Appl. Environ. Microbiol. 70:6518-6524(2004).
RN [15]
RP FUNCTION.
RX PubMed=15932995; DOI=10.1128/aem.71.6.2999-3006.2005;
RA Sakuno E., Wen Y., Hatabayashi H., Arai H., Aoki C., Yabe K., Nakajima H.;
RT "Aspergillus parasiticus cyclase catalyzes two dehydration steps in
RT aflatoxin biosynthesis.";
RL Appl. Environ. Microbiol. 71:2999-3006(2005).
RN [16]
RP FUNCTION.
RX PubMed=16332900; DOI=10.1128/aem.71.12.8963-8965.2005;
RA Ehrlich K.C., Montalbano B., Boue S.M., Bhatnagar D.;
RT "An aflatoxin biosynthesis cluster gene encodes a novel oxidase required
RT for conversion of versicolorin a to sterigmatocystin.";
RL Appl. Environ. Microbiol. 71:8963-8965(2005).
RN [17]
RP FUNCTION.
RX PubMed=15771506; DOI=10.1021/ja0455188;
RA Henry K.M., Townsend C.A.;
RT "Ordering the reductive and cytochrome P450 oxidative steps in
RT demethylsterigmatocystin formation yields general insights into the
RT biosynthesis of aflatoxin and related fungal metabolites.";
RL J. Am. Chem. Soc. 127:3724-3733(2005).
RN [18]
RP FUNCTION.
RX PubMed=16461654; DOI=10.1128/aem.72.2.1096-1101.2006;
RA Cary J.W., Ehrlich K.C., Bland J.M., Montalbano B.G.;
RT "The aflatoxin biosynthesis cluster gene, aflX, encodes an oxidoreductase
RT involved in conversion of versicolorin A to demethylsterigmatocystin.";
RL Appl. Environ. Microbiol. 72:1096-1101(2006).
RN [19]
RP FUNCTION.
RX PubMed=18486503; DOI=10.1016/j.fgb.2008.03.003;
RA Cai J., Zeng H., Shima Y., Hatabayashi H., Nakagawa H., Ito Y., Adachi Y.,
RA Nakajima H., Yabe K.;
RT "Involvement of the nadA gene in formation of G-group aflatoxins in
RT Aspergillus parasiticus.";
RL Fungal Genet. Biol. 45:1081-1093(2008).
RN [20]
RP FUNCTION.
RX PubMed=18403714; DOI=10.1126/science.1154711;
RA Crawford J.M., Thomas P.M., Scheerer J.R., Vagstad A.L., Kelleher N.L.,
RA Townsend C.A.;
RT "Deconstruction of iterative multidomain polyketide synthase function.";
RL Science 320:243-246(2008).
RN [21]
RP INDUCTION.
RX PubMed=26217023; DOI=10.3382/ps/pev207;
RA Yin H.B., Chen C.H., Kollanoor-Johny A., Darre M.J., Venkitanarayanan K.;
RT "Controlling Aspergillus flavus and Aspergillus parasiticus growth and
RT aflatoxin production in poultry feed using carvacrol and trans-
RT cinnamaldehyde.";
RL Poult. Sci. 94:2183-2190(2015).
CC -!- FUNCTION: Norsolorinic acid reductase; part of the gene cluster that
CC mediates the biosynthesis of aflatoxins, a group of polyketide-derived
CC furanocoumarins, and part of the most toxic and carcinogenic compounds
CC among the known mycotoxins (PubMed:8593042, PubMed:15006741). The four
CC major aflatoxins produced by A.parasiticus are aflatoxin B1 (AFB1),
CC aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2)
CC (PubMed:15006741). The first step of the pathway is the conversion of
CC acetate to norsolorinic acid (NOR) and requires the fatty acid synthase
CC subunits aflA and aflB, as well as the PKS aflC (PubMed:15006741). AflC
CC combines a hexanoyl starter unit and 7 malonyl-CoA extender units to
CC synthesize the precursor NOR (PubMed:18403714). The hexanoyl starter
CC unit is provided to the acyl-carrier protein (ACP) domain by the fungal
CC fatty acid synthase aflA/aflB (PubMed:16256699). The second step is the
CC conversion of NOR to averantin (AVN) and requires the norsolorinic acid
CC ketoreductase aflD, which catalyzes the dehydration of norsolorinic
CC acid to form (1'S)-averantin (PubMed:10584035). The norsolorinic acid
CC reductases aflE and aflF may also play a role in the conversion of NOR
CC to AVN (PubMed:8593042, PubMed:15006741). The cytochrome P450
CC monooxygenase aflG then catalyzes the hydroxylation of AVN to
CC 5'hydroxyaverantin (HAVN) (PubMed:8368836). The next step is performed
CC by the 5'-hydroxyaverantin dehydrogenase aflH that transforms HAVN to
CC 5'-oxoaverantin (OAVN) which is further converted to averufin (AVF) by
CC aflK that plays a dual role in the pathway, as a 5'-oxoaverantin
CC cyclase that mediates conversion of 5'-oxoaverantin, as well as a
CC versicolorin B synthase in a later step in the pathway
CC (PubMed:15006741, PubMed:11055914, PubMed:15932995). The averufin
CC oxidase aflI catalyzes the conversion of AVF to versiconal hemiacetal
CC acetate (VHA) (PubMed:15006741). VHA is then the substrate for the
CC versiconal hemiacetal acetate esterase aflJ to yield versiconal (VAL)
CC (PubMed:15006741). Versicolorin B synthase aflK then converts VAL to
CC versicolorin B (VERB) by closing the bisfuran ring of aflatoxin which
CC is required for DNA-binding, thus giving to aflatoxin its activity as a
CC mutagen (PubMed:15006741, PubMed:8368837, PubMed:15932995). Then, the
CC activity of the versicolorin B desaturase aflL leads to versicolorin A
CC (VERA) (PubMed:15006741, PubMed:8368837). A branch point starts from
CC VERB since it can also be converted to dihydrodemethylsterigmatocystin
CC (DMDHST), probably also by aflL, VERA being a precursor for aflatoxins
CC B1 and G1, and DMDHST for aflatoxins B2 and G2 (PubMed:15006741). Next,
CC the versicolorin reductase aflM and the cytochrome P450 monooxygenase
CC aflN are involved in conversion of VERA to demethylsterigmatocystin
CC (DMST) (PubMed:15006741, PubMed:1339261, PubMed:15771506). AflX and
CC aflY seem also involved in this step, through probable aflX-mediated
CC epoxide ring-opening step following versicolorin A oxidation and aflY-
CC mediated Baeyer-Villiger oxidation required for the formation of the
CC xanthone ring (PubMed:16332900, PubMed:16461654). The methyltransferase
CC aflO then leads to the modification of DMST to sterigmatocystin (ST),
CC and of DMDHST to dihydrosterigmatocystin (DHST) (PubMed:10543813). Both
CC ST and DHST are then substrates of the O-methyltransferase aflP to
CC yield O-methylsterigmatocystin (OMST) and dihydro-O-
CC methylsterigmatocystin (DHOMST), respectively (PubMed:8434913). Finally
CC OMST is converted to aflatoxins B1 and G1, and DHOMST to aflatoxins B2
CC and G2, via the action of several enzymes including O-
CC methylsterigmatocystin oxidoreductase aflQ, the cytochrome P450
CC monooxygenase aflU, but also the NADH-dependent flavin oxidoreductase
CC nadA which is specifically required for the synthesis of AFG1
CC (PubMed:15006741, PubMed:11996570, PubMed:15528514, PubMed:18486503).
CC {ECO:0000269|PubMed:10543813, ECO:0000269|PubMed:10584035,
CC ECO:0000269|PubMed:11055914, ECO:0000269|PubMed:11996570,
CC ECO:0000269|PubMed:1339261, ECO:0000269|PubMed:15528514,
CC ECO:0000269|PubMed:15771506, ECO:0000269|PubMed:15932995,
CC ECO:0000269|PubMed:16256699, ECO:0000269|PubMed:16332900,
CC ECO:0000269|PubMed:16461654, ECO:0000269|PubMed:18403714,
CC ECO:0000269|PubMed:18486503, ECO:0000269|PubMed:8368836,
CC ECO:0000269|PubMed:8368837, ECO:0000269|PubMed:8434913,
CC ECO:0000269|PubMed:8593042, ECO:0000305|PubMed:15006741}.
CC -!- PATHWAY: Mycotoxin biosynthesis; aflatoxin biosynthesis.
CC {ECO:0000269|PubMed:15094053, ECO:0000305|PubMed:15006741}.
CC -!- INDUCTION: Natural plant compounds carvacrol (CR) and trans-
CC cinnamaldehyde (TC) strongly reduce the expression (PubMed:26217023).
CC {ECO:0000269|PubMed:26217023}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. Aldo/keto
CC reductase 2 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=KJK60773.1; Type=Erroneous gene model prediction; Evidence={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; U24698; AAC49166.1; -; Genomic_DNA.
DR EMBL; AY371490; AAS66006.1; -; Genomic_DNA.
DR EMBL; JZEE01000729; KJK60773.1; ALT_SEQ; Genomic_DNA.
DR AlphaFoldDB; Q00258; -.
DR SMR; Q00258; -.
DR STRING; 1403190.Q00258; -.
DR EnsemblFungi; KJK60773; KJK60773; P875_00052990.
DR UniPathway; UPA00287; -.
DR Proteomes; UP000033540; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0045122; P:aflatoxin biosynthetic process; TAS:GO_Central.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR SUPFAM; SSF51430; SSF51430; 1.
PE 2: Evidence at transcript level;
KW NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..388
FT /note="Norsolorinic acid reductase A"
FT /id="PRO_0000070384"
FT ACT_SITE 74
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q8CG76"
FT BINDING 69
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O43488"
FT BINDING 148
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8CG76"
FT BINDING 178..179
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O43488"
FT BINDING 204
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O43488"
FT BINDING 233..243
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O43488"
FT BINDING 300..308
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O43488"
FT CONFLICT 36
FT /note="S -> T (in Ref. 3; KJK60773)"
FT /evidence="ECO:0000305"
FT CONFLICT 209
FT /note="S -> C (in Ref. 3; KJK60773)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 388 AA; 43721 MW; 8829491E66EF66BB CRC64;
MVLPTAPEPP TLLGYHRILS PSAGVRVSPL CLGTMSFGNG WKGVMGECDQ ATSFNMLDTF
YESGGNFIDV ANFYQGGDTE RWVGEWMAQR QNRDEIVLST KYTMGYTMFG PQKIKSNFQG
NHAKSLRLSV KASLQKLQTD YIDLLYVHMW DFTTSVEEVM RSLNHLVANG KVLYLGVSDT
PAWLVVKCNA FARANGLTPF SVYQGHWSSA FRDFERDILP MCESEGMGLA PWGVLGRGQF
RSAEEFSREG RKMGPQDEKH RRLGEKLDQM AQQKNTKATS IAQAYVMHKA PYVFPVIGGR
KVEHLKENIE ALGLVLSEEE IREIDDAEPF DVGFPMNFLF ETPTQSYRTN MTSKDIWQLS
CNTRLETVPK QQPIEPLQGA KYFGSASK
