AFLI_ASPPU
ID AFLI_ASPPU Reviewed; 285 AA.
AC Q12437; Q6UEF9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 2.
DT 25-MAY-2022, entry version 65.
DE RecName: Full=Averufin oxidase A {ECO:0000305|PubMed:7793957};
DE EC=1.-.-.- {ECO:0000305|PubMed:10806361};
DE AltName: Full=Aflatoxin biosynthesis protein I {ECO:0000303|PubMed:15006741};
GN Name=aflI {ECO:0000303|PubMed:15006741};
GN Synonyms=avfA {ECO:0000303|PubMed:10806361},
GN ord-2 {ECO:0000303|PubMed:7793957};
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 [MRNA], AND PATHWAY.
RC STRAIN=ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1;
RX PubMed=7793957; DOI=10.1128/aem.61.6.2365-2371.1995;
RA Yu J., Chang P.-K., Cary J.W., Wright M., Bhatnagar D., Cleveland T.E.,
RA Payne G.A., Linz J.E.;
RT "Comparative mapping of aflatoxin pathway gene clusters in Aspergillus
RT parasiticus and Aspergillus flavus.";
RL Appl. Environ. Microbiol. 61:2365-2371(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1;
RX PubMed=10806361; DOI=10.1016/s0378-1119(00)00126-8;
RA Yu J., Woloshuk C.P., Bhatnagar D., Cleveland T.E.;
RT "Cloning and characterization of avfA and omtB genes involved in aflatoxin
RT biosynthesis in three Aspergillus species.";
RL Gene 248:157-167(2000).
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).
CC -!- FUNCTION: Averufin oxidase; part of the gene cluster that mediates the
CC 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:15006741). The four major aflatoxins
CC produced by A.parasiticus are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2),
CC aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) (PubMed:15006741). The
CC first step of the pathway is the conversion of acetate to norsolorinic
CC acid (NOR) and requires the fatty acid synthase subunits aflA and aflB,
CC as well as the PKS aflC (PubMed:15006741). AflC combines a hexanoyl
CC starter unit and 7 malonyl-CoA extender units to synthesize the
CC precursor NOR (PubMed:18403714). The hexanoyl starter unit is provided
CC to the acyl-carrier protein (ACP) domain by the fungal fatty acid
CC synthase aflA/aflB (PubMed:16256699). The second step is the conversion
CC 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:15006741). The cytochrome P450 monooxygenase aflG then
CC catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN)
CC (PubMed:8368836). The next step is performed by the 5'-hydroxyaverantin
CC dehydrogenase aflH that transforms HAVN to 5'-oxoaverantin (OAVN) which
CC is further converted to averufin (AVF) by aflK that plays a dual role
CC in the pathway, as a 5'-oxoaverantin cyclase that mediates conversion
CC of 5'-oxoaverantin, as well as a versicolorin B synthase in a later
CC step in the pathway (PubMed:15006741, PubMed:11055914,
CC PubMed:15932995). The averufin oxidase aflI catalyzes the conversion of
CC AVF to versiconal hemiacetal acetate (VHA) (PubMed:10806361,
CC PubMed:15006741). VHA is then the substrate for the versiconal
CC 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:10806361, ECO:0000269|PubMed:11055914,
CC ECO:0000269|PubMed:11996570, ECO:0000269|PubMed:1339261,
CC ECO:0000269|PubMed:15528514, ECO:0000269|PubMed:15771506,
CC ECO:0000269|PubMed:15932995, ECO:0000269|PubMed:16256699,
CC ECO:0000269|PubMed:16332900, ECO:0000269|PubMed:16461654,
CC ECO:0000269|PubMed:18403714, ECO:0000269|PubMed:18486503,
CC ECO:0000269|PubMed:8368836, ECO:0000269|PubMed:8368837,
CC ECO:0000269|PubMed:8434913, ECO:0000305|PubMed:15006741}.
CC -!- PATHWAY: Mycotoxin biosynthesis; aflatoxin biosynthesis.
CC {ECO:0000305|PubMed:15006741, ECO:0000305|PubMed:7793957}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the avfA family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA87599.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA97502.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L41150; AAA87599.1; ALT_FRAME; mRNA.
DR EMBL; L40840; AAA97502.1; ALT_FRAME; mRNA.
DR EMBL; AY371490; AAS66010.1; -; Genomic_DNA.
DR EMBL; JZEE01000729; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; Q12437; -.
DR UniPathway; UPA00287; -.
DR Proteomes; UP000033540; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0045122; P:aflatoxin biosynthetic process; IDA:GO_Central.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF13460; NAD_binding_10; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Membrane; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..285
FT /note="Averufin oxidase A"
FT /id="PRO_0000058077"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CONFLICT 25
FT /note="S -> G (in Ref. 1; AAA87599/AAA97502)"
FT /evidence="ECO:0000305"
FT CONFLICT 36
FT /note="R -> T (in Ref. 1; AAA87599/AAA97502)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="P -> S (in Ref. 1; AAA87599/AAA97502)"
FT /evidence="ECO:0000305"
FT CONFLICT 107
FT /note="Q -> H (in Ref. 1; AAA87599/AAA97502)"
FT /evidence="ECO:0000305"
FT CONFLICT 110
FT /note="Q -> H (in Ref. 1; AAA87599/AAA97502)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="A -> G (in Ref. 1; AAA87599/AAA97502)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 285 AA; 30933 MW; 7AB1E6EF4349FB4E CRC64;
MVTYALLGAT GATGSSILRH LLQKSPDSLH IQVLVRSKVK LLQAFPDLET TRRPQVHVIQ
GMSTDSDALS ECLRNASIVF MCVAQNGSPI GTTLCQDSAR PIISVLQQQQ QSEGASYQPC
TIVQLRSASL NPALAAQVPA FVHRIVSFCL FANYADIKQA CQYYSEAQKQ GTLEYILVDP
PTLHDANGTH PTGYRLISTE PQATALSYAD LGAAMCEIAH RESEFHGRAV GVTATGRVRQ
TWGVLLRHLL EGGSSRLRET IAKEAVVVRV LCIFLVILAC LMSSL