ID AFLQ_ASPPU Reviewed; 528 AA.
AC O13345; A0A0F0I0P3;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 13-SEP-2023, entry version 107.
DE RecName: Full=O-methylsterigmatocystin oxidoreductase {ECO:0000303|PubMed:11996570};
DE Short=OMST oxidoreductase {ECO:0000303|PubMed:11996570};
DE EC=1.14.14.117 {ECO:0000269|PubMed:11996570};
DE AltName: Full=Aflatoxin B synthase;
DE AltName: Full=Aflatoxin biosynthesis protein Q {ECO:0000303|PubMed:15006741};
DE AltName: Full=Cytochrome P450 64;
DE AltName: Full=Cytochrome P450 monooxygenase aflQ {ECO:0000305};
DE Flags: Precursor;
GN Name=aflQ {ECO:0000303|PubMed:15006741}; Synonyms=cyp64, ordA;
GN ORFNames=P875_00052985;
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].
RC STRAIN=ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1;
RX PubMed=9835571; DOI=10.1128/aem.64.12.4834-4841.1998;
RA Yu J., Chang P.-K., Ehrlich K.C., Cary J.W., Montalbano B., Dyer J.M.,
RA Bhatnagar D., Cleveland T.E.;
RT "Characterization of the critical amino acids of an Aspergillus parasiticus
RT cytochrome P-450 monooxygenase encoded by ordA that is involved in the
RT biosynthesis of aflatoxins B1, G1, B2, and G2.";
RL Appl. Environ. Microbiol. 64:4834-4841(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 56775 / NRRL 5862 / SRRC 143 / SU-1;
RX PubMed=10855719; DOI=10.1007/s002530051660;
RA Yu J., Chang P.-K., Bhatnagar D., Cleveland T.E.;
RT "Genes encoding cytochrome P450 and monooxygenase enzymes define one end of
RT the aflatoxin pathway gene cluster in Aspergillus parasiticus.";
RL Appl. Microbiol. Biotechnol. 53:583-590(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [4]
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 [5]
RP CATALYTIC ACTIVITY, AND 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 [6]
RP 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).
CC -!- FUNCTION: O-methylsterigmatocystin oxidoreductase; part of the gene
CC cluster that mediates the biosynthesis of aflatoxins, a group of
CC polyketide-derived furanocoumarins, and part of the most toxic and
CC carcinogenic compounds among the known mycotoxins (PubMed:11996570,
CC PubMed:15006741). The four major aflatoxins produced by A.parasiticus
CC are aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and
CC aflatoxin G2 (AFG2) (PubMed:15006741). Within the aflatoxin pathway,
CC the O-methylsterigmatocystin oxidoreductase aflQ is involved in the
CC last steps in which OMST is converted to aflatoxins B1 and G1, and
CC DHOMST to aflatoxins B2 and G2 (PubMed:11996570, PubMed:15006741). The
CC biosynthesis of aflatoxins begins with the norsolorinic acid synthase
CC aflC that combines a hexanoyl starter unit produced by the fatty acid
CC synthase aflA/aflB and 7 malonyl-CoA extender units to synthesize the
CC precursor NOR. The second step is the conversion of NOR to averantin
CC and requires the norsolorinic acid ketoreductase aflD, which catalyzes
CC the dehydration of norsolorinic acid to form (1'S)-averantin. The
CC norsolorinic acid reductases aflE and aflF may also play a role in the
CC conversion of NOR to AVN. The cytochrome P450 monooxygenase aflG then
CC catalyzes the hydroxylation of AVN to 5'hydroxyaverantin (HAVN). The
CC next step is performed by the 5'-hydroxyaverantin dehydrogenase aflH
CC that transforms HAVN to 5'-oxoaverantin (OAVN) which is further
CC converted to averufin (AVF) by aflK that plays a dual role in the
CC pathway, as a 5'-oxoaverantin cyclase that mediates conversion of 5'-
CC oxoaverantin, as well as a versicolorin B synthase in a later step in
CC the pathway. The averufin oxidase aflI catalyzes the conversion of AVF
CC to versiconal hemiacetal acetate (VHA). VHA is then the substrate for
CC the versiconal hemiacetal acetate esterase aflJ to yield versiconal
CC (VAL). Versicolorin B synthase aflK then converts VAL to versicolorin B
CC (VERB) by closing the bisfuran ring of aflatoxin which is required for
CC DNA-binding, thus giving to aflatoxin its activity as a mutagen. Then,
CC the activity of the versicolorin B desaturase aflL leads to
CC versicolorin A (VERA). A branch point starts from VERB since it can
CC also be converted to dihydrodemethylsterigmatocystin (DMDHST), probably
CC also by aflL, VERA being a precursor for aflatoxins B1 and G1, and
CC DMDHST for aflatoxins B2 and G2. Next, the versicolorin reductase aflM
CC and the cytochrome P450 monooxygenase aflN are involved in conversion
CC of VERA to demethylsterigmatocystin (DMST). AflX and aflY seem also
CC involved in this step, through probable aflX-mediated epoxide ring-
CC opening step following versicolorin A oxidation and aflY-mediated
CC Baeyer-Villiger oxidation required for the formation of the xanthone
CC ring. The methyltransferase aflO then leads to the modification of DMST
CC to sterigmatocystin (ST), and of DMDHST to dihydrosterigmatocystin
CC (DHST). Both ST and DHST are then substrates of the O-methyltransferase
CC aflP to yield O-methylsterigmatocystin (OMST) and dihydro-O-
CC methylsterigmatocystin (DHOMST), respectively. Finally OMST is
CC converted to aflatoxins B1 and G1, and DHOMST to aflatoxins B2 and G2,
CC via the action of several enzymes including O-methylsterigmatocystin
CC oxidoreductase aflQ, the cytochrome P450 monooxygenase aflU, but also
CC the NADH-dependent flavin oxidoreductase nadA which is specifically
CC required for the synthesis of AFG1 (PubMed:15006741).
CC {ECO:0000269|PubMed:11996570, ECO:0000305|PubMed:15006741}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8-O-methylsterigmatocystin + 2 O2 + 2 reduced [NADPH--
CC hemoprotein reductase] = aflatoxin B1 + CO2 + 2 H(+) + H2O + methanol
CC + 2 oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:35759,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2504,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:17790, ChEBI:CHEBI:18171,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.117;
CC Evidence={ECO:0000269|PubMed:11996570};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35760;
CC Evidence={ECO:0000269|PubMed:11996570};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8-O-methyldihydrosterigmatocystin + 2 O2 + 2 reduced [NADPH--
CC hemoprotein reductase] = aflatoxin B2 + CO2 + 2 H(+) + H2O + methanol
CC + 2 oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:35763,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17790, ChEBI:CHEBI:48209, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:72678; EC=1.14.14.117;
CC Evidence={ECO:0000269|PubMed:11996570};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35764;
CC Evidence={ECO:0000269|PubMed:11996570};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis; aflatoxin biosynthesis.
CC {ECO:0000305|PubMed:15006741}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=KJK60756.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY371490; AAS66031.1; -; Genomic_DNA.
DR EMBL; JZEE01000729; KJK60756.1; ALT_SEQ; Genomic_DNA.
DR AlphaFoldDB; O13345; -.
DR SMR; O13345; -.
DR STRING; 1403190.O13345; -.
DR GlyCosmos; O13345; 1 site, No reported glycans.
DR KEGG; ag:AAS66031; -.
DR BioCyc; MetaCyc:MONOMER-14044; -.
DR BRENDA; 1.14.14.117; 523.
DR UniPathway; UPA00287; -.
DR Proteomes; UP000033540; Unassembled WGS sequence.
DR GO; GO:0140399; F:aflatoxin B synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IDA:UniProt.
DR GO; GO:0045122; P:aflatoxin biosynthetic process; IDA:UniProt.
DR CDD; cd11065; CYP64-like; 1.
DR Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR PANTHER; PTHR46300:SF7; P450, PUTATIVE (EUROFUNG)-RELATED; 1.
DR PANTHER; PTHR46300; P450, PUTATIVE (EUROFUNG)-RELATED-RELATED; 1.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR SUPFAM; SSF48264; Cytochrome P450; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..528
FT /note="O-methylsterigmatocystin oxidoreductase"
FT /id="PRO_0000052053"
FT BINDING 440
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 43
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VARIANT 143
FT /note="A -> S (in strain: SRRC 2043)"
FT VARIANT 400
FT /note="H -> L (in strain: SRRC 2043; loss of activity)"
FT VARIANT 528
FT /note="I -> Y (in strain: SRRC 2043)"
SQ SEQUENCE 528 AA; 60189 MW; AC32F9425D27F328 CRC64;
MIYSIIICAG ALLGFLILQK LLAPKDTRPP LPPGPWRKPI IGNLTDFPPK GTPEWLFWAK
HHERYGPMSS LEVMGQTIIM INDAHLGIEI MHKKSALSQM IPDAPFAHMA GWGMSLATER
NKQAWKTIRA NMKQEIGTRR AIATFHPKME IGIRRFLLRT LDNPDDLRFH IRKEANAFMM
DVAYGYTIAP HGKDELYDLT QQSVRQFSHI FSPGEWSVNF FPILRYVPSW FPGASFQIKA
AEYKRTIERM TMVPYLWIKD QVARGCTRPS ILLRLLQKGH YESGSHQEQV LVWTNAEFVM
GGSDTTVSAV SSFFVAMALY PEVQHQAREE LDRVVGPTTL ATFEHRSQLP FIDALVKEVF
RWHPASPLGA PHITQEDQIW DGYLLPKGAL LLPNIWTFTH DPSVYHDPMV FKPERFLERQ
SSPPETDPMK FVFGFGRRIC PGRFVTDEKL FLIACHAISC FLISPKDPGA PEPDWLPGVI
SQPGPFDLNV VPRSPAHEEL IRSIETDHPW KNADATDISQ FMARNQMI
//
