ATAF_ASPTN
ID ATAF_ASPTN Reviewed; 489 AA.
AC Q0CS63;
DT 05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Cytochrome P450 monooxygenase ataF {ECO:0000303|PubMed:23586797};
DE EC=1.-.-.- {ECO:0000305|PubMed:23586797};
DE AltName: Full=Acetylaranotin biosynthesis cluster protein F {ECO:0000303|PubMed:23586797};
GN Name=ataF {ECO:0000303|PubMed:23586797}; ORFNames=ATEG_03471;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=23586797; DOI=10.1021/ja3123653;
RA Guo C.J., Yeh H.H., Chiang Y.M., Sanchez J.F., Chang S.L., Bruno K.S.,
RA Wang C.C.;
RT "Biosynthetic pathway for the epipolythiodioxopiperazine acetylaranotin in
RT Aspergillus terreus revealed by genome-based deletion analysis.";
RL J. Am. Chem. Soc. 135:7205-7213(2013).
RN [3]
RP FUNCTION.
RX PubMed=30096370; DOI=10.1016/j.fgb.2018.08.001;
RA Sun W.W., Romsdahl J., Guo C.J., Wang C.C.C.;
RT "Genome-based deletion analysis in Aspergillus terreus reveals the
RT acetylaranotin bis-thiomethyltransferase gene.";
RL Fungal Genet. Biol. 119:1-6(2018).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of acetylaranotin, a member of the
CC epipolythiodioxopiperazine (ETP) class of toxins characterized by a
CC disulfide-bridged cyclic dipeptide (PubMed:23586797). The first step of
CC acetylaranotin biosynthesis is performed by the NRPS ataP which
CC produces diketopiperazine cyclo-L-Phe-L-Phe via the condensation of 2
CC phenylalanines (L-Phe) (PubMed:23586797). The ataC domain of ataTC then
CC catalyzes the formation of bishydroxylation of cyclo-L-Phe-L-Phe
CC (PubMed:23586797). The glutathione S-transferase domain ataG in ataIMG
CC further catalyzes the conjugation of two glutathiones to the
CC bishydroxylated intermediate (PubMed:23586797). Next, the dipeptidase
CC ataJ removes the Glu residues (PubMed:23586797). The following step is
CC performed by the carbon sulfur lyase domain ataI of ataIMG which may
CC convert the bis-cysteinyl adduct to yield an epidithiol intermediate
CC (PubMed:23586797). The ataT domain from ataTC then catalyzes the
CC oxidation of the free dithiols, followed by a cyclization step
CC catalyzed by the cytochrome P450 ataF (PubMed:23586797). AtaF probably
CC acts as an epoxidase to promote a dual epoxidation formation at C8 and
CC C9 along with C8' and C9', followed by the spontaneous nucleophilic
CC attack of the amide nitrogens N10 and N10' to yield an intermediate
CC with the pyrrolidine partial structure (PubMed:23586797). The final
CC steps of acetylaranotin biosynthesis involve the acetylation and ring
CC rearrangement of an epitetrathiodiketopiperazine intermediate to
CC produce acetylaranotin (PubMed:23586797). AtaH probably catalyzes the
CC acetylation of epitetrathiodiketopiperazine to produce a diacetate and
CC ataY is responsible for the formation of the dihydrooxepin moiety that
CC converts the diacetate intermediate to acetylaranotin via
CC acetylapoaranotin (PubMed:23586797). Both enzymes could function
CC independently in the absence of the other (PubMed:23586797). The
CC acetylaranotin bis-thiomethyltransferase ataS located outside of
CC acetylaranotin gene cluster is the main thiomethyltransferase
CC responsible for converting acetylaranotin and its related intermediates
CC to their methylated forms (PubMed:30096370).
CC {ECO:0000269|PubMed:23586797, ECO:0000269|PubMed:30096370}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:23586797}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of acetylaranotin and
CC accumulates chemically stable intermediates or shunt products such as
CC cyclo-L-Phe-L-Phe, prearanotin A, 2-hydroxy-2'-ene-cyclo-L-Phe-L-Phe,
CC 2-methoxy-2'-ene-cyclo-L-Phe-L-Phe, emethacin A and 2-imino-10'-
CC hydroxy-cyclo-L-Phe-L-Phe (PubMed:23586797).
CC {ECO:0000269|PubMed:23586797}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; CH476597; EAU36745.1; -; Genomic_DNA.
DR RefSeq; XP_001212649.1; XM_001212649.1.
DR AlphaFoldDB; Q0CS63; -.
DR SMR; Q0CS63; -.
DR EnsemblFungi; EAU36745; EAU36745; ATEG_03471.
DR GeneID; 4318084; -.
DR VEuPathDB; FungiDB:ATEG_03471; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_022195_0_2_1; -.
DR OMA; GEYSYMG; -.
DR OrthoDB; 574756at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0008152; P:metabolic process; IEA:UniProt.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 3: Inferred from homology;
KW Glycoprotein; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..489
FT /note="Cytochrome P450 monooxygenase ataF"
FT /id="PRO_0000440660"
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 434
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 289
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 489 AA; 55798 MW; 8BF38F7EA61B1168 CRC64;
MSLASLDLNA LWLEHSAVIA TLFAFGTALF LVSRSQKQSL NLPRFEVTND VLKTIEEAHA
QYPDDPFILS MVGMELAILP RSGIDVIKTL PEDQVSIKRH HHDVFLGEYT YMGTKSPEFD
EAMRYDLTRN TPTVLASFVA EVQYAVEDSF GRPDQWTAFQ PRACMSKIAS LMSGRAFVGL
PLSRDNTWVD ATVRYTQDVT RAWLVLRTIP WVLRPFVAPF LPQVRSLKNQ RRMTEERLTP
LLDPSNAKNR DEIPGGDMLR WFRQRYPQGP TPKQLARDQL LATFASIYNL SNALSYLLFD
LATYPEHIEP LRQELQEVLK GEPVNKENIQ KLKKLDSFIR ESQRLSPPSL ANMPRIVTNP
RGLKLPSGHT IPCGMRIMVR AHTLNLDPNL WPNPTRFDGF RFSKLREIPG NTFKYQHATT
GTDNINFGHG LWACPGRHFA SSQMKVVLAH LLLNYDIKLP NRMEKPQQQH FGLAIVPDTE
QMVLLKIRG
