ID   ATIMG_ASPTN             Reviewed;         874 AA.
AC   Q0CS62;
DT   05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 85.
DE   RecName: Full=Trimodular acetylaranotin synthesis protein ataIMG {ECO:0000303|PubMed:23586797};
DE   AltName: Full=Acetylaranotin biosynthesis cluster protein IMG {ECO:0000303|PubMed:23586797};
DE   Includes:
DE     RecName: Full=Aminotransferase ataI {ECO:0000303|PubMed:23586797};
DE              EC=2.6.1.- {ECO:0000305|PubMed:23586797};
DE   Includes:
DE     RecName: Full=O-methyltransferase ataM {ECO:0000303|PubMed:23586797};
DE              EC=2.1.1.- {ECO:0000255|PROSITE-ProRule:PRU01020};
DE   Includes:
DE     RecName: Full=Glutathione S-transferase ataG {ECO:0000303|PubMed:23586797};
DE              EC=2.5.1.18 {ECO:0000305|PubMed:23586797};
GN   Name=ataIMG {ECO:0000303|PubMed:23586797}; ORFNames=ATEG_03472;
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: Trimodular acetylaranotin synthesis protein; part of the gene
CC       cluster that mediates the biosynthesis of acetylaranotin, a member of
CC       the 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   -!- CATALYTIC ACTIVITY:
CC       Reaction=glutathione + RX = a halide anion + an S-substituted
CC         glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925,
CC         ChEBI:CHEBI:90779; EC=2.5.1.18;
CC         Evidence={ECO:0000269|PubMed:23586797};
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC         Evidence={ECO:0000250|UniProtKB:P00509};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:23586797}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of acetylaranotin and
CC       accumulates chemically stable intermediates or shunt products such as
CC       2-imino-3-phenyl-propionic acid amide (PubMed:23586797).
CC       {ECO:0000269|PubMed:23586797}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the class-I
CC       pyridoxal-phosphate-dependent aminotransferase family. {ECO:0000305}.
CC   -!- SIMILARITY: In the 2nd section; belongs to the class I-like SAM-binding
CC       methyltransferase superfamily. Cation-independent O-methyltransferase
CC       family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the GST superfamily.
CC       {ECO:0000305}.
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DR   EMBL; CH476597; EAU36746.1; -; Genomic_DNA.
DR   RefSeq; XP_001212650.1; XM_001212650.1.
DR   AlphaFoldDB; Q0CS62; -.
DR   SMR; Q0CS62; -.
DR   STRING; 33178.CADATEAP00008632; -.
DR   EnsemblFungi; EAU36746; EAU36746; ATEG_03472.
DR   GeneID; 4318085; -.
DR   VEuPathDB; FungiDB:ATEG_03472; -.
DR   eggNOG; KOG0256; Eukaryota.
DR   HOGENOM; CLU_328711_0_0_1; -.
DR   OrthoDB; 1231780at2759; -.
DR   Proteomes; UP000007963; Unassembled WGS sequence.
DR   GO; GO:0004364; F:glutathione transferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR   GO; GO:0009058; P:biosynthetic process; IEA:InterPro.
DR   GO; GO:0006749; P:glutathione metabolic process; IEA:InterPro.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.10.10; -; 1.
DR   Gene3D; 3.40.50.150; -; 2.
DR   Gene3D; 3.40.640.10; -; 1.
DR   InterPro; IPR004839; Aminotransferase_I/II.
DR   InterPro; IPR016461; COMT-like.
DR   InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR   InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR   InterPro; IPR004045; Glutathione_S-Trfase_N.
DR   InterPro; IPR004046; GST_C.
DR   InterPro; IPR001077; O_MeTrfase_dom.
DR   InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR   InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   Pfam; PF00155; Aminotran_1_2; 1.
DR   Pfam; PF00043; GST_C; 1.
DR   Pfam; PF13409; GST_N_2; 1.
DR   Pfam; PF00891; Methyltransf_2; 1.
DR   SUPFAM; SSF46785; SSF46785; 1.
DR   SUPFAM; SSF47616; SSF47616; 1.
DR   SUPFAM; SSF52833; SSF52833; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   SUPFAM; SSF53383; SSF53383; 1.
DR   PROSITE; PS50405; GST_CTER; 1.
DR   PROSITE; PS50404; GST_NTER; 1.
DR   PROSITE; PS51683; SAM_OMT_II; 1.
PE   3: Inferred from homology;
KW   Methyltransferase; Multifunctional enzyme; Reference proteome;
KW   S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..874
FT                   /note="Trimodular acetylaranotin synthesis protein ataIMG"
FT                   /id="PRO_0000440664"
FT   DOMAIN          699..766
FT                   /note="GST N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00684"
FT   DOMAIN          739..874
FT                   /note="GST C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00685"
FT   REGION          1..339
FT                   /note="Aminotransferase ataI"
FT                   /evidence="ECO:0000305|PubMed:23586797"
FT   REGION          20..39
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          340..668
FT                   /note="O-methyltransferase ataM"
FT                   /evidence="ECO:0000305|PubMed:23586797"
FT   REGION          669..874
FT                   /note="Glutathione S-transferase ataG"
FT                   /evidence="ECO:0000305|PubMed:23586797"
FT   BINDING         625
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
SQ   SEQUENCE   874 AA;  97280 MW;  E27F613C9BDC5D3A CRC64;
     MANLSGLSNR SRTTLASLRR FGFQTTQQAK PTESSKTPID ASVAENWSIR PELLSLFQET
     LQTELGAQVR IRPRPRILAL SHGRNTNTVS ADGFDFHFGV RAQVNPVAAP IRDLHDAFNP
     DGLLESLTAA FDTSPYPIRA VVLTYPGNPL GQCCSAEALR RCAKFCHDRE LHLICDEVYA
     LSYFGAADSE ATPFQSIVSF DLNAMGCDLS RVHVVWSMSK DFGCSGLRLG CVISQANPEL
     ILGLRVPTST EVSSLSTLCS TALLTSATLP DIIELNVKRL LLSYKAVIAT LECHGVEYIP
     ATAGLCVFAR LAPEAKTPDD EIGFQHRLRD SGLLRASSIS YNSMVKGSSD KIRPNNVRQK
     KMEPTLKILG ASLQEALSQL TGPLNKERLA ALHDHSEGRL VDANLGEAAA YTIDLLHQVE
     QLLEPSSLVL ADHFLGYLNT KCLCAAVEFH IPDLLVEGPK SVSQLAQLSG ARADRLGQVL
     RLLRNNGIFQ YDTENATYSN NPTSSMLRSD HWTQWHNWVD LYGNEFYDMA RGIPASLKQG
     TTRTPAQINF NTDQCMFDYF TAQGWLPRLH RTLGGGATAQ APGILADYPW EDFGDGPFLD
     IGGGEGALIA LILRRHTRTK AALLDTPRVI EHARTLFLSP DGKLSRYGDL TMMVSADGQE
     RTEAEWRTLA GRTGWEIRTI RKLRGAWPSD ETSYINYIKP LILAHELEIP HVLSVIDTKD
     EWFYRIHPER MVPSLKDQDP ETKAEVIVFE STACLQYLAD RFDDGTWTGR NAAERGSVLS
     WTAYQTAALG LHENCLRQWD ILEKRLARDG QEYIALKDRP TIADLSYFPF SMPWMFQFLG
     VDIKDWPSIE RWSQRMLARP AVQAVMEMGP QIGH