ID   ATAS_ASPTN              Reviewed;         274 AA.
AC   Q0CXW9;
DT   05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 52.
DE   RecName: Full=Acetylaranotin bis-thiomethyltransferase {ECO:0000303|PubMed:30096370};
DE            EC=2.1.1.- {ECO:0000269|PubMed:30096370};
DE   AltName: Full=Acetylaranotin biosynthesis protein S {ECO:0000303|PubMed:30096370};
GN   Name=ataS {ECO:0000303|PubMed:30096370}; ORFNames=ATEG_01465;
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.
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   IDENTIFICATION, FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
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: Acetylaranotin bis-thiomethyltransferase involved in the
CC       biosynthesis of acetylaranotin derivatives, members of the
CC       epipolythiodioxopiperazine (ETP) class of toxins characterized by a
CC       disulfide-bridged cyclic dipeptide (PubMed:30096370). 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   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30096370}.
CC   -!- INDUCTION: Expression is co-regulated with the acetylaranotin gene
CC       cluster. {ECO:0000269|PubMed:30096370}.
CC   -!- DISRUPTION PHENOTYPE: Diminishes greatly the production of the two bis-
CC       thiomethylated analogs of acetylaranotin, bisdethiobis(methylthio)-
CC       acetylaranotin and bisdethiobis(methylthio)-acetylapoaranotin.
CC       {ECO:0000269|PubMed:30096370}.
CC   -!- MISCELLANEOUS: AtaS is located outside of the acetylaranotin gene
CC       cluster. {ECO:0000303|PubMed:30096370}.
CC   -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC       superfamily. {ECO:0000305}.
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DR   EMBL; CH476595; EAU38222.1; -; Genomic_DNA.
DR   RefSeq; XP_001208830.1; XM_001208830.1.
DR   AlphaFoldDB; Q0CXW9; -.
DR   SMR; Q0CXW9; -.
DR   EnsemblFungi; EAU38222; EAU38222; ATEG_01465.
DR   GeneID; 4315831; -.
DR   VEuPathDB; FungiDB:ATEG_01465; -.
DR   eggNOG; ENOG502S4V1; Eukaryota.
DR   HOGENOM; CLU_065416_0_0_1; -.
DR   OMA; EGWVNTE; -.
DR   OrthoDB; 785883at2759; -.
DR   Proteomes; UP000007963; Unassembled WGS sequence.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.150; -; 1.
DR   InterPro; IPR041698; Methyltransf_25.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   Pfam; PF13649; Methyltransf_25; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
PE   2: Evidence at transcript level;
KW   Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW   Transferase.
FT   CHAIN           1..274
FT                   /note="Acetylaranotin bis-thiomethyltransferase"
FT                   /id="PRO_0000445937"
SQ   SEQUENCE   274 AA;  30491 MW;  0D49A56DC318FEE9 CRC64;
     MAKQELMNLF LSKEFASGYK LAELVTGPFA QLLVDYSGVV QSTQRPLVIL DNACGTGIIS
     EALNRSLDSQ TKGHWELTCG DISDSLVQYV NQRIQDEGWP RAKAQLVDAQ DTKLPSSHFT
     HIFAAFECLR ILQPGGTVAI SNWQLPEWLV IAKSAVEAMP GDLPFPTVKE FLASLNEGWD
     SEEPTRVKLE QEGFDMVQVA TVSQKLSLPK STLVELIKPM LPVILGRFWT DEQRAKHEKH
     IPTALQQYLD DKYGASDDVP VEPRVIIATA RKPC