ID   ATAL_ASPTN              Reviewed;         155 AA.
AC   Q0CS65;
DT   05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   25-MAY-2022, entry version 55.
DE   RecName: Full=Acetylaranotin biosynthesis cluster protein L {ECO:0000303|PubMed:23586797};
GN   Name=ataL {ECO:0000303|PubMed:23586797}; ORFNames=ATEG_03469;
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: Nonribosomal peptide synthetase; part of the gene cluster
CC       that 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       specific function of ataL within the pathway has still to be determined
CC       (PubMed:23586797). The acetylaranotin bis-thiomethyltransferase ataS
CC       located outside of acetylaranotin gene cluster is the main
CC       thiomethyltransferase responsible for converting acetylaranotin and its
CC       related intermediates to their methylated forms (PubMed:30096370).
CC       {ECO:0000269|PubMed:23586797, ECO:0000269|PubMed:30096370}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:23586797}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of acetylaranotin and
CC       accumulates chemically stable intermediate cyclo-L-phe-L-phe or shunt
CC       products such as 2-hydroxy-2'-ene-cyclo-L-Phe-L-Phe and 2-imino-10'-
CC       hydroxy-cyclo-L-Phe-L-Phe (PubMed:23586797).
CC       {ECO:0000269|PubMed:23586797}.
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DR   EMBL; CH476597; EAU36743.1; -; Genomic_DNA.
DR   RefSeq; XP_001212647.1; XM_001212647.1.
DR   AlphaFoldDB; Q0CS65; -.
DR   SMR; Q0CS65; -.
DR   EnsemblFungi; EAU36743; EAU36743; ATEG_03469.
DR   GeneID; 4318082; -.
DR   VEuPathDB; FungiDB:ATEG_03469; -.
DR   HOGENOM; CLU_111642_1_0_1; -.
DR   OMA; MANGAVH; -.
DR   OrthoDB; 1524517at2759; -.
DR   Proteomes; UP000007963; Unassembled WGS sequence.
DR   Gene3D; 3.30.530.20; -; 1.
DR   InterPro; IPR015075; AtaL.
DR   InterPro; IPR023393; START-like_dom_sf.
DR   Pfam; PF08982; DUF1857; 1.
PE   4: Predicted;
KW   Reference proteome.
FT   CHAIN           1..155
FT                   /note="Acetylaranotin biosynthesis cluster protein L"
FT                   /id="PRO_0000440659"
SQ   SEQUENCE   155 AA;  17201 MW;  07FC6B6F7FA5016F CRC64;
     MSTPTSFTFN IAYSVPINKD PSQPTLTLEE FWRGLHRGSE KPQLFAEYVA DTEVLPNSKS
     ANEFQRKLIM ANGAVHTAKG VELLQDVRNA DGLLDDGPDA LYLTAVYELH VPDVEPGSER
     AKEIEREYAQ LALGAARTVV ETIRRWKVEG GLEDA