ATATC_ASPTN
ID ATATC_ASPTN Reviewed; 718 AA.
AC Q0CS60;
DT 05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Bimodular acetylaranotin synthesis protein ataTC {ECO:0000303|PubMed:23586797};
DE AltName: Full=Acetylaranotin biosynthesis cluster protein TC {ECO:0000303|PubMed:23586797};
DE Includes:
DE RecName: Full=Thioredoxin reductase ataT {ECO:0000303|PubMed:23586797};
DE EC=1.8.1.- {ECO:0000305|PubMed:23586797};
DE Includes:
DE RecName: Full=Cytochrome P450 monooxygenase ataC {ECO:0000303|PubMed:23586797};
DE EC=1.-.-.- {ECO:0000305|PubMed:23586797};
DE Flags: Precursor;
GN Name=ataTC {ECO:0000303|PubMed:23586797}; ORFNames=ATEG_03474;
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: Bimodular 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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:E9RAH5};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:E9RAH5};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:23586797}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of acetylaranotin and
CC accumulates the intermediate cyclo-L-Phe-L-Phe (PubMed:23586797).
CC {ECO:0000269|PubMed:23586797}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the class-II pyridine
CC nucleotide-disulfide oxidoreductase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the cytochrome P450
CC family. {ECO:0000305}.
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DR EMBL; CH476597; EAU36748.1; -; Genomic_DNA.
DR RefSeq; XP_001212652.1; XM_001212652.1.
DR AlphaFoldDB; Q0CS60; -.
DR SMR; Q0CS60; -.
DR EnsemblFungi; EAU36748; EAU36748; ATEG_03474.
DR GeneID; 4317582; -.
DR VEuPathDB; FungiDB:ATEG_03474; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_384934_0_0_1; -.
DR OMA; PTEANHA; -.
DR OrthoDB; 825914at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
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:UniProtKB-KW.
DR Gene3D; 1.10.630.10; -; 1.
DR Gene3D; 3.50.50.60; -; 2.
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 InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR SUPFAM; SSF48264; SSF48264; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Glycoprotein; Iron; Metal-binding; Monooxygenase;
KW Multifunctional enzyme; NADP; Oxidoreductase; Reference proteome; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..718
FT /note="Bimodular acetylaranotin synthesis protein ataTC"
FT /id="PRO_0000440663"
FT REGION 1..215
FT /note="Thioredoxin reductase ataT"
FT /evidence="ECO:0000305|PubMed:23586797"
FT REGION 216..718
FT /note="Cytochrome P450 monooxygenase ataC"
FT /evidence="ECO:0000305|PubMed:23586797"
FT BINDING 72..90
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 109..114
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 515..516
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E9RAH5"
FT BINDING 658
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 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 548
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 718 AA; 80284 MW; 0086AE565E46703D CRC64;
MYAHLAQMLN LLVTPSSGPA TVFTDGPIPD NDAMKEALGK VDALKFNVET GKVIRLVPAV
APDIGVTVVV EGGKEYKLGY LGHKPYTVVA GKAMITRLGA EIEENPVMGE HVKTVDPLGS
TNVKGVFVAG DAATPMKAVA NAIGTGERYC RSWDRAAVDN GGHGEDLSLE EVHINTRPSS
TATEFDKTHH IIEKMYPLES VRHLVVEQSQ LCYILFGAVL AYAGWRWVLR LDILNEAITD
LMSNLLNYYL TRRYPIHHSE TGQQIPGRSY RWPNGQGDQG KFLDGIENRA QWAKEHGRIY
RIWAGTTPEV VLQTPEHIKL VFRDSDRHSK AVNNDSGYLM GQVLGQCLGL ISGGDWRRVR
EVCEAAFTHS KAINYLDLIH SRVGDYLQKC TALQRGTLNP ADDFKFLPFL VVGDILYGHM
TQEMEDELRQ MAPLRERLFQ FVIRGGLARY TWSQYLPTEA NHALREFRSR WVAFNQAAYC
RARERGATAT PVYQLFTAVS DGMITAANAY QTLDEMLFAN LDVTLGGLSW NPVFLAANPA
VQEELYENIT AAQEAEGPAM PMYLQDSSTY LAACILESSR LKPLAAFSVP QAAPTARVLD
GYVIAGGTNY IVDAYALNVE HEFWGPDRHE YRPGRFLGVK GADLRYHMWR FGFGPRQCLG
KYVADLILRV FLVHLVRNWR LGFEDGQIAD SREWKRDLDA WITHPTIELT CTPRGARA
