ID   ATAP_ASPTN              Reviewed;        1507 AA.
AC   Q0CS64;
DT   05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 1.
DT   25-MAY-2022, entry version 88.
DE   RecName: Full=Nonribosomal peptide synthetase ataP {ECO:0000303|PubMed:23586797};
DE            Short=NRPS ataP {ECO:0000303|PubMed:23586797};
DE            EC=6.3.2.- {ECO:0000305|PubMed:23586797};
DE   AltName: Full=Acetylaranotin biosynthesis cluster protein P {ECO:0000303|PubMed:23586797};
GN   Name=ataP {ECO:0000303|PubMed:23586797}; ORFNames=ATEG_03470;
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, DOMAIN, 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       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:23586797}.
CC   -!- DOMAIN: AtaP has the domain architecture (T1-C1-A1-T2-C2)
CC       (PubMed:23586797). The single adenylation (A) domain in ataP suggests
CC       that one specific substrate, L-Phe, is loaded onto the T (carrier)
CC       domains of ataP (PubMed:23586797). {ECO:0000269|PubMed:23586797}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of acetylaranotin and of
CC       the cyclo-L-Phe-L-Phe intermediate (PubMed:23586797).
CC       {ECO:0000269|PubMed:23586797}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; CH476597; EAU36744.1; -; Genomic_DNA.
DR   RefSeq; XP_001212648.1; XM_001212648.1.
DR   AlphaFoldDB; Q0CS64; -.
DR   SMR; Q0CS64; -.
DR   STRING; 341663.Q0CS64; -.
DR   EnsemblFungi; EAU36744; EAU36744; ATEG_03470.
DR   GeneID; 4318083; -.
DR   VEuPathDB; FungiDB:ATEG_03470; -.
DR   eggNOG; KOG1178; Eukaryota.
DR   HOGENOM; CLU_000022_0_5_1; -.
DR   OMA; AVYNCYG; -.
DR   OrthoDB; 4243at2759; -.
DR   Proteomes; UP000007963; Unassembled WGS sequence.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   Gene3D; 1.10.1200.10; -; 2.
DR   Gene3D; 3.30.300.30; -; 1.
DR   Gene3D; 3.30.559.10; -; 2.
DR   InterPro; IPR036736; ACP-like_sf.
DR   InterPro; IPR025110; AMP-bd_C.
DR   InterPro; IPR045851; AMP-bd_C_sf.
DR   InterPro; IPR020845; AMP-binding_CS.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig.
DR   InterPro; IPR023213; CAT-like_dom_sf.
DR   InterPro; IPR001242; Condensatn.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR006162; Ppantetheine_attach_site.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF13193; AMP-binding_C; 1.
DR   Pfam; PF00668; Condensation; 2.
DR   Pfam; PF00550; PP-binding; 2.
DR   SMART; SM00823; PKS_PP; 2.
DR   SUPFAM; SSF47336; SSF47336; 2.
DR   PROSITE; PS00455; AMP_BINDING; 1.
DR   PROSITE; PS50075; CARRIER; 2.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   3: Inferred from homology;
KW   Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat.
FT   CHAIN           1..1507
FT                   /note="Nonribosomal peptide synthetase ataP"
FT                   /id="PRO_0000440656"
FT   DOMAIN          1..72
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          988..1065
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          98..119
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          163..429
FT                   /note="Condensation 1"
FT                   /evidence="ECO:0000255"
FT   REGION          514..893
FT                   /note="Adenylation"
FT                   /evidence="ECO:0000255"
FT   REGION          1099..1471
FT                   /note="Condensation 2"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         33
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         1025
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1507 AA;  167139 MW;  53BBB5F166CD4076 CRC64;
     MQINIRNEIA RELNVPTTEL DDSLSFTALG GHSLSALRLV SICKRIGLSL AVGELLHDIP
     IKDIISRSTG MYDTAGSLPI LENTDPSHPD VSFNAIITPS PSPSGPSTGC PTPDTLDTTD
     SQDADKISIP EMQLSLIQST LANPGNNILA YHYMCSLADL PATRMAWQQV LEAESIFRTE
     FRIEHEGGYL VDTGFTPYRW RDTQVPNWEA LHAERDKRPS FDNVAFEFQV ITVAGDNSVA
     CILWHVHHSF IDGFSMQLVM RKVSRVVAGH PVEAGPSFAT VAWERDQIIK EREADARRYW
     KSQKRVLEAA ASEIRMPRCD FAPRSIEFWN KVATFVIDVA QSDLLGYAAR HHVTVPSVYY
     AAWALVLSII CDSNLVLLGV VMSGRSLPVP GILDVIGSLV NTLPMGVEVE LGMDTVGFIN
     RVFRQLVQLS SFDWSPPEHG YRRQFASVLA MQFDVGGHTG TTNEPSSRMN SEIPISITVE
     SDQVIHLQFA PEYQETQVQL MGTLFTRAIS CLAAAAENPE ACAARLGAQS MSYQELDRWS
     DCVAVHLSMY IDKGAVVCVH ASPCMHWLVA IYGILKAGGV YCPLNSKLDP ELRNNMFQSS
     GAAIYLTPSA SETKYRPRAS RYVWAVEDLL QRQDDNNQDE FDHIPRAEGN AYLCFTSGST
     GKPKGVLCTH RGLVAFQRDL EVRLHAQPGR RIAQTMSVSF DGSIHEIFSA LSYGATLVLP
     TPEDPFSHLY DVDSCIFTPS LAATLDPSDY PNLCYVYLVG EQVTQDINDR WAASVALYNM
     YGPTEATCGA SIKCLLPGRK VTVGRPNPTT RIYILDRNGR LAPPGVMGQI YLAGVQVSNG
     YIGQSDLTNE RFFPDSICCG LGERMYATGD IGYWDGDGDL ICLGRNDRQI KLRGFRLDLD
     DLEVRISKLP GVTRAAVSRR GDDLVALVQP ATACAADCRK HMAAVLPTHA IPRYIIPVER
     FPMTPIGKLD YRAIAQTADV RYSATPSNEM SPTEQRVAAI WADILNMDRA QISRDSNFLA
     AGGHSLLQLR LAGRLNRAFN CSVPITDLVK AATLRDLSQR IDKLQEQACW KAQRLPPKMD
     KRAISRMERE WISKYEGNTS NTSFTVSFAC RLDSAVDLAR LKQSWDSVME AHQVLRSRYC
     ACAERYERVF SDHAPVAQRI AECRVLEEIN RPFDLANDDL VRVVISPDTL LVTISHIICD
     LTTMQLLLSD VERVYDGAEP LGHRPMYMAA DAWQRVAADA DLAFWTSYLQ DCPHSKAKRE
     SYAGTSRVGI VPRETVLALE DFMRSSQFSH HQLALAAVAL ALKPNHDRID SVIGGPFLNR
     WSEADMNTIG LFLEPLPFRI QFDPKAVPNA DAHAFLQSVK CSSQAAISHA VPWQELVCHL
     GVTPEFPNHP LFETMVTFHT KGGGLSLQID GIEPLYTWSE GAKFGLMCEF TTLSNGDILL
     RLEYDQGIYA PRDISIIENR IMTALRLLIK NVPWLDLIGE LHEVDGATVC VTPGHKGSLF
     LSPLKRT