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 02-OCT-2024, entry version 97.
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; WTTPDNG; -.
DR OrthoDB; 1949608at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:TreeGrafter.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0043041; P:amino acid activation for nonribosomal peptide biosynthetic process; IEA:TreeGrafter.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:TreeGrafter.
DR CDD; cd19537; C_NRPS-like; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.980; -; 2.
DR Gene3D; 1.10.1200.10; ACP-like; 2.
DR Gene3D; 3.30.559.10; Chloramphenicol acetyltransferase-like domain; 2.
DR Gene3D; 3.30.559.30; Nonribosomal peptide synthetase, condensation domain; 2.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig_com.
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 PANTHER; PTHR45527:SF1; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR45527; NONRIBOSOMAL PEPTIDE SYNTHETASE; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 2.
DR Pfam; PF00550; PP-binding; 2.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF56801; Acetyl-CoA synthetase-like; 1.
DR SUPFAM; SSF47336; ACP-like; 2.
DR SUPFAM; SSF52777; CoA-dependent acyltransferases; 4.
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
//
