ID   DTPA_ASPFN              Reviewed;        2621 AA.
AC   B8NR69;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   03-MAR-2009, sequence version 1.
DT   03-AUG-2022, entry version 75.
DE   RecName: Full=Nonribosomal peptide synthase dtpA {ECO:0000303|PubMed:24677498};
DE            Short=NRPS dtpA {ECO:0000305};
DE            EC=6.3.2.- {ECO:0000269|PubMed:24677498};
DE   AltName: Full=Ditryptophenaline biosynthesis protein A {ECO:0000303|PubMed:24677498};
GN   Name=dtpA {ECO:0000303|PubMed:24677498}; ORFNames=AFLA_005440;
OS   Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS   / JCM 12722 / SRRC 167).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=332952;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC   167;
RX   PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA   Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA   Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT   "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT   aflatoxin contamination of food and feed.";
RL   Genome Announc. 3:E0016815-E0016815(2015).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=24677498; DOI=10.1002/cbic.201300751;
RA   Saruwatari T., Yagishita F., Mino T., Noguchi H., Hotta K., Watanabe K.;
RT   "Cytochrome P450 as dimerization catalyst in diketopiperazine alkaloid
RT   biosynthesis.";
RL   ChemBioChem 15:656-659(2014).
CC   -!- FUNCTION: Nonribosomal peptide synthase; part of the gene cluster that
CC       mediates the biosynthesis of the dimeric diketopiperazine alkaloid
CC       ditryptophenaline (PubMed:24677498). The nonribosomal peptide synthase
CC       dtpA accepts L-tryptophan and L-phenylalanine as its substrates and
CC       forms the phenylalanyl-tryptophanyl cyclic dipeptide product
CC       cyclophenylalanyltryptophenyl (PubMed:24677498). The N-
CC       methyltransferase dtpB is responsible for the N-methylation of
CC       cyclophenylalanyltryptophenyl to yield cyclo-N-
CC       methylphenylalanyltryptophenyl (PubMed:24677498). The cytochrome P450
CC       monooxygenase is responsible not only for pyrroloindole ring formation
CC       but also for concurrent dimerization of N-
CC       methylphenylalanyltryptophanyl diketopiperazine monomers into a
CC       homodimeric product (PubMed:24677498). {ECO:0000269|PubMed:24677498}.
CC   -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:24677498}.
CC   -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC       (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC       (C) domains) which when grouped together are referred to as a single
CC       module (By similarity). Each module is responsible for the recognition
CC       (via the A domain) and incorporation of a single amino acid into the
CC       growing peptide product (By similarity). Thus, an NRP synthetase is
CC       generally composed of one or more modules and can terminate in a
CC       thioesterase domain (TE) that releases the newly synthesized peptide
CC       from the enzyme (By similarity). Occasionally, epimerase (E) domains
CC       (responsible for L- to D-amino acid conversion) are present within the
CC       NRP synthetase (By similarity). The presence of two intact modules
CC       suggests that the two modules condense L-tryptophan and L-phenylalanine
CC       together (PubMed:24677498). The C-terminal condensation domain might be
CC       responsible for cyclization of the dipeptide to form the
CC       diketopiperazine structure (PubMed:24677498).
CC       {ECO:0000250|UniProtKB:Q4WMJ7, ECO:0000305|PubMed:24677498}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of ditryptophenaline
CC       (PubMed:24677498). {ECO:0000269|PubMed:24677498}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; EQ963482; EED47902.1; -; Genomic_DNA.
DR   RefSeq; XP_002382744.1; XM_002382703.1.
DR   AlphaFoldDB; B8NR69; -.
DR   SMR; B8NR69; -.
DR   STRING; 5059.CADAFLAP00010609; -.
DR   EnsemblFungi; EED47902; EED47902; AFLA_005440.
DR   VEuPathDB; FungiDB:AFLA_005440; -.
DR   eggNOG; KOG1178; Eukaryota.
DR   HOGENOM; CLU_000022_60_2_1; -.
DR   OMA; CICILNE; -.
DR   Proteomes; UP000001875; 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; -; 2.
DR   Gene3D; 3.30.559.10; -; 3.
DR   Gene3D; 3.40.50.12780; -; 1.
DR   InterPro; IPR010071; AA_adenyl_domain.
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.
DR   InterPro; IPR042099; ANL_N_sf.
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; 2.
DR   Pfam; PF00668; Condensation; 2.
DR   Pfam; PF00550; PP-binding; 2.
DR   SMART; SM00823; PKS_PP; 2.
DR   SUPFAM; SSF47336; SSF47336; 2.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR   PROSITE; PS00455; AMP_BINDING; 2.
DR   PROSITE; PS50075; CARRIER; 2.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   1: Evidence at protein level;
KW   Ligase; Phosphopantetheine; Phosphoprotein; Repeat.
FT   CHAIN           1..2621
FT                   /note="Nonribosomal peptide synthase dtpA"
FT                   /id="PRO_0000438201"
FT   DOMAIN          978..1054
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          2071..2147
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          446..844
FT                   /note="Adenylation 1"
FT                   /evidence="ECO:0000255"
FT   REGION          1095..1506
FT                   /note="Condensation 1"
FT                   /evidence="ECO:0000255"
FT   REGION          1534..1930
FT                   /note="Adenylation 2"
FT                   /evidence="ECO:0000255"
FT   REGION          2220..2618
FT                   /note="Condensation 2"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         1015
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         2108
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   2621 AA;  290811 MW;  08BAA5E55EC17C4B CRC64;
     MSCENEAPLT RSFCRTKRRD RFSHEEAARK CRIETHDIED IRACTQEQLV YATLLSQGDE
     GAIAEWSFDI PESINIDFLK KAWQDMVRSK AFLRTRIIAD DSPGIFLCVV MNGEPLLWTE
     GDGMDDPWVL GSSLARFRLI EVPNTNQRRL VVKIHHAICD PCSLYAVFES VDHAYQKKKL
     YNLQQNETPT ACTTEGSFDD ATAFPELPAS VQCPSARHSL EQSVSVGTLP PSLGEITANV
     WLAWAITQSQ YQSSDRVLFG TGSRHDEERP GFPAYVSPRL VVLDSQVAVA DILQELENMF
     IGPAQKRTAV RTPSAEKKGM SGAVQTVVSV RRLAQHRPLT CANLVKSEKQ NPFQNYALTL
     DCQLEKDFLI KVQAHYDHNV IPQWVTQRVL SHFMHVLPQT FHRNRDTKLA SLKSLSPYDE
     AQLAYWNSKH VPVAEEPTHH IIHRICMEQP NAEAICSWDG KFTYNEVDVL SDSLATQLTD
     LGLGGSGSII PVYMDKGRWV PIAILGVLKS GAAFTLFDPS HPLQRLKIMA EDVKAKAILC
     SRMTMELASQ IVPQTLQIDD ERGWDTIRAR PGSHFSRSSR QDDALYVAFT SGSTGKPKAI
     VIEHGSYCTG AKEHIKAFRL SRKARVLQFA LYAFDVSIME ILSTLMAGGC ICILNEVQRT
     TPQDFEKALS SFSVTHAFLT PSFARSLRNA QLPSLDVLIL GGEPMSPADA GHWASRNVVL
     MNAYGPAECS VNTTVQPCAA ACPGNIGFTT GAACWVVDPM NHNQLVPIGG IGELLVQGPI
     VGRGYLNNPT LTKASFVKFV PSISAHLPGA EIIDRAYRTG DLVRQQMDGS IVYIGRKDQQ
     VKIRGQRIEL SEVEFQVQKS LEGDVDVVIE AVDIEGKSQP LLVAFLNLGI HGAQANEDLA
     PLAMPCEEWF RRLESMEGAL KHYLPPSMIP NLFLPLVYTP TTPTGKIDRR LLRELSSRLS
     QAQLELYRNR NKDELKRQPY TQVEETLQRL FSQILGVEQR HISVTDSFFQ LGGDSISAIR
     LIGAARDAGL EFTVSELLSA PTISEVALYS RALSVPKEEA SPPPPFVLLG TSAKVPEILQ
     LVANQIKLSN LDNIEDIYPC TALQEGMFAL SLKSPGTYTG EVLLRLPGDV DMQRLLSAWQ
     ATVEANPILR TQIVQTPKGL FQVVMRRVDF ECKQHASLDA LGKLHVNQDK GVSINPMCQV
     ALVKHNGDQH FALKIHHALC DGWSLKLILG QLDLAYRKEA SLTPSYFNTF IKYLDSIAGW
     EDYWTSEFRD LQAPIYPALP SPSYMPRPTS LRDHAIHNLH MADSGMRLPI LIKLAWSILV
     SNYTDSDDVV IGLTLNGRNA PVPGIEQLIG PTITTVPLRT RIHEDDTVRT ASNCLHNKLT
     AMISYEQAGL QRIGKLNDNC RTACSFQMQV GIQPPADFNT ENYCFDVLEH SIGPSMDYSD
     FSTYGIVVVC ELSRSGTALH VKMRHDPDLV SPDEANCMVH LFEHLLRQLC ENPDMRLNQL
     ELAGPQDIKQ FAKWNATAPV PVERCLHELI MNHSRTQPGA SAICGWDGYV TYQELGLLIT
     QLAYYLRTRF HIRPGMNVPI CPNRSKWAIV SMLSVLYAGG SCVLLDPNHP QARMQTVISD
     TAADIIICNA GTEEKVTGLT RHLVIVGPEL LESLPTPASL PQCLSDATPM DPAFVIFTSG
     STGKPKGIIM SHKSLSTSIY YHSPQLGVNQ QTRTLHFCSY AFDASIYEIF TTLVCGGCVC
     VPSASDCTDN LAGFITHFDV NLAIMAPSVA RLLHPDSVPS LQCLVLGGEA LTWEIVNLWA
     DRVRLVNGYG PAEATIMAAG VVQASDWITG LIGPVVGANP WITKPFNPDQ LVARGMIGEL
     LIEGPVLADG YINAPEKSAD PFIPAPTWLR SIRPNSAGAT RLYRTGDLVQ QQRDGSIRFM
     GRRDNQVKLR GQRIELQEVE HCVTSHVPDA VVVAEVVSFL TNERRRNELV VFIRDSTAGT
     EPDNITSNPE ETSAIFSSPT KVDHTAMAEL KAHMARNLPR YMVPWIILPL DDIPKTASGK
     TDRARLRVAA GKLEQKTLDQ YMNIANIVKR QPSTTQEALV RSIFAQVLSL PESTIGVDDS
     FFNIGGDSIS AMRFLTLCRQ ANLHLAMPAF LTYNTVALFC TNASTSIDIS RFDASEEMDR
     NTPLVTIDHE KHISTLRTTL CNQLGLDSVL SIEDIYPCSS SHAGIIRGLA GSGDRHQVRA
     IFKLHGSKVV DPAHVLECWH KLIQRHAILR TVIVNNPLHP GEFLHVVLKQ PPIDMASLSF
     QSPNVVTQLC DIHPSFDWET SPAHQMVIAQ GYEGEAYCKL EAGKALIDWS SFSILVDELC
     LAINHLLPSK PAPLYKDFIS YVQRQPLDKI MNYWERTLSG VTSSIIPRSL PEAPADPDAV
     PVLHSTRITL DGFKDIDAFW RGNRLTLTNI FQVAWGLVLS FHSRLPEVCF GTVVSGRDIP
     VTNIEDMVGP CFNILPCRLD LSPDRNIMET LQQNQQDMQR RTDHQHCSIS EITRGVRQTT
     STPLFNTCLS VQVSLSSQME EPSGDLGHDI QVSMVDIHDP TEYDICLAVL IYRTQIEIDL
     RYWSFAFSEQ DATRLLNNLR QAISHIVAHS ARPIASIDWE A