ID   BENZ_ASPTE              Reviewed;        2406 AA.
AC   P9WEU9;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   12-AUG-2020, sequence version 1.
DT   25-MAY-2022, entry version 7.
DE   RecName: Full=Nonribisomal peptide synthetase benZ {ECO:0000303|PubMed:28604695};
DE            Short=NRPS benZ {ECO:0000303|PubMed:28604695};
DE            EC=6.3.1.- {ECO:0000305|PubMed:28604695};
DE   AltName: Full=Benzomalvin biosynthesis cluster protein Z {ECO:0000303|PubMed:28604695};
GN   Name=benZ {ECO:0000303|PubMed:28604695};
OS   Aspergillus terreus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=33178;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP   PATHWAY.
RC   STRAIN=ATCC 20542 / MF4845;
RX   PubMed=28604695; DOI=10.1038/nchembio.2408;
RA   Clevenger K.D., Bok J.W., Ye R., Miley G.P., Verdan M.H., Velk T., Chen C.,
RA   Yang K., Robey M.T., Gao P., Lamprecht M., Thomas P.M., Islam M.N.,
RA   Palmer J.M., Wu C.C., Keller N.P., Kelleher N.L.;
RT   "A scalable platform to identify fungal secondary metabolites and their
RT   gene clusters.";
RL   Nat. Chem. Biol. 13:895-901(2017).
CC   -!- FUNCTION: Nonribisomal peptide synthetase; part of the gene cluster
CC       that mediates the biosynthesis of benzomalvin A and D
CC       (PubMed:28604695). The pathway begins with the loading of amino acid
CC       precursors onto the A domains of the non ribosomal peptide synthetases
CC       benY and benZ (PubMed:28604695). BenY and the A1 domain of benZ are
CC       loaded with anthranilate (Anth), while the A2 domain of benZ is loaded
CC       with phenylalanine (Phe) (PubMed:28604695). N-methylation of Phe by the
CC       methyltransferase benX may happen before loading of Phe onto benZ,
CC       after loading of Phe, or after dipeptide formation (PubMed:28604695).
CC       Condensation of Anth with the secondary amine of NmPhe or Phe is
CC       catalyzed by the C1 domain of benZ, forming a dipeptide intermediate
CC       (PubMed:28604695). This is followed by in trans condensation of the
CC       Anth-NmPhe dipeptide with Anth bound to the T domain of benY by the C2
CC       domain of benZ to form the linear tripeptide Anth-NmPhe-Anth
CC       (PubMed:28604695). Cyclization and release of the tripeptide is then
CC       catalyzed by the C-terminal C domain of benY and the resulting 11-
CC       member macrocyclic intermediate is expected to spontaneously collapse
CC       to form the benzodiazepine core (PubMed:28604695). Benzomalvin A is in
CC       conformational equilibrium with its atropisomer, benzomalvin D
CC       (PubMed:28604695). {ECO:0000269|PubMed:28604695}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:28604695}.
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. Each module is responsible for the recognition (via the A
CC       domain) and incorporation of a single amino acid into the growing
CC       peptide product. Thus, an NRP synthetase is generally composed of one
CC       or more modules and can terminate in a thioesterase domain (TE) that
CC       releases the newly synthesized peptide from the enzyme. Occasionally,
CC       epimerase (E) domains (responsible for L- to D-amino acid conversion)
CC       are present within the NRP synthetase. BenZ as the following bimodular
CC       architecture: A1-T1-C1-A2-T2-C2. {ECO:0000305|PubMed:28604695}.
CC   -!- DISRUPTION PHENOTYPE: Leads to complete abolishment of the production
CC       of benzomalvins A and D. {ECO:0000269|PubMed:28604695}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; KX449366; AQM58287.1; -; Genomic_DNA.
DR   AlphaFoldDB; P9WEU9; -.
DR   SMR; P9WEU9; -.
DR   VEuPathDB; FungiDB:ATEG_09064; -.
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; -; 2.
DR   Gene3D; 3.40.50.12780; -; 2.
DR   InterPro; IPR010071; AA_adenyl_domain.
DR   InterPro; IPR036736; ACP-like_sf.
DR   InterPro; IPR045851; AMP-bd_C_sf.
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; 1.
DR   PROSITE; PS50075; CARRIER; 2.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   3: Inferred from homology;
KW   Ligase; Phosphopantetheine; Phosphoprotein; Repeat.
FT   CHAIN           1..2406
FT                   /note="Nonribisomal peptide synthetase benZ"
FT                   /id="PRO_0000450605"
FT   DOMAIN          794..871
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:28604695"
FT   DOMAIN          1875..1951
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:28604695"
FT   REGION          278..685
FT                   /note="Adenylation 1"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT   REGION          911..1183
FT                   /note="Condensation 1"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT   REGION          1364..1750
FT                   /note="Adenylation 2"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT   REGION          2001..2271
FT                   /note="Condensation 2"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT   REGION          2184..2205
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         831
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         1912
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   2406 AA;  263933 MW;  333D3220B2466018 CRC64;
     MTRIGFQQHI TGEDTGICIF PKLSKSKHNT TNATNFHETD IWEIPTPTIE ITLKDQGTDL
     NTVILAAWAV TVRAFTECQE VRYWVGHQPE ALADSTLDGL TQLLSVPINP QSSWKTLYGH
     NGWTIIQPHR PGHAPCNTGV IFNKPITIDC PTLCGGDDEL DRSPVGCKVG LIVCLSTDRL
     QISLGYSDSL LSRTAAGNVL SSVQQAILGG IQAPDQPICN HSLYTDLHLK DAGTPTLPAS
     TLSTPPTVPW WRGLSHSLIQ LGDHRDQLAI DGWDGRFTYG ELEDTCSSLA AHLQGLGIGP
     GMMIAVCFEK SVWAIVAAIS IHMAGAAFVP LDPALPVDRI HRIIAAAGSK FAVVSSKQKT
     RLVEGLSIQP IVLSAQTAAT FPPAHALVPS RVSMEDPAYC LFTSGSSGTP KGCIISQRAF
     AGISEHHPAV HLSGQSRALQ FASYSFGISI NEIYCTLSAG GTVCVVSDED CAGLSSLARA
     ITRMKVTWAF MTPTMIGSLH PKDVPCLEII ITGGEPLNKD QVLTWAHAVH LYQAFGFTEW
     CGTCCISPRV TASTPLGEIG TPVPNARAWL VDPVNPTVLA AVGAVAELCI EGTCLAKGYL
     HDPEQTSKAF IARPEWGPDE LPGTNGIYGG KGRLYRTGDL VRYLCDGSIQ YLGRRDSQRK
     VRGQRIEIAE VEYHLKECFP QAQRIFAEVI MPREGLSQVL TAFVQLHKPV VRSDDGDEWF
     EPIDAELQDQ VMSARKAMLT RIPRYMVPDL FLNLRRAPLT VTGKLDRRRL CTYAHQRSRD
     ELLGTVSADQ PRRSPSTKVE TMLVSLVAKA INRPMAMVGL DDNFFHLGGD SIKAMALVGE
     ARRLHGLQIT VGEIFTHPTV AKVAAVVQDK DTNQGAEFVV EPFSLLSEAD SRQDVVRAVE
     NQCHVDQALI EDIFPCTPLQ EGMFALGRRQ RGRYVGRWVF EFQGMSDTEI ARLTEAWAAV
     FKEDAILRTR IITSPSQRLY QVVLREPPKW ETSKILFNRD APNEKPDLSV DFGLPLAKMS
     IHRNDTPDCF QLALTMHHSV IDGWCFRKIL DQVEAIYHRH TLPASPPFTT FVNYLRQLPD
     HKEYWTSYLS GLNAEVFPAI LPSSYQPCPT AAATDYLDLA DFNPGRFTRS AVLRLAWAIT
     QAQYQGNHDI VYGMTVSGRN APVPGILAMI SPTVATMPFR VQLNPTASIE ASLDELVEQT
     VRGIPHEQTG LQNLMKMGGE VAAACDFQTL LVIQQIDGTD YSLLGRPAQE TSFSVFCTYT
     LTLVCDLNVD PVEFKAWYDP QLVPERQVRR LLRQMKHVVQ AICTSPASTV SDCMTLNPSD
     AAEISVWNRP LPTLSDYGVD HLFHQHCAEH PHRLAVDAWD VQFTYGALEE LSTHLSAHLV
     SLGVGHGDFV PICNEKSGWT VVAVFAVIQS GAAFILLDPS MPTKRLADSC QQARCSLVLT
     TTSSLQRVLE FATRVVLADD PYPAPSEISL APVQAEHVLF AVFTSGSTGV PKAAMADHQS
     FLGYSLPIMK RIGFGAGVRW LQFSSYAFDM SVNETLWTIL GGGCLCIPSD RQRLDDLVGA
     VTALRPTHAV LTPSLMRSLD PKDLPSLRAL MLGGEPTQST EIAAWSPYMQ LMIGYGPAEC
     GVTHLRYLSS SPNDPYSSVG FATGGASWLV VPGNTNKLVP IGAVGELLLE GPFVGPGYVH
     DVVKTQEAFI PAPQYVKELR RGPSRVYKTG DLMRYNVDGS LSFVGRIDSQ VKIRGQRLEL
     TDVEIHLQDC FPAPVQVVVE LIKPTGSPGA PYLAGFVHAP GDECAGATVS DAPRMPRCPA
     FYRPRQDFHK QAAGALARLW SRVPRFMVPS LLVNLAYLPQ TPSGKVDRKY LRNALAEMPE
     DELKEFRGGV QQKRGAANET ERKIQEFCAT ALQLPCEDIG LDDNFIQLGG DSISAMYVVA
     EARKHGVDLC VAEVLEHPRL SSLASDVASH YDPSKGQPSS TRIADVTPFA LVDGELRAVA
     TRELVSRGIV ARESQISDIL PVTESQRGFL EQWTPVFNCY LLSGLVDGRR LRNACHTVVA
     SRTILRTAFI KPSETTLQAV LQDIELPFRQ TITAEDLLTY CDSIWQGDSE PGSTLNTAPL
     RFILASRSAT EHAFIIRLSH AQYDGLSMPT LIGDLEQAYH GGKVEPLIDF ATYVHERALR
     DHAATFDFWR EYLLDSSITP LNLPSRAPSQ PSANRRGSAR ITTGQTIPMP ELPDGFTVAS
     LVKAATAWLF AQRGQRDDIV FGQTVTGRSM PVVGVEKMLG PCLNTVPLRV QLQAGWTVLD
     LLKHVQQQSS RTFAYDYVDF NDIVRSSTAW PHDSYLPCVI QHQNVAQSST LRLKDVECTP
     SGWAYFTPPS GMWILTTPQD SRLQVMVCSS RAVCDVEGAK SWVKDLCATI AAFASQPGEL
     LDKIKV