BENY_ASPTE
ID BENY_ASPTE Reviewed; 1110 AA.
AC P9WEU8;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 1.
DT 25-MAY-2022, entry version 5.
DE RecName: Full=Nonribisomal peptide synthetase benY {ECO:0000303|PubMed:28604695};
DE Short=NRPS benY {ECO:0000303|PubMed:28604695};
DE EC=6.3.1.- {ECO:0000305|PubMed:28604695};
DE AltName: Full=Benzomalvin biosynthesis cluster protein Y {ECO:0000303|PubMed:28604695};
GN Name=benY {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. BenY as the following
CC monomodular architecture: A-T-C. {ECO:0000305|PubMed:28604695}.
CC -!- DISRUPTION PHENOTYPE: Leads to the accumulation of the benzomalvin
CC dipeptide precursor anthranilate-N-methylphenylalanine (Anth-NmPhe).
CC {ECO:0000269|PubMed:28604695}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; KX449366; AQM58288.1; -; Genomic_DNA.
DR AlphaFoldDB; P9WEU8; -.
DR SMR; P9WEU8; -.
DR VEuPathDB; FungiDB:ATEG_06113; -.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
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; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Ligase; Phosphopantetheine; Phosphoprotein.
FT CHAIN 1..1110
FT /note="Nonribisomal peptide synthetase benY"
FT /id="PRO_0000450604"
FT DOMAIN 575..651
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:28604695"
FT REGION 47..443
FT /note="Adenylation"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT REGION 713..1025
FT /note="Condensation"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT MOD_RES 612
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1110 AA; 121887 MW; 02AFA3571C035AA2 CRC64;
MVSRKPALAV KELGCISDRD LRQLQRWNLR AATPATDQLM HEIIHQRALE FPEKIAVEAW
NGTFTYQQLD RLASHLASCL ASRGIGSNDF VPISFHKSRW AIVAMLAVNK SGAAFVPVDP
SLPAGRVIHI LRQTEARVAL ACDKRSTAMS EAGISVITVA DSMDCEHLDK PLWSPSFPGH
NAPAYCLFTS GSTGEPKGCV VGHAAFASIA SHSQSAYIHS GSRVLQFASL GFGMGLFEVF
CTLSTGATLC IPSDEDRMNC LAHAMTSMNV TWTILSPTTL STLSPADMDC LVTVVTGGEP
LSESQVTVWA PHVRLLQLYG LTECSGMFTV SDQIFSSDNP ERNIGYPISG RCWIADPQDH
HRLRAIGAVG ELLIDTPNLA QNYLHNPAKT AAAFISPPGW IEDQLPARQS RPAVLYKTGD
LARFNLDGSI CHLGRKDHQL KVRGQRVEPG ELEHHLRQLF PAVGDVVVDM ACPVEANGVA
SLTAFILQEN ECSDDLFVEP TEAFLECVQS VRQSLTKIVP AYMIPNLFLR LGTMPKTVSG
KKDRRRLRQE VGLLTWDRLR KYMTVDNARG RAAHTLETES EKILAQIWAD LLHLDVGTLG
PEDDILALGA DSITAMRAVA MARIRGLGLT VSDIFATPTL AEMAQSARVV PTTAVTTHRS
VSLVDDNVRE LCLSHLREQT SLLDSDEQTP LILPATGMQK FFLDRSSFDY FAYILDGDVD
FDRMQAACTT AVNQHSILRT VFVQNASGIF QVTLSSIPTA LYHITTARNV ADVSEKLWSP
NTSKTVTLDH PATRFMLVSN PDAQQHALIL RLSHSQYDGL SWPNLVGAIA ATYNGSALSP
CLQFSDYIRC RYQQDTTAGY NFWRRYLLGY TPTHMRDCTF EATTQSKAVS TDSDAVNVHH
TIPSPPDTPD GITMATLIKA AGALVLGQLT RRPDIVIGQT VHGRSSLPLA GIETILGPCL
NFVPIHVQIH PTWTAERFLH HVQDSHIQTT AYDYLELADI IEQSTSWAPG TSLGAIFHHQ
NIDTKMEISL QGMKNSKTIH HLTGSYIHQQ MRSEVWVYSM PVDQGLEISI RGSSHVISAP
QADELARKLG AFVQTLARHP EQALVNIMAP
