ESYN_GIBPU
ID ESYN_GIBPU Reviewed; 983 AA.
AC Q00868;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 2.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Enniatin synthase {ECO:0000250|UniProtKB:Q00869};
DE Includes:
DE RecName: Full=N-methylcyclopeptide synthetase {ECO:0000250|UniProtKB:Q00869};
DE EC=6.3.2.- {ECO:0000250|UniProtKB:Q00869};
DE Includes:
DE RecName: Full=S-adenosyl-L-methionine-dependent N-methyltransferase {ECO:0000303|PubMed:8673002};
DE EC=2.1.1.- {ECO:0000305|PubMed:8673002};
DE Flags: Fragment;
OS Gibberella pulicaris.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX NCBI_TaxID=5128;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BBA 63933;
RA Burmester J.;
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 334-840.
RC STRAIN=BBA 63933;
RX PubMed=8673002;
RA Burmester J., Haese A., Zocher R.;
RT "Highly conserved N-methyltransferases as an integral part of peptide
RT synthetases.";
RL Biochem. Mol. Biol. Int. 37:201-207(1995).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=9170286; DOI=10.1021/np970031g;
RA McKee T.C., Bokesch H.R., McCormick J.L., Rashid M.A., Spielvogel D.,
RA Gustafson K.R., Alavanja M.M., Cardelline J.H. II, Boyd M.R.;
RT "Isolation and characterization of new anti-HIV and cytotoxic leads from
RT plants, marine, and microbial organisms.";
RL J. Nat. Prod. 60:431-438(1997).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=15707993; DOI=10.1016/j.bbrc.2005.01.075;
RA Hiraga K., Yamamoto S., Fukuda H., Hamanaka N., Oda K.;
RT "Enniatin has a new function as an inhibitor of Pdr5p, one of the ABC
RT transporters in Saccharomyces cerevisiae.";
RL Biochem. Biophys. Res. Commun. 328:1119-1125(2005).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=16562855; DOI=10.1021/np050487v;
RA Jayasinghe L., Abbas H.K., Jacob M.R., Herath W.H., Nanayakkara N.P.;
RT "N-Methyl-4-hydroxy-2-pyridinone analogues from Fusarium oxysporum.";
RL J. Nat. Prod. 69:439-442(2006).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=17326668; DOI=10.1021/tx600259t;
RA Dornetshuber R., Heffeter P., Kamyar M.R., Peterbauer T., Berger W.,
RA Lemmens-Gruber R.;
RT "Enniatin exerts p53-dependent cytostatic and p53-independent cytotoxic
RT activities against human cancer cells.";
RL Chem. Res. Toxicol. 20:465-473(2007).
CC -!- FUNCTION: Nonribosomal peptide synthetase that synthesizes enniatin by
CC coupling three D-hydroxycarboxylic acids and three L-amino acids via
CC amide and ester bonds in an alternating fashion (By similarity).
CC Whereas ESYN1 can accept different amino acids as precursors (L
CC -valine, L-isoleucine or L-leucine), only one species of D-
CC hydroxycarboxylic acid can be found in natural enniatin isolates (D-
CC hydroxyisovaleric acid, D-Hiv) (By similarity). D-Hiv stems from L-
CC valine deanimation by a valine aminotransferase to 2-keto-isovaleric
CC acid (2-Kiv), which becomes subsequently reduced by a keto-isovaleric
CC acid reductase (KivR) to D-Hiv (By similarity). Peptide bond formation
CC and N-methylation of the amino acid occur before three enzyme-bound
CC dipeptidols are condensed to a hexapeptidol (By similarity).
CC {ECO:0000250|UniProtKB:Q00869}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000305};
CC Note=Binds 6 phosphopantetheines covalently. {ECO:0000305};
CC -!- PATHWAY: Antibiotic biosynthesis; enniatin biosynthesis.
CC {ECO:0000250|UniProtKB:Q00869}.
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 additional domains required for further modifications are also present
CC (Probable). Enniatin synthetase has the C1-A1-T1-C2-A2-MT-T2a-T2b-C3
CC domain organization (By similarity). The precursors D-hydroxycarboxylic
CC acids and L-amino acids become activated at the A1 and the A2 domains.
CC N-methylation of the amino acid takes place at the MT-domain. The
CC building blocks are transferred from one module to another by means of
CC T-domains and are ultimately stored at the waiting position T2b.
CC Condensation of the building blocks and final cyclization and release
CC from the enzyme is catalyzed by the C-domains (By similarity).
CC {ECO:0000250|UniProtKB:Q00869, ECO:0000255, ECO:0000305}.
CC -!- BIOTECHNOLOGY: Enniatins have antimicrobial, antiviral and cytotoxic
CC properties (PubMed:9170286, PubMed:16562855, PubMed:17326668). The
CC bioactivity of enniatins can be linked to their inhibition of drug
CC efflux pumps (PubMed:15707993). {ECO:0000269|PubMed:15707993,
CC ECO:0000269|PubMed:16562855, ECO:0000269|PubMed:17326668,
CC ECO:0000269|PubMed:9170286}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {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; Z48743; CAA88634.2; -; Genomic_DNA.
DR PIR; S53111; S53111.
DR AlphaFoldDB; Q00868; -.
DR SMR; Q00868; -.
DR UniPathway; UPA00234; -.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0046585; P:enniatin biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 2.
DR Gene3D; 3.40.50.150; -; 1.
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; IPR041698; Methyltransf_25.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13649; Methyltransf_25; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Ligase; Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Repeat; Transferase.
FT CHAIN <1..>983
FT /note="Enniatin synthase"
FT /id="PRO_0000180307"
FT DOMAIN 881..955
FT /note="Carrier"
FT /evidence="ECO:0000250|UniProtKB:A0A0A1EA36,
FT ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 5..338
FT /note="Adenylation"
FT /evidence="ECO:0000250|UniProtKB:A0A0A1EA36, ECO:0000255"
FT REGION 398..554
FT /note="S-adenosyl-L-methionine-dependent N-
FT methyltransferase"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:8673002"
FT REGION 961..983
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 915
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT NON_TER 1
FT NON_TER 983
SQ SEQUENCE 983 AA; 109070 MW; 1784588502EE7CBD CRC64;
EFNTGILKAS LAYLPLDVRS PVARMKDILS SVSGNTIVIM GTGVEDPGFG LPQLELVRIT
DTFDETIEDV QNMSRPSATS LAYVVFTSGS TGKPKGVMIE HRAIVRLVKS DNFPNFPSPA
RMSHVFNAAF DGASWEMFWM LLNGGTVVCI DYLATLDGKE LAAVFAKERV NCAFLAPAML
KLYLTDAREA LKNLDFLAVG GEKFDPRDAA EAMTLVRGNI ANVYGPTEAG MISTCYTIPK
DEAFTNGVQL GRSIYNSGAY VMDPNQQLAG LGVMGEHLFG DGVGRGYTKP ELNKNRFIDV
TIEGKTVRAY GTGDRMRARV GDGLLEFFGR LDNQFKMRGQ RIEAGEVESA MLSHKRVLNA
AIVLRGGQEE GEQLEMVGFI VADDDDNTEE EETGNQVEGW QDHFESGMYS DISTAVDQSA
IGNDFKGWTS MYDGNDIDKG EMQEWLDDAI HTLHNGQVPH HVLEIGTGSG MILFNLNPGL
QSYVGLDPSK SAVEFVNRAI ESSPKFAGKA KVHVGMATDV NKLGELHPDL VVFNSVVQYF
PTPEYLTEVI DGLIAIPSVK RIFLGDIRSY ATNRHFLAAR AIHTLGTNNN ATKDRVRQKV
QELEDREEES LVEPAFFTTL KERRPDVVKH VEVIPKNMKA TNELIAYRYT AVVHLRDETD
EPVYPTEKDS WIDFEEKQMD KKALLDHLRL SKDAMSVAVS NITYAHTAFE RRIVESLDED
SKDDAKDTLG GAAWLSAVRS ETESRASLTV PELFEIANEA GFRVEVSAAR QWSQNGALDA
VFHHFPSSNT DRTLIQFPTD NQLRSSLTLA NRPLQKLQRR RAALQVRESL QSLVPTYMVP
PNIVVLDTMP LNTNGKIDRK ELTRRARTLP KQQTAAPVPD FPISDIEITL CEEATEVFGM
KVEISDHFFQ LGGHSLLATK LISRIQHRLH VRVTVKDVFD SPVFADLAVI IRQGLAMQNP
VAEGQDKQGW SSRVAPRTEV EKM
