Q00869 · ESYN_FUSEQ

Function

function

Nonribosomal peptide synthetase that synthesizes enniatin by coupling three D-hydroxycarboxylic acids and three L-amino acids via amide and ester bonds in an alternating fashion (PubMed:10887181, PubMed:7601090).
Whereas ESYN1 can accept different amino acids as precursors (L -valine, L-isoleucine or L-leucine), only one species of D-hydroxycarboxylic acid can be found in natural enniatin isolates (D-hydroxyisovaleric acid, D-Hiv) (PubMed:10887181, PubMed:7601090).
D-Hiv stems from L-valine deanimation by a valine aminotransferase to 2-keto-isovaleric acid (2-Kiv), which becomes subsequently reduced by a keto-isovaleric acid reductase (KivR) to D-Hiv (PubMed:10887181, PubMed:7601090).
Peptide bond formation and N-methylation of the amino acid occur before three enzyme-bound dipeptidols are condensed to a hexapeptidol (PubMed:10887181, PubMed:7601090).

Cofactor

pantetheine 4'-phosphate (UniProtKB | Rhea| CHEBI:47942 )

Note: Binds 6 phosphopantetheines covalently.

Activity regulation

The N-methylation activity is inhibited by S-adenosyl-L-homocysteine and sinefugin.

Biotechnology

Enniatins have antimicrobial, antiviral and cytotoxic properties (PubMed:16562855, PubMed:17326668, PubMed:9170286).
The bioactivity of enniatins can be linked to their inhibition of drug efflux pumps (PubMed:15707993).

Pathway

Antibiotic biosynthesis; enniatin biosynthesis.

GO annotations

AspectTerm
Cellular Componentcytoplasm
Molecular Functionacid-amino acid ligase activity
Molecular Functionmethyltransferase activity
Molecular Functionphosphopantetheine binding
Molecular FunctionS-adenosylmethionine-dependent methyltransferase activity
Biological Processamino acid activation for nonribosomal peptide biosynthetic process
Biological Processenniatin biosynthetic process
Biological Processmethylation
Biological Processnonribosomal peptide biosynthetic process
Biological Processsecondary metabolite biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Enniatin synthase
  • Alternative names
    • Nonribosomal cyclopeptide synthetase ESYN1

Including 2 domains:

  • Recommended name
    N-methylcyclopeptide synthetase
  • EC number
  • Recommended name
    S-adenosyl-L-methionine-dependent N-methyltransferase
  • EC number

Gene names

    • Name
      ESYN1

Organism names

  • Taxonomic identifier
  • Strain
    • Lambotte et Fautrey
  • Taxonomic lineage
    Eukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Sordariomycetes > Hypocreomycetidae > Hypocreales > Nectriaceae > Fusarium > Fusarium incarnatum-equiseti species complex

Accessions

  • Primary accession
    Q00869

Subcellular Location

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis2106Reduces S-adenosyl-L-methionine binding.
Mutagenesis2106Has minimal effect on S-adenosyl-L-methionine binding.

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00001803061-3131Enniatin synthase
Modified residue1047O-(pantetheine 4'-phosphoryl)serine
Modified residue2538O-(pantetheine 4'-phosphoryl)serine
Modified residue2632O-(pantetheine 4'-phosphoryl)serine

Post-translational modification

The N-terminus is blocked.

Keywords

Structure

3D structure databases

Family & Domains

Features

Showing features for region, domain.

TypeIDPosition(s)Description
Region53-466Condensation 1
Region186-212Disordered
Region495-887Adenylation 1
Domain1010-1086Carrier 1
Region1105-1534Condensation 2
Region1563-1960Adenylation 2
Region2021-2177S-adenosyl-L-methionine-dependent N-methyltransferase
Domain2504-2578Carrier 2
Domain2598-2671Carrier 3
Region2718-3123Condensation 3

Domain

NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, additional domains required for further modifications are also present (Probable). Enniatin synthetase has the C1-A1-T1-C2-A2-MT-T2a-T2b-C3 domain organization (Probable). The precursors D-hydroxycarboxylic acids and L-amino acids become activated at the A1 and the A2 domains. N-methylation of the amino acid takes place at the MT-domain. The building blocks are transferred from one module to another by means of T-domains and are ultimately stored at the waiting position T2b. Condensation of the building blocks and final cyclization and release from the enzyme is catalyzed by the C-domains (Probable).

Sequence similarities

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    3,131
  • Mass (Da)
    346,499
  • Last updated
    2000-10-01 v2
  • Checksum
    AD7663E91FAB67C4
MSLHTPSDGQQDPALASKTLCEQISRALGLGQDKIENIFPGTPFQRDVIDCAADDKQRAVGHAVFEIPKDIDAARLAAAWKETVLHTPALRTCTFTSKSGDVLQVVLRDSFVFSWMSGPSVDLKEAVVQDEAAAALAGPRCNRFVLLEDPDTKERQLIWTFSHALVDSTFQERILRRVLKAYKDANDEHPRQFETPDSSQATPEEDLQPNPSKMLKIPQAADMDRAVEFWKDHLSGLKCFCLPAFVLSSVYAHPDAKAEHRISYSSSAQQKMSSATICRTALAILLSRYTHSPEALFGIVTEQTPLLEEQLMLDGPTRTVVPIRVSCASEQSVSDIMSTIDSYDQTMRQFAHAGLRNIASAGDDESAACGFQTVLLVSDGDAQPASTWEILKKTEEPEGFIPCTNRALLLSCQMTSSGAHLTARYDQSIIDAEQMARLLRQLGHLIQNLQTSTDLPVEKVDMMTQEDWLEIERWNSDSIDAQDTLIHSEMLKWTSQSPNKAAVAAWDGEWTYAELDNVSSRLAQHINSIDLGKEHAIVPIYFEKSKWVVASMLAVLKAGHAFTLIDPSDPPARTAQVVQQTSATVALTSKLHRETVQSTVGRCIVVDEEFVKSLPQSSELSASVKAHDLAYVIFTSGSTGIPKGIMIEHRSFSSCAIKFGPALGITSDTRALQFGSHAFGACILEIMTTLIHGGCVCIPSDDDRMNNVLEFINRTNVQLGHATPSYMGTFQPEVVPGLKTLVLVGEQMSASVNEVWAPRVQLLNGYGQSESSSICCVAKISPGSSEPNNIGHAVGAHSWIVDPEDPNRLAPIGAVGELVIESAGIARDYIVAPTQDKSPFIKTAPTWYPAKQLPDGFKIYRTGDLACYASDGSIVCLGRMDSQVKIRGQRVELGAVETHLRQQMPDDMTIVVEAVKFSDSSSTTVLTAFLIGAGEKNSHILDQRATREINAKMEQVLPRHSIPAFYISMNNLPQTATGKVDRRKLRIMGSKILSQKTHSTPSQQSQAAISSGTDTYTKLESIWITSLDLEPGSANMSATFFEMGGNSIIAIKMVNMARSNGIELKVSDIYQNPTLAGLKAIVIGTSLPYSLIPKVTRQGPVSEQSYAQNRMWFLDQLSEGASWYLIPFAVRMRGPVDVDALTRALLALEQRHETLRTTFENQDGVGVQIIHDRLSKELQVIDALDGDEGGLKTLYKVETTTFDITSEAGWSSTLIRLGKDDHILSIVMHHIISDGWSIDVLRRELIQLYAAALQGKDPSSALTPLPIQYSDFAVWQKQEAQAAEHERQLQYWKKQLADSSPAKIPTDFPRPDLLSGDAGVVPVAIDGELYQKLRGFCNKHNSTAFSILLAAFRAAHYRLTAVDDAVIGIPIANRNRWELENMIGFFVNTQCMRIAVDETDTFESLVRQVRSTTTAAFAHEDVPFERVVSALQPGHRDLSRTPLAQIMFAVHSQKDLGRFELEGIQSEPIASKAYTRFDVEFHLFQQADGLKGSCNFATDLFKPETIQNVVSVFFQILRHGLDQPETCISVLPLTDGVEELRRLDLLEIKRTNYPRDSSVVDVFREQAAANPEVIAVTDSSSRLTYAELDNKSELLSRWLRRRNLTPETLVSVLAPRSCETIVAYVGILKANLAYLPLDVRSPVTRMKDILSSVSGNTIVLMGSGVEDPGFDLPQLELVRITDTFDETIEDVQDSPQPSATSLAYVVFTSGSTGKPKGVMIEHRAIVRLVKSDNFPGFPSPARMSNVFNPAFDGAIWEINWMLLNGGTVVCIDYLTTLDGKELAAVFAKERVNAAFFAPAMLKLYLVDAREALKNLDFLIVGGERFDTKEAVEAMPLVRGKIANIYGPTEAGIISTCYNIPKDEAYTNGVPIGGSIYNSGAYVMDPNQQLVGLGVMGELVVTGDGVGRGYTNPELNKNRFIDITIEGKTFKAYRTGDRMRARVGDGLLEFFGRMDNQFKIRGNRIEAGEVESAMLSLKNVLNAAIVVRGGGEDEGPLEMVGFIVADDKNDTTEEEETGNQVEGWQDHFESGMYSDISTAVDQSAIGNDFKGWTSMYDGKDIDKGEMQEWLDDAIHTLHNGQIPRDVLEIGTGSGMILFNLNPGLNSYVGLDPSKSAVEFVNRAVESSPKFAGKAKVHVGMATDVNKLGEVHPDLVVFNSVVQYFPTPEYLAEVIDGLIAIPSVKRIFLGDIRSYATNGHFLAARAIHTLGTNNNATKDRVRQKIQELEDREEEFLVEPAFFTTLKERRPDVVKHVEIIPKNMKATNELSAYRYTAVVHLRDETDEPVYHIEKDSWVDFEAKQMDKTALLDHLRLSKDAMSVAVSNITYAHTAFERRIVESLDEDSKDDTKGTLDGAAWLSAVRSEAENRASLTVPDILEIAKEAGFRVEVSAARQWSQSGALDAVFHHFPPSSTDRTLIQFPTDNELRSSLTLANRPLQKLQRRRAALQVREKLQTLVPSYMVPPNIVVLDTMPLNTNGKIDRKELTRRARTLPKQQTAAPVPDFPISDIEITLCEEATEVFGMKVEISDHFFQLGGHSLLATKLISRIQHRLHVRVTVKDVFDSPVFADLAVIIRQGLAMQNPVAEGQDKQGWSSRVAPRTEVEKMLCEEFAAGLGVPVGITDNFFDLGGHSLMATKLAVRIGRRLIRHHSQGHLRLPCAFQLAKKLESSHSKSYEESGDDIQMADYTAFQLLDLEDPQDFVQSQIRPQLDSCYGTIQDVYPSTQMQKAFLFDPTTGEPRGLVPFYIDFPSNADAETLTKAIGALVDKLDMFRTVFLEAAGDLYQVVVEHLNLPIETIETEKNVNTATGDYLDVHGKDPVRLGHPCIQFAILKTASSVRVLLRMSHALYDGLSFEYIVRGLHVLYSGRNLPPPTQFARYMQYAAHSREEGYPFWREVLQNAPMTVLHDTNNGMSEQEMPASKAVHLSEVVNVPAQAIRNSTNTQATVFNTACALVLAKESGSQDVVFGRIVSGRQGLPVVWQDIIGPCTNAVPVHARVDDGNPQRIIRDLRDQYLRTLPFESLGFEEIKRNCTDWPEELTNFSVCVTYHNFEYHPESEVDNQKVEMGVLAKYVELSENEPLYDLAIAGEVEADGVNLKVTVVAKARLYNEARIRHVLEEVCKTFNGLNEAL

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
Z18755
EMBL· GenBank· DDBJ
CAA79245.2
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

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