Q00869 · ESYN_FUSEQ
- ProteinEnniatin synthase
- GeneESYN1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids3131 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
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).
The bioactivity of enniatins can be linked to their inhibition of drug efflux pumps (PubMed:15707993).
Pathway
Antibiotic biosynthesis; enniatin biosynthesis.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Molecular Function | acid-amino acid ligase activity | |
Molecular Function | methyltransferase activity | |
Molecular Function | phosphopantetheine binding | |
Molecular Function | S-adenosylmethionine-dependent methyltransferase activity | |
Biological Process | amino acid activation for nonribosomal peptide biosynthetic process | |
Biological Process | enniatin biosynthetic process | |
Biological Process | methylation | |
Biological Process | nonribosomal peptide biosynthetic process | |
Biological Process | secondary metabolite biosynthetic process |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameEnniatin synthase
- Alternative names
Including 2 domains:
- Recommended nameN-methylcyclopeptide synthetase
- EC number
- Recommended nameS-adenosyl-L-methionine-dependent N-methyltransferase
- EC number
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Sordariomycetes > Hypocreomycetidae > Hypocreales > Nectriaceae > Fusarium > Fusarium incarnatum-equiseti species complex
Accessions
- Primary accessionQ00869
Subcellular Location
UniProt Annotation
GO Annotation
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 2106 | Reduces S-adenosyl-L-methionine binding. | ||||
Sequence: Y → A, S, or V | ||||||
Mutagenesis | 2106 | Has minimal effect on S-adenosyl-L-methionine binding. | ||||
Sequence: Y → F |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000180306 | 1-3131 | Enniatin synthase | |||
Sequence: MSLHTPSDGQQDPALASKTLCEQISRALGLGQDKIENIFPGTPFQRDVIDCAADDKQRAVGHAVFEIPKDIDAARLAAAWKETVLHTPALRTCTFTSKSGDVLQVVLRDSFVFSWMSGPSVDLKEAVVQDEAAAALAGPRCNRFVLLEDPDTKERQLIWTFSHALVDSTFQERILRRVLKAYKDANDEHPRQFETPDSSQATPEEDLQPNPSKMLKIPQAADMDRAVEFWKDHLSGLKCFCLPAFVLSSVYAHPDAKAEHRISYSSSAQQKMSSATICRTALAILLSRYTHSPEALFGIVTEQTPLLEEQLMLDGPTRTVVPIRVSCASEQSVSDIMSTIDSYDQTMRQFAHAGLRNIASAGDDESAACGFQTVLLVSDGDAQPASTWEILKKTEEPEGFIPCTNRALLLSCQMTSSGAHLTARYDQSIIDAEQMARLLRQLGHLIQNLQTSTDLPVEKVDMMTQEDWLEIERWNSDSIDAQDTLIHSEMLKWTSQSPNKAAVAAWDGEWTYAELDNVSSRLAQHINSIDLGKEHAIVPIYFEKSKWVVASMLAVLKAGHAFTLIDPSDPPARTAQVVQQTSATVALTSKLHRETVQSTVGRCIVVDEEFVKSLPQSSELSASVKAHDLAYVIFTSGSTGIPKGIMIEHRSFSSCAIKFGPALGITSDTRALQFGSHAFGACILEIMTTLIHGGCVCIPSDDDRMNNVLEFINRTNVQLGHATPSYMGTFQPEVVPGLKTLVLVGEQMSASVNEVWAPRVQLLNGYGQSESSSICCVAKISPGSSEPNNIGHAVGAHSWIVDPEDPNRLAPIGAVGELVIESAGIARDYIVAPTQDKSPFIKTAPTWYPAKQLPDGFKIYRTGDLACYASDGSIVCLGRMDSQVKIRGQRVELGAVETHLRQQMPDDMTIVVEAVKFSDSSSTTVLTAFLIGAGEKNSHILDQRATREINAKMEQVLPRHSIPAFYISMNNLPQTATGKVDRRKLRIMGSKILSQKTHSTPSQQSQAAISSGTDTYTKLESIWITSLDLEPGSANMSATFFEMGGNSIIAIKMVNMARSNGIELKVSDIYQNPTLAGLKAIVIGTSLPYSLIPKVTRQGPVSEQSYAQNRMWFLDQLSEGASWYLIPFAVRMRGPVDVDALTRALLALEQRHETLRTTFENQDGVGVQIIHDRLSKELQVIDALDGDEGGLKTLYKVETTTFDITSEAGWSSTLIRLGKDDHILSIVMHHIISDGWSIDVLRRELIQLYAAALQGKDPSSALTPLPIQYSDFAVWQKQEAQAAEHERQLQYWKKQLADSSPAKIPTDFPRPDLLSGDAGVVPVAIDGELYQKLRGFCNKHNSTAFSILLAAFRAAHYRLTAVDDAVIGIPIANRNRWELENMIGFFVNTQCMRIAVDETDTFESLVRQVRSTTTAAFAHEDVPFERVVSALQPGHRDLSRTPLAQIMFAVHSQKDLGRFELEGIQSEPIASKAYTRFDVEFHLFQQADGLKGSCNFATDLFKPETIQNVVSVFFQILRHGLDQPETCISVLPLTDGVEELRRLDLLEIKRTNYPRDSSVVDVFREQAAANPEVIAVTDSSSRLTYAELDNKSELLSRWLRRRNLTPETLVSVLAPRSCETIVAYVGILKANLAYLPLDVRSPVTRMKDILSSVSGNTIVLMGSGVEDPGFDLPQLELVRITDTFDETIEDVQDSPQPSATSLAYVVFTSGSTGKPKGVMIEHRAIVRLVKSDNFPGFPSPARMSNVFNPAFDGAIWEINWMLLNGGTVVCIDYLTTLDGKELAAVFAKERVNAAFFAPAMLKLYLVDAREALKNLDFLIVGGERFDTKEAVEAMPLVRGKIANIYGPTEAGIISTCYNIPKDEAYTNGVPIGGSIYNSGAYVMDPNQQLVGLGVMGELVVTGDGVGRGYTNPELNKNRFIDITIEGKTFKAYRTGDRMRARVGDGLLEFFGRMDNQFKIRGNRIEAGEVESAMLSLKNVLNAAIVVRGGGEDEGPLEMVGFIVADDKNDTTEEEETGNQVEGWQDHFESGMYSDISTAVDQSAIGNDFKGWTSMYDGKDIDKGEMQEWLDDAIHTLHNGQIPRDVLEIGTGSGMILFNLNPGLNSYVGLDPSKSAVEFVNRAVESSPKFAGKAKVHVGMATDVNKLGEVHPDLVVFNSVVQYFPTPEYLAEVIDGLIAIPSVKRIFLGDIRSYATNGHFLAARAIHTLGTNNNATKDRVRQKIQELEDREEEFLVEPAFFTTLKERRPDVVKHVEIIPKNMKATNELSAYRYTAVVHLRDETDEPVYHIEKDSWVDFEAKQMDKTALLDHLRLSKDAMSVAVSNITYAHTAFERRIVESLDEDSKDDTKGTLDGAAWLSAVRSEAENRASLTVPDILEIAKEAGFRVEVSAARQWSQSGALDAVFHHFPPSSTDRTLIQFPTDNELRSSLTLANRPLQKLQRRRAALQVREKLQTLVPSYMVPPNIVVLDTMPLNTNGKIDRKELTRRARTLPKQQTAAPVPDFPISDIEITLCEEATEVFGMKVEISDHFFQLGGHSLLATKLISRIQHRLHVRVTVKDVFDSPVFADLAVIIRQGLAMQNPVAEGQDKQGWSSRVAPRTEVEKMLCEEFAAGLGVPVGITDNFFDLGGHSLMATKLAVRIGRRLIRHHSQGHLRLPCAFQLAKKLESSHSKSYEESGDDIQMADYTAFQLLDLEDPQDFVQSQIRPQLDSCYGTIQDVYPSTQMQKAFLFDPTTGEPRGLVPFYIDFPSNADAETLTKAIGALVDKLDMFRTVFLEAAGDLYQVVVEHLNLPIETIETEKNVNTATGDYLDVHGKDPVRLGHPCIQFAILKTASSVRVLLRMSHALYDGLSFEYIVRGLHVLYSGRNLPPPTQFARYMQYAAHSREEGYPFWREVLQNAPMTVLHDTNNGMSEQEMPASKAVHLSEVVNVPAQAIRNSTNTQATVFNTACALVLAKESGSQDVVFGRIVSGRQGLPVVWQDIIGPCTNAVPVHARVDDGNPQRIIRDLRDQYLRTLPFESLGFEEIKRNCTDWPEELTNFSVCVTYHNFEYHPESEVDNQKVEMGVLAKYVELSENEPLYDLAIAGEVEADGVNLKVTVVAKARLYNEARIRHVLEEVCKTFNGLNEAL | ||||||
Modified residue | 1047 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S | ||||||
Modified residue | 2538 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S | ||||||
Modified residue | 2632 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S |
Post-translational modification
The N-terminus is blocked.
Keywords
- PTM
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 53-466 | Condensation 1 | ||||
Sequence: ADDKQRAVGHAVFEIPKDIDAARLAAAWKETVLHTPALRTCTFTSKSGDVLQVVLRDSFVFSWMSGPSVDLKEAVVQDEAAAALAGPRCNRFVLLEDPDTKERQLIWTFSHALVDSTFQERILRRVLKAYKDANDEHPRQFETPDSSQATPEEDLQPNPSKMLKIPQAADMDRAVEFWKDHLSGLKCFCLPAFVLSSVYAHPDAKAEHRISYSSSAQQKMSSATICRTALAILLSRYTHSPEALFGIVTEQTPLLEEQLMLDGPTRTVVPIRVSCASEQSVSDIMSTIDSYDQTMRQFAHAGLRNIASAGDDESAACGFQTVLLVSDGDAQPASTWEILKKTEEPEGFIPCTNRALLLSCQMTSSGAHLTARYDQSIIDAEQMARLLRQLGHLIQNLQTSTDLPVEKVDMMTQE | ||||||
Region | 186-212 | Disordered | ||||
Sequence: NDEHPRQFETPDSSQATPEEDLQPNPS | ||||||
Region | 495-887 | Adenylation 1 | ||||
Sequence: SQSPNKAAVAAWDGEWTYAELDNVSSRLAQHINSIDLGKEHAIVPIYFEKSKWVVASMLAVLKAGHAFTLIDPSDPPARTAQVVQQTSATVALTSKLHRETVQSTVGRCIVVDEEFVKSLPQSSELSASVKAHDLAYVIFTSGSTGIPKGIMIEHRSFSSCAIKFGPALGITSDTRALQFGSHAFGACILEIMTTLIHGGCVCIPSDDDRMNNVLEFINRTNVQLGHATPSYMGTFQPEVVPGLKTLVLVGEQMSASVNEVWAPRVQLLNGYGQSESSSICCVAKISPGSSEPNNIGHAVGAHSWIVDPEDPNRLAPIGAVGELVIESAGIARDYIVAPTQDKSPFIKTAPTWYPAKQLPDGFKIYRTGDLACYASDGSIVCLGRMDSQVKIR | ||||||
Domain | 1010-1086 | Carrier 1 | ||||
Sequence: SSGTDTYTKLESIWITSLDLEPGSANMSATFFEMGGNSIIAIKMVNMARSNGIELKVSDIYQNPTLAGLKAIVIGTS | ||||||
Region | 1105-1534 | Condensation 2 | ||||
Sequence: SYAQNRMWFLDQLSEGASWYLIPFAVRMRGPVDVDALTRALLALEQRHETLRTTFENQDGVGVQIIHDRLSKELQVIDALDGDEGGLKTLYKVETTTFDITSEAGWSSTLIRLGKDDHILSIVMHHIISDGWSIDVLRRELIQLYAAALQGKDPSSALTPLPIQYSDFAVWQKQEAQAAEHERQLQYWKKQLADSSPAKIPTDFPRPDLLSGDAGVVPVAIDGELYQKLRGFCNKHNSTAFSILLAAFRAAHYRLTAVDDAVIGIPIANRNRWELENMIGFFVNTQCMRIAVDETDTFESLVRQVRSTTTAAFAHEDVPFERVVSALQPGHRDLSRTPLAQIMFAVHSQKDLGRFELEGIQSEPIASKAYTRFDVEFHLFQQADGLKGSCNFATDLFKPETIQNVVSVFFQILRHGLDQPETCISVLPLT | ||||||
Region | 1563-1960 | Adenylation 2 | ||||
Sequence: FREQAAANPEVIAVTDSSSRLTYAELDNKSELLSRWLRRRNLTPETLVSVLAPRSCETIVAYVGILKANLAYLPLDVRSPVTRMKDILSSVSGNTIVLMGSGVEDPGFDLPQLELVRITDTFDETIEDVQDSPQPSATSLAYVVFTSGSTGKPKGVMIEHRAIVRLVKSDNFPGFPSPARMSNVFNPAFDGAIWEINWMLLNGGTVVCIDYLTTLDGKELAAVFAKERVNAAFFAPAMLKLYLVDAREALKNLDFLIVGGERFDTKEAVEAMPLVRGKIANIYGPTEAGIISTCYNIPKDEAYTNGVPIGGSIYNSGAYVMDPNQQLVGLGVMGELVVTGDGVGRGYTNPELNKNRFIDITIEGKTFKAYRTGDRMRARVGDGLLEFFGRMDNQFKIR | ||||||
Region | 2021-2177 | S-adenosyl-L-methionine-dependent N-methyltransferase | ||||
Sequence: EGWQDHFESGMYSDISTAVDQSAIGNDFKGWTSMYDGKDIDKGEMQEWLDDAIHTLHNGQIPRDVLEIGTGSGMILFNLNPGLNSYVGLDPSKSAVEFVNRAVESSPKFAGKAKVHVGMATDVNKLGEVHPDLVVFNSVVQYFPTPEYLAEVIDGLI | ||||||
Domain | 2504-2578 | Carrier 2 | ||||
Sequence: FPISDIEITLCEEATEVFGMKVEISDHFFQLGGHSLLATKLISRIQHRLHVRVTVKDVFDSPVFADLAVIIRQGL | ||||||
Domain | 2598-2671 | Carrier 3 | ||||
Sequence: APRTEVEKMLCEEFAAGLGVPVGITDNFFDLGGHSLMATKLAVRIGRRLIRHHSQGHLRLPCAFQLAKKLESSH | ||||||
Region | 2718-3123 | Condensation 3 | ||||
Sequence: QDVYPSTQMQKAFLFDPTTGEPRGLVPFYIDFPSNADAETLTKAIGALVDKLDMFRTVFLEAAGDLYQVVVEHLNLPIETIETEKNVNTATGDYLDVHGKDPVRLGHPCIQFAILKTASSVRVLLRMSHALYDGLSFEYIVRGLHVLYSGRNLPPPTQFARYMQYAAHSREEGYPFWREVLQNAPMTVLHDTNNGMSEQEMPASKAVHLSEVVNVPAQAIRNSTNTQATVFNTACALVLAKESGSQDVVFGRIVSGRQGLPVVWQDIIGPCTNAVPVHARVDDGNPQRIIRDLRDQYLRTLPFESLGFEEIKRNCTDWPEELTNFSVCVTYHNFEYHPESEVDNQKVEMGVLAKYVELSENEPLYDLAIAGEVEADGVNLKVTVVAKARLYNEARIRHVLEEVCKT |
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
Belongs to the ATP-dependent AMP-binding enzyme family.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length3,131
- Mass (Da)346,499
- Last updated2000-10-01 v2
- ChecksumAD7663E91FAB67C4
Keywords
- Technical term