ESYN_FUSOX
ID ESYN_FUSOX Reviewed; 3132 AA.
AC A0A0A1EA36;
DT 07-NOV-2018, integrated into UniProtKB/Swiss-Prot.
DT 04-FEB-2015, sequence version 1.
DT 03-AUG-2022, entry version 31.
DE RecName: Full=Enniatin synthetase {ECO:0000303|PubMed:25398283};
DE AltName: Full=Nonribosomal cyclopeptide synthetase ESYN1 {ECO:0000303|PubMed:25398283};
DE Includes:
DE RecName: Full=Nonribosomal peptide synthetase {ECO:0000305|PubMed:28955446};
DE EC=6.1.2.- {ECO:0000305|PubMed:28955446};
DE Includes:
DE RecName: Full=S-adenosyl-L-methionine-dependent N-methyltransferase {ECO:0000305|PubMed:28955446};
DE EC=2.1.1.- {ECO:0000305|PubMed:28955446};
GN Name=ESYN1 {ECO:0000303|PubMed:28955446};
GN Synonyms=ESYN {ECO:0000303|PubMed:25398283};
OS Fusarium oxysporum (Fusarium vascular wilt).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium oxysporum species complex.
OX NCBI_TaxID=5507;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DOMAIN, AND PATHWAY.
RC STRAIN=ETH 1536;
RX PubMed=25398283; DOI=10.1007/s00253-014-6199-0;
RA Zobel S., Kumpfmueller J., Suessmuth R.D., Schweder T.;
RT "Bacillus subtilis as heterologous host for the secretory production of the
RT non-ribosomal cyclodepsipeptide enniatin.";
RL Appl. Microbiol. Biotechnol. 99:681-691(2015).
RN [2]
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 [3]
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 [4]
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 [5]
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).
RN [6]
RP FUNCTION, DOMAIN, AND PATHWAY.
RX PubMed=28955446; DOI=10.1186/s40694-014-0004-9;
RA Richter L., Wanka F., Boecker S., Storm D., Kurt T., Vural O.,
RA Suessmuth R., Meyer V.;
RT "Engineering of Aspergillus niger for the production of secondary
RT metabolites.";
RL Fungal Biol. Biotechnol. 1:4-4(2014).
RN [7]
RP FUNCTION, AND PATHWAY.
RX PubMed=28946884; DOI=10.1186/s12934-017-0780-z;
RA Schuetze T., Meyer V.;
RT "Polycistronic gene expression in Aspergillus niger.";
RL Microb. Cell Fact. 16:162-162(2017).
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 (PubMed:25398283,
CC PubMed:28955446, PubMed:28946884). Whereas ESYN1 can accept different
CC amino acids as precursors (L-valine, L-isoleucine or L-leucine), only
CC one species of D-hydroxycarboxylic acid can be found in natural
CC enniatin isolates (D-hydroxyisovaleric acid, D-Hiv) (PubMed:25398283,
CC PubMed:28955446). D-Hiv stems from L-valine deanimation by a valine
CC aminotransferase to 2-keto-isovaleric acid (2-Kiv), which becomes
CC subsequently reduced by a keto-isovaleric acid reductase (KivR) to D-
CC Hiv (PubMed:25398283, PubMed:28955446, PubMed:28946884).
CC {ECO:0000269|PubMed:25398283, ECO:0000269|PubMed:28946884,
CC ECO:0000269|PubMed:28955446}.
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:0000269|PubMed:25398283, ECO:0000269|PubMed:28946884,
CC ECO:0000269|PubMed:28955446}.
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 (Probable). 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 (Probable). {ECO:0000305,
CC ECO:0000305|PubMed:28955446}.
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 NRP synthetase family. {ECO:0000305}.
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DR EMBL; KP000028; AIY26286.1; -; Genomic_DNA.
DR SMR; A0A0A1EA36; -.
DR VEuPathDB; FungiDB:FOC1_g10003336; -.
DR VEuPathDB; FungiDB:FOC4_g10007672; -.
DR VEuPathDB; FungiDB:FOIG_15793; -.
DR VEuPathDB; FungiDB:FOMG_14063; -.
DR VEuPathDB; FungiDB:FOXG_11847; -.
DR VEuPathDB; FungiDB:FOZG_11978; -.
DR VEuPathDB; FungiDB:HZS61_016870; -.
DR UniPathway; UPA00234; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
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; -; 3.
DR Gene3D; 3.30.300.30; -; 3.
DR Gene3D; 3.30.559.10; -; 3.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
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; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR013216; Methyltransf_11.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF00501; AMP-binding; 2.
DR Pfam; PF00668; Condensation; 3.
DR Pfam; PF08241; Methyltransf_11; 1.
DR Pfam; PF00550; PP-binding; 3.
DR SMART; SM00823; PKS_PP; 3.
DR SUPFAM; SSF47336; SSF47336; 3.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR PROSITE; PS00455; AMP_BINDING; 2.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 3.
PE 1: Evidence at protein level;
KW Isomerase; Ligase; Methyltransferase; Multifunctional enzyme;
KW Phosphopantetheine; Phosphoprotein; Repeat; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..3132
FT /note="Enniatin synthetase"
FT /id="PRO_0000445602"
FT DOMAIN 1010..1086
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:28955446"
FT DOMAIN 2504..2578
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:28955446"
FT DOMAIN 2598..2672
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:28955446"
FT REGION 53..466
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28955446"
FT REGION 186..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 495..887
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28955446"
FT REGION 994..1013
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1105..1534
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28955446"
FT REGION 1563..1960
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28955446"
FT REGION 2021..2177
FT /note="S-adenosyl-L-methionine-dependent N-
FT methyltransferase"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28955446"
FT REGION 2719..3124
FT /note="Condensation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28955446"
FT MOD_RES 1047
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2538
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2632
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3132 AA; 346593 MW; F6403F1314FA2360 CRC64;
MSLHTPSDGQ QDPALASKTL CEQISRALGL GQDKIENIFP GTPFQRDVID CAADDKQRAV
GHAVFEIPKD IDAARLAAAW KETVLHTPAL RTCTFTSKSG DVLQVVLRDS FVFSWMSGPS
VDLKEAVVQD EAAAALAGPR CNRFVLLEDP DTKERQLIWT FSHALVDSTF QERILRRVLK
AYKDANDEHP RQFETPDSSQ ATPEEDLQPN PSKMLKIPQA ADMDRAVEFW KDHLSGLNAS
AFPHLSSHLS MPHPDAKAEH RISYSSSAQQ KMSSATICRT ALAILLSRYT HSPEALFGIV
TEQTPLLEEQ LMLDGPTRTV VPIRVSCASE QSVSDIMSTI DSYDQTMRQF AHAGLRNIAS
AGDDESAACG FQTVLLVSDG DAQPASTWEI LKKTEEPEGF IPCTNRALLL SCQMTSSGAH
LTARYDQSII DAEQMARLLR QLGHLIQNLQ TSTDLPVEKV DMMTQEDWLE IERWNSDSID
AQDTLIHSEM LKWTSQSPNK AAVAAWDGEW TYAELDNVSS RLAQHINSID LGKEHAIVPI
YFEKSKWVVA SMLAVLKAGH AFTLIDPSDP PARTAQVVQQ TSATVALTSK LHRETVQSTV
GRCIVVDEEF VKSLPQSSEL SASVKAHDLA YVIFTSGSTG IPKGIMIEHR SFSSCAIKFG
PALGITSDTR ALQFGSHAFG ACILEIMTTL IHGGCVCIPS DDDRMNNVLE FINRTNVNWV
MATPSYMGTF QPEVVPGLKT LVLVGEQMSA SVNEVWAPRV QLLNGYGQSE SSSICCVAKI
SPGSSEPNNI GHAVGAHSWI VDPEDPNRLA PIGAVGELVI ESAGIARDYI VAPTQDKSPF
IKTAPTWYPA KQLPDGFKIY RTGDLACYAS DGSIVCLGRM DSQVKIRGQR VELGAVETHL
RQQMPDDMTI VVEAVKFSDS SSTTVLTAFL IGAGEKNSHI LDQRATREIN AKMEQVLPRH
SIPAFYISMN NLPQTATGKV DRRKLRIMGS KILSQKTHST PSQQSQAAIS SGTDTETKLE
SIWITSLDLE PGSANMSATF FEMGGNSIIA IKMVNMARSN GIELKVSDIY QNPTLAGLKA
IVIGTSLPYS LIPKVTRQGP VSEQSYAQNR MWFLDQLSEG ASWYLIPFAV RMRGPVDVDA
LTRALLALEQ RHETLRTTFE NQDGVGVQII HDRLSKELQV IDALDGDEGG LKTLYKVETT
TFDITSEAGW SSTLIRLGKD DHILSIVMHH IISDGWSIDV LRRELIQLYA AALQGKDPSS
ALTPLPIQYS DFAVWQKQEA QAAEHERQLQ YWKKQLADSS PAKIPTDFPR PDLLSGDAGV
VPVAIDGELY QKLRGFCNKH NSTAFSILLA AFRAAHYRLT AVDDAVIGIP IANRNRWELE
NMIGFFVNTQ CMRIAVDETD TFESLVRQVR STTTAAFAHE DVPFERVVSA LQPGHRDLSR
TPLAQIMFAV HSQKDLGRFE LEGIQSEPIA SKAYTRFDVE FHLFQQADGL KGSCNFATDL
FKPETIQNVV SVFFQILRHG LDQPETCISV LPLTDGVEEL RRLDLLEIKR TNYPRDSSVV
DVFREQAAAN PEVIAVTDSS SRLTYAELDN KSELLSRWLR RRNLTPETLV SVLAPRSCET
IVAYVGILKA NLAYLPLDVR SPVTRMKDIL SSVSGNTIVL MGSGVEDPGF DLPQLELVRI
TDTFDETIED VQDSPQPSAT SLAYVVFTSG STGKPKGVMI EHRAIVRLVK SDNFPGFPSP
ARMSNVFNPA FDGAIWEINW MLLNGGTVVC IDYLTTLDGK ELAAVFAKER VNAAFFAPAM
LKLYLVDARE ALKNLDFLIV GGERFDTKEA VEAMPLVRGK IANIYGPTEA GIISTCYNIP
KDEAYTNGVP IGGSIYNSGA YVMDPNQQLV GLGVMGELVV TGDGVGRGYT NPELNKNRFI
DITIEGKTFK AYRTGDRMRA RVGDGLLEFF GRMDNQFKIR GNRIEAGEVE SAMLSLKNVL
NAAIVVRGGG EDEGPLEMVG FIVADDKNDT TEEEETGNQV EGWQDHFESG MYSDISTAVD
QSAIGNDFKG WTSMYDGKDI DKGEMQEWLD DAIHTLHNGQ IPRDVLEIGT GSGMILFNLN
PGLNSYVGLD PSKSAVEFVN RAVESSPKFA GKAKVHVGMA TDVNKLGEVH PDLVVFNSVV
QYFPTPEYLA EVIDGLIAIP SVKRIFLGDI RSYATNGHFL AARAIHTLGT NNNATKDRVR
QKIQELEDRE EEFLVEPAFF TTLKERRPDV VKHVEIIPKN MKATNELSAY RYTAVVHLRD
ETDEPVYHIE KDSWVDFEAK QMDKTALLDH LRLSKDAMSV AVSNITYAHT AFERRIVESL
DEDSKDDTKG TLDGAAWLSA VRSEAENRAS LTVPDILEIA KEAGFRVEVS AARQWSQSGA
LDAVFHHFPP SSTDRTLIQF PTDNELRSSL TLANRPLQKL QRRRAALQVR EKLQTLVPSY
MVPPNIVVLD TMPLNTNGKI DRKELTRRAR TLPKQQTAAP VPDFPISDIE ITLCEEATEV
FGMKVEISDH FFQLGGHSLL ATKLISRIQH RLHVRVTVKD VFDSPVFADL AVIIRQGLAM
QNPVAEGQDK QGWSSRVAPR TEVEKMLCEE FAAGLGVPVG ITDNFFDLGG HSLMATKLAV
RIGRRLDTAI TVKDIFDYPV LFQLAKKLES SHSKSYEESG DDIQMADYTA FQLLDLEDPQ
DFVQSQIRPQ LDSCYGTIQD VYPSTQMQKA FLFDPTTGEP RGLVPFYIDF PSNADAETLT
KAIGALVDKL DMFRTVFLEA AGDLYQVVVE HLNLPIETIE TEKNVNTATG DYLDVHGKDP
VRLGHPCIQF AILKTASSVR VLLRMSHALY DGLSFEYIVR GLHVLYSGRN LPPPTQFARY
MQYAAHSREE GYPFWREVLQ NAPMTVLHDT NNGMSEQEMP ASKAVHLSEV VNVPAQAIRN
STNTQATVFN TACALVLAKE SGSQDVVFGR IVSGRQGLPV VWQDIIGPCT NAVPVHARVD
DGNPQRIIRD LRDQYLRTLP FESLGFEEIK RNCTDWPEEL TNFSVCVTYH NFEYHPESEV
DNQKVEMGVL AKYVELSENE PLYDLAIAGE VEADGVNLKV TVVAKARLYN EARIRHVLEE
VCKTFNGLNE AL
