BEA1_GIBF5
ID BEA1_GIBF5 Reviewed; 3135 AA.
AC S0EN43;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Beauvericin nonribosomal cyclodepsipeptide synthetase BEA1 {ECO:0000303|PubMed:28125067};
DE Short=BEAS {ECO:0000250|UniProtKB:B6D9A8};
DE AltName: Full=Beauvericin biosynthesis cluster protein 1 {ECO:0000303|PubMed:27750383};
DE Includes:
DE RecName: Full=Nonribosomal peptide synthetase {ECO:0000250|UniProtKB:B6D9A8};
DE EC=6.1.2.- {ECO:0000250|UniProtKB:B6D9A8};
DE Includes:
DE RecName: Full=S-adenosyl-L-methionine-dependent N-methyltransferase {ECO:0000250|UniProtKB:B6D9A8};
DE EC=2.1.1.- {ECO:0000250|UniProtKB:B6D9A8};
GN Name=BEA1 {ECO:0000303|PubMed:27750383};
GN Synonyms=NRPS22 {ECO:0000303|PubMed:23825955}; ORFNames=FFUJ_09296;
OS Gibberella fujikuroi (strain CBS 195.34 / IMI 58289 / NRRL A-6831) (Bakanae
OS and foot rot disease fungus) (Fusarium fujikuroi).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium fujikuroi species complex.
OX NCBI_TaxID=1279085;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND IDENTIFICATION.
RC STRAIN=CBS 195.34 / IMI 58289 / NRRL A-6831;
RX PubMed=23825955; DOI=10.1371/journal.ppat.1003475;
RA Wiemann P., Sieber C.M.K., von Bargen K.W., Studt L., Niehaus E.-M.,
RA Espino J.J., Huss K., Michielse C.B., Albermann S., Wagner D.,
RA Bergner S.V., Connolly L.R., Fischer A., Reuter G., Kleigrewe K., Bald T.,
RA Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M., Brown D.W.,
RA Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U., Gueldener U.,
RA Tudzynski B.;
RT "Deciphering the cryptic genome: genome-wide analyses of the rice pathogen
RT Fusarium fujikuroi reveal complex regulation of secondary metabolism and
RT novel metabolites.";
RL PLoS Pathog. 9:E1003475-E1003475(2013).
RN [2]
RP FUNCTION.
RX PubMed=25543026; DOI=10.1016/j.fgb.2014.12.004;
RA Hansen F.T., Gardiner D.M., Lysoee E., Fuertes P.R., Tudzynski B.,
RA Wiemann P., Sondergaard T.E., Giese H., Brodersen D.E., Soerensen J.L.;
RT "An update to polyketide synthase and non-ribosomal synthetase genes and
RT nomenclature in Fusarium.";
RL Fungal Genet. Biol. 75:20-29(2015).
RN [3]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27750383; DOI=10.1111/1462-2920.13576;
RA Niehaus E.M., Studt L., von Bargen K.W., Kummer W., Humpf H.U., Reuter G.,
RA Tudzynski B.;
RT "Sound of silence: the beauvericin cluster in Fusarium fujikuroi is
RT controlled by cluster-specific and global regulators mediated by H3K27
RT modification.";
RL Environ. Microbiol. 18:4282-4302(2016).
RN [4]
RP FUNCTION, AND DOMAIN.
RX PubMed=28125067; DOI=10.3390/toxins9020045;
RA Liuzzi V.C., Mirabelli V., Cimmarusti M.T., Haidukowski M., Leslie J.F.,
RA Logrieco A.F., Caliandro R., Fanelli F., Mule G.;
RT "Enniatin and beauvericin biosynthesis in Fusarium species: production
RT profiles and structural determinant prediction.";
RL Toxins 9:0-0(2017).
CC -!- FUNCTION: Beauvericin nonribosomal cyclodepsipeptide synthetase; part
CC of the gene cluster that mediates the biosynthesis of beauvericin
CC (BEA), a non-ribosomal cyclic hexadepsipeptide that shows antibiotic,
CC antifungal, insecticidal, and cancer cell antiproliferative and
CC antihaptotactic activity (PubMed:25543026, PubMed:27750383,
CC PubMed:28125067). Ketoisovalerate reductase BEA2 catalyzes the NADPH-
CC specific reduction of ketoisovaleric acid to hydroxyisovalerate, a
CC precursor for beauvericin biosynthesis (By similarity). The
CC nonribosomal cyclodepsipeptide synthetase BEA1 then catalyzes the
CC formation of beauvericin via condensation and cyclization of 3
CC dipeptidol monomers, each composed of one unit of hydroxyisovalerate
CC and one unit of N-methyl-phenylalanine (By similarity).
CC {ECO:0000250|UniProtKB:B6D9A8, ECO:0000250|UniProtKB:G3GBU6,
CC ECO:0000269|PubMed:25543026, ECO:0000269|PubMed:27750383,
CC ECO:0000269|PubMed:28125067}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 (R)-2-hydroxy-3-methylbutyrate + 6 ATP + 3 L-phenylalanine +
CC 3 S-adenosyl-L-methionine = 6 AMP + beauvericin + 6 diphosphate + 6
CC H(+) + 3 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:62276,
CC ChEBI:CHEBI:3000, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57856, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:145660, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000250|UniProtKB:B6D9A8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62277;
CC Evidence={ECO:0000250|UniProtKB:B6D9A8};
CC -!- INDUCTION: Expression is highly repressed by the histone deacetylase
CC HDA1 and the beauvericin cluster-specific repressor BEA4
CC (PubMed:27750383). BEA biosynthesis is also repressed by the activity
CC of the H3K27 methyltransferase KMT6 (PubMed:27750383).
CC {ECO:0000269|PubMed:27750383}.
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 Beauvericin synthetase has the C1-A1-T1-C2-A2-MT-T2a-T2b-C3 domain
CC organization (PubMed:28125067). During catalysis, C3 and C2 take turns
CC to incorporate the two biosynthetic precursors into the growing
CC depsipeptide chain that swings between T1 and T2a/T2b with C3 cyclizing
CC the chain when it reaches the full length (By similarity).
CC {ECO:0000250|UniProtKB:B6D9A8, ECO:0000305|PubMed:28125067}.
CC -!- DISRUPTION PHENOTYPE: Leads to complete loss of beauvericin
CC biosynthesis (PubMed:27750383). {ECO:0000269|PubMed:27750383}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; HF679031; CCT73878.1; -; Genomic_DNA.
DR SMR; S0EN43; -.
DR STRING; 1279085.S0EN43; -.
DR EnsemblFungi; CCT73878; CCT73878; FFUJ_09296.
DR VEuPathDB; FungiDB:FFUJ_09296; -.
DR HOGENOM; CLU_000022_60_1_1; -.
DR Proteomes; UP000016800; Chromosome 9.
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: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; 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; 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; 1.
DR PROSITE; PS00455; AMP_BINDING; 2.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 3.
PE 2: Evidence at transcript level;
KW Isomerase; Ligase; Methyltransferase; Multifunctional enzyme;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..3135
FT /note="Beauvericin nonribosomal cyclodepsipeptide
FT synthetase BEA1"
FT /id="PRO_0000442145"
FT DOMAIN 1021..1097
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:28125067"
FT DOMAIN 2509..2583
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:28125067"
FT DOMAIN 2603..2677
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:28125067"
FT REGION 70..458
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28125067"
FT REGION 196..228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 499..896
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28125067"
FT REGION 1115..1542
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28125067"
FT REGION 1571..1974
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28125067"
FT REGION 2042..2182
FT /note="S-adenosyl-L-methionine-dependent N-
FT methyltransferase"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28125067"
FT REGION 2721..3127
FT /note="Condensation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28125067"
FT COMPBIAS 207..223
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1058
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2543
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2637
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3135 AA; 346309 MW; 82A8B2E7B86EF1FC CRC64;
MTSLNTKSGT PVVPLLLRSD DASHTDTLVE EVSCSLGLGR DRIENILPST AFQQDVIDCA
GSEKQRSIGH VAYEISNDID ISKLAAAWKD TINRTPALRT CAFTSSSGET YQVILKDSFV
FSWMFSTSAD QKDAVVKDEA AAAASGPRCN RFVLLDDPIQ KKILIWTFSH ALVDTSFQER
ILGRVLKAYT HGHDELSNRP YTPESSDPED DGLSLTPTDG SKTPETEGLH PATQYWKNYL
SDLNASAFPH LTSPLAVPYP NAKSEHRITF TASSSSTWPS VAVCRTALAI LLSRYTHSQE
ALFGVVTEQQ QLLVNGPTRT VVPFRVHCAS DQSLSDIIDV VNANDDAIRQ FADVGLRSIS
STGDDGVAAS GFQTVLLVTE GDNEQSSSTF EILQKTEESE LFMPCTNRAL LLHCQIASDG
LSIIARYDKS LIHSQQIARL LRQLGQLIQR LRGSPDKLPS AGELDISTSE DQAEIQSWNS
HPIPSQPTLI HKEMLKTASL SPSKVAICAW NGEWTYSELD NITSRLAALI KFSTPDQEHA
ILPIYFEKSK WVVASMLAVI KAGHAFALID PNDPPARVSQ VVGQTGATVA LTSKLYRSKV
QGIIERCIIV DDDLVQSLIC TCALKPDPTL AKVTPEDLAY VIFTSGSTGD PKGIMIEHRA
FSSCALQFGS ALGINSDTRA LQFGSHAFGA CLLEIMTTLI HGGCVCIPSD DDRMNNVPAF
VNRANVNWMM ATPSYMGTFQ PDDVPGLKTL VLVGEQMSPS VNAIWAPRVQ VLDGYGQSES
SSICFVGKIS SSGADPNNIG HSVGAHSWII DPSDPNRLVP IGAIGELVIE SPGIARDYII
PPPTENSPFF STVPPWYPFK ELPNGIKFYR TGDLARYASD GTVVCLGRMD SQVKIRGQRV
ELGAVETHLR QQLPDDMSIV VEAVKPSDLP TSTVLVAFLI TEATKSVRDA TILDLAATKA
MSVKLEHVLP RHSIPSCYIS MQHLPRTATG KVDRRKLRSI GRDMLAQQLQ GTSFRPSQLS
STTTSSQSKL EEVWRQCLGL EPGAANINST FFELGGHSIT AIKMVNMARS AGIDLKVSDI
YQNPTLAGLE AIVNGSAEPY AIIPTTTRDG PVEQSYSQGR LWFLDQLEVG ALWYLIPYAV
RMRGLVDIDA LSRALMALEQ RHETLRTTFE DCDGAGVQII HKILSKKLRV VDAPDSDYLD
LLKQEQTTPF DLTSEAGWRA LLIRLNDTDY ILSIVMHHIV SDGWSIDVLR HDLSQLYAAA
LQGRDLASAM NPLPIQYSDF AMWQKQEAQA LEHEKQLDYW KRQLADCSPA KLPTDFPRPA
LLSGEAGVVP VSIDRQLYQN LRDFCNENNT TSFAVLLAAF RAAHYRLTGV DDAVIGTPIA
NRNRWELENI IGFFVNTQCM RITVDDQDTF GSLVSQVRAT TTAAFENEDV PFERVVSTML
PGSRDLSRTP LAQLIFAVHS QKDLGRFELQ GLESEVVASK AYTRFDIEFH LFQEADGLRG
SCNFATDLFR PETVENMVSV FFQILRNGLE KPNIPISVLP LTDGIEELRR LDLLRIKKVE
YPRDASLVDI FRTQVAAYPD SLAVVDSSSR LTYTELDLQS DRLAARLRRQ GMPAETLVGV
LAPRSCEAIV AIIGILKANL AYLPFDVKSP SARLEDILSS IPGQTIVLLG SDVPVPELSI
PGLEFMRIVD AIECCDTNNL NGHAHVDNSN PTATSLAYVL FTSGSTGRPK GVMVEHRVIV
RLMTSNIIPD FPVQPRSAHM FNIAFDGATY EIFFTLLNGG TLVCIDYMTT LDVKALQDVF
LKEKINAACM APALLKLYLT DARDALRGLD FLMAAGDRFD GQDAIEAQSL VRGQCYNGYG
PTENGIMSTR YPIAVGDSFI NGVPIGRAVN NSGAYVTDLN QQLVGVGVMG ELVVTGDGLA
RGYFDPALNE NRFIHIEVDG QRVRAYRTGD RVRYRVGDGL IEFFGRMDTQ FKIRGNRIES
AEVEAAMLGH GSVRDAAVVV QKDDGEKADL VGFVVIDHDH SLEGDANDNQ VEGWQDHFET
EMYADIGDID PFTIGKDFKG WTSMYDGSEI DKVEMQEWLD DTIKTLRDGQ APGHVLEVGT
GSGMILFNLG DGLQSYRGLE PSKSAAAFTN SVIKSVPSLA SKAEVHVGTA QDVSQLTDLH
PDLVVINSVA QYFPSPEYLA QVADTLIHIP GVKRLFFGDM RTNATNKHFL AARAIRTLGD
TATKDFVRQK MAELEEREEE LLVEPAFFTA LQDRFPDLVH HVEILPKNMH ATNELSAYRY
AAVVHIRDSD SVPVHTIEKS TWVDFGASRM DRTSLLQFLR RSKGSPTVAI SNIPFAKTIF
ERQIVESLEA EDESKLDGAV WISAVGSDAD SRASLSVPDL RRLAEEAGFR LEVSAARQWS
QSGALDAVFH HLPSPSDTRR TLIKFPNDNH LRSSATLSNR PLQGLQRRRA TLQVRERLQS
LLPSYMIPSS IVVLDQMPLN PNGKVDRKEL ARQARIMPKQ QTALPVQAVP ISDIEAILCD
EATATFGMKV DISDDFFKLG GHSLLATKLI SRVEQRFNVR VTVKDVFDNP VFANLAVVIR
EGLASRTTLT NSQDKQGWSA RVAPRTETEI TLCDEASKLL GIEVGITDNF FDLGGHSMMA
TKLAMRLGRR LDTTIVVKDI FDYPVLFQLS KKLESTDSGT DNEEVQVDDY TPFELLSLEN
PQDFIQRQIC SQLNVSLESI QDMYQSTQMQ KSFLFSPGTG SPRPLTPFYI DFPVDSDPPT
LVNACHSLVQ HIDMFRTVFV LASEQLYQVV LKHLEVPIET IVTNQNVNTA TNDFLVEHAQ
DPIRLGESLI RIAILKQSSS VRVLLRLSHA LYDGLSLEPI VRNLHILFNG MSLLPPTQFR
RYMEYTANSQ EKGFEFWRDV IGDSPMTILS DAGNGAYHRE VSPSKALHLS KVVSVPSQAI
RSSIATQATV FNSACALVLS KESRSSDVVF GRIVSGRQGL PVNCQDIIGP CTNAVPVRAH
IGTDGNHHQM LRDMQDQYLR SLPFETLGFE EIKRNCTDWP DSTTNFACCV TYHNFEYHPE
SEVEQQRVEM GVLSKHVELR KDEPLYDLAI AGEVEPDGMS LKVTIIARAH LFEEERVQYF
LEEVCNTFQT LNFSL
