BEA1_BEABA
ID BEA1_BEABA Reviewed; 3189 AA.
AC B6D9A8;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 1.
DT 03-AUG-2022, entry version 58.
DE RecName: Full=Beauvericin nonribosomal cyclodepsipeptide synthetase {ECO:0000303|PubMed:18804027};
DE Short=BEAS {ECO:0000303|PubMed:18804027};
DE Includes:
DE RecName: Full=Nonribosomal peptide synthetase {ECO:0000303|PubMed:18804027};
DE EC=6.1.2.- {ECO:0000269|PubMed:18804027, ECO:0000269|PubMed:28534477};
DE Includes:
DE RecName: Full=S-adenosyl-L-methionine-dependent N-methyltransferase {ECO:0000303|PubMed:18804027};
DE EC=2.1.1.- {ECO:0000269|PubMed:18804027};
GN Name=Beas;
OS Beauveria bassiana (White muscardine disease fungus) (Tritirachium
OS shiotae).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Cordycipitaceae; Beauveria.
OX NCBI_TaxID=176275;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DOMAIN, FUNCTION, CATALYTIC ACTIVITY,
RP AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 7159;
RX PubMed=18804027; DOI=10.1016/j.chembiol.2008.07.011;
RA Xu Y., Orozco R., Kithsiri Wijeratne E.M., Leslie Gunatilaka A.A.,
RA Stock S.P., Molnar I.;
RT "Biosynthesis of the cyclooligomer depsipeptide beauvericin, a virulence
RT factor of the entomopathogenic fungus Beauveria bassiana.";
RL Chem. Biol. 15:898-907(2008).
RN [2]
RP FUNCTION.
RX PubMed=19105175; DOI=10.1002/cbic.200800570;
RA Xu Y., Wijeratne E.M., Espinosa-Artiles P., Gunatilaka A.A., Molnar I.;
RT "Combinatorial mutasynthesis of scrambled beauvericins, cyclooligomer
RT depsipeptide cell migration inhibitors from Beauveria bassiana.";
RL ChemBioChem 10:345-354(2009).
RN [3]
RP FUNCTION.
RX PubMed=27449895; DOI=10.1111/1462-2920.13461;
RA Kim J., Yoon D.H., Oh J., Hyun M.W., Han J.G., Sung G.H.;
RT "Calmodulin-mediated suppression of 2-ketoisovalerate reductase in
RT Beauveria bassiana beauvericin biosynthetic pathway.";
RL Environ. Microbiol. 18:4136-4143(2016).
RN [4]
RP FUNCTION, DOMAIN, AND CATALYTIC ACTIVITY.
RX PubMed=28534477; DOI=10.1038/ncomms15349;
RA Yu D., Xu F., Zhang S., Zhan J.;
RT "Decoding and reprogramming fungal iterative nonribosomal peptide
RT synthetases.";
RL Nat. Commun. 8:15349-15349(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:18804027, PubMed:28534477).
CC Ketoisovalerate reductase BEA2 catalyzes the NADPH-specific reduction
CC of ketoisovaleric acid to hydroxyisovalerate, a precursor for
CC beauvericin biosynthesis (PubMed:19105175, PubMed:27449895). 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 (PubMed:18804027,
CC PubMed:28534477). {ECO:0000269|PubMed:18804027,
CC ECO:0000269|PubMed:19105175, ECO:0000269|PubMed:27449895,
CC ECO:0000269|PubMed:28534477}.
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:0000269|PubMed:18804027, ECO:0000269|PubMed:28534477};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62277;
CC Evidence={ECO:0000269|PubMed:18804027, ECO:0000269|PubMed:28534477};
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:18804027, PubMed:28534477). During catalysis, C3
CC and C2 take turns to incorporate the two biosynthetic precursors into
CC the growing depsipeptide chain that swings between T1 and T2a/T2b with
CC C3 cyclizing the chain when it reaches the full length
CC (PubMed:28534477).
CC -!- DISRUPTION PHENOTYPE: Impairs the production of beauvericin
CC (PubMed:18804027). {ECO:0000269|PubMed:18804027}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {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; EU886196; ACI30655.1; -; Genomic_DNA.
DR SMR; B6D9A8; -.
DR STRING; 176275.XP_008603046.1; -.
DR PRIDE; B6D9A8; -.
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; 1.
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..3189
FT /note="Beauvericin nonribosomal cyclodepsipeptide
FT synthetase"
FT /id="PRO_0000442146"
FT DOMAIN 1036..1112
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2557..2631
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2654..2728
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 73..466
FT /note="Condensation 1"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT REGION 202..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 507..901
FT /note="Adenylation 1"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT REGION 1136..1569
FT /note="Condensation 2"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT REGION 1599..2004
FT /note="Adenylation 2"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT REGION 2072..2211
FT /note="S-adenosyl-L-methionine-dependent N-
FT methyltransferase"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT REGION 2773..3181
FT /note="Condensation 3"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT COMPBIAS 203..223
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1073
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2591
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2688
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3189 AA; 351910 MW; 8C67C08D2576A28B CRC64;
MEPLKNVNTG QPCSTVPFPV SDETVEHLNG LYEEINRRFG LDRDAIETIL PCTPFQYDVL
DCAANDARHA VGHAMYEISQ HVHVQRFIAA WRETVRRTPA LRACTFTSTT GESFQLVLRE
SFVLSRIYWS SSSSLQAAVL KDETTAAIAG PRCNRLVLLE DPDTRKQLLI WVFHLALVDS
TVQEPILRRV LAAYKSEDDQ LDSLPLTPDS SGGSDSDSPS TLKMPRAFDQ EKATQFWQRQ
LSGLDASVFP PLSSHLTTPK ADAKIEHYIS WPASAAQHRW SSTTVCQAAL AVLLSRYSHS
SEALFGVVTE QVCMFEGQRL LINGPTRSVV PFRVHCGPEQ SVTDLLKSIA SDNHDMRQFA
HVGLCNISRI GDDQSAACRF QTVLSVSNRR SSEDAASGEV LQILQESEGF APCADRALLL
RCETSRQGAL LVARYDQGVI EPPQMARFLR QLGWLMEQLQ SAADDALSVK QLDIVTREDR
AEIDSWNSDA LEVQESLLHS AFVKRAAESP SDPAVLSWDG AWTYSELDNV SSRLAAHIRS
LDLSHEQLIV PVYFEKSKWV VASILAVLKA GHAFTLIDPK DPPARTTRIV QQTSAKVALT
SKLHQDTVQA IIGRCIVVDD DFVQSLGSAS QCQEKSELTV KPHNLAYAIF TSGSTGDPKG
IMIEHQAFAS CVAKFGPALI PHNARALQFA SHGFGACLLE ILPTLLRGGC VCIPSDLDRM
HNIPDFIRRY NVNWMMATPS YMTTFKPEDV PGLQTLILVG EQMSASVNAT WASRLGLFDG
YGQSESCSIC FIGKISPVSE ANNIGRAVGA HSWIVHPDDP DRLAPVGAVG ELLIESPGIA
RGYIAAPATD RNPFLETAPA WYAPRQPPTG VKFYRTGDLA RYAADGTVVC LGRIDSQVKI
RGQRVEMGAV ETRLRQQVPS DITVVAEAVK RSGSSGSTVI TAFLIDSSDK NNSSAASAKD
ARILDQTATQ EMNAKLCQVL PPHSVPSCYI CMHALPRTAT GKVDRKTLRS IGSKLLEQQA
YKKSPETMQK SKSAETLETG PEARLKEVWL QSFNLEPASP KCGASFFELG GDSITAIKMV
NMARAAGLEL KVSDIFQNPT LARLQAVMSG DSTPSTITTP FATIPASTWD GPVEQSYSQG
RLWFLDQLDI GAVWYLIPYA VRMRGALNID ALRAALLALE QRHETLRTTF ENQNGVGVQI
VHQRLAKELK IIDASSHGDD GYLQPLEQEQ TTPFDLTCEA GWRASLICVG EDHHVLSIVM
HHIVSDGWSI DVLRQELGQL YAAVLHGDED PLSAVSPLPI QYRDFSMWQR RQQVAEHDRQ
LQYWRKQLAD CSPAKLPTDF PRPPLLSGDA GSVPVEISGE LFQKLHRFCN VTSTTPFAVL
LAAFRAAHYR LTGVDDAVVG TPIANRNRPE LERLIGFFVN TQCMRITVDD DDTFEGLVRQ
VRRTTTEAFE NEDVPFERVV SAMLPAGGGS RDLSQTPLAQ LIFAVHSQEN LGKFELEGLE
SEPVANKAYT RFDAEFHLFQ TRDGLNGYLN FAAELFKLET MQNVVSVFLQ ILRHGLEQPK
SLISVLPLTD GLKELDSMGL LKIHRGLEYQ RDSSLVDIFR SQVATCPDTI AVIDSSARLT
YAQLDHQSNL LEAWIRRKGL PAESLVGVLS PRSCETIIAF LGILKANLAY LPLDPKSPVS
RMRDVLSDLP GHTIILLGSD VAAPDLELPC LELVRISDAL KSGASAVNGS ETTDLSAPSA
NSLAYVLYTS GSTGRPKGVM VEHRAIVRLV QRGVIPNFPP LRGAIMAHLF NTVFDGATYE
IFLMLLNGGT LVCIDYLTTL SPKALETVFL REGINCAIMT PALLKLYLAN ARDGLKGLDM
LMVAGDRFDP QDAVEAQTLV RGDCYNAYGP TENGVMSTLY KIDTSDSFIN GVPLGRAIDN
SGAYITDPNQ QLVGPGVLGE LIVTGDGLAR GYTDPALDRD RFVQVVINGE SVRAYRTGDR
MRYRAGQDCL FEFFGRMDFQ FKIRSNRIES AEVEAAILSH PLVRDAAIVV VGVQEEQEPE
MVGFVVAADD AVEQEATDNQ VEGWQELFES SMYNGIDAIS PSALGKDFTG WTSMYDGSEI
DKSEMQEWLD DTIHTLRDGH VPGHVLEIGT GTGMILFNLG SVESYVGLEP TKSAVEFVNK
AIKTLPNLAG RAEVHTGTAT DIDQLSGLRP DLVILNSVVQ YFPTVEYLTR VVDALVRIRG
VKRLFFGDVR SQALHRQFLA ACAMHALGKT ATRDDVRRYM AEREEREEEL LVEPAFFTAL
MNRHPNLIQH VEILPKNIRA TNELSAYRYA AVVHLRDPES AARPVYPIAA DDWVDFQASQ
MRSDVLREYL RLSAGADTVA VCNIPYEKTI FERLIVESLD DNTGSDAPQS RLHGRSLDGA
PWISAVRSDA ESRASLSVPD LVQLAAESGF QVQVSAARQW SQSGALDAVF HRRHASSSQP
TMRTLFQFPD DNALRASATL TNRPLQRLQR RRVAAQIRER LQTLVPSYMI PAKIVVLDQM
PLNANGKVDR KELARRARTT TMTKKKKPQR LASEPACPIS DIEVALCEEA TATFGMQVGI
SDHFFKLGGH SLLATKLISR VGDRLKARLT VKDVFDHPIF SELAIVIREG LQNVVPVALN
GGGQAKQGSA GVVAPRNEME TMLCEEFANV LGMDVGVTDN FFDLGGHSLM ATKLAARIGR
RLNTTISVKE VFEHPIVFQL ANSLELGQLE SDRVKHTMLA DYTAFQLLSV EDLQGFLQNE
ISPQLECAHG GIQDVYPATH MQKAFLCDAS TGHPKPLVPF YIDFPPDSDC STLVEACSSL
VKRFDMFRTV VVEAAGELYQ VVLEHFDLQI DVVETEENVH AATNDFVDRI LEVPVHLGQP
LIQFTILKQA SSVRVLLCLS HALYDGLSLE HVVRDLHMLY KGRSLLPANQ FSRYMQYMDH
TRKAGCDFWR DVIQDTPITV LGHVDAGGRE LEVEAARTLH ATKIISIPLQ AVRSSIITQA
TVFNAACALV LSRETGAKDV VFGRIVSGRQ GLPVSWQNIV GPCTNAVPVR ARIIDDDDDN
HRQMLRDMQD QYLLSLPFET LDFDEVRRSC TNWPATANNY ACCVTYHDFS YHPESEMEQQ
RVEMGVLARK DALLKEEPVY DLGIAGEVEP DGVHLQVTVV AKTRLFSEER AAYLMEEVCR
LFESLNSAL
