BEA1_GIBIN
ID BEA1_GIBIN Reviewed; 3092 AA.
AC G3GBU7;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Beauvericin nonribosomal cyclodepsipeptide synthetase BEA1 {ECO:0000303|PubMed:23832252};
DE Short=BEAS {ECO:0000303|PubMed:23832252};
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};
OS Gibberella intermedia (Bulb rot disease fungus) (Fusarium proliferatum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium fujikuroi species complex.
OX NCBI_TaxID=948311;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DOMAIN, FUNCTION, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=LF061;
RX PubMed=23832252; DOI=10.1007/s11427-013-4505-1;
RA Zhang T., Zhuo Y., Jia X., Liu J., Gao H., Song F., Liu M., Zhang L.;
RT "Cloning and characterization of the gene cluster required for beauvericin
RT biosynthesis in Fusarium proliferatum.";
RL Sci. China Life Sci. 56:628-637(2013).
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:23832252). Ketoisovalerate reductase
CC BEA2 catalyzes the NADPH-specific reduction of ketoisovaleric acid to
CC hydroxyisovalerate, a precursor for beauvericin biosynthesis
CC (PubMed:23832252). The nonribosomal cyclodepsipeptide synthetase BEA1
CC then catalyzes the formation of beauvericin via condensation and
CC cyclization of 3 dipeptidol monomers, each composed of one unit of
CC hydroxyisovalerate and one unit of N-methyl-phenylalanine (By
CC similarity). {ECO:0000250|UniProtKB:B6D9A8,
CC ECO:0000269|PubMed:23832252}.
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 -!- 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:23832252). 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:23832252}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of beauvericin
CC (PubMed:23832252). {ECO:0000269|PubMed:23832252}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; JF826561; AEN14638.1; -; Genomic_DNA.
DR SMR; G3GBU7; -.
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; 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; 3.
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 PROSITE; PS00455; AMP_BINDING; 2.
DR PROSITE; PS50075; CARRIER; 3.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 3.
PE 3: Inferred from homology;
KW Isomerase; Ligase; Methyltransferase; Multifunctional enzyme;
KW Phosphopantetheine; Phosphoprotein; Repeat; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..3092
FT /note="Beauvericin nonribosomal cyclodepsipeptide
FT synthetase BEA1"
FT /id="PRO_0000442147"
FT DOMAIN 1022..1098
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2466..2540
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2560..2634
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 70..458
FT /note="Condensation 1"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT REGION 194..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 499..896
FT /note="Adenylation 1"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT REGION 1008..1028
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1116..1543
FT /note="Condensation 2"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT REGION 1572..1931
FT /note="Adenylation 2"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT REGION 1999..2139
FT /note="S-adenosyl-L-methionine-dependent N-
FT methyltransferase"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT REGION 2678..3084
FT /note="Condensation 3"
FT /evidence="ECO:0000250|UniProtKB:S0EN43, ECO:0000255"
FT MOD_RES 1059
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2500
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2594
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3092 AA; 341855 MW; 15CC2BE390F0F25B CRC64;
MTSLNTKSGT PVIPLLLRSD DASHTDTLVE EVSCSLGLGR DRIENILPST AFQQDVIDCA
GSEKQRSIGH VAYEISNDID ISKLAAAWKD TIHRTPALRT CAFTSSSGET YQVILKDSFV
FSWMFSTSAD QKDAVTKDEA AAAAYGPRCN RFVLLDDPIE KRKLLIWTFS HALVDTSFQE
RILERVLKAY THGHDEVPNR PYTPESSDPE DDDLSLTPTD GSKTPETEGL HPATQYWKNY
LSDLNASAFP HLTSPLAVPY PNAKSEHRFT FTASAQSTWP SLAICRTALA ILLSRYTHSQ
EALFGVVTEQ HQLLVNGPTR TVVPFRVHCA SDQSLSDIIG AVYANDDAIR QFSDVGLRSI
SSTGDDGVAA CGFQTVLSVT EGDNEQSSSC EILQKTGESE LFMPCTNRAL LLHCQMASDG
LSMIARYDKS LIDSQQIARL LRQLGQLIQR LRVSPDELPS AGELDILTSE DQAEIQSWNS
HPIPSQPTLI HKEMLKAASL SPSKVAICAW DGEWTYSELD NITSRLAALI RFSTPDQEHA
ILPIYFEKSK WVVASMLAVM KAGHAFTLID PNDPPARVAQ VVGQTGATVA LTSKLYRKKV
QGIIERCIIV DDDLVQSLIC TCALKPDPTL AKVAPEDLAY VIFTSGSTGD PKGIMIEHRA
FSSCALKFGS ALGINSDTRA LQFGSHAFGA CLLEIMTTLI HGGCVCIPSD DDRMNNVPAF
VNRANVNWMM ATPSYMGTFQ PDDVPGLKTL VLVGEQMSPS VNAIWAPRVQ LLDGYGQSES
SSICFVGKIS SSGADPNNIG HSVGAHSWII DPSDPNRLVP IGGIGELVIE SPGIARDYII
PLPTEKSPFF STVPPWYPFK ELPNGIRFYR TGDLARYASD GTVVCLGRMD SQVKIRGQRV
ELGAVETYLR QQLPEDMSIV VEAIKPSDSP TSSVLVAFLI ASEAAESIED AAILDLAATK
AMSVKLEQVL PRHSIPSCYI SMQYIPRTAT GKVDRRKLRS IGRDMLAQQL QGSSSRPSQS
SSPTTSSPSR LEEVWCQCLG LETGAANVGS TFFELGGHSI TAIKMVNMAR SAGIDLKVSD
IYQNPTLAGL EAIVNGSAVP YAIIPTTTRD GPVEQSYSQG RLWFLDQLEV GALWYLIPYA
VRMRGMVDIY ALSRALMALE QRHETLRTTF EDRDGAGVQI IHQTLFKDLR VVDTTDGNYL
QLLKQEQTTP FNLTSEAGWR VLLIRLNDTD YVLSIVMHHI VSDGWSIDVL RHDLSALYAA
ALQGRDLASA MNPLPIQYSD FAMWQKQEAQ ALEHEKQLDY WKRQLADCSP AKLPTDFPRP
ALLSGEAGVV PVSIDGQLYQ NLRDFCNENN TTSFAVLLAA FRAAHYRLTG VEDAVIGTPI
ANRNRWELEN IIGFFVNTQC MRITVDDQDT FGSLVRQVRA TTTAAFENED VPFERVVSTM
LPGSRDLSRT PLAQLIFAVH SQKDLGRFEL QGLESEIVAS KAYTRFDIEF HLFQEADGLK
GSCNFATDLF KPETVENVVS VFFQILRNGL EKPNIPISVL PLTDGIEELR RLDLLRIKKV
EYPRDASLVD IFRTQVAAYP DSLAVVDSSS RLTYTELDRQ SDRLAARLRR QGMPAETLVG
VLAPRSCEAI VAIIGILKAN LAYLPFDVKS PFARLEDILS SIPGQTIVLL GSDVPVPELS
IPGLEFMRIV DAIESYDTND LNGHAHVDDS NPTATSLAYV LFTSGSTGRP KGVMVEHRVI
VRLMTSNIIP DFPVQPRSAH MFNIAFDGAT YEIFFTLLNG GTLVCIDYMT TLDVKALQDV
FIKEQINAAC MAPALLKLYL TDARDALRGL DFLMAAGDRF DGQDAIEAQS LVRGQCYNGL
LALVSWGELV VTGDGLARGY FDPALNENRF IHIEVDGQRV RAYRTGDRVR YRVGDGLIEF
FGRMDTQFKI RGNRIESAEV EAAMLSHGSV RDAAVVVQKD DGEKSDLVGF VVIDHDHSLE
GDANDNQVEG WQDHFETEMY ADIGDIDPST IGKDFKGWTS MYDGSEIDKA EMQEWLDDTI
KTLCDVQAPG HVLEVGTGSG MILFNLGDGL QSYRGLEPSK SAAAFTNSVI KSVPSLAGKA
EVHVGTAQDI SQLTNLHPDL VVINSVAQYF PSPEYLAQVA DTLVHLSGVK RLFFGDMRTN
ATNKHFLAAR AIRTLGDTAT KDSVRQKMAE LEEREEELLV EPAFFTTLQD RFPDLVHHVE
ILPKNMHATN ELSAYRYAAV VHIRDHDSVP VHTIEKGSWV DFGASRMNRT SLLQFLRRSK
GSSTVAITNI PFAKTVFERQ IVESLEAEED SKLDGAAWTS AVRSDAESRA SLSVPDLHRL
AEEAGFRLEI SVARQWSQSG TLDAVFHHLP SPSNTGRTLI KFPTDNHLRS SATLANRPLQ
GLQRRRAALQ VRERLQSLLP SYMIPSSIVV LDQMPLNPNG KVDRKELARQ ARIIPKQQTA
LPVQAVPISD IEAILCDEAT ATFGMKVDIS DDFFKLGGHS LLATKLISRV EQRFNVRASV
KDVFDNPVFA HLAVVIREGL ASRTTLTNGQ DKQGWSARVA PRTETEIILC DEASKLLGIE
VGITDNFFDL GGHSMMATKL AMRLGRRLDT TIVVKDIFDY PVLFQLSKKL ESAGSGADSE
EVHVDDYNPF ELLSLEDPKE FIQREICSQL NVSLESIQDM YKSTQMQNSF LFSPGTGSPR
PLTPFYIDFP VDSDPPTLVN ACHSLVQHID MFRTVFVLAS GQLYQVVLKH LDVPIETIVT
NQNVNTATND FLDEHAQDPI RLGESLIRVA ILKQSSSVRV LLRLSHALYD GLSREPIVRN
LHILFNGMSL LPPTQFRRYM EYTANSQEKG FEFWRDVIGD SPMTILSDAN NGAYRREVSP
SKALHLSKVV SVPSQAIRSS IATQATVFNS ACALVLSKES GSSNVVFGRI VSGRQGLLVN
CQDIIGPCTN AVPVRAHIGT DENHHQMLRD MQDQYLRSLP FETLGFEEIK RNCTDWPDST
TNFACCVTYH NFEYHPESEV EQQRVEMGVL SKHVELRKDE PLYDLAIAGE VEPDGMSLKV
TIIARAHLFE EERVQYFLEE VCDTFQTLNF SL
