BACA_BACLI
ID BACA_BACLI Reviewed; 5255 AA.
AC O68006;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Bacitracin synthase 1;
DE Short=BA1;
DE Includes:
DE RecName: Full=ATP-dependent cysteine adenylase;
DE Short=CysA;
DE AltName: Full=Cysteine activase;
DE Includes:
DE RecName: Full=ATP-dependent leucine adenylase;
DE Short=LeuA;
DE AltName: Full=Leucine activase;
DE Includes:
DE RecName: Full=ATP-dependent glutamate adenylase;
DE Short=GluA;
DE AltName: Full=Glutamate activase;
DE Includes:
DE RecName: Full=ATP-dependent isoleucine adenylase;
DE Short=IleA;
DE AltName: Full=Isoleucine activase;
DE Includes:
DE RecName: Full=Glutamate racemase;
DE EC=5.1.1.3;
GN Name=bacA;
OS Bacillus licheniformis.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=1402;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 10716 / DSM 603 / NBRC 12199 / NCIMB 8874 / Tracy I;
RX PubMed=9427658; DOI=10.1016/s1074-5521(97)90301-x;
RA Konz D., Klens A., Schoergendorfer K., Marahiel M.A.;
RT "The bacitracin biosynthesis operon of Bacillus licheniformis ATCC 10716:
RT molecular characterization of three multi-modular peptide synthetases.";
RL Chem. Biol. 4:927-937(1997).
CC -!- FUNCTION: Activates five amino acids, incorporates two D-amino acids,
CC releases and cyclizes the mature bacitracin.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutamate = D-glutamate; Xref=Rhea:RHEA:12813,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:29986; EC=5.1.1.3;
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000305};
CC Note=Binds 5 phosphopantetheines covalently. {ECO:0000305};
CC -!- PATHWAY: Antibiotic biosynthesis; bacitracin biosynthesis.
CC -!- SUBUNIT: Large multienzyme complex of BA1, BA2 and BA3.
CC -!- DOMAIN: Consists of five modules and one epimerization domain in the
CC fourth module. Each module incorporates one amino acid into the peptide
CC product and can be further subdivided into domains responsible for
CC substrate adenylation, thiolation, condensation (not for the initiation
CC module), and epimerization (optional), and N methylation (optional).
CC -!- MISCELLANEOUS: Bacitracin is a mixture of at least ten cyclic
CC dodecapeptides, that differ by one or two amino acids. The most
CC abundant is bacitracin A, a branched cyclic dodecapeptide. It contains
CC an N-terminal linear pentapeptide moiety (Ile-Cys-Leu-D-Glu-Ile) with
CC an isoleucine-cysteine thiazoline condensation product and a C-terminal
CC heptapeptide ring (Lys-D-Orn-Ile-D-Phe-His-D-Asp-Asn), in which the
CC free alpha-carboxy group of the C-terminal Asn is bound to the epsilon-
CC amino group of Lys.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AF007865; AAC06346.1; -; Genomic_DNA.
DR PIR; T31677; T31677.
DR SMR; O68006; -.
DR PRIDE; O68006; -.
DR UniPathway; UPA00179; -.
DR GO; GO:0008881; F:glutamate racemase activity; IEA:UniProtKB-EC.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:1901576; P:organic substance biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 5.
DR Gene3D; 3.30.300.30; -; 5.
DR Gene3D; 3.30.559.10; -; 5.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR025110; AMP-bd_C.
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; IPR010060; NRPS_synth.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00501; AMP-binding; 5.
DR Pfam; PF13193; AMP-binding_C; 5.
DR Pfam; PF00668; Condensation; 5.
DR Pfam; PF00550; PP-binding; 5.
DR SMART; SM00823; PKS_PP; 5.
DR SUPFAM; SSF47336; SSF47336; 5.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 5.
DR TIGRFAMs; TIGR01720; NRPS-para261; 1.
DR PROSITE; PS00455; AMP_BINDING; 5.
DR PROSITE; PS50075; CARRIER; 5.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 3.
PE 3: Inferred from homology;
KW Antibiotic biosynthesis; Isomerase; Ligase; Multifunctional enzyme;
KW Phosphopantetheine; Phosphoprotein; Repeat.
FT CHAIN 1..5255
FT /note="Bacitracin synthase 1"
FT /id="PRO_0000193082"
FT DOMAIN 539..614
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1580..1655
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2616..2691
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3659..3733
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 5166..5241
FT /note="Carrier 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 39..612
FT /note="Domain 1 (isoleucine-activating)"
FT REGION 519..542
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 621..1037
FT /note="Cyclization"
FT /evidence="ECO:0000255"
FT REGION 1109..1648
FT /note="Domain 2 (cysteine-activating)"
FT REGION 2124..2689
FT /note="Domain 3 (leucine-activating)"
FT REGION 3164..3732
FT /note="Domain 4 (glutamine-activating)"
FT REGION 4668..5249
FT /note="Domain 5 (isoleucine-activating)"
FT MOD_RES 574
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1615
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2651
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3694
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 5201
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 5255 AA; 598269 MW; 906E8DD68450F85B CRC64;
MVAKHSLENG VFHKMTENEK ELILHFNNTK TDYPKNKTLH ELFEEQAMKT PDHTALVFGA
QRMTYRELNE KANQTARLLR EKGIGRGSIA AIIADRSFEM IIGIIGILKA GGAYLPIDPE
TPKDRIAFML SDTKAAVLLT QGKAADGIDC EADIVQLDRE ASDGFSKEPL SSVNDSGDTA
YIIYTSGSTG TPKGVITPHY SVIRVVQNTN YIDITEDNVI LQLSNYSFDG SVFDIFGALL
NGASLVMIEK EALLNINRLG SAINEEKVSV MFITTALFNM IADIHVDCLS NLRKILFGGE
RASIPHVRKV LNHVGRDKLI HVYGPTESTV YATYYFINEI DDEAETIPIG SPLANTSVLI
MDEAGKLVPI GVPGELCIAG DGLSKGYLNR EELTAEKFIP HPFIPGERLY KTGDLAKWLP
DGNIEFIGRI DHQVKIRGFR IELGEIESRL EMHEDINETI VTVREDEESR PYICAYITAN
REISLDELKG FLGEKLPEYM IPAYFVKLDK LPLTKNGKVD RKALPEPDRT AGAENEYEAP
RNETEEKLAA VWQDVLHVEK AGIHDHFAQM GGHSLHAMEL IAKIKEKMNV EIPLHQLFKL
ATIKELSAFI EANHQEDKGD TLVTRAADPE NIHEIFPLTG IQLAYLVGRD ETFEIGGVAT
NLTVEFEADV DLNRFQLTLQ KLIDRHPILR TIVFENGTQK ILEATQRYTI ETQDLRGFTE
EEINVRILEQ REKMTSKIID PSVWPLFELK TFMLPGEKKY FFLNVDPLIC DDSSMKRLIR
EFKQLYENPG LQLPSLEYSF RDYVLASINF KQTSRYQKDQ QYWLDKLDHF PSAPELPLKS
DPAHVAKPSF KKFSTFLDGH TWNELKKKAR HHHLTPTSVL CAAYAYILAY WSRQNHFAIN
LTVFNRIPFH PDVKNMIGDF TSLMLLDIHA EENMSSFWRF ALNVQDTLLE ALEHRHYDGV
DVIRNIAKKN GMNKKAVMPI VFTSVLSENP DDSFDSLVDF DNIHFFSTRT SQVYIDNQVY
EINGGLYITW DYVEQIFEHE VIESMFDQYI AVIQKAVSGE DVSTIQMNEK SRQMISAYND
TDQSFDAKPL HELFTGQVKH GPDRMALKHH DEVMTYQELD EKSNQVARFL IGKGVEKGDY
IGVIGKRSLG TIVNLLAVLK TGAAYIPLDP DYPEERKAYI QSKSNCKFFI SHDVYDKEHI
ERFSKAPVDR KVDLDDMAYV IFTSGSTGKP KGVQITHVPQ RNTILDINEK FNVTEQDNIM
GISSLCFDLS VYDVFGALSS GASLVIIDDQ RDVFSLKETA EKERITIWNS VPAIMGMTAD
VYPDNELNHH LRLILLSGDW IPLQLPATIK KTFKNAEVIS LGGATEGSIW SIYYPIQKVE
EDWKSIPYGK PLANQKIYVL NQNKQLCPVG VEGELYIGGA GVASGYIHDQ EKTEHSFIQH
QELGYIYKTG DYGVLKEDGY VEFLGRKDSQ VKIRGYRVEM GEIENTLVSH QEITKASVID
YTSPDGIKNL YAFVVAENAI SQLDVKEFLQ KTLPDYMIPA KFVQIEEIPL TVNGKVDKRT
LHDLAEQHTA DEGQRGGRML PENETQAMLL EIWKDIFGLD SINLDVSYYE IGGDSLKAIS
IITEINKRMN VEMPISEIFK NDTIIALDHY LKNREESDME HPIQKAREKE YYPTSPAQQR
MYMLSMLENE RGAYHIPMAL LVEGRINAMQ LENALKTFLQ RHEILRTGFE IQNNELIQKI
YENVDFRLEY ECLDASITDQ HALMEITSRY CKESIKPFDL SRPPLMRAKL IKIDDIRHIL
VINFHHIISD GVSQGILMNE ILELYSNVPL PEVNVQYKDY VEWNHTFNQS AAMKKQEAYW
LDVYRDIPSK LDFPYDYKRH HIDTFEGSSV FLEMERELSD HIRKLAKHNG TTLYTVMLSA
YYVLLNKYTN QTDIVVGTAA AGRLHPDLQD VFGVFVNTLA LRNEVDTSYS FKEFLQQTKE
RTIAAFDNSE YPFDDLIRKL NGVRESNRNP LFDTMFVLED ARMFTKQKGD VKLSPIIFEL
DNAKFDMIFN VLDFEQKIVL NIEYSTSLFK DETIQKIAED YFRILEEVSE NLDVALHQID
MISRQEKRTL LESFNHTKTA YPKGKAIHQL FEEQAKRIPD HTAVVFEDQK LTYRQLNEKA
NQVARLLREK GVKPDTLVGI MMERSSDMIA AILGVLKAGG AYLPIDPEYP PERMRYMAFD
SEVKVIISDV PLAEELTAES IELIHMDDER IAGQDRSDID NVNQSGDLAY VIYTSGSTGK
PKGVMIEHQS LINLCSWHQS CFEVGQNDNS SIYASISFDA FVWELFPYIT AGATVHVLNQ
ETRLDVEKLN RYFHDHHITI SFLPTPVCEQ FTALDNHSLR TLLTGGDKLN VFKEKSYQIV
NNYGPTENTV VATSFPIDKS HQNIPIGKPI DNVKVYILNK DLQLCPLGAS GELCIAGEGL
ARGYVNRPEL TREKFIGNPF VPGERMYRTG DLAKMLPDGN IQFLGRVDQQ VKIRGYRIEP
GEIENRLLKY EKIEEAAVIA REDGDHDPYL CAYVTVKKEV EPEKIRAFLK KSLPDYMIPQ
YFVQLDGLPL TVNGKVDKKS LPVPERSVTM DRRYEAPRDQ MEEKLVSIWE EALGINKIGI
NSHFFEAGGH SLKAAALVST IHKELNVKLP LRQIFETPTI KGLRDISVRR RKCFYIDRKT
EEKPYYRLSS AQKRLYILSQ TGSHVAYNMP FAMTLEGDFD IRRFENTLKN MVKRHESFRT
SFVMIDGEVM QQIEKEIDFQ VAYSDIGKES AEEKIKSFIR PFHLEKAPLL RAEVVKLNER
EHLLMFDMHH IISDGVSTDI FIQELGALYE GKSLKPFHIQ YKDYAEWENS HARSEELKRQ
EEYWLKTYKG DIPVLDLPID HKRPLTKSSE GDTVTAAIES ETFRKLQHMA KENGVTMYML
LLAGYTALLS KYTGQEDIIV GTPAAGRNHE DIQHLIGMFV NTLAIRNHPE GKKTFRDYLQ
EVKENTLQAY ENQDYPFEEL VEKVNIKRDM ARNPLFDTML VYHNTDVKPF EAEGLRSRLV
EIKRGISKFD ITVTASEAAD GLRLEVEYST TLFNKERMER LSEHLISLLE QAADHPDIAI
NQIDVLTKGE RHRVLYDFNR TDGVFCKEMT IPELFEKQAE KTPDHPAVAF GDETISYREL
NERANSLAFT LRQKGVGPDV IAGILTERSI EMIVGIMGIL KAGGAYLPID PAYPQERISY
IVKDSDVSVL CAAGDVDPGE AYTGDIIRID QTGQNDHVEN LKHDIKPQHL AYVIYTSGST
GKPKGVMIEH HSVNNLVHGL NERIYQHLDA HLNVALVAPY IFDASVKQIF AALLFGHTLC
IVPRETAWDA MSLIEYYSKN NINVSDMTPA HLNMLAYVDK TELEFDVKEL IVGGDALTPD
VIGGLFHKFP NLSCNITNVY GPTECCVDAA SHQIESGKVP QTPSIPIGRP LLNTSIYIVD
KELRPLPVGI AGELCIAGEG VARGYVNRPE LTAEKFVDHP FEPGKKMYKT GDLAMWLPDG
QIEFLGRADH QVKIRGYRIE LGEVEQQLLT HEKIKEAAVI AGKDQNGNSY LCAYIASDKE
LPAADVRQFL EREMPDYMIP SYFVKLDRLP RTPSGKVDRS ALPEADGNVN VMEGTGYDPP
RNEIERKLVQ VWREILGAED IGISHHFFAA GGDSIKALQI VSRLAKMNLK LEMKALFANP
KIKDLSRFIT EETRHRKHNK PVTGETELLP IQKRYFANNK EELDHFNQSF MLFRKDGYDE
NIVRTAFNKI LEQHDALRMI YEEKDGDIIQ YNRGYRENLF DLDVYDVRGF DSQEEKVFEL
ATGIQKKSSI RKGKLVHLGI FRADEGDHLL IAIHHLVVDG VSWRILFEDF ETLYLQALKG
EPLDIGYKTD SYQEFARQLK KYAQSRRLLK EREYWQKALE ADVPFIPAEK LERDTFEHSA
TLSIRIGPDV TAKLLRNAFK AYNTEINDIL LTALIAAVRD ITGENKLKVM MEGHGREDIL
DGVDITRTIG WFTTVYPVFI DLGEEKEISQ NIKMVKEALR KIPNKGIGYG VLKYMTEELQ
KIQTQAPLSF NYFGEMNNDM NRKVFSQSPF SPGESIGGKI VRHCAIEMNA ISLNGELTIY
TTFNQDQYQT STIEQLNQSF KENLEKIVDH CVDKEGSDMT PSDYGDVSLG LEELELIKDK
YSAFQIEKIY PLANMQKGML FHNAMDQTSG AYFQQIVIKL KGRVHPDILE ESFHEIVKRH
EILRASFEYE ITAEPRQIIA RDRKTPFTSI DLTGENRTRQ HRFIETYLKE DQEKGFDLSS
EALMRVCLIK MSDESYRLIW SHHHILLDGW CLGIVLSELF SLYGKIMKGE SRRLKEPKPY
GDYIKWLEKQ DQEEAVAYWK DYLKGYESRS ELPAFNRGAT SEEYCGKEKV ISFSKELTTK
ITRIAKQHHV TINTVLQGIW GMILAKYKNT DEVVFGTVVS GREAPVDGIE EMVGLFIHTI
PTRISFEGAR SFKEVLKKTQ AESIESNRYS YMNLSEIQVL SEMKRELITH VMAFQNYAFD
EELFRSQSGE TGFELEGVHG KERTNYNFNL TGVLEDEQLK LKLTFNENVY DNTIIETLEK
HIITVAEQVA EDETQTLRDI NLVSKEEQHR ILHTFNDTKT GYPKDKPLHE LFEEQAMKTP
DHTALVFGAQ RMTYRELNEK ANQTARLLRE KGIGRGSIAA IIADRSFEMI IGIIGILKAG
GTYLPIDPET PRDRIDYMLK NSGAALLVTT DSLLKPFDIK TVDLCSDELH LLSEENLPRV
NRSSDTAYIV YTSGSTGTPK GVVIPHYSAA RVVKNTNYID ITGNDVILQL SNYSFDGSVF
DIFGALLNGA SLVLIEKETV LNTHELAEVI KKEQVSVMFI TTALFNTLAD INIGCLAKLR
KILFGGERAS IPHVRKVLDH VGRDKLIHVY GPTESTVYAT YYFINEIDDE AETIPIGSPL
ANTSVLIMDE AGKLLPIGVP GELCIAGDGL SKGYLNREEL TAEKFIPHPF IPGERLYKTG
DLAKWLPDGN IEFIGRIDHQ VKIRGFRIEL GEIESRLEMH EDINETIVTV REDEESRPYI
CAYITANREI SLDELKGFLG EKLPDYMIPA YFVKMDKLPL TKNGKVDRKA LPEPDRSAGT
EAEYEAPRNY VEQRIISILE DVLGTERMGI SCHFFDKGGN SLKAMQAVHS INKTFGIDMR
ISTFFKHPTA KSLARFVLTA EAESAVSEEY AEEEV