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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
 
 
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