ID   DHBF_BACSU              Reviewed;        2378 AA.
AC   P45745; Q9R9I2;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   28-JUL-2009, sequence version 4.
DT   03-AUG-2022, entry version 154.
DE   RecName: Full=Dimodular nonribosomal peptide synthase {ECO:0000303|PubMed:11112781};
DE            EC=6.2.1.66 {ECO:0000269|PubMed:11112781};
DE            EC=6.2.1.70 {ECO:0000269|PubMed:11112781};
DE   AltName: Full=Glycine--[glycyl-carrier protein] ligase {ECO:0000305};
DE   AltName: Full=L-threonine--[L-threonyl-carrier protein] ligase {ECO:0000305};
GN   Name=dhbF; OrderedLocusNames=BSU31960;
OS   Bacillus subtilis (strain 168).
OC   Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX   NCBI_TaxID=224308;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP   PATHWAY.
RC   STRAIN=168;
RX   PubMed=11112781; DOI=10.1074/jbc.m009140200;
RA   May J.J., Wendrich T.M., Marahiel M.A.;
RT   "The dhb operon of Bacillus subtilis encodes the biosynthetic template for
RT   the catecholic siderophore 2,3-dihydroxybenzoate-glycine-threonine trimeric
RT   ester bacillibactin.";
RL   J. Biol. Chem. 276:7209-7217(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=168;
RX   PubMed=9384377; DOI=10.1038/36786;
RA   Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA   Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA   Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA   Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA   Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA   Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA   Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA   Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA   Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA   Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA   Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA   Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA   Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA   Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA   Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA   Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA   Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA   Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA   Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA   Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA   Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA   Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA   Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA   Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA   Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA   Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA   Yoshikawa H., Danchin A.;
RT   "The complete genome sequence of the Gram-positive bacterium Bacillus
RT   subtilis.";
RL   Nature 390:249-256(1997).
RN   [3]
RP   SEQUENCE REVISION.
RX   PubMed=10568751; DOI=10.1101/gr.9.11.1116;
RA   Medigue C., Rose M., Viari A., Danchin A.;
RT   "Detecting and analyzing DNA sequencing errors: toward a higher quality of
RT   the Bacillus subtilis genome sequence.";
RL   Genome Res. 9:1116-1127(1999).
RN   [4]
RP   SEQUENCE REVISION TO 2141.
RX   PubMed=19383706; DOI=10.1099/mic.0.027839-0;
RA   Barbe V., Cruveiller S., Kunst F., Lenoble P., Meurice G., Sekowska A.,
RA   Vallenet D., Wang T., Moszer I., Medigue C., Danchin A.;
RT   "From a consortium sequence to a unified sequence: the Bacillus subtilis
RT   168 reference genome a decade later.";
RL   Microbiology 155:1758-1775(2009).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-95.
RC   STRAIN=168 / Marburg / ATCC 6051 / DSM 10 / JCM 1465 / NBRC 13719 / NCIMB
RC   3610 / NRRL NRS-744 / VKM B-501;
RX   PubMed=8550523; DOI=10.1128/jb.178.3.854-861.1996;
RA   Rowland B.M., Taber H.W.;
RT   "Duplicate isochorismate synthase genes of Bacillus subtilis: regulation
RT   and involvement in the biosyntheses of menaquinone and 2,3-
RT   dihydroxybenzoate.";
RL   J. Bacteriol. 178:854-861(1996).
RN   [6]
RP   PHOSPHOPANTETHEINYLATION [LARGE SCALE ANALYSIS] AT SER-996, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=168;
RX   PubMed=17218307; DOI=10.1074/mcp.m600464-mcp200;
RA   Macek B., Mijakovic I., Olsen J.V., Gnad F., Kumar C., Jensen P.R.,
RA   Mann M.;
RT   "The serine/threonine/tyrosine phosphoproteome of the model bacterium
RT   Bacillus subtilis.";
RL   Mol. Cell. Proteomics 6:697-707(2007).
CC   -!- FUNCTION: Specifically adenylates L-threonine and, to a lesser extent,
CC       glycine and covalently loads both amino acids onto their corresponding
CC       peptidyl carrier domains. {ECO:0000269|PubMed:11112781}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + holo-[peptidyl-carrier protein] + L-threonine = AMP +
CC         diphosphate + L-threonyl-[peptidyl-carrier protein];
CC         Xref=Rhea:RHEA:61688, Rhea:RHEA-COMP:11480, Rhea:RHEA-COMP:15908,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57926,
CC         ChEBI:CHEBI:64479, ChEBI:CHEBI:144927, ChEBI:CHEBI:456215;
CC         EC=6.2.1.70; Evidence={ECO:0000269|PubMed:11112781};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61689;
CC         Evidence={ECO:0000269|PubMed:11112781};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + glycine + holo-[peptidyl-carrier protein] = AMP +
CC         diphosphate + glycyl-[peptidyl-carrier protein];
CC         Xref=Rhea:RHEA:61696, Rhea:RHEA-COMP:11480, Rhea:RHEA-COMP:15909,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57305,
CC         ChEBI:CHEBI:64479, ChEBI:CHEBI:144951, ChEBI:CHEBI:456215;
CC         EC=6.2.1.66; Evidence={ECO:0000269|PubMed:11112781};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61697;
CC         Evidence={ECO:0000269|PubMed:11112781};
CC   -!- COFACTOR:
CC       Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC         Evidence={ECO:0000305};
CC   -!- PATHWAY: Siderophore biosynthesis; bacillibactin biosynthesis.
CC       {ECO:0000305|PubMed:11112781}.
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       {ECO:0000305}.
CC   -!- CAUTION: The phosphoserine observed at Ser-996 in PubMed:17218307
CC       undoubtedly results from the secondary neutral loss of pantetheine from
CC       the phosphodiester linked cofactor. {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; AF184977; AAD56240.1; -; Genomic_DNA.
DR   EMBL; AL009126; CAB15186.3; -; Genomic_DNA.
DR   EMBL; U26444; AAC44634.1; -; Genomic_DNA.
DR   PIR; E69615; E69615.
DR   RefSeq; NP_391076.3; NC_000964.3.
DR   RefSeq; WP_009968094.1; NZ_JNCM01000033.1.
DR   AlphaFoldDB; P45745; -.
DR   SMR; P45745; -.
DR   IntAct; P45745; 3.
DR   MINT; P45745; -.
DR   STRING; 224308.BSU31960; -.
DR   ESTHER; bacsu-YUKL; Thioesterase.
DR   jPOST; P45745; -.
DR   PaxDb; P45745; -.
DR   PRIDE; P45745; -.
DR   EnsemblBacteria; CAB15186; CAB15186; BSU_31960.
DR   GeneID; 936569; -.
DR   KEGG; bsu:BSU31960; -.
DR   PATRIC; fig|224308.179.peg.3462; -.
DR   eggNOG; COG1020; Bacteria.
DR   InParanoid; P45745; -.
DR   OMA; FQIAPEM; -.
DR   PhylomeDB; P45745; -.
DR   BioCyc; BSUB:BSU31960-MON; -.
DR   BioCyc; MetaCyc:MON-13921; -.
DR   BRENDA; 6.2.1.66; 658.
DR   UniPathway; UPA00013; -.
DR   Proteomes; UP000001570; Chromosome.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   GO; GO:0043604; P:amide biosynthetic process; IEA:UniProt.
DR   GO; GO:1901566; P:organonitrogen compound biosynthetic process; IEA:UniProt.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR   Gene3D; 1.10.1200.10; -; 1.
DR   Gene3D; 3.30.300.30; -; 2.
DR   Gene3D; 3.30.559.10; -; 2.
DR   Gene3D; 3.40.50.1820; -; 1.
DR   InterPro; IPR010071; AA_adenyl_domain.
DR   InterPro; IPR029058; AB_hydrolase.
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; IPR023213; CAT-like_dom_sf.
DR   InterPro; IPR001242; Condensatn.
DR   InterPro; IPR020806; PKS_PP-bd.
DR   InterPro; IPR020802; PKS_thioesterase.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR001031; Thioesterase.
DR   Pfam; PF00501; AMP-binding; 2.
DR   Pfam; PF13193; AMP-binding_C; 2.
DR   Pfam; PF00668; Condensation; 2.
DR   Pfam; PF00550; PP-binding; 2.
DR   Pfam; PF00975; Thioesterase; 1.
DR   SMART; SM00823; PKS_PP; 2.
DR   SMART; SM00824; PKS_TE; 1.
DR   SUPFAM; SSF47336; SSF47336; 2.
DR   SUPFAM; SSF53474; SSF53474; 1.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR   PROSITE; PS00455; AMP_BINDING; 2.
DR   PROSITE; PS50075; CARRIER; 2.
PE   1: Evidence at protein level;
KW   Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat.
FT   CHAIN           1..2378
FT                   /note="Dimodular nonribosomal peptide synthase"
FT                   /id="PRO_0000193081"
FT   DOMAIN          961..1036
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          2036..2111
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         996
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:17218307"
FT   MOD_RES         2071
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   CONFLICT        2141
FT                   /note="S -> G (in Ref. 1; AAD56240)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   2378 AA;  263770 MW;  80216ABF9D6BFA66 CRC64;
     MPDTKDLQYS LTGAQTGIWF AQQLDPDNPI YNTAEYIEIN GPVNIALFEE ALRHVIKEAE
     SLHVRFGENM DGPWQMINPS PDVQLHVIDV SSEPDPEKTA LNWMKADLAK PVDLGYAPLF
     NEALFIAGPD RFFWYQRIHH IAIDGFGFSL IAQRVASTYT ALIKGQTAKS RSFGSLQAIL
     EEDTDYRGSE QYEKDRQFWL DRFADAPEVV SLADRAPRTS NSFLRHTAYL PPSDVNALKE
     AARYFSGSWH EVMIAVSAVY VHRMTGSEDV VLGLPMMGRI GSASLNVPAM VMNLLPLRLT
     VSSSMSFSEL IQQISREIRS IRRHHKYRHE ELRRDLKLIG ENHRLFGPQI NLMPFDYGLD
     FAGVRGTTHN LSAGPVDDLS INVYDRTDGS GLRIDVDANP EVYSESDIKL HQQRILQLLQ
     TASAGEDMLI GQMELLLPEE KEKVISKWNE TAKSEKLVSL QDMFEKQAVL TPERIALMCD
     DIQVNYRKLN EEANRLARLL IEKGIGPEQF VALALPRSPE MVASMLGVLK TGAAYLPLDP
     EFPADRISYM LEDAKPSCII TTEEIAASLP DDLAVPELVL DQAVTQEIIK RYSPENQDVS
     VSLDHPAYII YTSGSTGRPK GVVVTQKSLS NFLLSMQEAF SLGEEDRLLA VTTVAFDISA
     LELYLPLISG AQIVIAKKET IREPQALAQM IENFDINIMQ ATPTLWHALV TSEPEKLRGL
     RVLVGGEALP SGLLQELQDL HCSVTNLYGP TETTIWSAAA FLEEGLKGVP PIGKPIWNTQ
     VYVLDNGLQP VPPGVVGELY IAGTGLARGY FHRPDLTAER FVADPYGPPG TRMYRTGDQA
     RWRADGSLDY IGRADHQIKI RGFRIELGEI DAVLANHPHI EQAAVVVRED QPGDKRLAAY
     VVADAAIDTA ELRRYMGASL PDYMVPSAFV EMDELPLTPN GKLDRKALPA PDFSTSVSDR
     APRTPQEEIL CDLFAEVLGL ARVGIDDSFF ELGGHSLLAA RLMSRIREVM GAELGIAKLF
     DEPTVAGLAA HLDLAQSACP ALQRAERPEK IPLSFAQRRL WFLHCLEGPS PTYNIPVAVR
     LSGELDQGLL KAALYDLVCR HESLRTIFPE SQGTSYQHIL DADRACPELH VTEIAEKELS
     DRLAEAVRYS FDLAAEPAFR AELFVIGPDE YVLLLLVHHI VGDGWSLTPL TRDLGTAYAA
     RCHGRSPEWA PLAVQYADYA LWQQELLGNE DDPNSLIAGQ LAFWKETLKN LPDQLELPTD
     YSRPAEPSHD GDTIHFRIEP EFHKRLQELA RANRVSLFMV LQSGLAALLT RLGAGTDIPI
     GSPIAGRNDD ALGDLVGLFI NTLVLRTDTS GDPSFRELLD RVREVNLAAY DNQDLPFERL
     VEVLNPARSR ATHPLFQIML AFQNTPDAEL HLPDMESSLR INSVGSAKFD LTLEISEDRL
     ADGTPNGMEG LLEYSTDLFK RETAQALADR LMRLLEAAES DPDEQIGNLD ILAPEEHSSM
     VTDWQSVSEK IPHACLPEQF EKQAALRPDA IAVVYENQEL SYAELNERAN RLARMMISEG
     VGPEQFVALA LPRSLEMAVG LLAVLKAGAA YLPLDPDYPA DRIAFMLKDA QPAFIMTNTK
     AANHIPPVEN VPKIVLDDPE LAEKLNTYPA GNPKNKDRTQ PLSPLNTAYV IYTSGSTGVP
     KGVMIPHQNV TRLFAATEHW FRFSSGDIWT MFHSYAFDFS VWEIWGPLLH GGRLVIVPHH
     VSRSPEAFLR LLVKEGVTVL NQTPSAFYQF MQAEREQPDL GQALSLRYVI FGGEALELSR
     LEDWYNRHPE NRPQLINMYG ITETTVHVSY IELDRSMAAL RANSLIGCGI PDLGVYVLDE
     RLQPVPPGVA GELYVSGAGL ARGYLGRPGL TSERFIADPF GPPGTRMYRT GDVARLRADG
     SLDYVGRADH QVKIRGFRIE LGEIEAALVQ HPQLEDAAVI VREDQPGDKR LAAYVIPSEE
     TFDTAELRRY AAERLPDYMV PAAFVTMKEL PLTPNGKLDR KALPAPDFAA AVTGRGPRTP
     QEEILCDLFM EVLHLPRVGI DDRFFDLGGH SLLAVQLMSR IREALGVELS IGNLFEAPTV
     AGLAERLEMG SSQSALDVLL PLRTSGDKPP LFCVHPAGGL SWCYAGLMTN IGTDYPIYGL
     QARGIGQREE LPKTLDDMAA DYIKQIRTVQ PKGPYHLLGW SLGGNVVQAM ATQLQNQGEE
     VSLLVMLDAY PNHFLPIKEA PDDEEALIAL LALGGYDPDS LGEKPLDFEA AIEILRRDGS
     ALASLDETVI LNLKNTYVNS VGILGSYKPK TFRGNVLFFR STIIPEWFDP IEPDSWKPYI
     NGQIEQIDID CRHKDLCQPE PLAQIGKVLA VKLEELNK