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Description: trigger enzyme: transcriptional repressor (BirA family) of the biotin operon / biotin-protein ligase

Name: birA
Locus: BSU22440BsubCyc
pI: 6.0
MW: 36.0 kDa
Protein length: 325 aaBLASTSequence
Gene length: 975 bpBLASTSequenceSequence + Flanks
Function: regulation of biotin synthesis, addition of biotin to proteins
Product: trigger enzyme: transcriptional repressor (BirA family)/ biotin-protein ligase
Essential: yes
E.C. number:
Databases: SubtiListKEGGUniProtExpression data browser

Categories containing this gene/protein

biosynthesis of lipids, biosynthesis of cofactors, transcription factors and their control, trigger enzyme, essential genes

This gene is a member of the following regulons

Spx regulon

The BirA regulon


  • Coordinates on the chromosome (coding sequence): 2,354,918 -> 2,355,895
  • Phenotypes of a mutant

  • essential PubMed
  • The protein

    Catalyzed reaction/ biological activity

  • transcriptional repressor of the bioW-bioA-bioF-bioD-bioB-bioI-ytbQ operon PubMed and
  • ATP biotin apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] = AMP diphosphate [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] (according to Swiss-Prot)
  • Protein family

  • (BirA family), pyrroline-5-carboxylate reductase family (according to Swiss-Prot)
  • Paralogous protein(s)

    Kinetic information




    Effectors of protein activity


  • 4HA8
  • Localization

  • cytoplasm (according to Swiss-Prot)
  • Interactions

  • BirA-AccB PubMed
  • BirA-PycA PubMed
  • BirA-YngHB PubMed
  • Additional information

    Expression and Regulation


  • ypjD-dapB-mgsA-bshB1-bshA-cca-birA PubMed
  • Sigma factor

  • SigA PubMed
  • Regulation

  • induced by diamide stess (thiol depletion) (Spx) PubMed
  • Regulatory mechanism

  • Spx: transcription activation PubMed
  • Additional information

    Biological materials


    Expression vector

  • pGP2690: expression in E. coli, with N-terminal His-tag, in pWH844, available in Jörg Stülke' lab
  • pGP2700: expression in B. subtilis, with N-terminal Strep-tag, in pGP380, available in Jörg Stülke' lab
  • lacZ fusion

    GFP fusion

    two-hybrid system

  • B. pertussis adenylate cyclase-based bacterial two hybrid system (BACTH), available in Jörg Stülke's lab
  • FLAG-tag construct


  • available in Jörg Stülke's lab
  • Labs working on this gene/protein



    Commichau FM, Stülke J

    Trigger Enzymes: Coordination of Metabolism and Virulence Gene Expression

    Microbiol Spectr. 2015 Aug;3(4). doi: 10.1128/microbiolspec.MBP-0010-2014. Review. PubMed PMID: 26350309.
    Lin S, Cronan JE

    Closing in on complete pathways of biotin biosynthesis

    Mol Biosyst. 2011 Jun;7(6):1811-21. doi: 10.1039/c1mb05022b. Epub 2011 Mar 24. Review. PubMed PMID: 21437340.
    Commichau FM, Stülke J

    Trigger enzymes: bifunctional proteins active in metabolism and in controlling gene expression

    Mol Microbiol. 2008 Feb;67(4):692-702. Epub 2007 Dec 11. Review. PubMed PMID: 18086213.
    Rodionov DA, Mironov AA, Gelfand MS

    Conservation of the biotin regulon and the BirA regulatory signal in Eubacteria and Archaea

    Genome Res. 2002 Oct;12(10):1507-16. PubMed PMID: 12368242; PubMed Central PMCID: PMC187538.

    Original publications

    Henke SK, Cronan JE

    Successful conversion of the Bacillus subtilis BirA Group II biotin protein ligase into a Group I ligase

    PLoS One. 2014 May 9;9(5):e96757. doi: 10.1371/journal.pone.0096757. eCollection 2014. PubMed PMID: 24816803; PubMed Central PMCID: PMC4016012.
    Chakravartty V, Cronan JE

    The wing of a winged helix-turn-helix transcription factor organizes the active site of BirA, a bifunctional repressor/ligase

    J Biol Chem. 2013 Dec 13;288(50):36029-39. doi: 10.1074/jbc.M113.525618. Epub 2013 Nov 4. PubMed PMID: 24189073; PubMed Central PMCID: PMC3861651.
    Gaballa A, Antelmann H, Hamilton CJ, Helmann JD

    Regulation of Bacillus subtilis bacillithiol biosynthesis operons by Spx

    Microbiology. 2013 Oct;159(Pt 10):2025-35. doi: 10.1099/mic.0.070482-0. Epub 2013 Jul 26. PubMed PMID: 23894131.
    Soares da Costa TP, Tieu W, Yap MY, Pendini NR, Polyak SW, Sejer Pedersen D, Morona R, Turnidge JD, Wallace JC, Wilce MC, Booker GW, Abell AD

    Selective inhibition of biotin protein ligase from Staphylococcus aureus

    J Biol Chem. 2012 May 18;287(21):17823-32. doi: 10.1074/jbc.M112.356576. Epub 2012 Mar 21. PubMed PMID: 22437830; PubMed Central PMCID: PMC3366794.
    Gaballa A, Newton GL, Antelmann H, Parsonage D, Upton H, Rawat M, Claiborne A, Fahey RC, Helmann JD

    Biosynthesis and functions of bacillithiol, a major low-molecular-weight thiol in Bacilli

    Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6482-6. doi: 10.1073/pnas.1000928107. Epub 2010 Mar 22. PubMed PMID: 20308541; PubMed Central PMCID: PMC2851989.
    Lee JM, Zhang S, Saha S, Santa Anna S, Jiang C, Perkins J

    RNA expression analysis using an antisense Bacillus subtilis genome array

    J Bacteriol. 2001 Dec;183(24):7371-80. PubMed PMID: 11717296; PubMed Central PMCID: PMC95586.
    Perkins JB, Bower S, Howitt CL, Yocum RR, Pero J

    Identification and characterization of transcripts from the biotin biosynthetic operon of Bacillus subtilis

    J Bacteriol. 1996 Nov;178(21):6361-5. PubMed PMID: 8892842; PubMed Central PMCID: PMC178513.
    Bower S, Perkins JB, Yocum RR, Howitt CL, Rahaim P, Pero J

    Cloning, sequencing, and characterization of the Bacillus subtilis biotin biosynthetic operon

    J Bacteriol. 1996 Jul;178(14):4122-30. PubMed PMID: 8763940; PubMed Central PMCID: PMC178169.
    Bower S, Perkins J, Yocum RR, Serror P, Sorokin A, Rahaim P, Howitt CL, Prasad N, Ehrlich SD, Pero J

    Cloning and characterization of the Bacillus subtilis birA gene encoding a repressor of the biotin operon

    J Bacteriol. 1995 May;177(9):2572-5. PubMed PMID: 7730294; PubMed Central PMCID: PMC176921.
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