Elaborate transcription regulation of the Bacillus subtilis ilv-leu operon involved in the biosynthesis of branched-chain amino acids through global regulators of CcpA, CodY and TnrA

Mol Microbiol. 2005 Jun;56(6):1560-73. doi: 10.1111/j.1365-2958.2005.04635.x.


The Bacillus subtilis ilv-leu operon involved in the biosynthesis of branched-chain amino acids is under negative regulation mediated by TnrA and CodY, which recognize and bind to their respective cis-elements located upstream of the ilv-leu promoter. This operon is known to be under CcpA-dependent positive regulation. We have currently identified a catabolite-responsive element (cre) for this positive regulation (bases -96 to -82; +1 is the ilv-leu transcription initiation base) by means of DNase I-footprinting in vitro, and deletion and base-substitution analyses of cre. Under nitrogen-rich growth conditions in glucose-minimal medium supplemented with glutamine and amino acids, CcpA and CodY exerted positive and negative regulation of ilv-leu, respectively, but TnrA did not function. Moreover, CcpA and CodY were able to function without their counteracting regulation of each other, although the CcpA-dependent positive regulation did not overcome the CodY-dependent negative regulation. Furthermore, under nitrogen-limited conditions in glucose-minimal medium with glutamate as the sole nitrogen source, CcpA and TnrA exerted positive and negative regulation, respectively, but CodY did not function. This CcpA-dependent positive regulation occurred without the TnrA-dependent negative regulation. However, the TnrA-dependent negative regulation did not occur without the CcpA-dependent positive regulation, raising the possibility that this negative regulation might decrease the CcpA-dependent positive regulation. The physiological role of this elaborate transcription regulation of the B. subtilis ilv-leu operon in overall metabolic regulation in this organism is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Branched-Chain / biosynthesis*
  • Bacillus subtilis / genetics
  • Bacillus subtilis / growth & development
  • Bacillus subtilis / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • DNA Footprinting
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Bacterial*
  • Isoleucine / biosynthesis
  • Leucine / biosynthesis
  • Molecular Sequence Data
  • Nitrogen / metabolism
  • Operon*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Response Elements / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Valine / biosynthesis


  • Amino Acids, Branched-Chain
  • Bacterial Proteins
  • DNA-Binding Proteins
  • Repressor Proteins
  • ScgR protein, Bacillus subtilis
  • Transcription Factors
  • catabolite control proteins, bacteria
  • Isoleucine
  • Leucine
  • Valine
  • Nitrogen