CcpN (YqzB), a novel regulator for CcpA-independent catabolite repression of Bacillus subtilis gluconeogenic genes.
In Bacillus subtilis, the NADPH-dependent glyceraldehyde-3-phosphate dehydrogenase (GapB) and the phosphoenolpyruvate carboxykinase (PckA) enzymes are necessary for efficient gluconeogenesis from Krebs cycle intermediates. gapB and pckA transcription is repressed in the presence of glucose but not via CcpA, the major transcriptional regulator for catabolite repression in B. subtilis. A B. subtilis mini-Tn10 transposant library was screened for clones affected in catabolite repression of gapB. Inactivation of a previously unknown gene, yqzB (renamed ccpN for control catabolite protein of gluconeogenic genes), was found to relieve not only gapB but also pckA transcription from catabolite repression. Purified CcpN specifically bound to the gapB and pckA promoters. ccpN is co-transcribed constitutively with another unknown gene, yqfL. A yqfL deletion lowers the level of gapB and pckA transcription threefold under both glycolytic and gluconeogenic conditions and a ccpN deletion is epistatic over a yqfL deletion. YqfL is thus a positive regulator of the expression of gapB and pckA, the effect of which is not influenced by the metabolic regime of the cell but appears to be mediated by CcpN. ccpN has homologues in many Firmicutes, but not all, while yqfL homologues are widely distributed in Eubacteria and also present in some plants. In all analysed bacterial genomes, ccpN and yqfL are physically linked together or to putative gluconeogenic genes. CcpN thus orchestrates a novel CcpA-independent mechanism for catabolite repression of gluconeogenic genes highly conserved in Firmicutes and appears as a functional analogue of FruR in Enterobacteria. The physiological significance of the regulation mediated via the three B. subtilis global transcription regulators, CcpA, CggR and CcpN, is discussed.
Servant
Pascale
P
Microbiologie et Génétique Moléculaire, INRA (UMR1238) and CNRS (UMR2585), Institut National Agronomique Paris-Grignon, F-78850 Thiverval-Grignon, France.
Le Coq
Dominique
D
Aymerich
Stéphane
S
D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005943:Gluconeogenesis; D005947:Glucose / Q000494:pharmacology; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C069286:catabolite control proteins, bacteria; D005947:Glucose