title: Pleiotropic functions of catabolite control protein CcpA in Butanol-producing Clostridium acetobutylicum.
abstract: BACKGROUND
  Clostridium acetobutylicum has been used to produce butanol in industry. Catabolite control protein A (CcpA), known to mediate carbon catabolite repression (CCR) in low GC gram-positive bacteria, has been identified and characterized in C. acetobutylicum by our previous work (Ren, C. et al. 2010, Metab Eng 12:446-54). To further dissect its regulatory function in C. acetobutylicum, CcpA was investigated using DNA microarray followed by phenotypic, genetic and biochemical validation.
  
  
  RESULTS
  CcpA controls not only genes in carbon metabolism, but also those genes in solvent production and sporulation of the life cycle in C. acetobutylicum: i) CcpA directly repressed transcription of genes related to transport and metabolism of non-preferred carbon sources such as d-xylose and l-arabinose, and activated expression of genes responsible for d-glucose PTS system; ii) CcpA is involved in positive regulation of the key solventogenic operon sol (adhE1-ctfA-ctfB) and negative regulation of acidogenic gene bukII; and iii) transcriptional alterations were observed for several sporulation-related genes upon ccpA inactivation, which may account for the lower sporulation efficiency in the mutant, suggesting CcpA may be necessary for efficient sporulation of C. acetobutylicum, an important trait adversely affecting the solvent productivity.
  
  
  CONCLUSIONS
  This study provided insights to the pleiotropic functions that CcpA displayed in butanol-producing C. acetobutylicum. The information could be valuable for further dissecting its pleiotropic regulatory mechanism in C. acetobutylicum, and for genetic modification in order to obtain more effective butanol-producing Clostridium strains.
authors: Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 300 Fenglin Road, Shanghai 200032, China.
authors: Cong
authors: C
authors: Ren
authors: Yang
authors: Y
authors: Gu
authors: Yan
authors: Y
authors: Wu
authors: Weiwen
authors: W
authors: Zhang
authors: Chen
authors: C
authors: Yang
authors: Sheng
authors: S
authors: Yang
authors: Weihong
authors: W
authors: Jiang
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D000440:Butanols / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism; D046969:Clostridium acetobutylicum / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D015964:Gene Expression Regulation, Bacterial; D058685:Genetic Pleiotropy / Q000235:genetics*; D005947:Glucose / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D014994:Xylose / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D000440:Butanols; D012097:Repressor Proteins; C069286:catabolite control proteins, bacteria; D002244:Carbon; D014994:Xylose; D005947:Glucose