초록
<P><B>Background</B></P><P><I>Clostridium acetobutylicum</I> 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 <I>C. acetobutylicum</I> by our previous work (Ren, C. et al. 2010, Metab Eng <B>12:</B>446<B>–</B>54). To further dissect its regulatory function in <I>C. acetobutylicum</I>, CcpA was investigated using DNA microarray followed by phenotypic, genetic and biochemical validation.</P><P><B>Results</B></P><P>CcpA controls not only genes in carbon metabolism, but also those genes in solvent production and sporulation of the life cycle in <I>C. acetobutylicum</I>: <I>i</I>) CcpA directly repressed transcription of genes related to transport and metabolism of non-preferred carbon sources such as <SMALL>D</SMALL>-xylose and <SMALL>L</SMALL>-arabinose, and activated expression of genes responsible for <SMALL>D</SMALL>-glucose PTS system; <I>ii</I>) CcpA is involved in positive regulation of the key solventogenic operon <I>sol</I> (<I>adhE1-ctfA-ctfB</I>) and negative regulation of acidogenic gene <I>bukII</I>; and <I>iii</I>) transcriptional alterations were observed for several sporulation-related genes upon <I>ccpA</I> inactivation, which may account for the lower sporulation efficiency in the mutant, suggesting CcpA may be necessary for efficient sporulation of <I>C. acetobutylicum</I>, an important trait adversely affecting the solvent productivity.</P><P><B>Conclusions</B></P><P>This study provided insights to the pleiotropic functions that CcpA displayed in butanol-producing <I>C. acetobutylicum</I>. The information could be valuable for further dissecting its pleiotropic regulatory mechanism in <I>C. acetobutylicum</I>, and for genetic modification in order to obtain more effective butanol-producing <I>Clostridium</I> strains.</P>