Analysis of new target genes isolated from genome analysis : towards development of new antibiotics

点击翻译按钮获取中文摘要

I have examined functions of two new genes, yycFG and ywlC, essential for call growth of Bacillus subtilis. The gene products could be good targets for new antibiotics because of their newness and essentiality.1.yycF and yycG : The yycF gene encoding a response regulator of a two-component regulatory system was reported recently to be essential for the cell growth, although genes under their control have yet to be identified (Fabret & Hoch, 1998). We also noted the essential nature of the yycF regulator gene and its cognate kinase gene, yycG, in B.subtilis during the course of construction of a knockout mutant bank of the newly identified genes in the genome sequence project. In addition, we found production of mini-cells and reduction in cell length when the YycF regulator was overproduced in B.subtilis. These observations led to the finding that YycF overproduction up-regulated the expression from the P1 promoter of the cell division operon, ftsAZ. In addition, the YycF protein binds to the P1 promoter region in vitro. These results clearly indicate that the essential two-component regulatory system encoded by yycF and yycG genes has the potential to modulate expression of the ftsAZ operon in B.subtilis.2.ywlC : This gene belongs to the SUA5 family that is conserved in eubacteria and yeast but its function is unknown. As a disruption mutant yeast SUA5 gene is known not to grow in a medium containing lactate as the carbon source, we tested the possibility in B.subtilis under depletion of the YwlC protein. Cells could grow under the condition, suggesting that B.subtilis ywlC functions differently from yeast SUA5. Interestingly, it was also found that transcription of ywlC was repressed by DnaA, a key factor of initiation of chromosome replication.