SCREENING METHODS FOR THE IDENTIFICATION OF NOVEL ANTIBIOTICS

摘要

The present invention relates to screening methods for the identification of compounds and compositions useful as novel antibiotics and antibacterial agents. In particular, the present invention relates to methods utilizing twocomponent regulatory switches, for example, those comprising a prokaryotic enzyme such as histidine protein kinase that is activated to autophosphorylate by a signal transduction mechanism. The invention also relates to methods of identifying inhibitors of enzyme activity, particularly in bacterial cells. In particular, a high-throughput assay system useful in the large-scale screening of protein kinase inhibitors is disclosed. Related kits, compositions and components are also disclosed. The figure illustrates the phosphorylation of SpoOF including a histidine linker or tag ("His-SpoOF") by KinA.