Antibiotic Produced by Pseudomonas fluorescens

Rapid increase of resistance to antibacterial agents in recent years has become a major global public health problem.1,2) The development of antibiotics with novel mechanisms of action is one of the most important measures leading to the control of bacterial infectious diseases in the new millennium. The genomic antibacterial approach plays a critical role in the discovery of new targets by searching for genes essential to the growth of bacteria. In the course of screening with a broad set of genomicderived targets, a new metabolite Sch 419560 (1), was discovered from the fermentation culture broth of a bacterial strain identified as Pseudomonas fluorescens. The level of expression of the rpoE gene affected the biological activity for 1 against an E. coli laboratory strain. In E. coli, rpoE encodes a sigma factor that is responsible for the regulation of expression of a subset of genes.3) The genes known to be regulated by rpoE encompass stress responserelated activities described as extra-cytoplasmic-functions.4) rpoE activity is essential for the viability of E. coli and is considered an attractive target for the development of novel antibacterial agents.5) This paper describes fermentation, isolation, structure elucidation and biological activity of 1. The frozen whole broth of the producing organism (1ml) was transferred to a germination medium consisting of BBL Trypticase soy broth 30g/liter. The culture was