FemABX family members are novel nonribosomal peptidyltransferases and important pathogen-specific drug targets

Pathogen-specific antibiotics kill the offending species without inviting t he patient's flora to help develop a resistance mechanism The current scarc ity of pathogen-specific antibiotics reflects the rarity of essential genes that are also not widely represented in and conserved among species. The F emX enzyme that initiates the:synthesis of the interchain peptide of the pe ptidoglycan in a subset of bacterial species was purified from Lactobacillu s viridescens. Subsequently, the encoding femX gene was cloned and sequence d using reverse genetics. The femX gene is a member of the femAB family, a large family of genes previously implicated in interchain peptide synthesis but with unknown specific functions. Mutagenesis of the femX gene identifi ed the members of the extended FemABX family as novel nonribosomal peptidyl transferases. Determinants of FemX complex substrate recognition and a stro ng stimulator of FemX activity were also identified. The FemABX family memb ers are ideal candidates for pathogen-specific antibiotic development.