FemABX Family Members are Novel Nonribosomal Peptidyltransferases and Important Pathogen-specific Drug Targets

Abstract

Pathogen-specific antibiotics kill the offending species without inviting the patient's flora to help develop a resistance mechanism. The current scarcity of pathogen-specific antibiotics reflects the rarity of essential genes that are also not widely represented in and conserved among species. The FemX enzyme that initiates the synthesis of the interchain peptide of the peptidoglycan in a subset of bacterial species was purified from Lactobacillus viridescens. Subsequently, the encoding femX gene was cloned and sequenced 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 identified the members of the extended FemABX family as novel non-ribosomal peptidyltransferases. Determinants of FemX complex substrate recognition and a strong stimulator of FemX activity were also identified. The FemABX family members are ideal candidates for pathogen-specific antibiotic development.