FemABX family members are novel nonribosomal peptidyltransferases and important pathogen-specific drug targets.
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 nonribosomal 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.
Hegde
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Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Shrader
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TE
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000502:physiology*; D004926:Escherichia coli / Q000378:metabolism; D007778:Lactobacillus / Q000201:enzymology; D008954:Models, Biological; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010458:Peptidyl Transferases / Q000737:chemistry / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D021241:Spectrometry, Mass, Electrospray Ionization; D013379:Substrate Specificity
D001426:Bacterial Proteins; C096686:FemA protein, Bacteria; C102928:FemB protein, Staphylococcus epidermidis; D011994:Recombinant Proteins; D010458:Peptidyl Transferases