Peptide Antibiotics

Abstract

This chapter focuses on the peptide antibiotics, as these are the predominant class of Bacillus special metabolite that has been characterized biochemically and by the methods of molecular biology and genetics. Although the peptide antibiotics are composed of amino acids, they often show little similarity to gene-encoded polypeptides in terms of structure and mechanism of their biosynthesis. The amino acids can be linked to each other by peptide bonds or through the formation of lactones and esters. In some cases, they contain amino and hydroxy acids linked by alternating peptide and ester bonds, an arrangement found in a class of peptide antibiotics called depsipeptides. A compilation of peptide antibiotics produced by Bacillus spp. and other gram-positive bacteria is provided in the chapter. Peptide antibiotics are synthesized by one of two mechanisms, ribosomal and nonribosomal. The chapter discusses biochemistry and molecular biology of peptide antibiotic synthesis in BacillusSpp. The production of special metabolites is one of several complex responses to growth limitation, as is the case in Bacillus spp. Like Bacillus spp., actinomycetes such as Streptomyces spp. undergo cellular differentiation upon nutritional deprivation. A structural model of peptide synthetases began to emerge with the isolation and primary-structure determination of a tripeptide-synthesizing enzyme found in β-lactam producers. Biosynthesis of β-lactams begins with synthesis of the tripeptide d-(L-a-aminoadipoyl)-L-cysteinyl-D-valine (ACV) followed by the cyclization of ACV to form isopenicillin N. The continued study of special metabolites is of fundamental importance to one's understanding of the microbial world.