Gene-encoded antibiotics made in bacteria

Production of antimicrobial peptides and proteins is very common among bacteria and a variety of such substances has been described. In general Gram-negative bacteria produce protein bacteriocins (e.g. colicins) with narrow action spectra based on receptor-mediated activity. They produce comparatively few peptides, such as the post-translationally modified microcin B17. In contrast Gram-positive bacteria tend to produce peptide bacteriocins smaller than 10 kDa and of wider activity spectra. These show particular potential for application. They can be divided into unmodified peptides (e.g. lactococcins, lactacins, pediocins) and lanthionine-containing peptides (lantibiotics, e.g. nisin, epidermin, Pep5). The unmodified peptides are mostly hydrophobic or amphiphilic and act by disturbing the function of the cytoplasmic membrane. They are synthesized as prepeptides with a characteristic N-terminal leader peptide. In some cases genes for immunity peptides were found in close proximity to structural genes; furthermore, two-component response regulators seem to be involved in the regulation of their synthesis. The biosynthetic genes for lantibiotics are also organized in operons. Lantibiotic gene clusters include genes encoding the unique enzymes which dehydrate serine and threonine and form the characteristic thioether-bridged lanthionines. Three types of lantibiotics are currently distinguished on the basis of structural features and functional aspects: type A, which include elongated, amphiphilic, pore-forming peptides (e.g. nisin); type B, which are of globular shape and inhibit phospholipases (e.g. duramycins); and type C (e.g. actagardine) with intermediate features which act by inhibiting bacterial cell wall biosynthesis.