Natural Peptides with Antimicrobial Activity

Antibiosis is a mechanism by which many cell types control potential environmental takeover or pathogenicity by microbes, especially bacteria. It is now clear that a large proportion of the antimicrobial compounds produced by various cells and organisms including bacteria, fungi, plants, insects, amphibia and mammals are antibiotics based around peptides. These antimicrobial peptides can be broadly subdivided into two groups: those which are produced by multienzyme complexes and those which are encoded by a structural gene, the transcription and translation of which results in a peptide template which may (in some cases) undergo further enzymatic modifications. In this context, the chemistry, biosynthesis and functional aspects of a broad range of bioactive peptides from both subgroups will be briefly discussed, including: gramicidin, bacitracin, valinomycin, alamethicin and polymixin B from the first group, and defensins (and related peptides), bacteriocins, lantibiotics and microcins from the second subgroup. From a biotechnological perspective, the peptide antibiotics produced by multienzyme complexes are open to a variety of manipulations to produce novel antibiotic compounds, whilst the ribosomally synthesised peptides may be specifically altered by site-directed mutagenesis. Furthermore, the enzymes capable of transforming some ribosomally synthesised peptide antibiotics may be of particular interest to the biotechnologist, because of the novel transformations of peptide substrates which they are able to perform.