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Lantibiotics—Ribosomally Synthesized Biologically Active Polypeptides containing Sulfide Bridges and α,β‐Didehydroamino Acids

1991; Wiley; Volume: 30; Issue: 9 Linguagem: Inglês

10.1002/anie.199110513

1521-3773

Günther Jung,

Monoclonal and Polyclonal Antibodies Research

Abstract Lantibiotics are polycyclic peptide antibiotics containing intrachain sulfide bridges, formed from the thioether groups of the amino acids lanthionine and β‐methyllanthionine. They also contain α,β‐unsaturated amino acids such as didehydroalanine and didehydroaminobutyric acid. A knowledge of the lantibiotic biosynthetic steps and the enzymes involved makes possible a gene technological construction of analogous highly modified polypeptides. To the family of lantibiotics belong nisin, an important food preservative, epidermin, a highly specific therapeutic agent against acne, a series of enzyme inhibitors, as well as immunologically interesting active peptides. Lantibiotics are produced by ribosomal synthesis, starting from inactive precursor proteins (prelantibiotics). The latter are post‐translationally converted into the active peptide antibiotics through enzymic modifications. The modifying enzymes effect dehydrations at the serine and threonine residues and stereospecific additions of the cysteine thiol groups to the resulting α,β‐unsaturated double bonds, which lead to the formation of several sulfide bridges. Upon subsequent proteolytic cleavage of the leader peptide, the biologically active lantibiotic is formed. Conformational analyses of the lantibiotics, as well as of their prepeptides, enables one to obtain information about the mechanism and steps of the biosynthesis. Antibodies against synthetic prepeptide sequences, and modern instrumental methods for the analysis of peptides, allow structural elucidation of the biosynthetic intermediates.