RiPPs: Ribosomally Synthesized and Posttranslationally Modified Peptides

This chapter discusses the biosynthesis, structure, and bioengineering of the main classes of bacterially produced ribosomally synthesized and posttranslationally modified peptides (RiPPs). Lanthionine-containing peptides (lanthipeptides) represent the longest known class of RiPPs. Thiazol(in)e and (methyl)oxazol(in)e containing RiPPs are produced by many genera of Gram-negative and Gram-positive bacteria and have been identified through genome mining and PCR analysis. Thiopeptides are thiazole and oxazole rich, macrocyclic natural products with a central six-membered nitrogen-containing heterocycle. Cyanobactins are a class of small, head-to-tail cyclized peptides produced by cyanobacteria that often contain thiazolines and oxazolines, or their oxidized counterparts thiazoles and oxazoles. Cyanobactins have been interesting to the medical community for decades because of their cytotoxic, antimalarial, and antibacterial activities. Many secondary metabolites produced by cyanobacteria, including the depsipeptides anabaenopeptilide 90A and 90B, are of non-ribosomal origin. The biosynthetic machinery of sactipeptides has been partially characterized for subtilosin A.