CHAPTER 2: The Biosynthesis of Cyclic Peptides – RiPPs – An Overview

Cyclic peptides are of considerable interest because they possess protease resistant, rigid scaffolds that can be almost infinitely diversified. Their size and molecular complexity means that they are able to target protein–protein interactions, a task that current small molecule drugs struggle to achieve. Macrocyclic peptides can be synthesized using non-ribosomal peptide synthesis machineries – NRPS for short (see next chapter) – or through extensive modification of ribosomally synthesized peptide precursors (ribosomally synthesized and post-translationally modified peptides – RiPPs). RiPPs are attractive because they are genetically encoded and can be easily diversified. The same peptide precursors can be utilized to generate a wide array of natural products by “mixing-and-matching” enzymes involved in their post-translational modification. Here, we discuss the biosynthetic machineries producing the main classes of cyclic RiPPs.