CHAPTER 4: The Biosynthetic Machinery and Its Potential to Deliver Unnatural Cyclic Peptides

Biologically active cyclic peptides represent an important part of the secondary metabolites produced by fungi and bacteria. Based on their biosynthesis pathways, peptides can be divided into two main groups; the first group involves ribosomally synthesized and post-translationally modified peptides (RiPPs), while members of the second group are synthesized by non-ribosomal peptide synthetases (NRPSs). This chapter covers the main methods used for in vivo generation of non-natural cyclic peptides, in RiPP or NRP pathways, shedding light on the most prominent examples of these methodologies, which in future may serve in Chemical Biology as probes to investigate cellular processes and biosynthesis mechanisms or lead to new drug leads.