Mechanisms and Evolution of Diversity-Generating RiPP Biosynthesis

This review focuses on the prochlorosin and cyanobactin biosynthetic pathways, unusual examples of pathways in cyanobacteria that appear to be diversity generating. In the case of prochlorosins, a single enzyme catalyzes post-translational modifications on an impressive number (10–80) of peptide substrates, resulting in polycyclic peptides of very different sizes and sequences. Like the prochlorosins, the cyanobactins are an extraordinarily diverse group of (mostly) cyclic peptides, but they are decorated further in parallel fashion by substrate-tolerant enzymes. This review discusses the current understanding of catalysis and possible evolutionary models that might explain the perplexing enzymatic tolerance of these systems.