Ribosomal Biosynthesis of Two Cyclic Peptides from Cyanobacteria: Identification and Characterisation of Microcyclamide and Microviridin Biosynthesis Pathways in Freshwater Cyanobacteria

Microbial natural products represent a major source for the development of new therapeutic agents. A diverse array of compounds is produced by cyanobacteria. A variety of bioactive metabolites with potential anti-cancer, anti-microbial and anti-HIV activities have been isolated. Microcystis aeruginosa NIES298 produces various peptides including microcystin, aeruginosin, microviridin and microcyclamide. For the latter two classes of peptides ribosomal biosynthesis pathways could be identified in the course of this study. The cytotoxic hexapeptide microcyclamide is formed through the activity of a set of enzymes closely related to those involved in patellamide biosynthesis. The multicyclic microviridin family of protease inhibitors are synthesised from a precursor peptide by a unique pathway involving uncharted ATP-grasp type ligases as well as an N-acetyltransferase and a specialised transporter peptidase. Finally, this work showed that such scanning approaches could lead to the discovery of novel peptide variants and demonstrated new examples of succesful genome mining.