Using Marine Natural Products to Discover a Protease that Catalyzes Peptide Macrocyclization of Diverse Substrates

Small N-C terminally cyclic ribosomal peptides are common in nature, yet the mechanisms underlying their biosyntheses remain largely unknown. We recently identified candidate peptide cyclase genes in the metagenomes of marine animals. Here we report that PatG, a protease discovered in this analysis, cleaves variables, short peptides out of a precursor protein, and cyclizes these peptides in vivo and in vitro.