Abstract:

The posttranslational modifications (PTMs) in RiPPs (ribosomally synthesized and post-translationally modified peptides) dictate their 3D structure and their bioactivity. An underlying structural feature of many RiPPs is macrocyclization, installed by a growing number of different enzymatic strategies. Another common class of PTM in RiPPs is backbone modification, such as the formation of thiazol(in)es and oxazol(in)es. Our group has recently been interested in aspartimidylation, a backbone modification occurring at Asp residues that installs a metastable succinimide moiety into several different RiPPs. This talk will focus on recent work on the O-methyltransferase enzymes that install aspartimide in lasso peptides, graspetides, and a new class of peptides, the imiditides. The surprising stability of these aspartimide moieties will also be discussed within a kinetic framework. Finally, the talk will discuss potential chemical and biological ramifications of the aspartimide moiety in RiPPs.