Exploring the Post-translational Enzymology of PaaA by mRNA Display

PaaA is a RiPP enzyme that catalyzes
the transformation of two
glutamic acid residues within a substrate peptide into the bicyclic
core of Pantocin A. Here, for the first time, we use mRNA display
techniques to understand RiPP enzyme–substrate interactions
to illuminate PaaA substrate recognition. Additionally, our data revealed
insights into the enzymatic timing of glutamic acid modification.
The technique developed is quite sensitive and a significant advancement
over current RiPP studies and opens the door to enzyme modified mRNA
display libraries for natural product-like inhibitor pans.