Project Summary/Abstract Lantibiotics are ribosomally synthesized and post-translationally modified peptide natural products. The biosynthetic enzymes that convert peptide substrates into constrained antibiotics are not well understood, especially with regards to substrate recognition. Here, we seek to carry out biochemical, and structural biological studies on several of these enzymes and address questions regarding substrate recognition, and substrate tolerance. We anticipate that this work will be of use not only towards the discovery of new compounds but to enable the production of peptide-based compounds of any structure.