Ribosomally synthesized and Post translationally modified Peptides (RiPPs) are a group of natural products. RiPPs are synthesized from a genetically encoded precursor peptide. The leader peptide and the core peptide are the two regions that make up the precursor peptide. The biosynthetic enzymes that install post-translational modifications (PTMs) recognize the leader peptide, and the core peptide is where those modifications are installed. The leader peptide is proteolytically cleaved after the PTMs are installed on the core peptide to produce the matured product. Microviridins, produced by cyanobacteria, are a class of RiPPs, whose precursor peptide is modified by ATP grasp ligases (MdnC and MdnB) to form two (2) lactone rings and one (1) lactam ring by the MdnC and MdnB respectively. This research project is geared towards gaining insight into how these enzymes in the RiPP biosynthetic pathways control reactivity and selectivity through deep mutational analysis and use this knowledge to generate enzymes with new and altered selectivity and reactivity. To achieve this goal, we will use Yeast surface display technology to screen enzyme mutants. As proof of concept, we have displayed MdnC on the surface of yeast cells. We were able to observe MdnC on the cell surface by flow cytometry, and that surface displayed MdnC was able to modify MdnA, determined by mass spectrometry. In the future, we will use directed evolution to create a library of yeast surface displayed mutant enzymes, and screen them for improved selectivity and reactivity with a library of genetically encoded precursor peptide substrates. The genetically encoded precursor peptide substrates modified by the mutant enzymes of highest selectivity and reactivity will be assayed for their biological activities and as a source of potential drug candidates.