Research

Engineering RiPP Biosynthetic Enzymes

In addition to discovery, the Chekan Lab is also interested in engineering new RiPP pathways, enzymes, and novel compounds with the goal of identifying new drug leads. Many RiPP biosynthetic enzymes found in nature contain two domains. One is responsible for binding to the leader portion of the peptide substrate and is called the RiPP Recognition Element (RRE). The other domain catalyzes modification to the core peptide to generate the product. This two domain architecture has the advantage of separating substrate binding from catalysis and produces an enzyme that can perform chemistry on a wide range of peptide substrates. The Chekan lab is working to exploit this feature of RiPP enzymes by engineering new peptide modification enzymes that can be added to existing RiPP pathways or combined together to create novel RiPP pathways not found in nature. Ultimately, these engineered RiPP enzymes will be used to develop new bioactive RiPP natural product analogs.