Posttranslational formation of cyclophanes in bacteria
Cyclic peptide natural products are important chemical entities for human health and treating
diseases. The identification and application of methods that can robustly cyclize peptides has broad applications in research and industry.
Of particular interest are transformations that can create novel scaffolds for unique binding to biological targets and that protect the peptide from proteolytic degradation. The use of genome mining and synthetic biology expedites the discovery, design, production, and application processes to discover these biocatalysts.
I will share how our group used the radical SAM superfamily of enzymes as a starting point to identify a broadly distributed and novel subfamily that creates unique peptide-derived cyclophanes.
The cyclophane forming reaction is characterized by C(sp2)-Cb(sp3) bond formation on 3-residue motifs. Our objectives are to understand the chemical diversity that can be achieved using posttranslational cyclophane forming enzymes and then move to targeted applications relevant to infectious diseases.
Our results to date will demonstrate the range of peptide scaffolds that can be created, their potential uses, and direction of our research group.