Macrocyclic peptide natural products are highly valued for their potent antibacterial, antifungal, antiviral, anticancer, and immunosuppressive activities. They possess desirable properties such as proteolytic stability, increased cell-membrane permeability, and conformational restrictions, making them attractive for therapeutic applications. Ribosomally synthesized and post-translationally modified peptides (RiPPs) often have macrocyclic structures, with biosynthesis involving gene-encoded precursor peptides modified by enzymes in a biosynthetic gene cluster. Thiopeptides, a type of macrocyclic RiPP, are known for inhibiting bacterial protein translation. However, creating thiopeptide derivatives with multiple variations is challenging.
This technology is a method for biosynthesis of novel pyritides thiopeptides, pyridine-based macrocyclic peptides. Pyritides may be useful for targeting pathogens and diseases that cannot be targeted with small molecules. The steps in the process constrain the peptides allowing modifications of the inner ring without interfering with the reaction.
Publication
Accessing Diverse Pyridine-Based Macrocyclic Peptides by a Two-Site Recognition Pathway