Research

One of the disadvantages of using peptides as pharmaceuticals is that they are degraded by peptidases. Since exo-type peptidases acting on peptide termini are mostly responsible for degradation in humans, attachments of non-proteinogenic amino acids to the peptide termini is valuable from the viewpoint of protecting them from degrading enzymes for drug development. In this study, as a result of biosynthetic studies of the peptide antibiotic pheganomycin, we found an enzyme that capped the amino terminus of various peptides consisting of 2 to 18 amino acids with a phenylglycine derivative, which is a non-proteinogenic amino acids. To understand the broad substrate specificity, we solved the crystal structure of the enzyme and found that the enzyme has a large substrate binding site, which is not found with other enzymes, and that can thus accept a variety of substrates. Nat. Chem. Biol., 11, 71 (2015).