Discovery and Application of a Novel Enzyme Capping the N-Terminus of Peptides
Novel peptide ligase
・We discovered a novel enzyme catalyzing the attachment of non-proteinogenic amino acids to the amino termini of various peptides.
・It is expected to lead to the protection of useful bioactive peptides and the development of new anti-tuberculosis drugs.
Content of 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).
Potential for social implementation
- ・Protection of useful bioactive peptides against degrading enzymes
- ・Creation of internal standards for quantitative proteomic analysis using mass spectrometry (MS)
- ・Development of new anti-tuberculosis drugs
Appealing points to industry and local governments
At the Dairi Laboratory, biosynthetic engineering is the key concept underlying the (1) biosynthetic studies and their application to produce useful compounds with microorganisms. Enzymatic methods are also applied to produce valuable compounds. We also (2) explore new primary metabolic pathways essential for growth of pathogenic microorganisms and search for inhibitors of these new pathways.