Three Ring Posttranslational Circuses: Insertion of Oxazoles Thiazoles and Pyridines into Protein-Derived Frameworks

摘要

Nitrogen heterocycles are the key functional and structural elements in both RNA and DNA, in half a dozen of the most important coenzymes, and in many synthetic drug scaffolds. On the other hand, only three of twenty proteinogenic amino acids have nitrogen heterocycles: proline, histidine and tryptophan. This inventory can be augmented in microbial proteins by posttranslational modifications downstream of leader peptide regions that convert up to ten serine, threonine and cysteine residues, side chains and peptide backbones, into oxazoles, thiazoles, and pyridine rings. Subsequent proteolysis releases these heterocyclic scaffolds in both linear and macrocyclic frameworks as bioactive small molecules.