Development of a bio-enabled synthesis for the Glycopeptide Antibiotics

This project aims to develop an in vitro biomimetic synthesis for glycopeptide antibiotics (GPAs) by combining peptide synthesis and crosslinking catalysed by biosynthetic Cytochrome P450 enzymes. The crosslinking step in GPA biosynthesis is a unique and complex process that is essential for antibiotic activity and is the major impediment to their chemical synthesis. Thus, by studying the in vitro behaviour and characteristics of the biosynthetic P450 enzymes goals are to recreate the natural enzymatic crosslinking cascade in vitro; characterize the mechanism and substrate specificity of these P450 enzymes; determine the structural basis that underpins their activity; and exploit these P450s in novel chemical synthesis.