Combining biocatalysis and chemoselective chemistries for glycopeptide antibiotics modification

Abstract

Glycopeptide antibiotics are clinically important medicines to treat serious Gram-positive bacterial infections. The emergence of glycopeptide resistance among pathogens has motivated considerable interest in expanding structural diversity of glycopeptide to counteract resistance. The complex structure of glycopeptide poses substantial barriers to conventional chemical methods for structural modifications. By contrast, biochemical approaches have attracted great attention because ample biosynthetic information and sophisticated toolboxes have been made available to change reaction specificity through protein engineering, domain swapping, pathway engineering, addition of substrate analogs, and mutagenesis.