Unveiling the Origins of Modern Lipid II Targeting Glycopeptides: Resurrecting Ancestral Antibiotics

Researchers have used ancient DNA to investigate the evolutionary history of lipid II targeting glycopeptide antibiotics (GPAs), a class of antibiotics used to treat resistant bacterial infections. They discovered that modern GPAs have evolved from an ancestral GPA called paleomycin, which resembles the more complex structure of teicoplanin. By reconstituting the biosynthesis of paleomycin, the researchers confirmed its antibiotic activity. They also identified the genetic changes that led to the evolution of modern GPAs, including alterations in the peptide core and changes in the biosynthesis of key components. This study provides insights into the evolution of GPAs and could aid in the development of new antibiotics.