Engineering Clickable Peptides for Selective Antibiotic Derivatisation

Antibiotics are the foundation of modern healthcare. Without them, standard surgeries, cancer treatment and modern maternity care are impossible. The antimicrobial resistance crisis continues to grow as antibiotic development stagnates. Technology to produce new antibiotics and derivatise existing ones are rapidly needed. Our traditional source of antibiotics has been microorganisims through their extraordinary ability to produce complex small molecules. Much effort has focused on engineering these pathways to produce novel derivatives, however these have faltered due to a lack of understanding of the constituent enzymes. Here we propose to integrate a chemical approach with pathway engineering to producing natural product peptide antibiotics both, to generate a greater understanding of these pathways and, develop a platform for antibiotic derivatisation to combat resistance and extend the life of existing antibiotics.