Non-ribosomal peptide synthetases (NRPSs) are large enzymes that generate a variety of important natural products, from antibiotics to immunosuppressants. In fact, a majority of drugs in clinical use today were inspired by non-ribosomal peptide or polyketide natural products, discovered from environmental sources. These modular enzymes function like an assembly line, selecting and incorporating specific (and frequently non- proteinogenic) amino acids into a growing peptide chain. This modular structure offers promise for re-engineering NRPS units to generate new useful products, but progress has to date been limited by the complex and dynamic nature of key domains, and a failure to define generally applicable “rules” to guide engineering efforts. NRPS research in the Ackerley lab explores ways to overcome these hurdles, aiming to re-engineer NRPS biosynthetic gene clusters to produce novel natural products with useful bioactivities, or superior drug leads.
Combinatorial biosynthesis of natural products