Exploiting a novel peptide cyclase to make new antibiotics

Without new antibiotics the global healthcare system will collapse. Many antibiotics originate from a class of microbial natural products called non-ribosomal peptides, the vast majority of which are cyclic. Cyclisation of these peptides is often inefficient so new approaches are sought after in this area. We recently identified a novel non-ribosomal peptide cyclase with considerable substrate promiscuity. If this promiscuity can be understood, then it can be harnessed for biotechnology to improve chemical synthesis of antibiotics and other high-value cyclic peptides.

In this project you will purify the peptide cyclase and interrogate its substrate specificity in vitro. You will also pursue structural studies with the cyclase using X-ray crystallography and use the resulting structure to rationally re-engineer its substrate specificity. The activities pursued during the project are supported by World-class infrastructure and support within the Astbury Centre for Structural Molecular Biology. You will have an opportunity to learn a wide range of techniques including: protein purification, peptide synthesis, LC-MS, NMR, X-ray crystallography and many others. The outcomes of this project will have a direct impact on the AMR crisis by developing methodology for enhancing the synthesis of novel peptide antibiotics.