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Exploiting a novel peptide cyclase to make new antibiotics

Project Description

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.

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2020:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference and research funding

At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.

EU candidates require 3 years of UK residency to receive full studentship

Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.

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How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

Research output data provided by the Research Excellence Framework (REF)

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