Evolution and engineering of non-ribosomal peptide synthetases


The discovery & development of penicillin sparked ‘The Golden Age of Antibiotics’ which spanned the 1940’s to 1960’s when most major classes of antibiotics were discovered. Indeed, most antibiotics in clinical use today are derived from natural products made by bacteria.

Alarmingly, the pipeline of new antibiotics has dried up at a time when Antimicrobial Resistance (AMR) and emerging new pathogens has made their discovery a matter of extreme urgency. AMR is an increasingly serious threat to global public health.

This project will use principles learned from evolutionary studies, in combination with protein modelling, to rationally engineer the machinery bacteria use to produce new antibiotics for the treatment of drug resistant pathogens.

The successful candidate will have access to cutting-edge research facilities as well as a stimulating research and training environment. They will be part of an interdisciplinary team and the project provides an exceptional training opportunity in microbiology & molecular microbiology, enzymology and protein purification, protein modelling, antibiotic biosynthesis and function, and analytical & natural products chemistry.

The combination of skills and experience provided by this studentship will make the successful candidate highly employable in both academia and industry.

[1] K. A. J. Bozhueyuek, J. Micklefield & Barrie Wilkinson (2019). Engineering enzymatic assembly lines to produce new antibiotics. Curr. Opin. Microbiol. 51:88-96.

[2] T. J. Booth et al (2021). Bifurcation drives the evolution of assembley-line biosynthesis. BioRxiv preprint. Doi.org/10.1101/2021.06.23.449585.

[3] M. I. Hutchings, A. W. Truman & Barrie Wilkinson (2019). Antibiotics: past, present and future. Curr. Opin. Microbiol. 51:72-80.