Bacteria have evolved the ability to produce natural products with potent bioactivities, which makes these compounds excellent candidates as medicines and agrochemicals. Actinobacteria are particularly “talented” at producing natural products (also known as specialised metabolites), including the majority of clinically used classes of antibiotics, as well as many other compounds used across medicine and agriculture. However, surprisingly little is known about when and why these molecules are made in nature. The aim of this project is to understand how an agriculturally important bacterium uses specialised metabolites to infect plants.
This project will focus on a plant-associated actinobacterial pathogen, and will span microbiology, genetics, mass spectrometry, natural product chemistry and plant science. The project will lead to the discovery of new natural products, as well as understanding the mechanism of their activity towards plants or other microbes. This multidisciplinary project will be based in the laboratory of Dr Andrew Truman in the Department of Molecular Microbiology at the John Innes Centre, which has world-class facilities for bacterial genetics and natural product biosynthesis. Further expertise is provided by secondary supervisor Prof. Barrie Wilkinson (John Innes Centre), who is an expert in studying the biosynthesis and ecology of antibiotic production by Actinobacteria.
This project provides an exciting opportunity to discover new bioactive molecules and develop skills across biology and chemistry, including the purification and structural elucidation of natural products. Applications are welcomed from students across the biological and chemical sciences who have a desire to work on a multidisciplinary project.
1. Eyles, T. H., Vior, N. M., Lacret, R. & Truman, A. W. Understanding thioamitide biosynthesis using pathway engineering and untargeted metabolomics. Chem. Sci. 12, 7138–7150 (2021).
2. Heine, D., Holmes, N. A., Worsley, S. F., Santos, A. C. A., Innocent, T. M., Scherlach, K., Patrick, E. H., Yu, D. W., Murrell, J. C., Vieria, P. C., Boomsma, J. J., Hertweck, C., Hutchings, M. I. & Wilkinson, B. Chemical warfare between leafcutter ant symbionts and a co-evolved pathogen. Nat. Commun. 9, 2208 (2018).
3. Leipoldt, F., Santos-Aberturas, J., Stegmann, D. P., Wolf, F., Kulik, A., Lacret, R., Popadić, D., Keinhörster, D., Kirchner, N., Bekiesch, P., Gross, H., Truman, A. W. & Kaysser, L. Warhead biosynthesis and the origin of structural diversity in hydroxamate metalloproteinase inhibitors. Nat. Commun. 8, 1965 (2017).