Understanding the dynamics of non-ribosomal peptide synthetases

Non-ribosomal peptide synthetases are dynamic molecular machines which produce some of the most important medicinal compounds including the antibiotic vancomycin, the immunosuppressant rapamycin and the anticancer agent Bleomycin. In this project, you will investigate how the dynamic conformational changes of these large proteins contribute to their success as catalysts. You will apply new protein-labelling methods to site-specifically label proteins before using EPR and FRET approaches to analyse how the protein conformational state and the movement between them change in response to the catalytic cycle of the protein. This project will be a critical step in generating designer enzymes capable of producing new variants of these high-value medicinal projects.