Join us in a RSC Prize Lecture with winner of the 2022 Interdisciplinary Prize, Professor Jason Micklefield (University of Manchester)
Speaker: Professor Jason Micklefield (University of Manchester)
Hosts: Chris Willis and Matt Crump
Time and Location: 12:00PM - 13:00PM, 15th June 2023 - Chemistry Building: LT2
Title: Discovery, characterisation and engineering synthetic pathways to bioactive molecules
Abstract:
Jason’s research involves the discovery, characterisation and engineering of biosynthetic pathways to new bioactive natural products, particularly antibiotics. He is also interested in the discovery, structure, mechanism and engineering of enzymes for synthetic applications, including the integration of enzymes with chemocatalysis for telescoping routes to pharmaceuticals and other valuable products [1-7]. The Micklefield lab is also engaged in nucleic acids research.
Nature uses enzymes to catalyse reactions building all of the molecules required for life. Enzymes also break down molecules to release energy that enables all living organisms to move forward. Our lab discovers novel enzymes from unusual bacteria in nature. We characterise these enzymes to determine their structures and mechanisms. With this knowledge, we can re-programme the enzymes to create variants that can catalyse new reactions. These engineered enzymes are used to produce novel antibiotics to combat antimicrobial resistance, antiviral agents that entered clinical trials for COVID-19, anticancer agents and other useful molecules [1-7]. The enzymatic pathways we have developed are cleaner and more sustainable than the traditional chemical synthesis routes that are currently used to prepare pharmaceuticals and other molecules.
Further information
[1] Merging enzymes with chemocatalysis for sustainable amide bond synthesis. L. Bering, E. J. Craven, S. A. Sowerby Thomas, S. A. Shepherd & J. Micklefield* Nature Commun. 2022, 13, 380 https://doi.org/10.1038/s41467-022-28005-4.
[2] Discovery, characterisation and engineering of ligases for amide synthesis. M. Winn, M. Rowlinson, F. Wang, L. Bering, D. Francis, C. Levy & J. Micklefield* Nature 2021, 593, 391-398 https://doi.org/10.1038/s41586-021-03447-w
[3] Gene editing enables rapid engineering of complex antibiotic assembly lines. W. L. Thong, Y. Zhang, Y. Zhuo, K. J. Robins, J. Fyans, A. J. Herbert, B. J. C. Law, & J. Micklefield* Nature Commun. 2021, 12, 6872 https://doi.org/10.1038/s41467-021-27139-1
[4] Programmable late-stage C–H bond functionalization enabled by integration of enzymes with chemocatalysis. E. J. Craven, J. Latham, S. A. Shepherd, I. Khan, A. Diaz-Rodriguez, M. F. Greaney & J. Micklefield* Nature Catalysis 2021, 4, 385–394 https://doi.org/10.1038/s41929-021-00603-3
[5] Engineering orthogonal methyltransferases to create alternative bioalkylation pathways. A. J. Herbert, S. A. Shepherd, V. A. Cronin, M. R. Bennett, R. Sung & J Micklefield* Angew. Chem. Int. Ed. 2020, 59, 14950–14956 https://doi.org/10.1002/anie.202004963
[6] A vitamin K-dependent carboxylase is involved in antibiotic biosynthesis. B. J. C. Law, Y. Zhuo, M. Winn, D. Francis, Y. Zhang, M. Samborskyy, A. Murphy, L. Ren, P. F. Leadlay & J. Micklefield*. Nature Catalysis 2018, 1, 977-984 https://doi.org/10.1038/s41929-018-0178-2
[7] Integrated catalysis opens new arylation pathways via regiodivergent enzymatic C-H activation. J. Latham, J.-M. Henry, H. H. Sharif, B. R. K. Menon, S. A. Shepherd, M. F. Greaney & J.Micklefield.* Nature Commun. 2016, 7, 11873 https://doi.org/10.1038/ncomms11873
