ProfessorJason Micklefield
Chair of Chemistry
Department of Chemistry - Faculty of Natural Sciences
- Chair of ChemistryDepartment of Chemistry - Faculty of Natural Sciences
- Imperial College London, Department of Chemistry, Molecular Sciences Research Hub (MSRH), 82 Wood Lane, London, W12 0BZ, United Kingdom
RESEARCH
The Micklefield Lab develop more sustainable bio-inspired ways to build molecules. Our lab has an eclectic philosophy and is highly interdisciplinary, engaged in Chemical and Synthetic Biology research tackling diverse challenges at the Chemistry-Biology interface. We exploit techniques and knowledge from organic chemistry and enzymology through to molecular microbiology and genetics to develop sustainable routes to target molecules for therapeutic and other applications. The main research themes include:
1) Biosynthesis and biosynthetic pathway engineering providing novel bioactive natural products particularly new antibiotics to combat antimicrobial resistance (AMR) and treat neglected diseases. https://www.micklefieldlab.chemistry.manchester.ac.uk/?page_id=37
2) Biocatalysis & integrated catalysis – Enzyme discovery, characterisation & engineering for enzymatic synthesis. Merging chemo- and biocatalysis for telescoping more sustainable routes to pharmaceuticals and other valuable products. https://www.micklefieldlab.chemistry.manchester.ac.uk/?page_id=34
3) Nucleic acids chemistry and biology, including developing new routes to nucleic acid therapeutics (NAT) and functional tools such as riboswitches and aptamers. https://www.micklefieldlab.chemistry.manchester.ac.uk/?page_id=32
Selected publications:
Cryptic enzymatic assembly of peptides armed with β-lactone warheads. G. Xu, D. Torri, S. Cuesta-Hoyos, D. Panda, L. R. L. Yates, R. Zallot, K. Bian, D. Jia, A. I. Iorgu, C. Levy, S. A. Shepherd & Jason Micklefield* Nature Chem Biol 2024, 20, 1371-1379 https://doi.org/10.1038/s41589-024-01657-7
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
Discovery, Characterisation and Engineering of Ligases for Amide Synthesis. M. Winn, F. Wang, M. Rowlinson, L. Bering, D. Francis, C. Levy & J Micklefield Nature 2021, 593, 391–398. https://doi.org/10.1038/s41586-021-03447-w
Gene editing enables rapid engineering of complex antibiotic assembly lines. W. L. Thong, Y. Zhang, Y. Zhuo, K. J. Robins, J. K. Fyans, A. J. Herbert, B. J. C. Law & J. Micklefield Nature Commun 2021, 12, 6872. https://doi.org/10.1038/s41467-021-27139-1
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
A vitamin K-dependent carboxylase is involved in antibiotic biosynthesis. B. J. C. Law, Y. Zhuo, D. Francis, M. Winn, 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
Integrated Catalysis Opens New Arylation Pathways via Regiodivergent Enzymatic C-H Activation. J Latham, HH Sharif, JM Henry, BRK Menon, SA Shepherd, MF Greaney, J.Micklefield Nature Commun. 2016, 7, 11873. https://doi.org/10.1038/ncomms11873
1) Biosynthesis and biosynthetic pathway engineering providing novel bioactive natural products particularly new antibiotics to combat antimicrobial resistance (AMR) and treat neglected diseases. https://www.micklefieldlab.chemistry.manchester.ac.uk/?page_id=37
2) Biocatalysis & integrated catalysis – Enzyme discovery, characterisation & engineering for enzymatic synthesis. Merging chemo- and biocatalysis for telescoping more sustainable routes to pharmaceuticals and other valuable products. https://www.micklefieldlab.chemistry.manchester.ac.uk/?page_id=34
3) Nucleic acids chemistry and biology, including developing new routes to nucleic acid therapeutics (NAT) and functional tools such as riboswitches and aptamers. https://www.micklefieldlab.chemistry.manchester.ac.uk/?page_id=32
Selected publications:
Cryptic enzymatic assembly of peptides armed with β-lactone warheads. G. Xu, D. Torri, S. Cuesta-Hoyos, D. Panda, L. R. L. Yates, R. Zallot, K. Bian, D. Jia, A. I. Iorgu, C. Levy, S. A. Shepherd & Jason Micklefield* Nature Chem Biol 2024, 20, 1371-1379 https://doi.org/10.1038/s41589-024-01657-7
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
Discovery, Characterisation and Engineering of Ligases for Amide Synthesis. M. Winn, F. Wang, M. Rowlinson, L. Bering, D. Francis, C. Levy & J Micklefield Nature 2021, 593, 391–398. https://doi.org/10.1038/s41586-021-03447-w
Gene editing enables rapid engineering of complex antibiotic assembly lines. W. L. Thong, Y. Zhang, Y. Zhuo, K. J. Robins, J. K. Fyans, A. J. Herbert, B. J. C. Law & J. Micklefield Nature Commun 2021, 12, 6872. https://doi.org/10.1038/s41467-021-27139-1
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
A vitamin K-dependent carboxylase is involved in antibiotic biosynthesis. B. J. C. Law, Y. Zhuo, D. Francis, M. Winn, 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
Integrated Catalysis Opens New Arylation Pathways via Regiodivergent Enzymatic C-H Activation. J Latham, HH Sharif, JM Henry, BRK Menon, SA Shepherd, MF Greaney, J.Micklefield Nature Commun. 2016, 7, 11873. https://doi.org/10.1038/ncomms11873