Prof Jason Micklefield PhD

Biography

PhD Studentship – New Routes to amides through discovery and development of amide ligase enzymes – is available in the Micklefield Lab in collaboration CoEBio3 affiliates including including GSK, AstraZeneca and Merck. Deadline 15th April 2019. For more details see: https://www.jobs.ac.uk/job/BQW866/phd-studentship-in-biocatalysis-new-routes-to-amides-through-discovery-and-development-of-amide-ligase-enzymes

Jason Micklefield is Professor of Chemical Biology within the School of Chemistry and the Manchester Institute of Biotechnology. He graduated from the University of Cambridge in 1993 with a PhD in Chemistry, working with Prof Sir Alan R. Battersby FRS to complete the first total synthesis of haem d1. He then moved to the University of Washington, USA, as a NATO postdoctoral fellow investigating various biosynthetic pathways and enzyme mechanisms with Prof Heinz G. Floss. In 1995 he began his independent research career as a Lecturer in Organic Chemistry at Birkbeck College, University of London before moving to Manchester in 1998.

Selected Publications

• 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. Also see Nature Catalysis News & Views (https://rdcu.be/bdd6j) and Nature Research Community News (https://go.nature.com/2r4Smbu)

• De novo Biosynthesis of 'Non-Natural' Thaxtomin Phytotoxins. M Winn, D Francis & J Micklefield Angew. Chem. Int. Ed. 2018, 57, 6830–6833.

• Structure and Biocatalytic Scope of Coclaurine N-Methyltransferase. MR Bennett, ML Thompson, SA Shepherd, MS Dunstan, AJ Herbert, DRM Smith, VA Cronin, BRK Menon, C Levy  & J Micklefield Angew. Chem. Int. Ed. 2018, 57, 10600-10604.

• RadH: A Versatile Halogenase for Integration into Synthetic Pathways. BRK Menon, E Brandenburger, HH Sharif, U Klemstein, MF Greaney & J. Micklefield Angew. Chem. Int. Ed. 2017, 56, 11841–11845.

• 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

• An Enzyme Cascade for Selective Modification of Tyrosine Residues in Structurally Diverse Peptides and Proteins. AW Struck, MR Bennett, SA Shepherd, BJC Law, Y Zhou & L S Wong, J Micklefield J. Am. Chem. Soc. 2016, 138, 3038–3045

• Effects of Active Site Modification and Quaternary Structure on the Regioselectivity of Catechol-O-Methyltransferase. BJC Law, MR Bennett, ML Thompson, C Levy, SA Shepherd, D Leys, J Micklefield Angew. Chem. Int. Ed. 2016, 55, 2683–2687

• A flavin-dependent decarboxylase-dehydrogenase-monooxygenase assembles the warhead of α, β-epoxyketone proteasome inhibitors. D Zabala, J Cartwright, D Roberts, BJC Law, L Song, M Samborskyy, PF Leadlay, J Micklefield, GL Challis J. Am. Chem. Soc. 2016, 138, 4342–4345

• Rational Re-engineering of the Transcriptional Silencing PreQ1 Riboswitch. MC Wu, PT Lowe, CJ Robinson, HA Vincent, N Dixon, J Leigh, J Micklefield J. Am. Chem. Soc. 2015, 137, 9015–9021

• Extending the biocatalytic scope of regiocomplementary flavin-dependent halogenase enzymes. SA Shepherd, C Karthikeyan, J Latham, AW Struck, ML Thompson, B Menon, C Levy, D Leys, J Micklefield Chemical Science 2015, 6, 3454–3460

• Site-specific Bioalkylation of Rapamycin by the RapM 16-O-Methyltransferase. BJC Law, AW Struck, MR Bennett, B Wilkinson, J Micklefield Chemical Science 2015, 6, 2885–2892 

• Modular Riboswitch Toolsets for Synthetic Genetic Control in Diverse Bacterial Species. CJ Robinson, HA. Vincent, M-C Wu, PT. Lowe, MS. Dunstan, D Leys, J Micklefield J Am Chem Soc 2014, 136, 10615–10624

• Introduction of a non-natural amino acid into a nonribosomal peptide by modification of adenylation domain specificity. J Thirlway, R Lewis, L Nunns, M Al Nakeeb, M Styles, A-W Struck, CP Smith, J Micklefield Angew Chem Int Ed 2012, 51, 7181–7184

• Thermal Bifunctionality of Bacterial MIO-Dependent Mutase and Lyase Enzymes. C Chesters, M Wilding, M Goodall, J. Micklefield Angew Chem Int Ed 2012, 51, 4344–4348

• Orthogonal Riboswitches for Tuneable Co-expression in Bacteria. N Dixon, C Robinson, JN Duncan, T Geerlings, SP Drummond, J. Micklefield Angew Chem Int Ed 2012, 51, 3620–3624

• Protein micro- and nano-patterning using aminosilanes with protein-resistant photolabile protecting groups. SA Alang Ahmad, LS Wong, E ul-Haq, JK Hobbs, GJ Leggett, J. Micklefield J Am Chem Soc 2011, 133, 2749–2759

• Reengineering orthogonally selective riboswitches. N Dixon, J Duncan, T Geerlings, MS Dunstan, D Leys, J. Micklefield Proc Natl Acad Sci USA 2010, 107, 2830-2835.

• Structure guided directed evolution of alkenyl and arylmalonate decarboxylases. K Okrasa, C Levy, M Wilding, M Goodall, N Baudendistel, B Hauer, D Leys, J Micklefield Angew Chem Int Ed 2009, 48, 7691-7694

• Direct site-selective covalent protein immobilization catalyzed by a phosphopantetheinyl transferase. LS Wong, J Thirlway, J. Micklefield J Am Chem Soc 2008, 130, 12456-12464

• Engineered biosynthesis of nonribosomal lipopeptide antibiotics with modified fatty acid side chains. A Powell, M Borg, B Amir-Heidari, JM Neary, J Thirlway, B Wilkinson, CP Smith, J Micklefield J Am Chem Soc 2007, 129, 15182-15191

• Mining and engineering natural-product biosynthetic pathways. B. Wilkinson & J. Micklefield Nature Chem. Biol. 2007, 3, 379–386.