... understanding life in molecular detail

Dr Michael Webb

Enzymology, Bioorganic Chemistry, Protein modification, Regulation of biosynthesis


The research groups interests are wide-ranging: from regulation of biosynthesis in bacteria to the development of new synthetic methodology. Linking most of this work is an over-arching interest in protein modifications, whether the formation of natural covalently-linked cofactors or the development of chemical and chemoenzymatic strategies to make specifically-modified macromolecules. Current and recent projects in the group include: the development of effective isosteric replacements for phosphohistidine; the development of effective new strategies for quantitative modification of proteins using sortase; the biophysical and structural characterisation of regulatory proteins in pantothenate biosynthesis (with Dr Arwen Pearson and Prof Hironori Niki) and  the role of biological material in the Atmosphere (with Dr Ben Murray). Together with Dr Bruce Turnbull, we are now engaged in a major European network to generate synthetic biological approaches to protein-glycan interactions.

Current major projects include:
  • Regulation and mechanism of pantothenate biosynthesis
  • Chemical and enzymatic strategies for protein modification
  • Use of bacterial toxoids as tools for cell and synthetic biology
  • Synthesis and application of stable analogues of phosphohistidine
  • Role of biological material in the atmosphere

My research interests lie in the chemical biology of essential metabolic pathways. Such pathways are often candidate pathways for the development of small molecules with the potential to act as antibiotic or antineoplastic chemotherapeutics and my research feeds into this objective. Through our research we also hope to gain an understanding of the regulation of these pathways in the context of living organisms.

Through the use of a combination of traditional approaches and new biophysical techniques, we are seeking to understand the mechanism and regulation of several different biosynthetic pathways. These pathways include those of bacterial and plant pantothenate and mammalian de novo purine biosynthesis. We are studying the kinetics and thermodynamics of substrate binding and catalysis by proteins in these pathways using both traditional and biophysical methods including isothermal titration calorimetry. We are also studying the mechanism of the unusual regulatory protein for pyruvate phosphodikinase, and the interactions that this makes with its substrates.

We use a combination of biochemical and chemical approaches to these biosynthetic systems including collaboration with plant physiologists and crystallographers, and the use of synthetic chemistry to generate small molecule probes of these systems. Where appropriate, we seek to extend studies to probe the fundamental physical chemistry of these interactions.

Detailed research programme                  Close ▲
MEW.jpg

Associate Professor in Chemical Biology
MA (Cambridge) PhD (Cambridge)


PhD (Cambridge) 2000-2004
Postdoc (Penn State Chemistry) 2004-2006
Postdoc (Cambridge Plant Sciences) 2006-2007
Lecturer (Leeds) 2007-2014

Chemistry G16
School of Chemistry
0113 343 6423
m.e.webb@leeds.ac.uk
http://www.chem.leeds.ac.uk/MEW/

Selected Publications

  1. D. C. F. Monteiro, V. Patel, C. P. Bartlett, S. Nozaki, T. D. Grant, J. A. Gowdy, G. S. Thompson, A. P. Kalverda, E. H. Snell, H. Niki, A. R. Pearson and M. E. Webb The Structure of the PanD/PanZ Complex Reveals Negative Feedback Regulation of Pantothenate Biosynthesis by Coenzyme A Chem. Biol. (2015) 22, 492-503

  2. D. J. Williamson, M. A. Fascione, M. E. Webb and W. B. Turnbull Efficient N-terminal labelling of proteins by use of Sortase Angew. Chemie Int. Ed. (2012) 51, 9377-9380

  3. T. E. McAllister, M. G. Nix and M. E. Webb Triazole phosphohistidine analogues compatible with the Fmoc-strategy Org. Biomol. Chem. (2012) 10, 4043-4049

  4. B. J. Murray, D. O'Sullivan, J.D. Atkinson and M.E.Webb Ice nucleation by particles immersed in super-cooled cloud droplets Chem. Soc. Rev. (2012) 41, 6519