Dr Andrew Truman

I carry out my research within the Department of Chemistry and in collaboration with the Leadlay group in the Department of Biochemistry.  My PhD thesis was concerned with understanding and subsequently modifying the biosynthesis of glycopeptides and aminoglycosides. These are natural product antibiotics that are biosynthesised by bacteria and which are important clinically as “drugs of last resort” to combat infection by multiply drug-resistant pathogenic microorganisms - the glycopeptide teicoplanin for example (pictured).

The primary focus of my research is the use of chemical and biological techniques to understand and modify the attachment of sugars and lipids to natural products.  These processes are catalysed by enzymes called glycosyltransferases and acyltransferases.  By elucidating the three-dimensional structures of these enzymes bound to chemically synthesised inhibitors we can understand how they bind substrates and carry out catalysis.  In addition, I am using a variety of genetic engineering approaches to probe and modify the substrate specificity of glycosyltransferases towards aminoglycosides, glycopeptides and other drugs.  Antibiotic-producing bacteria are then being genetically modified to generate “biological factories” for the production of novel, structurally complex drug-like compounds.

A secondary focus of my research is an investigation into the chemistry of non-ribosomal peptide synthetases (NRPSs).  These are some of the largest enzymes known and catalyse a step-wise series of reactions in an assembly line manner (see the biosynthetic pathway of the teicoplanin aglycone) to produce complex natural products that often possess potent bioactivity.

I supervise a number of organic and biological chemistry courses in Part IA, Part IB and Part III of the Natural Science Tripos.  I am also a senior demonstrator for Part IB practical organic chemistry.

Publications

A. W Truman, L. Robinson, J. B. Spencer, Identification of a Deacetylase Involved in the Maturation of Teicoplanin, ChemBioChem, 2006, 7, 1670-1675.

A. W. Truman, F. L. Huang, N. M. Llewellyn, J. B. Spencer, Characterization of the Enzyme BtrD from Bacillus circulans and Revision of its Functional Assignment in the Biosynthesis of Butirosin, Angew. Chem. Int. Ed. 2007, 46, 1462-1464.

A. W. Truman, Q. Fan, M. Röttgen, E. Stegmann, P. F. Leadlay, J. B. Spencer, The Role of Cep15 in the Biosynthesis of Chloroeremomycin: Reactivation of an Ancestral Catalytic Function, Chem. Biol. 2008 15, 476-484.

A. W. Truman, M. V. B. Dias, S. Wu, T. L. Blundell, F. Huang, J. B. Spencer, Chimeric Glycosyltransferases for the Generation of Novel Natural Products, Chem. Biol. 2009, 16, 676-685.