Prof Alan Berry

Alan Berry is Professor of Molecular Enzymology in the Astbury Centre for Structural Molecular Biology at the University of Leeds. He obtained a B.Sc. in Biochemistry with Physiology at the University of Southampton in 1979 and his Ph.D. in Biochemistry, also from Southampton, in 1983. He held an SERC Overseas Research Fellowship in the Laboratorium fur Organische Chemie at ETH-Zentrum in Zurich, followed by a Research Fellowship in the Department of Biochemistry at the University of Cambridge. He was then a Royal Society Research Fellow at Cambridge before joining the academic staff at the University of Leeds in 1994 where he was promoted to a Senior Lectureship in 1997, Reader in 2006 and Professor in 2009.

Research Areas: Protein Engineering, Directed Evolution, Molecular Enzymology, Aldolases

Professor Berry's laboratory works in the areas of protein engineering and directed evolution with particular interest in the alteration of substrate specificity to produce novel enzymes with tailored specificities. This work spans the interface between biochemistry and chemistry and uses a wide range of techniques including protein expression and purification, enzyme kinetics, protein chemistry, many spectroscopic methods (including CD, fluorescence, NMR and FTIR), X-ray crystallography and mass spectrometry.

Engineering proteins for new functions

Protein engineering is a powerful tool for the study of the relationship between structure and function of enzymes and has important applications in the design of new enzymes. Both rational redesign and directed evolutionary approaches are being used in my laboratory to alter the specificity and chemistry of selected enzymes. The aldolases are important catalysts within the cell and man has made significant biotechnological use of this family of enzymes in the synthesis of carbon-carbon bonds. However, the substrate specificity of the family has restricted their use to a more significant level. There are two classes of aldolase: the Class I enzymes which utilise an active site lysine in their reaction mechanism and the zinc-dependent Class II enzymes. We are working on both classes of aldolase. Much of our work has been directed at the Class II fructose bisphosphate aldolase (FBP-aldolase), but we have also cloned the Class I FBP-aldolase from E.coli, two Class II tagatose bisphosphate aldolases and the N-acetyl neuraminic acid aldolase. We are studying their mechanisms of action, the methods the enzymes use to recognise and discriminate between substrates and the possibility of altering specificity both by rational means and by directed evolution. We are using DNA shuffling or STEPing to make libraries of random mutations and are screening for novel enzymes with new properties. These are then subjected to rigourous analysis by a wide range of enzymological techniques such as kinetics, ESI-MS, CD, FTIR, NMR and X-ray crystallography. Similar approaches are being used with the tagatose bisphosphate aldolase, N-acetylneuraminate lyase and N-acetylneuraminate synthase. These latter two enzymes are involved in the biosynthesis of sialic acid, an important molecule in many recognition events. Our experiments are aimed at understanding the functioning of these important enzymes and their redesign to act as catalysts for the synthesis of useful analogs of sialic acid (with Dr Nelson, Chemistry).

For further information see http://bmbsgi10.leeds.ac.uk/index.html