Page 32 - Visions of the Future Chemistry and Life Science

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Enzymology takes a quantum leap forward

Michael J. Sutcli≈e and Nigel S. Scrutton 2
1
1 Department of Chemistry, University of Leicester, Leicester LE1 7RH, UK
2 Department of Biochemistry, University of Leicester, Leicester LE1 7RH, UK

2.1 Introduction

Enzymes facilitate life via a plethora of reactions in living organisms. Not
only do they sustain life – they are also involved in a myriad of processes
that affect our everyday lives. These include applications in medicine,
household detergents, fine chemical synthesis, the food industry, bioelec-
tronics and the degradation of chemical waste. Since the discovery of
enzymes just over a century ago, we have witnessed an explosion in our
understanding of enzyme catalysis, leading to a more detailed appreciation
of how they work. Over many years, much effort has been expended in the
quest to create enzymes for specific biotechnological roles. Prior to the
early 1980s, the only methods available for changing enzyme structure
were those of chemical modification of functional groups (so-called ‘forced
evolution’). The genetic engineering revolution has provided tools for dis-
secting enzyme structure and enabling design of novel function. Chemical
methods have now been surpassed by knowledge-based (i.e. rational) site-
directed mutagenesis and the grafting of biological function into existing
enzyme molecules (so-called ‘retrofitting’). More recently, gene-shuffling
techniques have been used to generate novel enzymes. Rational redesign
of enzymes is a logical approach to producing better enzymes. However,
with a few notable exceptions, rational approaches have been generally
unsuccessful, reiterating our poor level of understanding of how enzymes
work. This has led to a more ‘shot-gun’ approach to redesign, involving

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