New theory from University of Leicester scientists underpins drug development and food processing

Scientists at the University of Leicester have shown that the textbook explanation of how enzymes work is wrong – at least for some enzymes.

Their discovery may explain why attempts to make artificial enzymes have often been disappointing. Industry must now re-think the rationale for the design of biological catalysts and its approaches to drug design. Enzymes are biological molecules that accelerate chemical reactions and are central to the existence of life. The new breakthrough that could revolutionise the application of enzymes in human well-being has been made at the University of Leicester.

Professors Nigel Scrutton and Michael Sutcliffe, of the Department of Biochemistry, have discovered a new phenomenon occurring at the atomic level that dictates how enzymes work. Their study of enzymes – which are vital for catalysis within industry – reveals that chemical reactions can proceed through energy barriers. This is contrary to received wisdom on how enzyme reactions work.

Professor Scrutton said: “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. However, despite the huge efforts to redesign enzyme molecules for specific applications (e.g. the synthesis of fine chemicals, food processing, bio sensing, brewing), progress in this area has been generally disappointing. This stems from our limited understanding of the subtleties by which enzymes enhance reaction rates. “Based on current dogma, the vast majority of studies have concentrated on understanding how enzymes facilitate passage of a reaction over an energy barrier. However, our studies have revealed that passage through, rather than over, the barrier can occur – a process that relies on quantum mechanical effects such as tunnelling.

Professor Sutcliffe added: “Quantum tunnelling is akin to traversing a landscape by tunnelling at the foot of a hill rather than walking over the summit. In the quantum world, small particles like the electron and hydrogen atom are able to ‘tunnel’ through energy barriers (or hills), and the Leicester team and demonstrated this occurs in enzyme-catalysed reactions. “Since electron and hydrogen transfer is common to virtually all naturally occurring enzymes, the discovery has wide ranging implications for our understanding of how enzymes work.

Professor Scrutton stated: “These new ideas are breaking all the rules of classical models of enzyme catalysis. The discovery has wide ranging implications in the use of enzymes in industry and biomedical research, as the new theory is likely to underpin the mode of action of all enzymes. “For example, the new discovery questions current approaches used to rationally design enzyme inhibitors for the production of pharmaceuticals or novel enzyme catalysts for industrial applications.”