Column by Lynn Kamerlin
Tracing the mechanisms of enzymes
Enzymes are Nature’s catalysts – reducing the time needed for the chemical reactions that drive life from millions of years to fractions of seconds, thereby driving life itself. Despite extensive effort, such tremendous proficiencies have never been matched in any manmade catalyst.
However, it is possible to extract enzymes from plants and microorganisms for use outside the biological cell. Your home is filled with enzymes that you are using in everything from detergents to cosmetics and even meat tenderizer. The use of enzymes in biotechnology is not a new field – it dates back thousands of years, to the Sumerians and Egyptians who, without realizing what they were doing, used enzymes to brew beer and bake bread. Over three thousand years later, enzymes are crucial for the generation of fine chemicals and pharmaceuticals, as they are environmentally friendly, cheap and reusable catalysts.
The central importance of enzymes to both biology and technology creates a number of crucial questions: where do enzymes come from? How are they such powerful catalysts? How can we manipulate them to get them to do what we want them to do? Yet despite decades of research, really understanding the origins of the tremendous catalytic proficiencies of enzymes remains one of the Holy Grails of biochemistry.
The overall aim of my research is to use computational biology to understand where enzymes come from, how their function evolves, and why they choose to catalyze one particular reaction and not another. In addition, my focus is to develop relevant tools to design enzymes with new and/or improved functions. Over the past few years, this has led to significant insights, such as which factors are driving the evolution of new function in enzymes.
In my latest project, the goal is to increase our knowledge about evolution at a molecular level. Together with colleagues from Spain and the US, my research group and I will generate new enzyme functions in ancient proteins - some of them billions of years old – to study their biochemical properties. By studying ancient proteins, we can learn why modern proteins behave the way they do, reconstructing evolutionary timelines for how new functions arise. Finally, by learning how nature teaches enzymes to catalyze new reactions, we can harness ancient enzymes to teach them new biochemical functions.
Lynn Kamerlin, Professor in Structural Biology at the Department of Cell and Molecular Biology