The Enzyme Engineers: Crafting Life’s Tiny Machines

Our understanding of how enzymes work is limited because proteins are made up of hundreds of individual amino acid components, many of which are essential components of the machinery. A more complete understanding requires testing the role of each of these, not possible via traditional lab approaches. This talk introduces the role of enzymes, how they are built, problems leading to disease and how to engineer them. The Markin lab tackles this challenging problem by developing microfluidic technologies, enabling the analysis of thousands of reactions in parallel – All on the micro scale.

Traditionally, the development of enzymes for pharmaceuticals and biofuel production can take years of laboratory-based development. Recent improvement in our ability to design proteins from scratch using deep learning (AI) algorithms means it is now possible to generate 1000’s of new proteins on a computer. These new techniques mean that for a given reaction you can design and evaluate bespoke catalysts, often using natural or lab-engineered enzymes as blueprints. In this talk I will discuss the development of these design techniques, and the challenges involved.

Creation of enzymes with new activities from scratch would have significant technological implications. To date, the activities of human devised enzymes are far below those of natural enzymes. Directed evolution, which is a mimic of Darwinian Evolution, can significantly improve enzyme activity and bring artificial enzymes within the activity range of their natural counterparts. This talk will highlight how technology, more specifically droplet microfluidics can be used to accelerate enzyme engineering to produce new proteins that work better than any of those found in nature.