Directed Evolution

While the field of directed evolution is vast and varied, it comes from a simple principle: to apply the principles of biological evolution in the laboratory to generate useful molecules. This widely used technique has yielded blockbuster drugs, essential biological tools, and many more useful chemicals. Considering its impact, it's unsurprising that the 2018 Chemistry Nobel Prize was awarded for the use of directed evolution of proteins. Directed Evolution is an excellent starting point for any scientist interested in directed evolution. This primer aims to provide readers with the foundational knowledge and vocabulary that enables them to tackle the literature and begin designing their projects. Directed evolution, as a field, can be challenging to start in; one of the biggest challenges to starting work in this field is that it requires a different style of thinking than many areas of chemistry. CHAPTER 1 explains this different mentality and then gives an overview of directed evolution: what it is, why it is useful, how evolution is applied in the lab, and how evolution can be applied for human benefit. Given the diversity and quantity of methods and approaches in directed evolution, the remaining chapters focus on helping the readers find the right approach to their specific problem by outlining the basic thought process and classical methods in directed evolution. Specifically, CHAPTER 2 discusses applying directed evolution to nucleic acids. Nucleic acid evolution has several unique features that make it easier to understand conceptually, making it a good starting point for understanding how to think about and leverage evolution. CHAPTERS 3 through 6 cover approaches to evolving proteins. CHAPTER 3 discusses the strengths and weaknesses of different approaches to the diversification of proteins, giving the reader a framework for designing libraries. CHAPTERS 4, 5, and 6 introduce different approaches to sorting by applying selection pressures to find the best variant from a large complex library. Upon completing this primer, the reader will have a theoretical basis to design and execute a directed evolution campaign. They will have the core knowledge to dive into the larger world of directed evolution and begin designing projects that leverage this powerful technique.