Frances H. Arnold: Nobel Lecture in Chemistry 2018

Francis Arnold's introduction and her journey to becoming a professor at Caltech, where she pioneered directed evolution of enzymes. She discusses her method's versatility in creating biocatalysts for sustainable chemical reactions, reducing waste. Arnold's gratitude is expressed to the Nobel Committee and her collaborators, emphasizing the inspiration she draws from the complexity and efficiency of enzymes in nature, which catalyze almost all reactions in the living world. She also touches on the challenges of protein engineering and the limitations in understanding DNA sequence-function relationships.

Arnold explores the vast universe of possible proteins beyond those found in nature, likening it to an infinite playground for future exploration. She discusses the challenge of searching this vast space and the inspiration she drew from John Maynard Smith's work on the ordered space of proteins. Arnold explains her approach to protein optimization as an evolutionary process, using directed evolution to improve enzymes' performance on a fitness landscape, despite the lack of understanding of the fitness landscape's structure in the 1980s.

This paragraph delves into the experimental process of directed evolution, highlighting the absence of affinity selection and the need to measure enzyme activities one by one. Arnold describes her methodical approach of making random mutations, carefully measuring their effects, and iterating over multiple generations to optimize enzymes for new tasks. She discusses the意外 success of adapting enzymes to non-natural environments and the collaboration with Tim Stemmer, which led to the widespread industrial application of directed evolution in products like laundry detergents and pharmaceuticals.

Arnold shifts focus from optimization to the creation of novelty in enzymes, exploring how evolution can generate new functions and catalyze reactions not found in nature. She discusses the discovery of promiscuous capabilities in enzymes, which serve as a foundation for further invention through directed evolution. Arnold provides examples of enzymes adapted to perform human-invented chemistry, such as the transformation of double bonds into cyclopropanes, showcasing the potential for enzymes to be trained to perform complex chemistry within living cells.

The speaker discusses the discovery and evolution of enzymes capable of forming carbon-silicon and carbon-boron bonds, which were previously unknown in biological systems. She describes how these natural proteins can be adapted to perform stable and efficient chemistry that rivals or exceeds the best human-made catalysts. Arnold emphasizes the potential for further expanding the chemical capabilities of biological systems and the implications for a more sustainable future.

Arnold concludes by reflecting on the power of directed evolution as a design algorithm capable of optimization and innovation in real-time. She envisions a future where the barriers between natural and human-invented chemistry are broken down, allowing for the import of human chemical inventions into the biological world. Arnold also highlights the vast diversity of the biological world as a resource for solving complex problems and the potential for a more sustainable approach to producing fuels and chemicals using biological systems.

The final paragraph acknowledges the collective effort of the scientific community in advancing the field of directed evolution. It features a tribute to Frances Arnold, George Smith, and Gregor Winter for their contributions and a group applause for their achievements. The paragraph concludes with an invitation for the speakers to join on stage, marking a celebratory moment in the recognition of their work.