Frances H. Arnold: Nobel Lecture in Chemistry 2018

Transcript

Francis Arnold was born in 1956 in Pittsburgh United States she got her PhD in 1985 at the University of California at Berkeley she is now active as a professor at California Institute of Technology in Pasadena also in California Francis Arnold pioneered directed evolution of enzymes she used her engineering skills to make this method a most versat... Read More

Summary

In this video, Francis Arnold, a professor at the California Institute of Technology, discusses her work on directed evolution of enzymes. She explains how enzymes are the remarkable molecular machines that catalyze reactions in all living organisms. Arnold describes how she turned to nature's process of evolution to create new enzymes, as there is still much we do not understand about how DNA sequences encode function to reliably design enzymes. She explains her approach of making small mutations in enzymes and iterating over multiple generations to optimize their performance for specific tasks. Arnold shares examples of her work, including creating enzymes for non-natural environments and catalyzing reactions not found in biology. She emphasizes the potential of this technology to bridge the gap between natural and human-invented chemistry, and how it can lead to a more sustainable future by using biological systems to produce fuels and chemicals.

Questions & Answers

Q: What is Francis Arnold's background and area of expertise?

Francis Arnold is a professor at the California Institute of Technology and a pioneer in the field of directed evolution of enzymes. She has a background in engineering and has used her skills to develop this method into a versatile tool for developing biocatalysts for new environments and tasks.

Q: Why did Francis Arnold turn to nature's process of evolution?

Francis Arnold and her fellow protein engineers struggled with the problem of not understanding how DNA sequences encode function, making it difficult to reliably design new enzymes. Therefore, she turned to nature's process of evolution as it is a remarkable diversity-generating machine that creates adaptation, optimization, and innovation. She saw evolution as a way to create new enzymes for specific tasks.

Q: What is the main problem in designing new enzymes?

The main problem in designing new enzymes is not knowing how to reliably encode function through DNA sequences. While we can read and write DNA, we lack the knowledge and understanding of how to compose the intricate "code of life" like Beethoven's symphony. Nature, on the other hand, has the process for creating enzymes encoded in DNA through billions of years of evolution.

Q: How does Francis Arnold approach the optimization of enzymes?

Francis Arnold's approach to enzyme optimization involves making small mutations in enzymes and iterating over multiple generations to accumulate these mutations in a directed evolution process. By carefully measuring the small effects of each mutation and selecting starting points that are different from the desired end product, she can optimize enzyme performance for new tasks and environments.

Q: How does Francis Arnold's optimization process compare to other experiments in the field?

Unlike other experiments that use affinity selection to search through a large number of molecules, Francis Arnold's optimization process requires measuring enzymes one by one due to the limitations of available tools. This means that the optimization process must be carried out carefully and gradually, making small mutations and measuring their effects. Despite this limitation, the process has proven to be valuable and effective.

Q: How does Francis Arnold's work contribute to making the planet a better place?

Francis Arnold's work on directed evolution of enzymes contributes to making the planet a better place by providing a sustainable way to speed up chemical reactions and reduce waste. The enzymes she develops can be used to perform reactions in a cleaner and more efficient manner, reducing the environmental impact of industrial processes. This technology has applications in various industries, such as detergent manufacturing and pharmaceutical production.

Q: How does Francis Arnold's work challenge the notion that enzymes are conservative?

Francis Arnold's work challenges the notion that enzymes are conservative by showing that they have the inherent capability to perform promiscuous reactions and can be evolved to perform new functions. Enzymes already have promiscuous capabilities, and evolution uses them as a fuel for further invention. Through directed evolution, enzymes can be trained to carry out reactions that have not been seen in the biological world, such as creating highly strained carbon cycles or inserting carbon into silicon or boron bonds.

Q: How does Francis Arnold use directed evolution to create enzymes for non-natural environments?

Francis Arnold uses directed evolution to create enzymes for non-natural environments by providing a synthetic environment that emulates the desired conditions. By starting with a donkey enzyme that is well-adapted to its natural environment and making small mutations to it, she can optimize it for the non-natural environment of interest. This process has proven successful in adapting enzymes to work in highly non-natural environments, such as dimethyl formamide.

Q: What is the potential of Francis Arnold's technology to bridge the gap between natural and human-invented chemistry?

Francis Arnold believes that her technology has the potential to bridge the gap between natural and human-invented chemistry by importing human inventions into biological systems. By genetically encoding chemistry, it becomes possible to use the powerful design algorithm of evolution to optimize and innovate chemical reactions. This opens up opportunities to easily implement human-invented chemistry in biological systems and create a more sustainable future.

Q: How does Francis Arnold's work contribute to the toolset of biocatalysis?

Francis Arnold's work on directed evolution of enzymes has contributed greatly to the toolset of biocatalysis. Enzymes created through directed evolution have found applications in various industries, including laundry detergents, pharmaceutical manufacturing, and many others. By providing a simple and versatile framework, her work has enabled researchers worldwide to use directed evolution to create enzymes for specific tasks and environments.

Q: What is the promise of genetically encoding chemistry using Francis Arnold's technology?

The promise of genetically encoding chemistry using Francis Arnold's technology is the ability to easily import human-invented chemical reactions into biological systems. By using the powerful optimization and innovation process of evolution, these reactions can be optimized and improved in a sustainable manner. This technology provides a way to explore and utilize the vast potential of biological systems, leading to a more environmentally friendly and efficient production of fuels and chemicals.

Takeaways

Francis Arnold's work on directed evolution of enzymes provides a revolutionary approach to creating bio catalysts for new environments and tasks. By using nature's evolutionary process, she can optimize existing enzymes and create enzymes for non-natural environments. This technology has wide-ranging applications in various industries and contributes to a more sustainable future. Furthermore, Francis Arnold's work has the potential to bridge the gap between natural and human-invented chemistry by genetically encoding chemistry in biological systems. This opens up possibilities for importing human inventions into the biological world and utilizing the vast potential of biological systems for more efficient and environmentally friendly production of fuels and chemicals.