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2015 Julian C. Smith Lecturer: Francis H. Arnold, Caltech

Frances H. Arnold
Division of Chemistry and Chemical Engineering
California Institute of Technology

Design by Evolution (or "Sex and the Better Biocatalyst")
Monday, April 13, 2015 at 4:00 pm
Olin Hall, 155

We use the one proven algorithm for biological design—evolution—to engineer biological molecules and systems to solve human problems.  A powerful approach to engineering the biological world, directed evolution both circumvents and underscores our profound ignorance of how sequence encodes function. I will describe ways to emulate evolution in order to create enzymes with desirable properties. An enzyme can take on new capabilities by accumulating beneficial mutations over a small fraction of its sequence. Structure-guided recombination, in contrast, generates sequences that are much more diverse, but still retain the parental fold and function.  Some of these also exhibit new properties. This work exploits the remarkable ability of biological systems to adapt to new challenges.Evolution of Novelty: Expanding Nature's Catalytic RepertoireSynthetic biology for fuels and chemicals has depended on reassembling existing enzymes into new biosynthetic pathways. Unfortunately, many desired transformations fall outside the reach of known enzyme-catalyzed transformations or can be made more efficiently using synthetic chemistry. Thus, a future where metabolic engineering might produce nearly all of the organic molecules upon which society depends is still a ways off. Not satisfied with nature's vast catalytic repertoire, we want to create new enzymes to expand the range of genetically encoded chemistry. I will describe how we use the most powerful algorithm for biological design, evolution, to create new enzymes. Mimicking nature's evolutionary tricks and using a little chemical intuition, we can engineer enzymes to catalyze important reactions not known in nature.   

Evolution of Novelty: Expanding Nature's Catalytic Repertoire
Tuesday, April 14, 2015 at 4:00 pm
Olin Hall, 155 

Synthetic biology for fuels and chemicals has depended on reassembling existing enzymes into new biosynthetic pathways. Unfortunately, many desired transformations fall outside the reach of known enzyme-catalyzed transformations or can be made more efficiently using synthetic chemistry. Thus, a future where metabolic engineering might produce nearly all of the organic molecules upon which society depends is still a ways off. Not satisfied with nature's vast catalytic repertoire, we want to create new enzymes to expand the range of genetically encoded chemistry. I will describe how we use the most powerful algorithm for biological design, evolution, to create new enzymes. Mimicking nature's evolutionary tricks and using a little chemical intuition, we can engineer enzymes to catalyze important reactions not known in nature.   

Frances H. Arnold, Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry; Director, Donna and Benjamin M. Rosen Bioengineering Center:

B.S., Mechanical and Aerospace Engineering, Princeton University, 1979;
Ph.D., Chemical Engineering, University of California, Berkeley, 1985;
Postdoctoral, UC Berkeley, Chemistry, 1985;
Postdoctoral, Caltech, Chemistry, 1986 

http://www.che.caltech.edu/faculty/arnold_f/