The Elmer L. Gaden Lecture Series

Chemical Engineering at Columbia University is proud to present:

How Enzymes Adapt: Lessons from Artificial Selection of Cytochrome P450

Frances H. Arnold

California Institute of Technology, Pasadena, CA

When making his case for the key role of natural selection in evolution, Darwin pointed to the enormous phenotypic variation that could be achieved in relatively few generations of artificial selection. Today, artificial selection (or ‘directed evolution') applied to proteins allows us to observe how readily the functional molecules of life adapt in the face of defined selection pressures. Circumventing our profound ignorance of how sequence encodes function, directed evolution is a powerful approach to generating useful new biological molecules. Here I will describe our efforts to evolve a cytochrome P450 enzyme (CYP102A1 from Bacillus megaterium). Properties such as catalytic activity or stability can frequently be enhanced by single amino acid substitutions, and accumulating relatively few beneficial mutations (as little as 1-2% of the sequence) can make very significant changes to enzyme function. I will show how a P450 fatty acid hydroxylase has been converted into a whole family of catalysts for oxidation of small alkanes to carbohydrate synthesis and drug lead diversification. Where natural evolution has gone (e.g. impressive diversification of function in the P450 enzyme superfamily), directed evolution can follow. Even more interesting are the catalysts nature may not care about, but chemists dream of. While yielding useful biocatalysts for chemical synthesis, these studies provide new insights into the mechanisms underlying evolution of natural enzymes.

 

About our guest speaker:

Frances H. Arnold is the Dick and Barbara Dickinson Professor of Chemical Engineering and Biochemistry at the California Institute of Technology, where her research focuses on evolution of biological systems in the laboratory. Frances Arnold has co-authored 220 scientific publications and edited several books on protein engineering and laboratory protein evolution. She also has more than 40 patents and patent applications. She is a co-founder of advanced biofuels company Gevo, Inc. and serves on the Science Advisory Boards of Mascoma, Codexis, Arzeda and Fluidigm. 

Prof. Arnold was elected to the National Academy of Engineering in 2000, the Institute of Medicine of the National Academies in 2004, and the National Academy of Sciences in 2008. Her other recent awards and honors include Fellowship in the American Academy of Microbiology (2009), the Linnaeus Lectureship at Uppsala University (2008), the Genencor Award in Enzyme Engineering (2007), the FASEB Excellence in Science Award (2007), the Olin-Garvin Medal of the American Chemical Society (2005), the Food, Pharmaceuticals and Bioengineering Division Award of the AIChE (2005), the David Perlman Memorial Lectureship of the ACS Biochemical Technology Division (2003), the Carothers Award from the Delaware ACS (2003), and the Professional Progress Award of the AIChE (2000)

Location:

4 PM
Tuesday, October 20, 2009
Davis Auditorium - 412 CEPSR
Reception to follow


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