Student Hosted Colloquium

Thursday, June 7th
Professor Frances Arnold
"Cytochrome P450-catalyzed C-H activation: innovation by evolution"


4:15pm - 5:15pm
Braun Lecture Hall
S.G.Mudd Chemistry Building
Stanford University




This seminar is free and open to the public. All Stanford University Chemistry students are encouraged to attend this special event.

About the Seminar:
We are investigating ways to emulate evolution in the laboratory in order to create new proteins with desirable properties. This approach circumvents our profound ignorance of how the amino acid sequence encodes protein function and exploits the ability of biological systems to evolve and adapt. Engineering multi-domain, multi-cofactor cytochrome P450 catalytic systems to function efficiently on nonnative substrates is challenging, yet crucial for synthetic applications of these versatile oxygenases. Here I will describe the laboratory evolution of P450PMO, a P450 whose activity and coupling efficiency on the structurally challenging, non-native substrate propane rival those of the non-heme monooxygenases in alkane-degrading organisms. This example of convergent evolution demonstrates how a specialized enzyme, the P450BM3 fatty acid hydroxylase, passes through a series of functional intermediates to become re-specialized for reactions catalyzed in nature by structurally and mechanistically unrelated gaseous alkane monooxygenases. This work demonstrates the evolutionary versatility of nature’s catalysts and illustrates how readily new and improved catalytic functions can be acquired through point mutation and/or recombination combined with screening for the desired properties. While yielding useful biocatalysts for chemical synthesis, these studies also provide fascinating insights into the mechanisms underlying evolution of natural enzymes.

About Arnold:
Frances Arnold’s research group studies how proteins evolve and develops methods of directed evolution, which they apply to engineering novel enzymes, biosynthetic pathways, and synthetic genetic regulatory circuits. Frances received her B.S. in Mechanical and Aerospace Engineering from Princeton University in 1979 and her Ph.D. in Chemical Engineering from the University of California, Berkeley, in 1985. Following post-doctoral research in Chemistry at U. C. Berkeley and the California Institute of Technology, she joined the faculty of Caltech's Division of Chemistry and Chemical Engineering in 1987. Dr. Arnold has co-authored more than 200 publications and edited several books on protein engineering and laboratory protein evolution. She was elected to the National Academy of Engineering in 2000 and the Institute of Medicine in 2004. Her recent awards include the 2007 FASEB Excellence in Science Award and the 2005 Olin-Garvan Medal of the American Chemical Society. She serves on the Science Advisory Boards of Gevo, Amyris, Fluidigm and Mascoma and has more than 27 patents issued or pending.

Questions
Please contact Patricia Dwyer at 650-723-4770.