New Enzymes by Evolution: Expanding Nature’s Catalytic Repertoire

Arnold, F. H., California Institute of Technology

Enzymes are admired for their ability to selectivity catalyze myriad transformations. Not satisfied with nature’s vast catalytic repertoire, we are constantly searching for new ones to add to the toolkit of genetically encoded chemistry. My group uses the one proven algorithm for biological design—evolution—to optimize existing catalysts and create whole new ones.  A powerful approach to engineering useful biological molecules, directed evolution both circumvents and underscores our profound ignorance of how sequence encodes catalytic function. I will describe various ways we have used evolution (contaminated with a little chemical intuition) to generate new catalysts starting from one of nature’s most impressive, the cytochrome P450 monooxygenase.  I will share several examples of engineered versions that catalyze important synthetic reactions not known in nature.