Enzymes by Evolution: Bringing New Chemistry to Life
Frances H. Arnold
Professor of Chemical Engineering, Bioengineering, and Biochemistry:
California Institute of Technology
Not satisfied with nature’s vast catalyst repertoire, we want to create new protein catalysts and expand the space of genetically encoded enzyme functions. I will describe how we use the most powerful biological design process, evolution, to optimize existing enzymes and invent new ones, thereby circumventing our profound ignorance of how sequence encodes function. Using chemical intuition and mimicking nature’s evolutionary processes, we can generate whole new enzyme families that catalyze synthetically important reactions not known in biology. Exploiting the vast world of non-natural carbene chemistry, we recently reported the first enzymes that forge C-Si and C-B bonds in living cells and other enzymes that catalyze alkyne cyclopropanation to make highly strained carbocycles. We are also exploring enzyme-catalyzed nitrene transfer chemistry, to make new C-N bonds. Uncovering the mechanisms of these new enzymes derived from natural iron-heme proteins provides a basis for discovering yet more new biocatalysts for increasingly challenging reactions. These new capabilities expand the scope of molecules and materials we can build using synthetic biology and move us closer to fully DNA-programmed chemical synthesis.