“Ex Vivo Metabolism: Novel Enzyme Cascades to Synthesize Active Pharmaceutical Ingredients”
Enzymes are exceptional catalysts with unparalleled selectivity and rate enhancement. In many cases, enzymes also offer significant advantages over traditional catalysts with respect to cost, safety, and environmental impact. Due to these properties, the use of enzymes as biocatalysts in industrial settings has grown dramatically. Central to the growth of biocatalysis as a chemistry tool has been the ability to create novel enzyme functions and properties using protein design and engineering. The fields of biocatalysis and protein engineering have matured to the point where the identification of new enzyme activity and further engineering of an enzyme for synthetic chemistry purposes have become almost routine. These advancements have made it practical to consider moving beyond the engineering of a single enzyme and to consider the invention of entirely novel multi-enzyme cascades not found in nature to synthesize compounds not found in nature. These novel pathways could be considered ex vivo metabolic processes; enzyme cascades created and occurring outside the confines of living systems. For the past three years, the Merck Biocatalysis and Protein Engineering group has focused on the creation of ex vivo enzyme cascades to synthesize Merck drug compounds. This talk will highlight recent examples of our group’s successful efforts to engineer novel enzyme cascades to synthesize Merck compounds from simple starting materials.
~Coffee/tea will be served prior to lecture~