11/28/17 - 9:45 AM to 11:00 AM
Department Seminar: David K. Romney, Ph.D.
"Evolvable Catalysts for Organic Synthesis"
Catalysts based on chains of amino acids, such as peptides or proteins, are able to mediate a wide array of chemical transformations. Furthermore, one can tune the properties of such catalysts and optimize them for specific reactions by varying their amino-acid sequences in a combinatorial process that mimics evolution. In one demonstration, this approach was used to create a peptide catalyst that can mediate the Baeyer-Villiger oxidation of functionalized ketones to esters. The catalyst controls both the regio- and enantioselectivity of the reaction, and can even favor Baeyer-Villiger oxidation in the presence of reactive functional groups that can undergo competing oxidation processes like epoxidation. This sets the stage to perform reactions with complex substrates, such as natural products. In a second demonstration, directed evolution was used to engineer the β-subunit of tryptophan synthase (TrpB) to serve as a catalyst for the synthesis of noncanonical amino acids. This enzyme naturally exists in a complex with its partner protein TrpA and is responsible for synthesis of the amino acid tryptophan. Multiple rounds of mutagenesis and selection were used to develop variants of TrpB that function independently of TrpA and can synthesize analogs of tryptophan that were previously difficult to obtain by existing synthetic and biological methods. These products are precursors to bioactive natural products and other functional molecules, and are frequently used as probes in chemical biology. Together, these examples demonstrate the versatility of modular catalyst scaffolds to be optimized for challenging synthetic transformations.
Event DetailsLocation: 331 Smith HallHost: Professor Mark DistefanoSpeakers:
- David K. Romney, Ph.D.
- Division of Chemistry & Chemical Engineering
- California Institute of Technology