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Organic Chemistry Seminar Series: Jeff Martell (University of Wisconsin-Madison)
March 13 | 9:30 am - 10:30 am
About the Seminar:
“Enzyme-Mimicking Catalysts for Chemical Biology and Sustainable Synthesis”
The development of new catalysts is essential for myriad applications, spanning therapeutics, energy, sustainable synthesis, and environmental remediation. A long-standing challenge has been to create catalysts that mimic the 3-D active sites of natural enzymes while incorporating more diverse functional groups. I will describe three projects that seek to address this challenge, drawing from synthetic catalysis, biomaterials, and directed evolution. First, we have developed DNA-scaffolded synthetic catalysts, featuring multiple abiotic functional groups in supramolecular active sites, and we are applying these catalysts in synthetic methodology and chemical biology. These DNA-based catalysts accelerate synergistic catalytic reactions >100-fold, bind to complex substrates to enable selective transformations, facilitate the discovery of novel reactivity through rapid testing of supramolecular catalyst libraries, and activate in response to specific chemical triggers on living cells. Second, we are embedding abiotic catalysts within porous protein frameworks to create enzyme-mimicking active sites. These protein-based frameworks exhibit tunable swelling to form hydrogel materials in which both small molecule catalysts and enzymes can be immobilized. Third, we are coupling natural enzymes with abiotic cofactors and developing high-throughput platforms to rapidly evaluate millions of mutants. We are applying these evolved enzymatic catalysts for synthetic transformations of small molecules and for recycling and upgrading of plastic waste.
About the Speaker:
B.A. 2009, Northwestern University
Ph.D. 2015, Massachusetts Institute of Technology
Postdoctoral Researcher at the University of California, Berkeley, 2015 – 2019
Enzyme-Mimicking Catalysis in Evolvable Three-Dimensional Scaffolds
Naturally occurring enzymes catalyze a remarkably wide range of reactions with excellent efficiency and selectivity under mild conditions, making them potentially useful for numerous applications. However, the applications of natural enzymes are limited because they are generally expensive, difficult to prepare on large scale, too specific in their activity, and prone to deactivation outside their host organisms. A long-standing challenge has been to develop synthetic enzyme-mimicking catalysts, but nearly all synthetic catalysts reported to date are orders of magnitude less efficient than natural enzymes, which contain pre-organized functional groups in flexible three-dimensional cavities that are challenging to replicate synthetically. By combining innovative three-dimensional cage-like architectures, combinatorial synthetic strategies, and biotechnology-inspired high-throughput screening, my group will seek to create highly efficient enzyme-mimicking catalysts.
This interdisciplinary research program—drawing from organic chemistry, biochemistry, inorganic chemistry, and materials—is expected to yield novel and practically useful catalysts and to provide fundamental insights into catalytic mechanisms. My group will explore diverse applications of these catalysts, including synthetic methodology, energy, environmental remediation, and diagnostics. The molecules and materials developed during this research will have applications beyond enzyme-mimicking catalysis, including targeted therapeutics, drug delivery, and chemical separations.