Dr. David Berkowitz is active at the interface of synthetic organic chemistry and enzymatic chemistry. Projects in the group include the synthesis and study of unnatural analogues of biological molecules that have been designed to display interesting properties. This includes (a) fluorinated phosphonates designed to act as stable phosphate surrogates or ‘Teflon phosphates,’ (b) unnatural, alpha-branched amino acids designed to function as ‘Trojan horse inactivators’ for vitamin B-6 dependent enzymes, and (c) unnatural analogues of the lignan natural product (-)-podophyllotoxin, designed to probe its binding to tubulin. Synthetic methodology development becomes part and parcel of these endeavors. The newest area of activity in the group is catalyst development. In particular, we are attempting to address the need for efficient and information-rich screening methods to support combinatorial approaches to catalyst discovery and optimization. This has led to the development of a method that we term In Situ Enzymatic Screening (ISES) that exploits enzyme-based reporters enabling the experimentalist to rapidly rank catalysts, ideally, in terms of relative rate and stereoselectivity. The scope, limitations, and application of this technology are currently under investigation.
Awards and Honors
- 2016-2018: Co-Chair – Biocatalysis Gordon Research Conference
- 2015: AAAS Fellow (American Association for the Advancement of Science)
- 2010: Kickoff- Plenary Lecturer, World Congress on Catalytic Asymmetric Synthesis (WCCAS), Beijing, China
- 2010: Outstanding Research and Creative Activity (ORCA) Award, College of Arts & Sciences, University of Nebraska-Lincoln
- Christopher D. McCune, Su Jing Chan, Matthew L. Beio, Weijun Shen, Woo Jin Chung, Laura M. Szczesniak, Chou Chai, Shu Qing Koh, Peter T.-H. Wong, and David B. Berkowitz. “Zipped Synthesis” by Cross-Metathesis Provides a Cystathionine β-Synthase Inhibitor that Attenuates Cellular H2S Levels and Reduces Neuronal Infarction in a Rat Ischemic Stroke Model. ACS Central Science, 2016, 2, 242-252. DOI: 10.1021/acscentsci.6b00019. The study was featured in Nebraska Today, Science Daily, Medical News Today, Scicasts, and Science360.
- Kannan R. Karukurichi, Xiang Fei, Robert A. Swyka, Sylvain Broussy, Sangeeta Dey, Weijun Shen, Sandip K. Roy, David B. Berkowitz* “Mini-ISES Identifies Promising (Carba)fructopyranose-Based Salens for Asymmetric Catalysis: Tuning Ligand Shape via the Anomeric Effect.” Science Advances 2015, 1(6), e1500066; DOI: 10.1126/sciadv.1500066, featured in Nebraska Today: http://news.unl.edu/newsrooms/unltoday/article/chemists-discover-tuning-of-new-catalyst-family/
- Gregory A. Applegate and David B. Berkowitz* “Exploiting Dynamic Reductive Kinetic Resolution (DYRKR) in Stereocontrolled Synthesis” Advanced Synthesis & Catalysis 2015, 357, 1619-1632, chosen as a VIP (Very Important Publication) by the editors. DOI 10.1002/adsc.201500316
- Kaushik Panigrahi, Gregory A. Applegate, Guillaume Malik, David B. Berkowitz* “Combining a Clostridial Enzyme Exhibiting Unusual Active Site Plasticity with a Remarkably Facile Sigmatropic Rearrangement: Rapid Stereocontrolled Entry into Densely Functionalized Fluorinated Phosphonates for Chemical Biology. J. Am. Chem. Soc, 2015, 137, 3600-3609. DOI: 10.1021/jacs.5b00022; featured as a JACS Spotlight: DOI: 10.1021/jacs.5b02757, featured in Nebraska Today
- Christopher D. McCune, Matthew L. Beio, Jacob A. Friest, Sandeep Ginotra, David B. Berkowitz* “A Useful Methoxyvinyl Cation Equivalent: a-t-Butyldimethylsilyl-a-methoxyacetaldehyde” Tetrahedron Lett. 2015, 56, 3575-3579 (Special Symposium-In-Print honoring Harry H. Wasserman) DOI: 10.1016/j.tetlet.2015.02.122
- David B. Berkowitz, Sylvain Broussy “Analogues of (-)-Picropodophyllin, Synthesis and Uses Thereof” U.S. Patent 8,859,614, issued October 14, 2014.
- Xiang Fei, Thomas Holmes, Julianna Diddle, Lauren Hintz, Dan Delaney, Alex Stock, Danielle Renner, Molly McDevitt, David B. Berkowitz, Juliane K. Soukup “Phosphatase-Inert Glucosamine 6-Phosphate Mimics Serve as Actuators of the glmS Riboswitch” ACS Chemical Biology 2014 9; 2875-2882; DOI: 10.1021/cb500458f.
Postdoctoral and Researchers, Graduates
- Christopher D. McCune, Ph.D. 2016 – Lecturer, University of Nebraska-Lincoln
- Kaushik Panigrahi, Ph.D. 2014 – Postdoctoral Fellow, U. of Chicago/Stanford U.
- Xiang Fei, Ph.D. 2014 – Scientific Intern, GlaxoSmithKline
- Jacob Friest, Ph.D. 2012 – Senior Scientist I, Sanofi-Aventis
- Weijun Shen, Ph.D. 2007 – Postdoctoral Fellow, Scripps Research Institute
- Sangeeta Dey, Ph.D. 2007 – Postdoctoral Fellow, Princeton University
- Kannan Karukurichi, Ph.D. 2006 – Postdoctoral Fellow, Johns Hopkins University
- Roberto de la Salud-Bea, Ph.D. 2006 – Postdoctoral Fellow, University of Michigan
- Mohua Bose, Ph.D. 2002, Postdoctoral, Scripps Res. Inst.
- Sungjo Choi, Ph.D. 2001 – Postdoctoral, Texas A&M
- Huijie Li, M.S. 2001 – GlaxoSmithKline
- Esmort Chisowa, M.S. 2001 – Pfizer
- Wan-Jin Jahng, Ph.D. 2000 – Postdoctoral, Harvard
- Jill McFadden, Ph.D. 2000 – NIH postdoctoral fellowship, Johns Hopkins