David Berkowitz

Willa Cather Professor
Willa Cather Professor Profile Image

Department of Chemistry
University of Nebraska-Lincoln
824A Hamilton Hall
Lincoln, NE 68588-0304
(402) 472-2738


Merck Postdoctoral Fellowship, Yale University
Ph.D., Harvard University
M.A., Harvard University
B.S., University of Chicago

National/International Leadership

Division Director, NSF Division of Chemistry (2015)
Co-Chair, Gordon Research Conference on Biocatalysis (2018)


Alfred P. Sloan Fellow (1997-2001)
Visiting Professor, U. de Rouen, Rouen, France (2005)
Visiting Professor, Max Planck Institute for Molecular Physiology, Dortmund, Germany (2006)
Japan Society for the Promotion of Science Fellow (2008)
Inaugural WCCAS, Kickoff Plenary Lecturer, Beijing, China (2010)

Research Interests

Catalyst screening and reaction development, asymmetric synthesis, fluorinated phosphonates , mechanism-based enzyme inhibitors, PLP enzymes, lignan natural products

Current Research
Figure 1
Figure 1 Stereocontrolled and Ring-E Modular Synthesis of Bioactive Lignan Natural Products

Our group uses the power of stereocontrolled organic synthesis to address questions in biological chemistry, particularly those related to protein-ligand interactions. For example, Fig. 1 illustrates the first catalytic, asymmetric synthesis of (-)-podophyllotoxin, which serves as a tool for us to examine how the structure of the E-ring affects drug binding to tubulin. Total synthesis has yielded compounds more potent than the natural product itself, both in the tubulin assay and against human cancer cell lines.

Figure 2a
Figure 2a
Figure 2b
Figure 2b

We are also engaged in the synthesis and evaluation of unnatural analogues of amino acids (e.g. Fig. 2), designed to inactivate target enzymes. Coworkers on this project learn protein purification skills (Fig. 3), as well as enzyme kinetics, to characterize the nature of the inactivation. In a complementary endeavor, we construct mimics of natural phosphate esters that are inert to ubiquitous, digestive phosphatase enzymes. We use these phosphate mimics as bioorganic tools to build unnatural ligands for important natural phosphate binding pockets in enzymes (e.g. glucose 6-phosphate dehydrogenase) or receptors (e.g. M6P-IGF2R). Our phosphoserine mimic has served as an important bioorganic tool for biomedical scientists, at the NIH and Johns Hopkins, respectively, to study signal transduction in human tumor suppression (p53 pathway), and in production of the time-keeping hormone, melatonin.

Figure 3
Figure 3 Purification of Lysine Decarboxylase and Inactivation with a Designed, Mechanism-Based Inhibitor

In an exciting new development, we have turned the tables, and use enzymes to assist organic chemists in inventing new reactions through combinatorial catalysis. Arrays of potential catalysts are screened with "reporting" enzymes to provide the chemist with on the fly information about catalyst rate and enantioselectivity. We term this approach ISES (In Situ Enzymatic Screening).

For more information, please visit the Berkowitz Research Group Homepage.

Selected Publications

(1) David B. Berkowitz,* Sylvain Broussy  “Analogues of (-)-Picropodophyllin, Synthesis and Uses Thereof”  U.S. Patent 8,859,614, issued October 14, 2014.

(2) 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 Biology2014, ASAP. [pdf]

(3) Kaushik Panigrahi, David L. Nelson, David B. Berkowitz "Unleashing a 'True' pSer-Mimic in the Cell" Chem. Biol. 2012, 19, 666-667. [pdf]

(4) Sandeep K. Ginotra, Jacob A. Friest and David B. Berkowitz. “Halocarbocyclization Entry into the Oxabicyclo[4.3.1]decyl Exomethylene--Lactone Cores of Linearifolin and Zaluzanin A: Exploiting Combinatorial Catalysis.” Org. Lett., 2012, 14, 968–971. [pdf]

(5) Jacob A. Friest, Sylvain Broussy, Woo Jin Chung, and David B. Berkowitz. “Combinatorial Catalysis Employing a Visible Enzymatic Beacon in Real Time: Synthetically Versatile (Pseudo)Halometalation/Carbocyclizations.” Angewandte Chemie, Int. Ed. 2011, 50, 8895-8899. [pdf]

(6) Gregory A. Applegate, Ross W. Cheloha, David L. Nelson, and David B. Berkowitz. "A New Dehydrogenase from Clostridium acetobutylicum for Asymmetric Synthesis: Dynamic Reductive Kinetic Resolution entry into the Taxotère side chain." Chem. Comm. 2011, 47, 2420-2422. [pdf]

Complete list of publications