Wilfred A. van der Donk
Richard E. Heckert Endowed Chair in Chemistry
Professor van der Donk received his B.S. from Leiden University, the Netherlands, in 1989 and his Ph.D. from Rice University in 1994. He went on to do postdoctoral work at the Massachusetts Institute of Technology, and joined the faculty at Illinois in 1997. His research interests are in organic chemistry and chemical biology.
Research
Our research program focuses on the discovery and design of new antibiotics and anti-inflammatory agents. These projects combine synthetic organic, and protein chemistry to address problems at the interface of chemistry and biology.
Antibiotics Numerous reports of multi-drug resistant bacterial strains have appeared in recent years, with several strains posing the threat of becoming immune against all commercially available antibiotics. It is evident that in order to prevent potential epidemic outbreaks of infectious diseases, a renewed focus on antibiotic research is highly desired, including the search for new drugs with alternative cellular targets, the investigation of the mechanisms of cytotoxicity and resistance, and the understanding of biosynthetic pathways. Unfortunately, at this time of critical need for new antimicrobial agents, the large pharmaceutical companies have almost entirely withdrawn from this area due to small projected profits. The van der Donk group focuses on the mode of action and mechanism of biosynthesis of two classes of antibiotics that have been underexplored but have great potential for human therapeutic use, lantibiotics and phosphonate antibiotics.
Inflammation. Our interest in prostaglandin H synthase (PGHS), sometimes called cyclooxygenase (COX), stems both from the unusual chemistry the enzyme catalyzes as well as its pharmaceutical importance. The protein is the target of anti-inflammatory drugs such as aspirin and ibuprofen. In recent years, it has become clear that two COX genes are present in humans. One of the enzymes, COX-1, is not involved in inflammation, while the second isozyme (COX-2) is. Aspirin and ibuprofen inactivate both COX-1 and COX-2, which is undesirable. Both isozymes catalyze the conversion of arachidonic acid into prostaglandin H2 generating five new chiral centers in one enzymatic reaction. Despite the attention the enzymes have received, the actual mechanism of catalysis is still incompletely understood. We have recently synthesized a number of isotopically labeled arachidonic acids to further investigate this intriguing reaction. A detailed understanding of these differences may be useful for the design of COX-2 specific inhibitors.
Publications
Levengood, M.R.; Patton, G.C.; van der Donk, W.A. "The Leader Peptide is not Required for Post-translational Modification by Lacticin 481 Synthetase" J. Am. Chem. Soc. 2007, 129, 10314-5.
Li, Bo; van der Donk, W.A. "Identification of Essential catalytic Residues of the Nisin Cyclase NisC.", J. Biol. Chem. 2007 282, 21169-21175.
Zhang, X.; van der Donk, W.A. "On the Substrate Specificity of Dehydration by Lacticin 481 Synthetase." J. Am. Chem. Soc. 2007 129, 2212-2213.
Woodyer, R.; Li, G.; Zhao, H.; van der Donk, W.A. "New Insight into the Mechanism of Methyl Transfer during the Biosynthesis of Fosfomycin." Chem. Comm. 2007, 359-361.
van der Donk, W. A. "Rings, Radicals, and Regeneration: the Early Years of a Bioorganic Laboratory." J. Org. Chem. 2006 71, 9561-9571.
McClerren, A.L.; Cooper, L.E.; Quan, C.; Thomas, P.M.; Kelleher, N.L.; van der Donk, W.A.* "Discovery and in vitro Biosynthesis of Haloduracin, a New Two-component Lantibiotic." Proc. Natl. Acad. Sci. USA 2006 103, 17243-17248
Li, B.; Yu, J.-P. J.; Brunzelle, J. S.; Moll, G. N.; van der Donk, W. A.*; Nair, S. K.* "Structure and Mechanism of the Lantibiotic Cyclase Involved in Nisin Biosynthesis" Science, 2006, 311, 1464.
Chatterjee, C.; Miller, L. M.; Leung, Y. L.; Xie, L.; Yi, M.; Kelleher, N.L.; van der Donk, W.A.* "Lacticin 481 Synthetase Phosphorylates its Substrate during Lantibiotic Production." J. Am. Chem. Soc. 2005, 127, 15332-3.
"Biosynthesis and Mode of Action of Lantibiotics," C. Chatterjee, M. Paul, L. Xie, W.A. van der Donk, Chem. Rev., 105, 633-84 (2005).
Awards
- Tetrahedron Young Investigator Award in Bioorganic & Medicinal Chemistry Cope Scholar Award
- University Scholar, UIUC
- Pfizer Award
- Helen Corley Petit Award
- Burroughs-Wellcome New Investigator Award
- Beckman Young Investigator Award
- Research Corporation Innovation Award
- Alfred P. Sloan Fellowship
- Cottrell Scholar
- Camille Dreyfus Teacher-Scholar
Highlights
"Five Golden Rings" - SCIENCE 2006 311, 1382-1383
"Amended Route To Odd Natural Product" -
C&EN 2007, 85(29), 928.
"Nisin Engineered In Test Tube" -
C&EN 2006, 84, 9.
"TOWARD NOVEL LANTIBIOTICS" - C&EN 2004, 82, 10.
"Antimicrobials: A ringing success" - Nature Reviews Microbiol. 2006, 4, 322-323;
"RESISTING THE RESISTANCE" - ACS Chem. Biol. 2006, 1, 119;
"Getting Back to Nature" - NIGMS Newsletter "Biomedical Beat" April 18, 2006
"Hot Article" - Biochemistry (ACS Publications)
"Hot Papers:" - ACS Publications May 2007 - Chemical Reviews
"Methyl mystery unravelled" - Chemical Biology 2007 (UK)
"Cloning techniques produce FDA-approved antibiotic" - Innovations Report
"Scientists Discover Two-component Lantibiotic With Therapeutic Potential" - Science Daily
