03/01/18 -9:45 AM to 11:00 AM
Dow Lecture Series: Professor Wilfred A. van der Donk
Dow Lecture Series
"Phosphonate Biosynthesis: A Treasure Trove for Novel Enzymology"
Natural products containing carbon-phosphorus bonds (phosphonic and phosphinic acids) have found widespread use in medicine and agriculture. They include the clinically used antibiotic fosfomycin, the common herbicide phosphinothricin (BASTA or Liberty), and the antimalarial candidate fosmidomycin. Recent years have seen a renewed interest in the biosynthesis of these compounds with the cloning of the biosynthetic gene clusters for several family members and the use of genome mining for novel phosphonates.1 Investigations of their biosynthetic pathways have uncovered much unprecedented chemistry. These include transformations carried out by non-heme iron dependent enzymes,2,3 tRNA dependent enzymes,4 and enzymes involved in methane production in the oceans.5 This presentation will focus on some of these enzymes, including two enzymes that use the same substrate but achieve radically different reaction outcomes.6
- Ju, K.S.; Gao, J.; Doroghazi, J.R.; Wang, K.K.; Thibodeaux, C.J.; Li, S.; Metzger, E.; Fudala, J.; Su, J.; Zhang, J.K.; Lee, J.; Cioni, J.P.; Evans, B.S.; Hirota, R.; Labeda, D.P.; van der Donk, W.A.; Metcalf, W. W. Proc. Natl Acad. Sci. U.S.A. 2015, 112, 12175.
- Cicchillo, R.M.; Zhang, H.; Blodgett, J.A.V.; Whitteck, J.T.; Li, G.; Nair, S.K.; van der Donk, W.A.; Metcalf, W.W. Nature 2009, 459, 871.
- Whitteck, J.T.; Malova, P.; Peck, S.C.; Cicchillo, R.M.; Hammerschmidt, F.; van der Donk, W.A. J. Am. Chem. Soc. 2011, 133, 4236.
- Bougioukou, D.J.; Mukherjee, S.; van der Donk, W.A. Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 10952.
- Metcalf, W.W.; Griffin, B.M.; Cicchillo, R.M.; Gao, J.; Janga, S.; Cooke, H.A.; Circello, B.T.; Evans, B.S.; Martens-Habbena, W.; Stahl, D.A.; van der Donk, W.A. Science 2012, 337, 1104.
- Born, D.A.; Ulrich, E.C.; Ju, K.S.; Peck, S.C.; van der Donk, W.A.; Drennan, C.L. Science 2017, 358, 1336.
Professor van der Donk's research program focuses on the discovery and design of new antibiotics and natural products. These projects combine synthetic organic and protein chemistry to address problems at the interface of chemistry and biology. His research group uses genome mining strategies to discover new natural products, uses microbiology and genomic tools to determine their mode of action, uses chemical biology techniques to study their biosynthesis, and uses synthetic chemistry to improve their activities and therapeutic properties.
Professor van der Donk
Professor van der Donk received his bachelor’s degree from Leiden University, the Netherlands, and his doctorate from Rice University. He did post-doctoral work at the Massachusetts Institute of Technology, and joined the faculty at Illinois in 1997. He is the Richard E. Heckert Endowed Chair in Chemistry and director of Graduate Studies. In 2008, he was appointed as an investigator of the Howard Hughes Medical Institute.