Issue Date: March 17, 2014
Cope Scholar Award: Hung-wen (Ben) Liu
As a child, Hung-wen (Ben) Liu marveled at the world around him. “ ‘Why is this plant red?’ and ‘Why does something smell a particular way?’ were the kinds of questions that always occurred to me when I was young,” he says.
This curiosity foreshadowed a later passion for chemistry—especially in the area of natural product biosynthesis. For three decades, Liu, a medicinal chemist at the University of Texas, Austin, has picked apart the mechanisms of several of nature’s catalytic tools. Many have proved to be biomedically important.
Colleagues praise him for his ingenuity and boldness. Succeeding in his field “requires a multidisciplinary approach involving synthetic and structural analysis chemistry, genetics, molecular biology, and many types of spectroscopies,” says chemist Peter G. Schultz of Scripps Research Institute, La Jolla, Calif. “His work has provided fundamental insights into nature’s strategies for making novel chemical structures, and his contributions have helped lay the foundation for several modern approaches to drug development and discovery.”
JoAnne Stubbe of Massachusetts Institute of Technology says Liu’s “fearless and creative” work is “of fundamental and translational interest.”
Early in his career, Liu uncovered a two-enzyme mechanism by which nature makes 3-deoxygenated sugars—“a gutsy system for a young assistant professor to study,” Stubbe explains. Liu’s ensuing work has advanced the mechanistic understanding of metalloenzyme catalysis, of chemical transformations using coenzymes in unusual ways, and of flavoprotein catalysis of nonredox reactions.
More recently, Liu and colleagues discovered the first example of an enzymatic reaction in nature resulting in a Diels-Alder-type [4+2] cycloaddition. Although four gene products are involved, Liu found that one, the protein SpnF, boosts the reaction rate by a factor of 500. His discovery, along with work to unravel other enzymes’ functions in that pathway, “beautifully demonstrates his chemical intuition and experimental abilities,” Stubbe says.
Liu earned a Ph.D. in 1981 from Columbia University, after which he joined Christopher Walsh’s lab at MIT as a postdoctoral fellow. In 1984, Liu became an assistant professor at the University of Minnesota, Twin Cities, later becoming a tenured professor. He moved to UT Austin in 2000, where he is a professor in the College of Pharmacy and the department of chemistry and biochemistry.
A coauthor on 236 peer-reviewed publications, Liu currently holds editorial positions for seven journals, including as associate editor for Organic Letters. He received the Horace S. Isbell Award from ACS’s Division of Carbohydrate Chemistry, the Repligen Award in Chemistry of Biological Processes from ACS’s Division of Biological Chemistry, the Nakanishi Prize from ACS’s Division of Organic Chemistry, and the A. I. Scott Medal for biochemistry research.
He also is a fellow of the American Association for the Advancement of Science and the American Academy of Microbiology, and he was elected to chair ACS’s Division of Biological Chemistry for 2013–14. At UT Austin, he holds the George H. Hitchings Regents Chair in Drug Design.
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