- Repligen Award in Chemistry of Biological Processes: Hung-Wen (Ben) Liu
Repligen Award in Chemistry of Biological Processes: Professor Hung-Wen (Ben) Liu, Department of Medicinal Chemistry, University of Texas. For outstanding contributions to the understanding of the chemistry of biological processes with particular emphasis on structure, function and mechanism.
This award recognizes Professor Liu’s studies to elucidate and exploit Nature’s strategies to synthesize unusual sugars and secondary metabolites. His discoveries in this area have changed the way chemists and biologists think about the biosynthetic pathways for unusual sugars. Most notably, Liu has been a pioneer in the field of combinatorial biosynthesis that leads to the diversification of sugars found in macrolide antibiotics.
Professor Liu’s research focuses on the elucidation of the chemistry of mechanistically novel biological reactions that are of unusual physiological importance. The Repligen award recognizes his research accomplishments in three areas at the interface of chemistry and biology.
Many of the most intriguing and complex enzymatic transformations proceed through radical intermediates that are transient in nature and exceedingly difficult to detect and characterize. Professor Liu has made many seminal contributions to the characterization of radical intermediates. Two prominent examples are medium-chain acyl-CoA dehdyrogenase, which Liu showed proceeds by two successive single electron transfers from the reduced flavin to the a,b-unsaturated CoA ester; and, ascarylose biosynthesis where Liu established a new role for coenzyme B6. These studies were driven by the development of several useful radical probes and have greatly increased our understanding of radical-based enzymatic transformations.
Ben Liu has a well-developed program in the design, synthesis and use of novel mechanism-based inhibitors of enzymatic reactions. These inhibitors have potential applications as drugs that target enzymes in pathogenic bacteria. Most notably, Liu has designed and synthesized several fluorinated substrate analogue inhibitors. The design and study of these compounds is characterized by an elegant fusion of synthetic organic chemistry and mechanistic enzymology.
Finally, Professor Liu has recognized that the biological activities of macrolide antibiotics are often controlled by the type, position and number of unusual sugars contained in the macrolide. Liu has concentrated on the portions of antibiotic biosynthetic pathway responsible for biosynthesis and attachment of unusual sugars. He has cloned the genes responsible for the biosynthesis of several unusual sugars, and expressed these genes in engineered Streptomyces species capable of producing antibiotics. This has led to the construction of new bacteria that produce hybrid antibiotics. This work opens the door for even more extensive engineering of these biosynthetic pathways.
Liu is thickly involved in the scientific enterprise. Under his wing as the George H. Hitchings Regents Chair in Drug Design are some two-dozen graduate students and postdoctoral fellows. He is a member of many scientific societies, an organizer of conferences, a grant reviewer, and an editor or adviser for a range of scientific journals. When asked what accomplishment makes him most proud, Liu says, “The best things have yet to come.”
In summary, Ben Liu is an outstanding representative of a new generation of bioorganic chemists. His laboratory is a training ground for future scientists, to whom he transfers his passion and enthusiasm for chemistry and biology.