Time：Monday 9:00 AM, September 21, 2015
Location：Conference room in Biotechnology Building
Speaker：Professor Hung-wen LIU
University of Texas at Austin, USA
Abstract: The Diels–Alder reaction is a [4+2]-cycloaddition reaction in which a cyclohexene ring is formed between a 1,3-diene and an alkene via a single pericyclic transition state. This reaction has been proposed as a key transformation in the biosynthesis of many secondary metabolites. Although several purified enzymes have been implicated in Diels–Alder alike reaction, these enzymes typically demonstrate more than one catalytic activity, leaving their specific influence on the cycloaddition step uncertain. We identified a cyclase, SpnF, that catalyzes a [4+2]-cycloaddition to form the fused cyclohexene ring in spinosyn A, an important insecticide from Saccharopolyspora spinosa. SpnF is unique, because it is the only known enzyme that specifically catalyzes a [4+2]-cycloaddition without introducing any other changes to its substrate. The same cycloaddition also takes place non-enzymatically, but at a much reduced rate. We measured alpha-secondary deuterium kinetic isotope effects at both points of rehybridization in the diene during both enzymatic and non-enzymatic reactions, and demonstrated that SpnF is the first example of a natural Diels-Alderase.
About the Speaker: Professor Hung-wen (Ben) Liu obtained his PhD from Columbia University (1981) with Prof. Koji Nakanishi and did postdoc research at MIT with Prof. Christopher Walsh. In 1984, he became an Assistant Professor at University of Minnesota, and then the Distinguished McKnight University Professor in 1999. In 2000, Liu moved to University of Texas at Austin. He currently holds the George Hitchings Regent Chair in Drug Design, and is a Professor in the Medicinal Chemistry Division of the College of Pharmacy and the Department of Chemistry and Biochemistry at the University of Texas at Austin.
Liu's research lies at the crossroads of chemistry and biology, and focuses on the elucidation of the chemical mechanisms of enzymes that catalyze mechanistically unusual and physiologically important steps in the biosynthetic pathways of natural products. Over the years, he earned many awards including the National Institutes of Health Research Career Development Award (1990), the Horace S. Isbell Award from the American Chemical Society Carbohydrate Division (1993), the MERIT Award from the National Institute of General Medicine (1999), the Nakanishi Prize from the American Chemical Society Organic Division (2007), the Repligen Award from the American Chemical Society Biological Division (2008), the A. I. Scott Medal (2011), and the Arthur C. Cope Late Career Scholars Award from the American Chemical Society (2014). He is a Fellow of the American Association for the Advancement of Science, the American Academy of Microbiology, the Japan Society for the Promotion of Science, the American Chemical Society, and an academician of Academia Sinica (2008). He serves on many review panels and editorial boards. He is currently an Associate Editor of Organic Letters since 2004. He is also an active member in many professional societies, and was the chair of the American Chemical Society Biological Division during 2013-2014.
Contact: Prof. Zongbao K. Zhao