Time：Friday 9:00 AM, September 25, 2015
Location：Room 106 at Biotechnology Building
Speaker：Professor Hung-wen LIU
University of Texas at Austin, USA
Abstract: Sulphur is an essential element for life. Yet, how the sulphur atom is incorporated in secondary metabolites remains poorly understood. For C-S bond formation in primary metabolites, the major ionic sulphur sources are the protein-persulphide and protein-thiocarboxylate. In each case, the persulphide and thiocarboxylate group on these sulphur-carrier (donor) proteins are post-translationally generated. To study 2-thiosugar production in BE-7585A, an antibiotic from Amycolatopsis orientalis, we identified a putative 2-thioglucose synthase, BexX, whose protein sequence appear similar to that of ThiG, the enzyme catalyzing thiazole formation in thiamin biosynthesis. However, no sulphur-carrier protein gene could be located in the BE-7585A cluster. Subsequent genome sequencing revealed the presence of a few sulphur-carrier proteins likely involved in the biosynthesis of primary metabolites, but surprisingly only a single activating enzyme gene in the entire genome of A. orientalis. Further experiments showed that this activating enzyme is capable of adenylating each of these sulphur-carrier proteins, and likely also catalyzing the subsequent thiolation taking advantage of its rhodanese activity. A proper combination of these sulphur delivery systems is effective for BexX-catalyzed 2-thioglucose production. The ability of BexX to selectively distinguish sulphur-carrier proteins is given a structural basis using X-ray crystallography. These studies represent the first complete characterization of a thiosugar formation and also demonstrate the receptor promiscuity of the sulphur-delivery system in A. orientalis. Our results also provide evidence that exploitation of sulphur-delivery machineries of primary metabolism for the biosynthesis of sulphur-containing natural products is likely a general strategy in nature.
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