主讲人: Dr. Jixun Zhan, Associate Professor in the Department of Biological Engineering at Utah State University
主持人: 黄静 副教授
报告时间: 2016-4-19 9:00-10:30 （周二上午）
讲座地址: 闵行校区天美娱乐534报告厅
主办单位: 天美娱乐 科技处
报告人简介𓀁🍆：Dr. Jixun Zhan is an associate professor in the Department of Biological Engineering at Utah State University. He earned a Ph.D. in biochemical engineering from East China University of Science and Technology in 2003. He received his postdoctoral training at the University of Arizona and the University of California, Los Angeles. He joined the Department of Biological Engineering at Utah State University as an assistant professor in August 2008, and was promoted to Associate Professor in 2013. Dr. Zhan leads a Metabolic Engineering Laboratory and his research focuses on metabolic engineering of natural product biosynthetic pathways for industrially and pharmaceutically important molecules. Dr. Zhan’s research has led to the publication of 82 papers in peer-reviewed journals such as PNAS, Metabolic Engineering, and JACS and 3 book chapters. He serves as a member of the editorial boards of several international journals including Journal of Biological Engineering and Pharmacognosy Magazine.
报告摘要：Nature provides a variety of molecules with diverse biological activities, such as the plant natural products resveratrol and curcumin. While production of these molecules largely relies on the extraction from the producing plants, combinatorial biosynthesis has become an attractive tool to generate natural and unnatural molecules. In this work, we show that biosynthetic enzymes from different sources can be recombined to make various molecules. Seven biosynthetic genes from plants and bacteria were used to establish a variety of complete biosynthetic pathways in Escherichia coli to make valuable compounds. Different combinations of these biosynthetic bricks yielded four phenylpropanoid acids (cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid), three bioactive natural stilbenoids (resveratrol, piceatannol and pinosylvin), and three natural curcuminoids (curcumin, bisdemethoxycurcumin and dicinnamoylmethane). An "unnatural" natural product dicafferolmethane was synthesized by rationally removing a methyltransferase from the curcumin biosynthetic pathway. Furthermore, addition of a fungal flavin-dependent halogenase into the resveratrol biosynthetic pathway yielded a novel chlorinated molecule 2-chloro-resveratrol. This work thus provides a novel and efficient biosynthetic approach to creating pharmaceutically important or novel molecules. Further expansion of the library of the biosynthetic bricks may provide a huge resource for rational design of natural and unnatural molecules via the combinatorial biosynthesis approach. We also studied the biosynthesis of fungal benzenediol lactone (BDL) polyketides that are important pharmacophores with a wide range of bioactivities, including heat shock response and immune system modulatory effects. Expression of random pairs of iterative PKS subunits from four BDL biosynthetic systems in a yeast host created a diverse library of BDL congeners, including a product with an unnatural skeleton and heat shock response-inducing activity. This plug and play approach provides a novel tool to create chemical diversity in fungal natural products for drug discovery.
