报告题目：Mechanistic Studies of Hydroxylation and Cyclization Reactions Catalyzed by Hyoscyamine 6b-Hydroxylase (H6H)

报告人: Prof. Hung-Wen Liu
              Fellow of American Academy of Microbiology
              Fellow of American Association for the Advancement of Science
              Fellow of Japan Society for the Promotion of Science

时间: 2019年10月15日（星期二），9:30-11:30

地点: 闵行校区生物药学楼树华多功能厅报告厅

简介:

Prof. Liu is the George H. Hitchings Regents Chair in Drug Design, Professor of Chemical Biology & Medicinal Chemistry, Professor of Chemistry in College of Pharmacy and Departments of Chemistry, University of Texas at Austin; the Fellow of American Academy of Microbiology, Fellow of American Association for the Advancement of Science, Fellow of American Chemical Society,  Fellow of Japan Society for the Promotion of Science, Associate Editor of Organic Letters. His research interests focus on Enzyme Mechanism and Inhibitor Design, Metabolic Pathway Engineering and Protein Function Regulation. He has authored 280+ scientific publications including Nature, Science, Chem Rev, Nature Chem Biol, Proc Natl Aca Sci USA, Nature Commun, J Am Chem Soc, Angew Chem Int Ed Engl, and Nat Prod Rep.

报告摘要:

Scopolamine is a tropane alkaloid found in the Solanaceae family of plants. It has antagonistic activity against muscarinic acetylcholine receptors. The construction of the epoxide ring in scopolamine is of great interest, because it is formed by oxidation of two unactivated methylene groups of hyoscyamine, the precursor to scopolamine. The epoxidation is catalyzed by hyoscyamine 6β-hydroxylase (H6H) which is a mononuclear non-heme iron- and α-ketoglutarate-dependent dioxygenase. The overall transformation involves a two-step oxidation of hyoscyamine: hydroxylation of an aliphatic carbon followed by dehydrogenation of the resulting secondary alcohol. A high-valent iron(IV)-oxo species generated via activation of molecular oxygen is believed to be involved in both steps. However, the detailed mechanism regarding how H6H controls these two sequential oxidation reactions remains unclear. To address these mechanistic questions, experiments were carried to gain more insights into the catalysis of H6H. The results of these experiments will be presented and discussed.

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