报告题目：Directed Evolution of Stereoselective Enzymes: A Prolific Source of Catalysts for Asymmetric Reactions
报 告 人：Prof. Manfred T. Reetz
报告摘要：Since its conception two decades ago (M. T. Reetz, et al, Angew. Chem. Int. Ed. Engl. 1997, 36, 2830-2832) the idea of directed evolution of stereoselective enzymes as a new approach to asymmetric catalysis in synthetic organic chemistry and biotechnology has been generalized. We as well as many groups have since joined efforts by focusing on essentially all known enzyme types, including hydrolases, reductases, oxygenases, transferases, glycosidases and C-C bond forming enzymes such as aldolases, oxynitrilases and pyruvate decarboxylases. Evolution in the test-tube involves repeating cycles of gene mutagenesis and screening, which builds up “evolutionary pressure” at each stage. Since the screening step is the bottleneck of Darwinian laboratory evolution, the real challenge is to obtain mutant libraries of highest quality requiring a minimum of screening effort. In this endeavor we have proposed iterative saturation mutagenesis (ISM), which has proven to be an extremely valuable tool. In order to beat the numbers problem in directed evolution, we also introduced the use of reduced amino acid alphabets. Examples concern the control of regio- and stereoselectivity of P450-catalyzed oxidative hydroxylation of steroids and of purely synthetic non-natural compounds, enantioselectivity of difficult to reduce prochiral ketones catalyzed by alcohol dehydrogenases, and stereoselective epoxide hydrolases. Such selectivities are generally not possible using modern transition metal catalysts or organocatalysts. The lecture will focus on current methodology developments as well as the construction of stereoselective designer cells in multi-step cascade sequences. These recent advances expand the toolbox of organic chemists in their quest to prepare chiral compounds for a variety of different applications.
报告人简介：Manfred T. Reetz教授是国际著名有机化学家，生物催化领域专家，德国科学院院士，荷兰皇家人文和科学院外籍院士，从事生物催化研究20多年来，于1997年首次将定向进化概念和方法应用到对酶的手性改造，并引入到有机化学领域用于不对称催化合成，创立了用于酶立体选择性改造的CASTing方法，与定向进化领域易错PCR创始人Frances Arnold，以及DNA Shuffling的创始人 Willem P. C. Stemmer并称为定向进化方法学的三大开创者。
Reetz教授现任职于马克斯-普朗克煤炭研究所/菲利普斯马尔堡大学（Max-Planck-Institut für Kohlenforschung/Philipps-University Marburg），曾担任马克斯-普朗克煤炭研究所所长20年（1991-2011），曾是国际著名杂志德国应用化学（Angewandte Chemie）的编委，现担任Cell Chemical Biology编委，也是中国新创杂志Bioresources and Bioprocessing的编委，发表文章560多篇，引用次数达38,000余次，H-index指数达101 （Google Scholar），申请授权国际/欧洲专利27项，著书10余部，获国际奖项20余次。