报告1：Recent Methodology Developments in Directed Evolution of Enzymes
报告人：Manfred T. Reetz, 马克斯-普朗克煤炭研究所（Max-Planck Institute For Coal Research）/菲利普斯马尔堡大学（Philipps-University Marburg）教授
报告摘要：Since its conception two decades ago (M. T. Reetz, A. Zonta, K. Schimossek, K. Liebeton, K.-E. Jaeger, Angew. Chem. Int. Ed. Engl. 1997, 36, 2830-2832), directed evolution of stereoselective enzymes as a fundamentally novel approach to asymmetric catalysis has been generalized by us and others to include hydrolases, ligases, reductases, oxygenases, transferases, and C-C bond forming enzymes such as aldolases, oxynitrilases and pyruvate decarboxylases. In addition to asymmetric catalysis using chiral transition metal complexes or organocatalysts, directed evolution is the third major way to catalytically access enantiomerically enriched or pure compounds in a reliable manner. Recently, a comprehensive monograph has appeared (Reetz, M. T. Directed Evolution of Selective Enzymes: Catalysts for Synthetic Organic Chemistry and Biotechnology, Wiley-VCH, Weinheim, 2016). This protein engineering approach involves repeating cycles of gene mutagenesis and screening, which builds up “evolutionary pressure” in each round. Since the screening step is the bottleneck of this Darwinian laboratory evolution, the real challenge is to obtain mutant libraries of highest quality requiring a minimum of screening effort. Keeping this in mind, we introduced some time ago systematic saturation mutagenesis at sites lining the binding pocket (CASTing) as well as the use of highly reduced amino acid alphabets in addition to iterative saturation mutagenesis (ISM), which have proven to be exceptionally valuable tools (see for example: Z. Sun, R. Lonsdale, X.-D. Kong, J.-H. Xu, J. Zhou, M. T. Reetz, Angew. Chem. Int. Ed. 2015, 54, 12410-12415). Since methodology development constitutes the heart of directed evolution, we have recently increased our efforts for obtaining even more efficient methods and concepts, which is the subject of this lecture. Applications of these refined techniques concern the control of regio- and stereoselectivity of P450-catalyzed late-stage oxidative hydroxylation of steroids and of non-natural compounds, ADH-catalyzed asymmetric reduction of “difficult-to-reduce” ketones, regioselective Baeyer-Villiger reactions with formation of “abnormal” products catalyzed by BVMOs, and designer cells for cascade processes. Many of these transformations can be considered to be “dream reactions”. Yet another new development concerns the generation of focused mutant libraries generated not by the traditional molecular biological technique of saturation mutagenesis, but by combinatorial chemical solid-phase gene synthesis, especially synthetic systems functioning on micro-chips.
报告2：Highly Efficient Oxygenation and Nitrogenation Reactions
报告摘要：Oxygen- or nitrogen-containing compounds are widely present in both natural products and synthetic compounds, for example, they show up within functional materials, top-selling drugs, as well as bioactive molecules. Thus, organic chemists have paid considerable attention in developing novel methodologies for their preparation. To synthesize these compounds in a green and sustainable way, researchers have focused on the direct functionalization of hydrocarbons via C–H and/or C–C bond cleavage. Although significant progress have made in the direct functionalization of simple hydrocarbons, direct incorporation of O-or N-atoms into the simple substrates via C–H and/or C–C bond cleavageremains challenging due to the inert chemical bonds and the unstable character of some N-sources under oxidative conditions. By using molecular oxygen1as oxygen source as well as azides as nitrogen source, we recently developed some C-H/C-C bond oxygenation and nitrogenation reactions for the synthesis O-and/or N-containing compounds.In this presentation, our recent progress on the direct oxygenation and nitrogenation will be introduced.