Design of Reaction Catalysts Based on Fatty Acid Binding Protein

Mark D.Distefano博士，明尼苏达大学双子城分校化学系，由化学系无机化学、生物无机化学和有机金属化学计划支持，在学院早期职业发展奖下设计半合成酶，将催化有机分子的区域选择性转化，承担研究生和本科生水平的课程和课程开发，并参与社区外展计划。通过将过渡金属催化剂固定在脂肪酸结合蛋白上，并在同一类型的蛋白质内部引入噻唑杂环，将制备出用于聚烯烃的区域和立体选择性氧化以及对映选择性碳-碳键形成反应的催化剂。为了获得没有共价修饰的蛋白质催化剂，辅因子结合域将通过诱变或融合酶引入蛋白质中。利用当前的教育理论，将重新设计一门关于反应机理的大型有机化学课程和一门研究生课程，以增加这些经验的有效性和智力刺激。为了向当地学校传达科学外展项目的兴奋之情，将扩大这一范围。许多合成化学品的制造过程涉及有毒物质，产生的废物的处理造成了巨大的环境问题。这些困难的一种解决方案是使用酶(基于蛋白质的催化剂)来催化化学反应。该项目的目标是制备新的酶，以完成重要的化学转化。该项目的成功将导致制备半合成酶的能力，这种酶能够执行天然酶所不知道的非常有效的转化。教育活动的目的是提高学生对化学的鉴赏力，并将涉及到从小学生到研究生。

Dr. Mark D. Distefano, Chemistry Department, University of Minnesota - Twin Cities, is supported by the Inorganic, Bioinorganic, and Organometallic Chemistry Program of the Chemistry Division under a Faculty Early Career Advancement Award to design semi-synthetic enzymes which will catalyze regioselective transformations of organic molecules, to undertake course and curriculum development at the graduate and undergraduate level, and to engage in community outreach programs. By attaching a transition metal catalyst to a fatty acid binding protein and by introducing a thiazolium heterocycle into the interior of the same type of protein, catalysts for the regio- and stereo-selective oxidation of polyolefinic species and for enantioselective carbon-carbon bond forming reactions will be prepared. To obtain catalysts using proteins without covalent modification, cofactor binding domains will be introduced into the protein by mutagenesis or by fusion enzymes. Using current educational theory a large organic chemistry course and a graduate course in reaction mechanisms will be redesigned to increase the effectiveness and intellectual stimulation of these experiences. To communicate the excitement of science out-reach programs to local schools will be expanded. Many synthetic chemicals are made using processes that involve toxic materials and the disposal of the resulting waste products has created enormous environmental problems. One solution to these difficulties employs enzymes (protein based catalysts) to catalyze chemical reactions. The goal of this project is to prepare new enzymes which will accomplish important chemical transformations. Success in this project would lead to the ability to prepare semi-synthetic enzymes which are capable of performing very efficient transformations for which no natural enzymes are know. The educational activities are designed toward increasing student appreciation of chemistry and will involve school children to graduate students.