Design of Reaction Catalysts Based on Fatty Acid Binding Protein

Mark D. Distefano博士，明尼苏达大学双城分校化学系，由化学系无机、生物无机和有机金属化学项目（教师早期职业发展奖）支持，设计半合成酶，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，并参与社区外展项目。通过将过渡金属催化剂连接到脂肪酸结合蛋白上，并将噻唑杂环引入到同一类型蛋白质的内部，将制备用于区域和立体选择性氧化聚烯烃物种和对映选择性碳-碳键形成反应的催化剂。为了使用没有共价修饰的蛋白质获得催化剂，将通过诱变或融合酶将辅因子结合域引入蛋白质中。利用当前的教育理论，我们将重新设计一门大型有机化学课程和一门有关反应机制的研究生课程，以提高这些经验的有效性和智力刺激。将扩大向当地学校宣传科学活动的范围。许多合成化学品的生产过程中都含有有毒物质，由此产生的废物的处理造成了巨大的环境问题。解决这些困难的一种方法是利用酶（基于蛋白质的催化剂）催化化学反应。该项目的目标是制备将完成重要化学转化的新酶。这个项目的成功将导致制备半合成酶的能力，这种酶能够进行非常有效的转化，而没有天然酶是已知的。这些教育活动旨在提高学生对化学的认识，并将包括在校学生和研究生。

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.