Enzymatic C-H Oxidation by Tyrosyl Radicals

该奖项将支持约翰霍普金斯大学的Justine Roth教授的工作，以检查植物来源的脂肪酸α-双加氧酶，该酶被认为是利用酪氨酰自由基进行催化的酶家族的成员。 蛋白质衍生自由基介导使用分子氧的选择性C-H氧化的能力尚未被理解。该项目的特点是一个机制的研究，将允许动力学和热力学的脂肪酸氧化的特点。 作为温度和底物C-H键强度的函数的氘动力学同位素效应的测量将揭示反应屏障的性质，在这种情况下，反应屏障也控制酶的周转。 结果将使用马库斯理论进行分析，以阐明酶催化的起源。 这种见解在生物和化学催化剂的合理工程以及酶在商品化学品工业生产中的应用中具有根本的重要性。 这项研究的一个更广泛的目标是让学生了解氧化现象在化学和生物学中的重要性。一个针对巴尔的摩市高中学生的教育充实计划已经与美国巴尔的摩教育团合作启动。 该计划将使学生接受生物和物理科学的高等教育，特别是在约翰霍普金斯大学。 该计划还将培养P.I.内部的暑期实习和研究经验的机会。的实验室。

This award will support work by Professor Justine Roth at Johns Hopkins University to examine a plant-derived fatty acid alpha-dioxygenase which is believed to be a member of a family of enzymes that utilize tyrosyl radicals for catalysis. The ability of protein-derived radicals to mediate selective C-H oxidation using molecular oxygen has not been understood. The project features a mechanistic study that will allow the kinetics and thermodynamics of fatty acid oxidation to be characterized. Measurements of deuterium kinetic isotope effects as a function of temperature and substrate C-H bond strength will reveal the nature of the reaction barrier, which in this case also controls enzyme turnover. The results will be analyzed using Marcus Theory to elucidate the origins of enzyme catalysis. Insights of this kind are fundamentally important in the rational engineering of biological and chemical catalysts as well as the applications of enzymes in the industrial production of commodity chemicals. A broader objective of this research is to expose students to the importance of oxidative phenomena in chemistry and biology. An educational enrichment program for Baltimore City high school students has been initiated in collaboration with the Teach for America Baltimore Corps. This program will expose students to higher education in the biological and physical sciences, specifically at Johns Hopkins University. The program will also cultivate opportunities for summer internships and research experiences within the P.I.'s laboratories.