Enzymatic C-H Oxidation by Tyrosyl Radicals

该奖项将支持约翰·霍普金斯大学的贾斯汀·罗斯教授对一种植物衍生的脂肪酸-双加氧酶的研究，该酶被认为是利用酪氨酸自由基进行催化的酶家族的一员。蛋白质来源的自由基利用分子氧介导选择性C-H氧化的能力尚不清楚。该项目的特点是一项机制研究，将使脂肪酸氧化的动力学和热力学得到表征。氘动力学同位素效应作为温度和底物C-H键强度的函数的测量将揭示反应屏障的性质，在这种情况下，反应屏障也控制着酶的周转。结果将用马库斯理论来分析，以阐明酶催化的起源。这种见解对于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至关重要。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。一项针对巴尔的摩市高中生的教育充实计划已与“为美国而教”巴尔的摩队合作启动。该项目将使学生接触到生物和物理科学方面的高等教育，特别是在约翰霍普金斯大学。该项目还将为学生提供暑期实习和在P.I.进行研究的机会的实验室。

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.