CAREER: Kinetic and Spectroscopic Studies of Catalytically Versatile Non-heme Mononuclear Iron Enzymes

有了这个奖项，化学系的生命过程化学项目资助卡内基梅隆大学的郭义松教授研究在微生物中制造新型高生物活性化合物所需的三种酶催化反应。 这三种酶在铁原子周围使用相同的基本结构，但进行三种完全不同的反应;结构-功能关系差异的原因是生物化学中的基本问题。 例如，铁在相同的碱性环境中可以导致一方面形成碳-氧键或另一方面形成碳硫键。 该研究采用尖端的方法来揭示这些反应是如何在原子的基础上发生的。 这些研究结果可以为设计新的分子催化剂和生物催化剂来进行这些重要而具有挑战性的化学转化提供有用的指导。 该奖项支持的研究也为物理化学，生物无机化学，生物化学，酶学和催化的学生提供了一个培训基地。通过该项目产生的知识被整合到教育活动中，研究生，本科生和高中生在发现反应如何被铁依赖性酶催化方面发挥积极作用。 非血红素单核铁（NHM-Fe）依赖性酶催化极其多样的酶促反应，范围从“经典”羟基化到去饱和、环氧化、卤化、差向异构化、芳环膨胀、环收缩和开环。 催化这些不同反应的铁中心的结构非常简单。 铁的第一配位球仅含有组氨酸（His）和/或天冬氨酸/谷氨酸（Asp/Glu）残基。 该项目的目标是提供一个分子水平的理解这些结构基序的相似性和差异，在控制氧活化和随后的化学转化，以及在铁中心附近的氧化还原活性蛋白残基的催化作用。 为了实现这一目标，详细的机制研究进行了三个NHM-Fe酶，含有2-His-1-Asp或3-His铁结合基序。 一个组合的生物化学，动力学和光谱的方法。 这项研究有望为NHM-Fe酶的催化多功能性提供重要见解。 该项目包括研究生和本科生水平的综合教育计划，以及围绕与反应速率和催化有关的概念向K-12学生进行宣传。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Professor Yisong Guo from Carnegie Mellon University to study three enzyme-catalyzed reactions that are required to make novel highly bioactive compounds in microorganisms. The three enzymes employ the same basic structure around the iron atom, yet carry out three quite different reactions; the reasons for this difference in structure-function relationship is a fundamental question in biological chemistry. For example, iron in the same basic environment can result in the formation of carbon-oxygen bonds on the one hand or carbon sulfur bonds on the other. The research applies cutting edge methodology to reveal just how these reactions take place on an atom-by-atom basis. The research results may provide useful guidelines in designing new molecular catalysts and biocatalysts to perform these important and challenging chemical transformations. Research supported by this award also provides a training ground for students in physical chemistry, bioinorganic chemistry, biochemistry, enzymology, and catalysis. The knowledge generated through this project is integrated into educational activities where graduate, undergraduate, and high school students play an active role in discovering how reactions are catalyzed by iron-dependent enzymes. Non-heme mononuclear iron (NHM-Fe) dependent enzymes catalyze exceedingly diverse enzymatic reactions, ranging from "classical" hydroxylation, to desaturation, epoxidation, halogenation, epimerization, aromatic ring expansion, ring contraction, and ring opening. The structures of the iron centers catalyzing these diverse reactions are surprisingly simple. The first coordination sphere of the iron only contains histidine (His) and/or aspartic/glutamic acid (Asp/Glu) residues. The goal of this project is to provide a molecular level understanding of the similarity and difference of these structural motifs in controlling oxygen activation and the subsequent chemical transformations, as well as on the catalytic roles of redox active protein residues near the iron centers. To achieve this goal, detailed mechanistic studies are conducted on three NHM-Fe enzymes that contain 2-His-1-Asp or 3-His iron binding motifs. A combined biochemical, kinetic and spectroscopic approach is used. This research is expected to provide crucial insights into the catalytic versatility of NHM-Fe enzymes. The project includes a comprehensive educational program at the graduate and undergraduate levels and outreach to K-12 students around the concepts that relate to reaction rates and catalysis.