Collaborative Research: CAS: Mechanistic Studies on Fe-Type Nitrile Hydration Catalysts

合作研究：CAS：铁型腈水合催化剂的机理研究

• 批准号: 2204024
• 负责人: Richard Holz
• 金额: $ 20.89万
• 依托单位: Colorado School of Mines
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2204024&HistoricalAwards=false
• 关键词: Collaborative; Research; CAS; Mechanistic; Studies

With the support of the Chemistry of Life Processes program in the Division of Chemistry, Professors Brian Bennett and Adam Fiedler from Marquette University and Professor Richard Holz from the Colorado School of Mines will investigate the chemical function of the enzyme nitrile hydratase (NHase), which catalyzes the reaction of nitrile compounds with water (hydration) to give the corresponding amides. NHases hydrate a range of natural and synthetic nitriles with strict selectivity under mild conditions. As such, these enzymes have several industrial and pharmaceutical applications, including the removal of chemicals and pesticides from the environment. To expand the biocatalytic potential of NHases, a better understanding of the catalytic mechanism is essential. Professors Bennett, Fiedler and Holz will employ a combination of experimental and computational approaches to detect and probe intermediates generated during the hydration reaction. In addition, the assembly of the enzyme active site, which contains a cobalt or iron ion, will be examined. The project will provide exceptional training for undergraduate and graduate-level scientists. The emphasis on green chemistry and biophysical methods will serve as the basis for community engagement activities. The award will also enhance the research and educational infrastructures at both Marquette University and the Colorado School of Mines. This research project seeks to gain molecular-level insights into NHase catalysis through a combination of kinetic, spectroscopic, biochemical, computational, and X-ray crystallographic methods. The studies will (i) test competing prevailing mechanistic hypotheses and refine the catalytic mechanism by interrogating observed intermediates, (ii) determine the catalytic function of proton transfer and the protonation states of ionizable groups in the active site, and (iii) elucidate steps in the maturation process of the metal-based (Fe or Co) active sites. The insights gained from the studies are expected to aid in the development of green catalytic approaches to hydrolytic reactions in nature and industry.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学系生命过程化学项目的支持下，来自马凯特大学的Brian Bennett教授和Adam Fiedler教授以及科罗拉多矿业学院的Richard Holz教授将研究腈水合酶（NHase）的化学功能，该酶能催化腈化合物与水的反应（水合作用），生成相应的酰胺。在温和的条件下，nase能水合物一系列天然和合成腈，具有严格的选择性。因此，这些酶有几种工业和制药应用，包括从环境中去除化学物质和农药。为了扩大nase的生物催化潜力，更好地了解其催化机制是必不可少的。Bennett， Fiedler和Holz教授将采用实验和计算相结合的方法来检测和探测水化反应中产生的中间体。此外，还将检查含有钴或铁离子的酶活性位点的组装。该项目将为本科生和研究生水平的科学家提供特殊的培训。强调绿色化学和生物物理方法将作为社区参与活动的基础。该奖项还将加强马奎特大学和科罗拉多矿业学院的研究和教育基础设施。该研究项目旨在通过动力学、光谱、生化、计算和x射线晶体学方法的结合，获得对nase催化的分子水平的见解。这些研究将(i)通过询问观察到的中间体来测试相互竞争的主流机制假设并完善催化机制，（ii）确定质子转移的催化功能和活性位点中可电离基团的质子化状态，以及（iii）阐明金属基（Fe或Co）活性位点成熟过程中的步骤。从这些研究中获得的见解预计将有助于开发自然界和工业中水解反应的绿色催化方法。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。