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.

在化学过程中的化学过程中的支持下，马奎特大学的布莱恩·贝内特（Brian Bennett）和亚当·菲德勒（Adam Fiedler）和科罗拉多州矿业学院的理查德·霍尔兹（Richard Holz）将研究硝酸酶（NHase酶）的化学功能，从而催化了与水的反应相： NHases在轻度条件下具有严格选择性的一系列天然和合成硝化物。 因此，这些酶具有多种工业和药物应用，包括从环境中去除化学物质和农药。 为了扩大NHASE的生物催化潜力，对催化机制的更好理解是必不可少的。 Bennett教授，Fiedler和Holz将采用实验和计算方法的组合来检测和探测在水合反应过程中产生的中间体。 此外，将检查含有钴或铁离子的酶活性位点的组装。 该项目将为本科和研究生水平的科学家提供出色的培训。 对绿色化学和生物物理方法的重视将成为社区参与活动的基础。 该奖项还将增强马奎特大学和科罗拉多州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来获得分子级别对NHASE催化的见解。 研究将（i）通过询问观察到的中间体来测试竞争的主要机械假设，并通过询问观察到的中间体来完善催化机制，（ii）确定质子转移的催化功能和活性位点可电离基团的质子化状态，以及（iii）在基于金属基于金属的（Fe或CO）活性位点的成熟步骤中（III）阐明步骤。预计从研究中获得的见解有助于开发自然界和行业中水解反应的绿色催化方法。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子和更广泛影响的评估来审查标准的评估值得支持的。