Collaborative Research: Mechanistic Studies on Fe-type Nitrile Hydration Catalysts

合作研究：铁型腈水合催化剂的机理研究

• 批准号: 1410411
• 负责人: Brian Bennett
• 金额: $ 10.2万
• 依托单位: Medical College of Wisconsin
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2014-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1410411&HistoricalAwards=false
• 关键词: Collaborative; Research; Mechanistic; Studies; Fe

Nitriles are used extensively in the production of specialty chemicals like the polyamide nylon. Nitrile hydratases (NHases) catalyze the hydration of nitriles to amides at ambient temperatures in neutral water. The currently employed industrial conditions for the hydration of nitriles to amides use either strong acids or bases, and are often incompatible with the sensitive structures of the compounds to be produced. NHases have therefore attracted substantial interest as biocatalysts in preparative organic chemistry. Despite the industrial importance of NHase enzymes, the details of how they work remain poorly understood. The objective of this research proposal is to fill this knowledge gap. The interdisciplinary nature of the effort will serve as a platform to increase the participation of women and classically underrepresented graduate and undergraduate students in scientific careers in biophysics, chemistry, and biochemistry. As part of the proposed project, both PI's will participate in the SMART program that mentors Milwaukee area public high school students in research projects.With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Drs. Richard C. Holz and Brian Bennett from Marquette University to elucidate the catalytic mechanism of NHase enzymes. An interdisciplinary approach will be used that will incorporate kinetics, spectroscopy, biochemistry, computational chemistry, and both X-ray and neutron crystallography. The proposed experimental approach is designed to address three key questions: i) What is the transition-state structure of nitrile hydration? ii) What are the protonation states of catalytically important species throughout the reaction? and iii) What controls metallocenter assembly in a purported eukaryotic NHase? The successful completion of this research will greatly benefit society by facilitating the intelligent design and manufacture of nitrile-based chiral pharmaceuticals and industrially important specialty chemicals, with enhanced synthetic flexibility and lower environmental impact, than at present.

硝酸盐广泛用于多酰胺尼龙等特殊化学物质的生产中。 硝酸水合物（NHASE）在中性水中的环境温度下催化氮与酰胺的水合。 目前使用的工业条件用于氮化物用于酰胺的水合使用强酸或碱，并且通常与要生产的化合物的敏感结构不相容。因此，NHases在制备有机化学中引起了生物催化剂的重大兴趣。 尽管NHASE酶的工业重要性，但其工作方式的细节仍然知之甚少。 该研究建议的目的是填补这一知识差距。 这项工作的跨学科性质将成为一个平台，以增加妇女的参与，并在生物物理学，化学和生物化学领域的科学职业中代表性不足的研究生和本科生。 作为拟议项目的一部分，这两个PI都将参加智能计划，该计划指导密尔沃基地区的公立高中生研究项目。在此奖项的情况下，化学过程的化学过程中的化学过程是资助DRS。来自马奎特大学的Richard C. Holz和Brian Bennett阐明了NHase酶的催化机制。 将使用一种跨学科方法，该方法将结合动力学，光谱，生物化学，计算化学以及X射线和中子晶体学。 所提出的实验方法旨在解决三个关键问题：i）硝酸盐水合的过渡状态结构是什么？ ii）在整个反应中，催化重要物种的质子化状态是什么？ iii）是什么控制着所谓的真核NHASE中的金属中心装配？ 这项研究的成功完成将通过促进基于氮的手性药物和工业重要的特种化学品的智能设计和制造，从而极大地使社会受益，并具有增强的合成灵活性和更低的环境影响。

项目成果

Cellular maturation of an iron-type nitrile hydratase interrogated using EPR spectroscopy

• DOI: 10.1007/s00775-019-01720-y
• 发表时间: 2019-10-01
• 期刊: JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
• 影响因子: 3
• 作者: Lankathilaka, K. P. Wasantha;Stein, Natalia;Bennett, Brian
• 通讯作者: Bennett, Brian