Towards vibrational control of enzymes for biotechnology and biocatalysis

用于生物技术和生物催化的酶的振动控制

• 批准号: 2268086
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2268086
• 关键词: Towards; vibrational; control; enzymes; biotechnology

The vast majority of biological reactions are catalysed by enzymes, which often exhibit exquisite selectivity and massive catalytic rate enhancements. With advances in enzyme engineering and an increasing desire for more sustainable synthesis, enzyme-mediated biocatalysis is becoming an established alternative to traditional methods of both commodity and high-value chemical production. In many cases, it would be desirable to have a rapid and real-time method of tuning enzyme activity, e.g. to control flux through a multi-enzyme cascade or in vivo metabolic pathway. One possibility is through direct vibrational control of the enzyme reaction. Chemical reactions typically involve the making and breaking of bonds, which are accompanied by changes in molecular vibrations of the reactants and surrounding environment, so it is possible to alter the rate of reaction through excitation of promoting or demoting vibrational modes. In condensed matter (proteins, surfaces, etc) energy from excited molecular vibrations is expected to dissipate in picoseconds, making continuous excitation impossible due to resulting sample heating. Recent advances in ultrafast laser spectroscopy allows a solution - It is now becoming practical to directly excite molecular vibrations using ultrafast (sub-picosecond) pulses of infrared (IR) light, which can lead to significant rate enhancements of thermal reactions in the gas-phase and on surfaces without excessive heating. This project now aims to extend and develop this methodology, using ultrafast IR light pulses to control the rate of enzyme reactions.This work will involve instrument and method development alongside new data analysis and experimental design procedures. Computational chemistry (MD simulations and/or DFT modelling) will be used to aid in experimental design and interpretation of results. Ultimately, we will aim to design and test a new ultrafast laser-controlled bioreactor. The project falls within the remit of both 'technologies and methodological development' and 'industrial biotechnology' and is firmly embedded at the interface of chemistry, biology and physics, a key driver for BBSRC in the 'Exploiting new ways of working' agenda. It draws on key bioscience skills, including new areas of applicable to bioscience (e.g. protein engineering, dynamic structural science) and state-of-the-art time resolved spectroscopy approaches. These are 'at risk' skills in the UK landscape and training in these areas is therefore vital to ensure a balanced and knowledgeable talent pool is maintained in the UK biosciences. Overall, the work will provide a highly interdisciplinary approach to (bio)chemistry/ biophysics-based research, offering highly diverse training opportunities to a PhD student, who will have the additional benefit of being able to access the supervisors' laboratories on a daily basis, as they are all co-located within the same building (MIB).

绝大多数的生物反应是由酶催化的，酶通常表现出精细的选择性和大量的催化速率增强。随着酶工程的进步和对更可持续合成的日益增长的渴望，酶介导的生物催化正在成为传统的商品和高价值化学生产方法的替代方案。在许多情况下，希望有一种快速实时的调节酶活性的方法，例如通过多酶级联或体内代谢途径控制通量。一种可能是通过直接振动控制酶的反应。化学反应通常涉及键的形成和断裂，这伴随着反应物和周围环境的分子振动的变化，因此可以通过激发增强或减弱振动模式来改变反应速率。在凝聚态物质（蛋白质、表面等）中，激发分子振动产生的能量预计会在皮秒内消散，由于样品加热导致不可能持续激发。超快激光光谱学的最新进展提供了一种解决方案——使用超快（亚皮秒）红外（IR）光脉冲直接激发分子振动现在变得切实可行，这可以在不过度加热的情况下显著提高气相和表面的热反应速率。这个项目现在的目标是扩展和发展这种方法，使用超快红外光脉冲来控制酶反应的速度。这项工作将涉及仪器和方法的开发以及新的数据分析和实验设计程序。计算化学（MD模拟和/或DFT建模）将用于帮助实验设计和解释结果。最终，我们将致力于设计和测试一种新的超快激光控制生物反应器。该项目属于“技术和方法发展”和“工业生物技术”的范围，并牢固地嵌入化学，生物学和物理学的界面，这是BBSRC在“开发新的工作方式”议程中的关键驱动因素。它借鉴了关键的生物科学技能，包括适用于生物科学的新领域（如蛋白质工程，动态结构科学）和最先进的时间分辨光谱方法。在英国，这些都是“处于风险”的技能，因此，这些领域的培训对于确保英国生物科学领域保持平衡和知识渊博的人才库至关重要。总的来说，这项工作将为基于（生物）化学/生物物理学的研究提供高度跨学科的方法，为博士生提供高度多样化的培训机会，他们将有额外的好处，即能够每天访问导师的实验室，因为它们都位于同一栋楼（MIB）内。

项目成果

Photoinduced Electron Transfer from a 1,4,5,6-Tetrahydro Nicotinamide Adenine Dinucleotide (Phosphate) Analogue to Oxidized Flavin in an Ene-Reductase Flavoenzyme.

• DOI: 10.1021/acs.jpclett.3c00176
• 发表时间: 2023-04-06
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY LETTERS
• 影响因子: 5.7
• 作者: Speirs, Magnus;Hardman, Samantha J. O.;Iorgu, Andreea I.;Johannissen, Linus O.;Heyes, Derren J.;Scrutton, Nigel S.;Sazanovich, Igor, V;Hay, Sam
• 通讯作者: Hay, Sam