Enzyme e-map - Modernising Electrochemical Enzymology To Map Electron Transfer

酶电子图 - 现代化电化学酶学以绘制电子转移图

• 批准号: EP/X027724/1
• 负责人: Alison Parkin
• 金额: $ 218.91万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX027724%2F1
• 关键词: Enzyme; map; Modernising; Electrochemical; Enzymology

In Nature the production of hydrogen and methane fuel molecules from readily available starting materials such as water and carbondioxide is achieved selectively, efficiently and rapidly by electrocatalytic redox-metalloenzymes containing non-precious transitionmetal active sites. The outstanding recent scientific advances made in molecular biology have made the development of biofueltechnologies based on these enzymes a reality, but such applications require a complementary toolkit of physical chemistry methodsthat can dissect how DNA sequence and protein structure relates to function. Classic bio-electrochemistry methods developed in the1980s have been a powerful way to probe the active site reactivity of such enzymes, but they have been unable to map the electrontransfer processes which underpin the catalysis. Therefore, we have been limited to a narrowly active-site focussed view of enzymemechanism. This project will transform the state of the art in bio-electrochemistry to deliver a powerful new technique that can "see"the electron-transfer processes of the highly evolved and essential electron-transfer reaction centres in redox-enzymes, and deconvolutetheir role in electrocatalysis. This will be achieved by deploying advanced computational methods to integrate intelligentexperimental design into electrochemistry to develop a methodology that lets us separate and accurately model the electron transferprocesses of an enzyme bound to substrate, and chemical biology methods to develop linker molecules for light-activated electrograftingof proteins and enzymes onto electrodes. We will showcase the power of this new electrochemical enzymology toolkit byconducting previously impossible hypothesis-led investigations and enzyme-discovery projects into i) cellulose-degrading LPMOsthat play a crucial role in biorefinery enzyme cocktails and ii) hydrogenases, Ni+Fe or Fe-only metalloenzymes that are as rapid andefficient at hydrogen-catalysis as platinum.

在《自然》中，氢和甲烷燃料分子是通过电催化氧化还原金属酶选择性地、高效地、快速地从水和二氧化碳等现成的起始材料中生产出来的，这些金属酶含有非贵重过渡金属活性位点。分子生物学最近取得的杰出科学进展使基于这些酶的生物燃料技术的发展成为现实，但这种应用需要物理化学方法的补充工具包，可以解剖DNA序列和蛋白质结构如何与功能相关。20世纪80年代发展起来的经典生物电化学方法是探测这些酶的活性位点反应性的有力方法，但它们无法绘制支撑催化作用的电子转移过程。因此，我们一直被限制在一个狭窄的活性位点集中的酶机制的观点。该项目将改变生物电化学的现状，提供一种强大的新技术，可以“看到”氧化还原酶中高度进化和基本的电子转移反应中心的电子转移过程，并解开它们在电催化中的作用。这将通过部署先进的计算方法来实现，将智能实验设计集成到电化学中，以开发一种方法，使我们能够分离并准确地模拟与底物结合的酶的电子转移过程，以及化学生物学方法来开发连接分子，用于光激活的蛋白质和酶的电接枝到电极上。我们将通过进行以前不可能的假设主导的研究和酶发现项目来展示这种新的电化学酶学工具包的力量：1)纤维素降解lpmos，它在生物炼制酶鸡尾酒中起着至关重要的作用；2)氢化酶，Ni+Fe或纯铁金属酶，它们在氢催化方面与铂一样快速和有效。

项目成果

Crossing the Solubility Rubicon: 15-Crown-5 Facilitates the Preparation of Water-Soluble Sulfo-NHS Esters in Organic Solvents.

• DOI: 10.1021/acs.bioconjchem.3c00396
• 发表时间: 2024-01-17
• 期刊: BIOCONJUGATE CHEMISTRY
• 影响因子: 4.7
• 作者: Yates, Nicholas D. J.;Miles, Connor G.;Spicer, Christopher D.;Fascione, Martin A.;Parkin, Alison
• 通讯作者: Parkin, Alison

Recovering biological electron transfer reaction parameters from multiple protein film voltammetric techniques informed by Bayesian inference

从贝叶斯推断的多种蛋白质膜伏安技术中恢复生物电子转移反应参数

• DOI: 10.1016/j.jelechem.2023.117264
• 发表时间: 2023
• 期刊: Journal of Electroanalytical Chemistry
• 影响因子: 4.5
• 作者: Lloyd-Laney H