Artificial metalloproteins: photochemical and electrochemical approaches for understanding mechanism and catalysis

人造金属蛋白：用于理解机制和催化的光化学和电化学方法

• 批准号: RGPIN-2014-05559
• 负责人: Warren, Jeffrey
• 金额: $ 2.55万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=588480
• 关键词: Artificial; metalloproteins; photochemical; electrochemical; approaches

Accelerating climate change demands the development of new technologies that enable access to renewable chemical fuels and feedstocks. Despite the many approaches currently being pursued, catalysis using proteins remains an unrealized resource, especially for redox transformations (e.g., carbon dioxide to methanol). Redox enzymes are ideal candidates for catalysis because they naturally exert exquisite control over the energetic electrons required for complex transformations. Recent advances in our understanding of multistep electron transfer reactions, as well as protein design, open new avenues for investigations of artificially modified protein catalysts. To that end, a long-term goal of my bioinorganic chemistry research program is to develop a new generation of biocatalysts that can compete with “state-of-the-art” industrial approaches. Further, as we design, synthesize, and investigate new protein-based catalysts we will also develop a comprehensive set of metrics that can be used to assess and improve redox functions. We will address fundamental questions about how electrons move in artificial proteins and how we can best exploit biological redox machinery for essential chemical transformations. The proposed research will focus on the following three short-term objectives over the next 5 years: (1) to demonstrate photoelectrochemical catalysis by novel protein + indium tin oxide electrodes; (2) to selectively oxidize organic biopolymers with engineered heme proteins; and (3) to modify metalloproteins for renewable energy redox catalysis. These three complementary research objectives address key hurdles to using enzymes on large scales: constructing devices, optimizing protein catalysis, and elucidating design criteria for new, targeted catalysts. In Objective 1 we will establish methods for immobilizing functional proteins on electrode surfaces (device development). This opens the way for electrochemical- and photo-catalysis. In Objective 2 we focus on careful modifications to the easily obtained protein cytochrome c peroxidase to elicit new redox functions (catalyst optimization). A conservative and systematic approach will provide specific information about structure-function relationships. Ideally, these new systems will be amenable to immobilization strategies developed through Objective 1. Finally, our work on Objective 3 will take a more ambitious tact (designing new catalysts). Starting from very stable, heat tolerant metalloproteins, we will generate proteins with exposed (coordinatively unsaturated) metal sites. Hydrogen bonding and steric constraints make proteins exceptional “ligands” for supporting unusual coordination geometries and imparting unique reactivity upon first-row transition metals. However, few studies have taken advantage of this control to build proteins with reactivity that mirrors or improves upon that of small molecule catalysts. We will produce and extensively characterize artificial proteins to establish design elements, and then investigate the reactivity of the metal sites toward substrates (e.g., reduction of protons to dihydrogen). Taken together, the knowledge gained from this research program will provide new ways to approach our growing need for renewable chemical catalysis as we accelerate a global transition away from fossil fuels. Our work ranges from the development of photoelectrochemical devices (Objective 1) to design and optimization of protein redox catalysts (Objectives 2 and 3). The range of projects in my program will enable new approaches and technologies for catalysis using artificial proteins, while providing fruitful opportunities for the intellectual and professional development of highly qualified personnel in biological inorganic chemistry and catalysis.

气候变化的加速要求开发新技术，使人们能够获得可再生化学燃料和原料。尽管目前正在追求许多方法，但使用蛋白质的催化仍然是未实现的资源，特别是对于氧化还原转化（例如，二氧化碳到甲醇）。氧化还原酶是催化的理想候选者，因为它们自然地对复杂转化所需的高能电子施加精细的控制。我们对多步电子转移反应的理解以及蛋白质设计的最新进展为人工修饰蛋白质催化剂的研究开辟了新的途径。为此，我的生物无机化学研究计划的一个长期目标是开发新一代的生物催化剂，可以与“最先进的”工业方法竞争。此外，当我们设计、合成和研究新的蛋白质基催化剂时，我们还将开发一套全面的指标，可用于评估和改善氧化还原功能。我们将解决有关电子如何在人工蛋白质中移动的基本问题，以及我们如何最好地利用生物氧化还原机制进行必要的化学转化。 在未来五年，拟议的研究将集中于以下三个短期目标： (1)通过新型蛋白质+氧化铟锡电极展示光电化学催化; (2)用工程血红素蛋白选择性氧化有机生物聚合物;和 (3)以修饰金属蛋白质用于可再生能源氧化还原催化。 这三个互补的研究目标解决了大规模使用酶的关键障碍：构建设备，优化蛋白质催化，并阐明新的靶向催化剂的设计标准。在目标1中，我们将建立在电极表面固定功能蛋白质的方法（设备开发）。这为电化学和光催化开辟了道路。在目标2中，我们专注于仔细修改容易获得的蛋白质细胞色素c过氧化物酶引起新的氧化还原功能（催化剂优化）。保守和系统的方法将提供有关结构-功能关系的具体信息。理想情况下，这些新系统将服从通过目标1开发的固定策略。最后，我们在目标3上的工作将采取更雄心勃勃的策略（设计新的催化剂）。从非常稳定的耐热金属蛋白质开始，我们将产生具有暴露的（配位不饱和的）金属位点的蛋白质。氢键和空间限制使蛋白质成为特殊的“配体”，用于支持不寻常的配位几何形状，并赋予第一行过渡金属独特的反应性。然而，很少有研究利用这种控制来构建具有反映或改善小分子催化剂的反应性的蛋白质。我们将生产并广泛表征人工蛋白质以建立设计元素，然后研究金属位点对底物的反应性（例如，质子还原为二氢）。 总之，从这项研究计划中获得的知识将提供新的方法来满足我们对可再生化学催化剂日益增长的需求，因为我们加速了全球从化石燃料的过渡。我们的工作范围从光电化学器件的开发（目标1）到蛋白质氧化还原催化剂的设计和优化（目标2和3）。在我的计划项目的范围将启用新的方法和技术，催化使用人工蛋白质，同时提供了富有成效的机会，高素质的人才在生物无机化学和催化的智力和专业发展。