Generalised Photocatalysis by Enzymes (GENPENZ)

广义酶光催化 (GENPENZ)

• 批准号: BB/X003027/1
• 负责人: Nigel Scrutton
• 金额: $ 404.95万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX003027%2F1
• 关键词: Generalised; Photocatalysis; Enzymes; GENPENZ

Enzyme catalysis is being industrialised at a phenomenal rate, offering routes to chemical transformations that avoid expensive heavy metal catalysts, high temperatures and pressures, and providing impressive enantio-, regio- and chemo-selectivities. In short, biocatalysts are a cornerstone of the bioeconomy: they are required individually, or as cascades, in live cells or cell-free preparations to manufacture every day chemicals, materials, healthcare products, fuels and pharmaceuticals; and they are integral to many diagnostic and industrial sensing applications. They are central components of technologies underpinning the circular economy and offer engineering biology routes to realising global challenges, including net zero, clean growth and the bioeconomy. An ability to exploit and tailor biocatalyst activities both rapidly and predictably is essential to realising the contemporary global challenges and the UK Government's Innovation Strategy.Despite their central importance, the vast majority of natural and engineered enzymes are thermally-activated. This dependence on thermally-activated catalysis: i) limits biocatalysis to those reaction types found naturally in biology; ii) places a high dependence on expensive and unstable cofactors / coenzymes; and iii) places a sizeable demand on the provision of energy source (biochemical / artificial reductants), 'bioreactor' designs (e.g. within cell-free formats, nanoscale devices or microbial cell factories); and iv) restricts approaches to regulating biocatalyst / bioprocess activity. The use of light to drive enzyme catalysis would bypass many of these hurdles. However, with only three known exceptions, nature does not make use of enzymatic photocatalysis. Therefore, biology cannot access a broad range of 'difficult-to-achieve' reactions that would be transformational in catalysis science, and applications of these reactions in the modern world. Light is freely available and non-invasive, yet the photochemical versatility of natural cofactors such as flavin is seldom used by enzymes. Therefore, securing generalised routes to predictive photobiocatalysis design is a fundamental biological challenge. If successful, identifying generalised routes to the engineering and design of photobiocatalysts would be transformative for catalysis science in the emerging bioeconomy. This project will address this urgent need by using the natural photochemistry of flavin to make possible photocatalysis by any flavin-containing protein. This programme (termed GENPENZ) is positioned at the frontier of biological photocatalysis and enzyme design and engineering. It will generalise the concept of photo-biocatalyst design and engineering using existing (top down) and man-made (bottom up) protein scaffolds to biologically encode new photo-biocatalysts with wide reaction scope, or to assemble de novo protein frameworks from synthetic peptides. It will unite time-resolved 1D / 2D spectroscopy in the visible / infra-red spectral regions, across 12 decades of time (fs - s), with emerging capabilities in photo mass spectrometry (ion mobility; hydrogen-deuterium exchange), EPR spectroscopy, and photo-biocatalyst design engineering. High-level computational chemistry will underpin all protein-design/engineering work, spectroscopy, and structure elucidation. GENPENZ is based on breakthroughs in discovery science relating to mechanisms of enzyme photocatalysis. Realisation of a generalised platform for photo-biocatalyst design will open up new high-energy reaction pathways, enrich catalysis outcomes, and sidestep many of the scientific / economic constraints of working with thermally-activated biocatalysis in the emerging bioeconomy.

酶催化正在以惊人的速度实现工业化，提供了避免昂贵的重金属催化剂、高温和高压的化学转化途径，并提供了令人印象深刻的对映选择性、区域选择性和化学选择性。简而言之，生物催化剂是生物经济的基石：它们需要单独或级联地存在于活细胞或无细胞制剂中，以制造日常化学品、材料、保健产品、燃料和药品；它们是许多诊断和工业传感应用不可或缺的一部分。它们是支撑循环经济的技术的核心组成部分，并为实现净零排放、清洁增长和生物经济等全球挑战提供工程生物学途径。快速且可预测地开发和定制生物催化剂活性的能力对于实现当代全球挑战和英国政府的创新战略至关重要。尽管它们至关重要，但绝大多数天然酶和工程酶都是热激活的。这种对热激活催化的依赖：i) 将生物催化限制为生物学中自然发现的反应类型； ii) 高度依赖昂贵且不稳定的辅因子/辅酶； iii) 对提供能源（生化/人工还原剂）、“生物反应器”设计（例如在无细胞形式、纳米级装置或微生物细胞工厂内）提出了相当大的需求； iv) 限制调节生物催化剂/生物过程活性的方法。使用光来驱动酶催化将绕过许多这些障碍。然而，除了三个已知的例外，自然界并没有利用酶光催化作用。因此，生物学无法获得广泛的“难以实现”的反应，而这些反应将在催化科学以及这些反应在现代世界中的应用中产生变革。光是免费且非侵入性的，但黄素等天然辅助因子的光化学多功能性很少被酶利用。因此，确保预测性光生物催化设计的通用途径是一项基本的生物学挑战。如果成功，确定光生物催化剂工程和设计的通用途径将为新兴生物经济中的催化科学带来变革。该项目将通过利用黄素的天然光化学使任何含黄素蛋白质的光催化作用成为可能，从而满足这一迫切需求。该项目（称为 GENPENZ）位于生物光催化和酶设计与工程的前沿。它将概括光生物催化剂设计和工程的概念，使用现有（自上而下）和人造（自下而上）蛋白质支架对具有广泛反应范围的新光生物催化剂进行生物编码，或从合成肽组装蛋白质框架。它将跨 12 个十年 (fs - s) 的可见光/红外光谱区域的时间分辨一维/二维光谱与光质谱（离子淌度；氢-氘交换）、EPR 光谱等新兴功能结合起来，以及光生物催化剂设计工程。高水平计算化学将支撑所有蛋白质设计/工程工作、光谱学和结构阐明。 GENPENZ 基于与酶光催化机制相关的科学发现突破。光生物催化剂设计通用平台的实现将开辟新的高能反应途径，丰富催化结果，并避开新兴生物经济中热激活生物催化的许多科学/经济限制。