Development of novel halogenase enzymes for biopharmaceutical applications

开发用于生物制药应用的新型卤化酶

• 批准号: 2265874
• 金额: --
• 依托单位: University of Warwick
• 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-2265874
• 关键词: Development; novel; halogenase; enzymes; biopharmaceutical

Identification of new halogenated synthetic, natural and non-natural compounds; and further exploitation and synthesis of these compounds are of extreme importance in this modern era. This is due to the profound role of organohalides as pharmaceuticals, agrochemicals and valuable synthons in various organic reactions. As organic synthetic intermediates, halogenated molecules are of particular importance in many metal-catalysed cross-coupling reactions. Nature has evolved a number of biocatalysts to regioselectively halogenate a diverse range of biosynthetic precursors and secondary metabolites, and this unexplored repertoire is ever growing. Biosynthetic halogenation can occur over simple to extremely complex ring structures of natural compounds and in some cases, it initiates the formation of complex structures and scaffolds. These reactions often range from simple aromatic substitutions to complex stereoselective C-H functionalization and activation of remote carbon centres. These reliable, facile and cleaner biosynthetic routes have potential utility and greater demand over traditional nonenzymatic halogenation chemistry that requires deleterious reagents and lacks regio-control. In the past few years we have identified a number of pharmaceutically important halogenase systems by genome mining in natural product pathways. In this project, we are planning to explore their enzyme structure, substrate scope along with their potential applications in organic synthesis. The ultimate aim is to incorporate these enzymes in to synthetic and biosynthetic pathways and into various natural product pathways for biotechnological and pharmaceutical applications.

新卤代合成、天然和非天然化合物的鉴定；这些化合物的进一步开发和合成在当今时代极为重要。这是由于有机卤化物作为药物、农用化学品和有价值的合成子在各种有机反应中发挥着深远的作用。作为有机合成中间体，卤化分子在许多金属催化的交叉偶联反应中特别重要。大自然已经进化出许多生物催化剂来区域选择性地卤化各种生物合成前体和次级代谢物，并且这种未开发的库正在不断增长。生物合成卤化可以在天然化合物的简单到极其复杂的环结构上发生，并且在某些情况下，它引发复杂结构和支架的形成。这些反应的范围通常从简单的芳香族取代到复杂的立体选择性 C-H 官能化和远程碳中心的活化。与需要有害试剂且缺乏区域控制的传统非酶卤化化学相比，这些可靠、简便和清洁的生物合成路线具有潜在的实用性和更大的需求。在过去的几年中，我们通过天然产物途径中的基因组挖掘鉴定了许多药学上重要的卤化酶系统。在这个项目中，我们计划探索它们的酶结构、底物范围以及它们在有机合成中的潜在应用。最终目标是将这些酶纳入合成和生物合成途径以及生物技术和制药应用的各种天然产物途径中。