Harnessing the Power of Diels-Alderases in Sustainable Chemoenzymatic Synthesis

利用 Diels-Alderases 进行可持续化学酶合成

• 批准号: BB/Y000846/1
• 负责人: Chris Willis
• 金额: $ 109.96万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY000846%2F1
• 关键词: Harnessing; Power; Diels; Alderases; Sustainable

Every chemical element is special, but some elements are more special than others! Carbon, the sixth element of the periodic table, is unique with respect to its versatility and impact on our lives. Carbon is the foundational element of all organic molecules including for example, materials, pharmaceuticals and fuels. No other element has shaped the world around us more than carbon. For this reason, the development of innovative methods to link carbon atoms together in desirable structures is of tremendous importance and is an overarching ambition in the field of organic chemistry. An important example of a reaction that can be used to link carbon atoms together is the Diels-Alder reaction, which since its discovery has been used to construct the complex carbon skeletons of numerous important molecules including pharmaceuticals, vitamins, hormones, agrochemicals and a raft of fragrance and flavour compounds. Historically, the Diels-Alder reaction has been performed using either chemical catalysts or high temperatures and pressures. Unfortunately, these approaches can give a mixture of products and have detrimental sustainability issues (use of energy and metal catalysts). However, biological catalysts for this reaction, so called 'Diels-Alderases', offer an attractive alternative, circumventing many of the complexities associated with chemical catalysis, and thus enabling Diels-Alder reactions to be performed under ambient conditions, with exquisite regio- and stereochemical control, and in an inherently 'greener' way. In this academic-industrial project, which builds on a strong foundation of interdisciplinary collaborative research by the applicants in the study of natural Diels-Alderases, the researchers will: i) Develop flow systems using immobilised enzymes to catalyse Diels-Alder reactions on gram scales; ii) investigate the ability of natural Diels-Alderases and rationally-engineered variants to catalyse both intramolecular (with both reactive groups within the same molecule) and intermolecular (with reactive groups in different molecules) cycloaddition reactions; iii) study hitherto uncharacterised natural Diels-Alderases and their associated natural products from cryptic biosynthetic gene clusters; iv) Deploy our portfolio of natural and engineered Diels-Alderases, in combination with auxiliary enzymes, to undertake chemoenzymatic total syntheses of high-value target compounds.

每个化学元素都是特殊的，但是有些元素比其他元素更特别！碳是周期表的第六个要素，在其多功能性和对我们生活的影响方面是独一无二的。碳是所有有机分子的基础元素，包括例如材料，药物和燃料。没有其他元素比碳更能塑造我们周围的世界。因此，在理想结构中将碳原子联系在一起的创新方法的发展至关重要，并且是有机化学领域的总体野心。可用于将碳原子联系在一起的反应的一个重要例子是Diels-Alder反应，因为它的发现已被用来构建许多重要分子的复杂碳骨架，包括药物，维生素，激素，农业化学和一系列香气和香水和风味和风味和风味。从历史上看，使用化学催化剂或高温和压力进行了Diels-Alder反应。不幸的是，这些方法可以混合产品，并存在有害的可持续性问题（使用能量和金属催化剂）。然而，这种反应的生物催化剂（所谓的“ Diels-Alderase”）提供了一种有吸引力的替代方案，可以避免与化学催化有关的许多复杂性，从而使Diels-Alder反应能够在环境条件下进行，并具有精致的区域和刻板的和刻板的控制，并以固有的“ Greener”方式进行。在这个学术工业项目中，申请人在天然Diels-Alderases研究中建立在跨学科合作研究的基础上，研究人员将：i）使用固定的酶开发流动系统，以催化Diels-Alder反应在Gram尺度上； ii）研究天然多代碱和理性工程变体的能力，可以催化分子内（同一分子内的反应性基团）和分子间（不同分子中的反应性基团）环载反应的能力； iii）研究迄今未表征的天然Diels-Alderase及其相关的天然产物，来自隐秘的生物合成基因簇； iv）部署我们的天然和工程二极管 - 碱酶的组合，并结合辅助酶，以进行高价值靶化合物的化学酶总合成。