Development of new amine donors for biocatalysis

开发用于生物催化的新胺供体

• 批准号: 2581394
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2581394
• 关键词: Development; new; amine; donors; biocatalysis

Natural and engineered biocatalysts are already having impact in the manufacture of high value pharmaceuticals by catalysing the conversion of functional groups in high yield. The use of enzymes for organic synthesis will be more routine once their limitations, such as narrow substrate range, are overcome (1). The range of chemical transformations displayed by enzymes continues to grow, fuelled by the discovery of new enzymes involved in natural product biosynthesis and accelerated by genome sequencing. Once a new enzyme is selected, modern enzyme engineering techniques (e.g. directed evolution) can be applied to generate a bespoke biocatalyst with broad synthetic utility. The impact of this technology was recognised by the award of the Nobel prize in Chemistry in 2018 to Prof. Frances Arnold (2). In these projects we will exploit members of large families of enzymes to develop efficient routes for the preparation of both commodity chemicals and high value active pharmaceutical ingredients (APIs, ref. 3).This project will source natural enzymes from metabolic pathways and where necessary, evolve them to expand their substrate scope. We will combine these biocatalysts with compatible chemo-catalysts to expand the synthetic utility of the optimised route. We will specifically work with transaminase (TA) biocatalysts and explore novel synthetic amine donors (4). The project will provide training in modern biocatalyst methodology and analysis (recombinant DNA technology, enzyme characterisation and engineering). We will aim to collaborate with experts in x-ray crystallography to guide engineering/evolution of target enzymes. Moreover, this project will have specific links with our industrial biocatalysis partner Johnson Matthey.

天然和工程生物催化剂已经通过催化高收率的官能团转化在高价值药物的制造中产生影响。一旦克服酶的局限性（例如底物范围窄），酶在有机合成中的使用将更加常规（1）。由于发现了参与天然产物生物合成的新酶，并通过基因组测序加速了酶所显示的化学转化的范围继续增长。一旦选择了一种新的酶，现代酶工程技术（例如定向进化）可以应用于产生具有广泛合成用途的定制生物催化剂。这项技术的影响得到了2018年诺贝尔化学奖授予Frances Arnold教授的认可。在这些项目中，我们将开发酶大家族的成员，以开发制备商品化学品和高价值活性药物成分的有效途径（API，参考文献3）。该项目将从代谢途径中获取天然酶，并在必要时对其进行进化，以扩大其底物范围。我们将联合收割机这些生物催化剂与兼容的化学催化剂，以扩大优化路线的合成效用。我们将专门研究转氨酶（TA）生物催化剂，并探索新的合成胺供体（4）。该项目将提供现代生物催化剂方法学和分析方面的培训（重组DNA技术、酶特性鉴定和工程）。我们的目标是与X射线晶体学专家合作，指导目标酶的工程/进化。此外，该项目还将与我们的工业生物催化合作伙伴约翰逊万丰公司建立具体联系。