High-throughput approaches in enzyme discovery and engineering

酶发现和工程的高通量方法

• 批准号: RGPIN-2016-05464
• 负责人: Kwan, David
• 金额: $ 1.82万
• 依托单位: Concordia University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615708
• 关键词: throughput; approaches; enzyme; discovery; engineering

Enzymes are extraordinary biocatalysts - they are the machinery of cell factories, crafted by Nature over aeons of evolution. In Nature, enzymes catalyze the chemical reactions within living organisms, whereas in biotechnological applications, they are taken out of their natural context and used for chemical processes that are important in many industries. Since enzymes in industrial biocatalysis are often used in conditions and for purposes quite different from the natural context and function for which they have evolved, there is much room to improve their performance in these processes. The potential of enzymes in bioindustrial applications is greatly expanded through enzyme engineering efforts, such as directed evolution. I propose a research program focused on the discovery and engineering of enzyme biocatalysts for the production of high-value bioactive compounds and of biorenewable chemicals as alternatives to petroleum products. This will be achieved by initially targeting two classes of enzymes: glycosyltransferases that attach sugar units onto natural product scaffolds to produce bioactive glycosylated small molecules; and decarboxylases involved in the conversion of fatty acids into hydrocarbons that can potentially be used to replace petrochemicals as fuels and chemical building blocks. We will develop methods that will enable us not only to discover, but to engineer the enzymes that produce these valuable compounds. Using directed evolution we will improve the efficiency of these enzyme biocatalysts in producing such compounds, and alter their specificity to expand the kinds of molecules that they can produce. The engineering of biocatalyst tools for producing renewable resources and high-value bioactive chemicals will be of significant social and economic benefit.

酶是非凡的生物催化剂--它们是细胞工厂的机器，是大自然经过亿万年的进化而精心制作的。在自然界中，酶催化生物体内的化学反应，而在生物技术应用中，它们被从自然环境中取出，用于许多行业中重要的化学过程。由于工业生物催化中的酶通常用于与它们进化的自然环境和功能完全不同的条件和目的，因此在这些过程中有很大的空间来改善它们的性能。酶在生物工业应用中的潜力通过酶工程的努力，如定向进化，大大扩展。我提出了一个研究计划，重点是酶生物催化剂的发现和工程，用于生产高价值的生物活性化合物和生物可再生化学品作为石油产品的替代品。这将通过最初针对两类酶来实现：糖基转移酶，其将糖单元连接到天然产物支架上以产生生物活性的糖基化小分子;和脱羧酶，其参与将脂肪酸转化为烃，该烃可潜在地用于替代石化产品作为燃料和化学构件。我们将开发方法，使我们不仅能够发现，而且能够设计产生这些有价值化合物的酶。利用定向进化，我们将提高这些酶生物催化剂生产此类化合物的效率，并改变它们的特异性以扩大它们可以生产的分子种类。利用生物催化剂生产可再生资源和高价值生物活性化学品具有重要的社会效益和经济效益。