NEW BIOCATALYST FOR ENATIOSELECTIVE SYNTHESIS

用于对映选择性合成的新型生物催化剂

• 批准号: 6071719
• 负责人: Mikhail Gololobov
• 金额: $ 10万
• 依托单位: POLIUM TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6071719
• 关键词: catalyst; chemical reaction; chemical synthesis; enzyme activity; enzyme structure; immobilized enzymes; polymers; protein engineering; spectrometry; stereoisomer

The development of enzyme biocatalysts that are reusable and able to work in heterogeneous reaction systems is the focus of this proposal. A reversibly soluble polymer is to be attached to the enzymes. Consequently, the biocatalyst can be precipitated without enzyme denaturation after product separation. Later the biocatalyst can be solubilized again in a suspension of the starting materials at the initial conditions. Therefore, these biocatalysts acquire the advantages of free enzymes (high activity in heterogeneous systems) and of immobilized enzymes (the possibility of a reuse). Biocatalysis is underutilized in industry due to the industry requirement that the biocatalyst should be reusable and the reaction have a high throughput. Solubility of the compounds is limited and this necessitates running the reactions in heterogeneous suspension of the starting materials and the products. However, today all biocatalysts on the market either cannot be reused or do not work in heterogeneous systems. Potential of the idea proposed was demonstrated on model systems. The proposal focuses on the optimization of the process using the enzymes of industrial interests. This biocatalyst will be marketed to pharmaceutical companies and used to manufacture chiral pharmaceuticals. In 1999, the market for such biocatalysts is $150 - 200 million. PROPOSED COMMERCIAL APPLICATIONS: The enzyme of biocatalysts described are unique because they combine advantages of free and immobilized enzymes. There are no biocatalysts of this kind commercially available and an enormous potential exists because most drugs are developed in a single enantioselective form.

开发可重复使用且能够在非均相反应体系中工作的酶生物催化剂是本提案的重点。一种可逆可溶的聚合物将附着在酶上。因此，产物分离后无需酶变性即可沉淀生物催化剂。随后，可以在初始条件下将生物催化剂再次溶解在起始材料的悬浮液中。因此，这些生物催化剂获得了游离酶（在非均相系统中的高活性）和固定化酶（重复使用的可能性）的优点。由于工业要求生物催化剂应可重复使用并且反应具有高通量，因此生物催化在工业中未得到充分利用。化合物的溶解度是有限的，这需要在起始材料和产物的非均相悬浮液中进行反应。然而，目前市场上的所有生物催化剂要么不能重复使用，要么不能在异构系统中工作。在模型系统上证明了所提出的想法的潜力。该提案的重点是使用工业利益的酶的过程的优化。这种生物催化剂将销售给制药公司，用于制造手性药物。1999年，这种生物催化剂的市场为1.5 - 2亿美元。建议的商业应用：所述的生物催化剂的酶是独特的，因为它们结合了游离酶和固定化酶的联合收割机优点。 目前还没有这种商业上可获得的生物催化剂，并且存在巨大的潜力，因为大多数药物都是以单一的对映选择性形式开发的。