New Biocatalyst for Enantioselective Synthesis

用于对映选择性合成的新型生物催化剂

• 批准号: 6337210
• 负责人: Mikhail Gololobov
• 金额: $ 40.04万
• 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 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6337210
• 关键词: catalyst; chemical reaction; chemical synthesis; enzyme activity; enzyme structure; immobilized enzymes; polymers; protein engineering; stereoisomer; technology /technique development

DESCRIPTION: (Applicant's abstract) 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 dissolved 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 has a high throughput. Solubility of the compounds in limited and this necessitates running the reaction 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. Feasibility of the idea was demonstrated on during Phase I. Phase II focuses on the optimization of the process using the enzymes of industrial interests. These biocatalysts will be marketed to pharmaceutical companies and used to manufacture chiral pharmaceuticals. In 2000, the market for such biocatalysts is about $200 million. PROPOSED COMMERCIAL APPLICATION: The enzyme biocatalysts described in proposal are unique because they combine advantages of free and immobilized enzymes. There are no biocatalysts of this kind commercially available and an enormous commercial potential exists because most drugs are developed in a single enantiomer form. Sales of the reversibly soluble biocatalyst for a production of just one drug can generate up to several million US dollars per year.

描述：（申请人摘要）酶生物催化剂的开发， 是可重复使用的，并能够在多相反应系统中工作是重点， 这个提议。一种可逆可溶的聚合物将附着在酶上。 因此，生物催化剂可以在没有酶变性的情况下沉淀 产品分离后。稍后，生物催化剂可以再次溶解在 在初始条件下悬浮起始材料。因此，我们认为， 这些生物催化剂获得了游离酶的优点（高活性， 异构系统）和固定化酶（重复使用的可能性）。 生物催化在工业中未得到充分利用，因为工业要求 生物催化剂应该是可重复使用的，并且反应具有高通量。 化合物的溶解度是有限的，这就需要运行 在起始材料的非均相悬浮液中反应， 产品.然而，目前市场上的所有生物催化剂要么不能重复使用， 或者在异构系统中不工作。这个想法的可行性是 在第一阶段展示。第二阶段的重点是优化 使用工业上感兴趣的酶的方法。这些生物催化剂将 销售给制药公司，用于生产手性药物 大药厂2000年，这种生物催化剂的市场约为200美元， 万 拟定商业应用： 建议中描述的酶生物催化剂是独特的，因为它们结合了联合收割机的优点 游离酶和固定化酶。 商业上还没有这种生物催化剂 由于大多数药物都是在 单一对映体形式。 销售用于生产以下产品的可逆可溶性生物催化剂： 仅一种药物每年就能产生高达数百万美元的收入。