NEW BIOCATALYST FOR ENATIOSELECTIVE SYNTHESIS

开发可重复使用且能够在非均相反应系统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被附着在酶上。因此，生物催化剂可以在产物分离后不经酶变性而沉淀。之后，生物催化剂可以在初始条件下的起始材料的悬浮液中再次溶解。因此，这些生物催化剂具有游离酶（在多相系统中具有高活性）和固定化酶（可重复使用）的优点。由于工业要求生物催化剂可重复使用和反应具有高通量，生物催化在工业上的利用不足。化合物的溶解度是有限的，这就需要在原料和产物的非均相悬浮液中进行反应。然而，今天市场上所有的生物催化剂要么不能重复使用，要么不能在异质系统中工作。在模型系统上验证了该思想的潜力。该建议侧重于利用工业感兴趣的酶对工艺进行优化。这种生物催化剂将被销售给制药公司，并用于制造手性药物。1999年，这种生物催化剂的市场规模为1.5亿至2亿美元。建议的商业应用：所描述的酶的生物催化剂是独特的，因为它们结合了游离酶和固定化酶的优点。目前市面上还没有这种生物催化剂，而且由于大多数药物都是以单一的对映选择性形式开发的，因此存在巨大的潜力。

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.