Novel Racemases for Enzymatic Dynamic Kinetic Resolution

描述(申请人提供)：水解酶是用于制备光学纯化合物的有价值的工业生物催化剂。尽管有这些优点，但这些酶在外消旋底物上的最大单程产物产量限制在50%。底物特定的外消旋酶如果在动态动力学拆分中与水解酶一起原位使用，则有可能在不回收的情况下实现100%的产率。然而，很少有工业上合适的消旋酶的例子被描述。 Ingenza建议使用体内选择来分离和开发新的外消旋酶，并建立动态动力学拆分作为合成过程化学的更一般方法。最初的重点将是分离N-酰基氨基酸外消旋酶，以便与L-或D-氨基酰基酶一起用于制备非天然氨基酸和胺。这些化合物是抗病毒和抗肿瘤药物合成的必需品。来自蛋白质组学预期进展的新药物可能会增加对这项技术的需求。 Ingenza建议开发一个外消旋酶工具箱和一种高效、可扩展的技术，用于有机合成反应。第一阶段将展示选择性方法分离新型外消旋酶的可行性。在第二阶段，我们将优化酶的性质和作为应用生物催化剂的应用。在第三阶段，我们将把这项技术商业化，供合成有机化学家和制药商使用。

DESCRIPTION (provided by applicant): Hydrolases are valuable industrial biocatalysts used to prepare optically pure compounds. Despite advantages, these enzymes are restricted to a maximum single pass product yield of 50% with racemic substrates. Substrate specific racemases offer the potential to achieve 100% yield without recycling if used in situ with hydrolases in dynamic kinetic resolutions. However, few examples of industrially appropriate racemases have been described. Ingenza proposes to use in vivo selections to isolate and develop novel racemases and establish dynamic kinetic resolution as a more general method for synthetic process chemistry. The initial focus will be the isolation of N-acylamino acid racemases for use with L- or D-aminoacylases to prepare unnatural amino acids and amines. Such compounds are requisites as synthons for antiviral and antineoplastic drugs. New pharmaceuticals from anticipated advances in proteomics will likely increase demand for this technology. Ingenza proposes to develop a toolbox of racemases and an efficient, scaleable technologyfor use in organic synthetic reactions. Phase I will show feasibility of the selective approach in isolating novel racemases. In Phase II we will optimize enzyme properties and application as applied biocatalysts. In Phase III, we will commercialize the technology for use by synthetic organic chemists and pharmaceutical manufacturers.