Novel Enzymatic Reductive Amination

描述（由申请人提供）：手性胺是一类重要的手性化合物。 医药中间体在第一阶段，我们建议使用定向进化 产生第一组胺脱氢酶的方法逐渐发展， 催化酮的立体选择性还原胺化， 相应的手性胺。一种正在申请专利的高通量检测方法 已经开发并验证了用于检测新的 氨基酸脱氢酶活性，我们将采用这种方法来建立 用于检测新的“胺转移酶”的高通量筛选。“这些新 然后将对酶进行表征和评价，用于生产手性 胺通过酮的还原胺化反应制得。与决议相反 方法，还原胺化过程是手性合成，并且高达100 %的起始材料可以转化为对映异构体 使用容易获得的廉价酮在一个步骤中得到纯产物 起始材料第一阶段的成功将为扩大 开发能够催化产生一种 广泛的手性胺在阶段2。 拟定商业应用：使用所开发的技术生产的手性胺作为合成广泛的药物活性化合物的关键中间体具有应用。

DESCRIPTION (provided by applicant): Chiral amines are an important class of pharmaceutical intermediates. In Phase 1 we propose to use directed evolution methods to create the first group of amine dehydrogenase enzymes evolved to catalyze the stereoselective reductive amination of ketones to the corresponding chiral amines. A patent-pending assay for use in high throughput screening has already been developed and validated for the detection of new amino acid dehydrogenase activities, and we will adapt this method to establish a high throughput screen for detecting new "amine dehydrogenases." These new enzymes will then be characterized and evaluated for the production of chiral amines by the reductive amination of ketones. In contrast to resolution methods, the reductive amination process is a chiral synthesis, and up to 100 percent of the starting material can be converted into the enantiomerically pure product in a single step using readily available, inexpensive ketone starting materials. Success in Phase 1 will lay the foundation for an expanded development of amine dehydrogenases capable of catalyzing the production of a wide range of chiral amines in Phase 2. PROPOSED COMMERCIAL APPLICATION: Chiral amines produced using the technology developed have applications as key intermediates for the synthesis of a wide range of pharmaceutically active compounds.