Whole-Cell Biocatalysts for Stereoselective C-H Amination Reactions
Whole-Cell Biocatalysts for Stereoselective C-H Amination Reactions
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DOI：
10.1002/anie.201510028
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发表时间：
2016-01-22
影响因子：
16.6
通讯作者：
Flitsch, Sabine L.
中科院分区：
文献类型：
--
作者：
Both, Peter;Busch, Hanna;Flitsch, Sabine L.
对映体纯的手性胺是生物活性药物产品中普遍存在的化学结构单元，并且从简单的起始材料合成它们引起了极大的兴趣。最有吸引力的策略之一是通过 C-H 胺化立体选择性安装手性胺，这是一种具有挑战性的化学转化。在此，我们报告了在单个细菌全细胞系统中产生的多酶级联的应用，该级联能够催化立体选择性苯甲基胺化，ee 值为 97.5%。该级联使用四种异源表达的重组酶，其辅因子由宿主细胞提供，并添加异丙胺作为胺供体。该级联展示了用于正式立体选择性 C-H 胺化的单一全细胞生物催化剂的成功从头设计的第一个例子。
Enantiomerically pure chiral amines are ubiquitous chemical building blocks in bioactive pharmaceutical products and their synthesis from simple starting materials is of great interest. One of the most attractive strategies is the stereoselective installation of a chiral amine through C-H amination, which is a challenging chemical transformation. Herein we report the application of a multienzyme cascade, generated in a single bacterial whole-cell system, which is able to catalyze stereoselective benzylic aminations with ee values of 97.5%. The cascade uses four heterologously expressed recombinant enzymes with cofactors provided by the host cell and isopropyl amine added as the amine donor. The cascade presents the first example of the successful de novo design of a single whole-cell biocatalyst for formal stereoselective C-H amination.