While biocatalysis is increasingly incorporated into drug development pipelines, it is less commonly used in the early stages of drug discovery. By engineering a protein to produce a chiral motif with a derivatizable functional handle, biocatalysts can be used to help generate diverse building blocks for drug discovery. Here we show the engineering of two variants of Rhodothermus marinus nitric oxide dioxygenase (RmaNOD) to catalyze the formation of cis- and trans-diastereomers of a pinacolboronate-substituted cyclopropane which can be readily derivatized to generate diverse stereopure cyclopropane building blocks.

中文翻译：

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面向多样性的环丙烷构件的酶促合成

尽管生物催化越来越多地纳入药物开发流程，但在药物发现的早期阶段却很少使用。通过工程化蛋白质以产生具有可衍生功能手柄的手性基序，生物催化剂可用于帮助产生用于药物发现的多种结构单元。在这里，我们展示了罗丹色海藻一氧化氮双加氧酶（Rma NOD）的两个变体工程化，以催化频哪醇硼酸酯取代的环丙烷的顺式和反式非对映异构体的形成，可以容易地将其衍生化以生成各种立体纯的环丙烷构件。