Diversity-Oriented Enzymatic Synthesis of Cyclopropane Building Blocks

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.