Asymmetric Enzymatic Carbon–Silicon Bond Formation

Key words

carbenes - directed evolution - heme protein - carbon–silicon bond formation - cytochrome c - enzyme modification

Significance

The insertion of carbenes into silicon–hydrogen bonds under physiological conditions is reported by the Arnold group. Three selective modifications of the active site of cytochrome c from Rhodothermus marinus resulted in a highly active catalyst (Rma cyt c, V75T M100D M103E) that gave the desired products with remarkable total turnover numbers (≤8210) and enantioselectivities (er > 97.5:2.5). The transformation was performed in vivo on a preparative scale by using Escherichia coli expressing the mutant enzyme.

Comment

Despite the high abundance of carbon and silicon, no known lifeform can form a bond between these two elements. The authors impressively showed that just three modifications of the wild-type enzyme can force nature to create this unusual bond with extraordinary efficiency. Interestingly, no cyclopropanation, cyclopropenation or insertion into O–H or N–H bonds occurs when the required functional groups are present. The system achieved a 15-fold higher activity and chemoselectivity than the best synthetic catalysts.