Kan SB. J, Lewis RD, Chen K, Arnold FH * California Institute of Technology, Pasadena,
USA
Directed Evolution of Cytochrome c for Carbon–Silicon Bond Formation: Bringing Silicon
to Life.
Science 2016;
354: 1048-1051
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.
