An enzymatic route to carbon-silicon bonds

Bacterial cytochrome c demonstrated the first example of ‘natural’ organosilicon chemistry

Jyllian Kemsley

The heme group (blue) of R. marinus cytochrome c catalyzes carbenoid insertion into Si–H bonds.
Credit: Science

Silicon is the second most abundant element in Earth’s crust after oxygen, but carbon-silicon bonds are unheard of in nature: Neither biological organosilicon compounds nor biosynthetic pathways to create them have been identified. But researchers from California Institute of Technology found this year that, when given the right starting materials, some heme proteins can stereospecifically form carbon-silicon bonds (Science 2016, DOI: 10.1126/science.aah6219).

“Nature’s iron heme chemistry just jumps on this opportunity because we provided it with the right precursors,” says Frances H. Arnold, who led the work with S. B. Jennifer Kan. “It’s a profound demonstration of how easily nature can innovate.”

Prior work in Arnold’s lab and elsewhere had demonstrated that heme proteins can catalyze nonnatural carbene transfer reactions through insertion into N–H and S–H bonds. In the new experiments, the Caltech researchers screened a panel of heme proteins to find ones that could catalyze insertion of ethyl 2-diazopropanoate into the Si–H bond of dimethyl(phenyl)silane.

Three mutations of R. marinus cytochrome c turn the protein into an enzyme that produces organosilicon compounds with greater than 99% enantiomeric excess.
Credit: Science

Cytochrome c from the bacterium Rhodothermus marinus, which is found in submarine hot springs in Iceland, catalyzed the reaction with 97% enantiomeric excess, albeit with low catalytic turnover. Cytochrome c proteins normally don’t catalyze chemical reactions. Instead, they transfer electrons between biomolecules in cells.

But that did not stop the Caltech team from pushing the R. marinus cytochrome c to improve its newfound ability to perform organosilicon catalysis. Using directed evolution, the researchers found that a set of three mutations could increase the new enzyme’s enantioselectivity to greater than 99% and its turnover to about 15 times as much as that of typical catalysts.

“It seems that we are a big step closer to potentially facilitating industrially relevant reactions such as alkene hydrosilylation with biomolecules,” comment Hendrik F. T. Klare and Martin Oestreich of the Technical University of Berlin in a perspectives article that accompanied the paper.

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