Journal Article 2 Mentions
Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life
S. B. Jennifer Kan2016
Russell D. LewisKai Chen
Top 5% · 95th percentile
572 citations · Organic Chemistry

TLDR

Scientists changed a natural protein so it could help living cells make new types of silicon-containing chemicals, something nature doesn't usually do.

Summary

1 Study Aim

The main goal of this study is to create an enzyme (a protein that speeds up chemical reactions) that can form bonds between carbon and silicon atoms. The authors want to show that it is possible to use directed evolution (a method of making small changes to proteins and selecting the best ones) to give living systems the ability to make organosilicon compounds, which are not found in nature. Simply put: The study aims to make a protein that helps living things build new silicon-based chemicals.

2 Study Design

The researchers started by testing whether heme proteins (proteins containing an iron-based molecule called heme) could help join carbon and silicon atoms together. They used cytochrome c from the bacterium Rhodothermus marinus and changed its genetic code to create many slightly different versions. They tested these versions in bacteria to see which ones worked best at making carbon–silicon bonds. The best mutants were further improved through several rounds of directed evolution, and their ability to make silicon-containing products was tested both in test tubes and inside living E. coli cells. Simply put: The team changed a protein in bacteria step by step, picking the best ones to help make new silicon-based chemicals.

3 Findings

The study reveals that the evolved cytochrome c enzyme can efficiently and selectively form carbon–silicon bonds, outperforming the best synthetic (non-biological) catalysts by more than 15 times. The enzyme works with many different starting materials and produces single-enantiomer (mirror-image pure) products, even inside living cells. The authors demonstrate that this method avoids the need for harsh chemicals or precious metals and can tolerate many functional groups, making it practical for making complex molecules. They suggest that this approach could open new possibilities for making silicon-based chemicals in an environmentally friendly way. Simply put: The improved protein lets bacteria make a wide variety of pure silicon-containing chemicals quickly and cleanly, even inside living cells.

Abstract

Enzymes that catalyze carbon-silicon bond formation are unknown in nature, despite the natural abundance of both elements. Such enzymes would expand the catalytic repertoire of biology, enabling living systems to access chemical space previously only open to synthetic chemistry. We have discovered that heme proteins catalyze the formation of organosilicon compounds under physiological conditions via carbene insertion into silicon-hydrogen bonds. The reaction proceeds both in vitro and in vivo, accommodating a broad range of substrates with high chemo- and enantioselectivity. Using directed evolution, we enhanced the catalytic function of cytochrome c from Rhodothermus marinus to achieve more than 15-fold higher turnover than state-of-the-art synthetic catalysts. This carbon-silicon bond-forming biocatalyst offers an environmentally friendly and highly efficient route to producing enantiopure organosilicon molecules.

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