Scientists at Caltech have “bred” a bacterial protein with the ability to make silicon-carbon bonds, with applications in several industries — something only chemists could do before. The research was published in the Nov. 24 issue of the journal Science.

Molecules with silicon-carbon (organosilicon) compounds are found in pharmaceuticals and many other products, including agricultural chemicals, paints, semiconductors, and computer and TV screens. Currently, these products are made synthetically, since silicon-carbon bonds are not found in nature.

The new research demonstrates that biology can be used to manufacture these bonds in ways that are more environmentally friendly and potentially much less expensive, according to the researchers.



Caltech | Bringing Silicon to Life: Scientists Persuade Nature to Make Silicon-Carbon Bonds

Directed evolution

The key to this research involves deliberate messing with nature: a method called directed evolution* pioneered in the early 1990s by Frances Arnold, Caltech’s Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry, and principal investigator of this project.

Directed evolution has been used for years to make enzymes for household products, like detergents; and for “green” sustainable routes to making pharmaceuticals, agricultural chemicals, and fuels.

In directed evolution, new and better enzymes are created in labs by artificial selection, similar to the way that breeders modify corn, cows, or cats. Enzymes are a class of proteins that catalyze, or facilitate, chemical reactions. The directed evolution process begins with an enzyme that scientists want to enhance. The DNA coding for the enzyme is mutated in more-or-less random ways, and the resulting enzymes are tested for a desired trait. The top-performing enzyme is then mutated again, and the process is repeated until an enzyme that performs much better than the original is created.

Going where no enzyme has gone before

In the new study, the goal was not just to improve an enzyme’s biological function but to actually persuade it to do something that it had not done before. The researchers’ first step was to find a suitable candidate, an enzyme showing potential for making the silicon-carbon bonds.

“It’s like breeding a racehorse,” says Arnold, who is also the director of the Donna and Benjamin M. Rosen Bioengineering Center at Caltech. “A good breeder recognizes the inherent ability of a horse to become a racer and has to bring that out in successive generations. We just do it with proteins.”

The ideal candidate turned out to be a protein from a bacterium, Rhodothermus marinus, that grows in hot springs in Iceland. That protein, called cytochrome c, normally shuttles electrons to other proteins, but the researchers found that it also happens to act like an enzyme to create silicon-carbon bonds at low levels. The scientists then mutated the DNA coding for that protein within a region that specifies an iron-containing portion of the protein thought to be responsible for its silicon-carbon bond-forming activity. Next, they tested these mutant enzymes for their ability to make organosilicon compounds better than the original.

After only three rounds, they had created an enzyme that can selectively make silicon-carbon bonds 15 times more efficiently than the best catalyst invented by chemists. Furthermore, the enzyme is highly selective, which means that it makes fewer unwanted byproducts that have to be chemically separated out.

“This iron-based, genetically encoded catalyst is nontoxic, cheaper, and easier to modify compared to other catalysts used in chemical synthesis,” says Jennifer Kan, a postdoctoral scholar in Arnold’s lab and lead author of the new study. “The new reaction can also be done at room temperature and in water.”

The synthetic process for making silicon-carbon bonds often uses precious metals and toxic solvents, and requires extra processing to remove unwanted byproducts, all of which add to the cost of making these compounds.

Could life on Earth (or elsewhere) have evolved based on silicon-carbon?

The study is the first to show that nature can adapt to incorporate silicon into carbon-based molecules, the building blocks of life.

Carbon and silicon are chemically very similar, and silicon is the second most abundant element in Earth’s crust. They can both form bonds to four atoms simultaneously, making them well suited to form the long chains of molecules found in life, such as proteins and DNA. Science-fiction authors have imagined alien worlds with silicon-based life, like the lumpy Horta creatures portrayed in an episode of the 1960s TV series Star Trek.

“This study shows how quickly nature can adapt to new challenges,” says Arnold. “The DNA-encoded catalytic machinery of the cell can rapidly learn to promote new chemical reactions when we provide new reagents and the appropriate incentive in the form of artificial selection.”

However, no living organism is known [yet] to put silicon-carbon bonds together, even though silicon is so abundant, all around us, in rocks and all over the beach,” says Kan.

What about other planets (Mars has both silicon and carbon, for example) and asteroids? And could alien life have evolved silicon-carbon semiconductor brains? It would also be interesting to see if such a lifeform could be invented on Earth.

This research is funded by the National Science Foundation, the Caltech Innovation Initiative program, and the Jacobs Institute for Molecular Engineering for Medicine at Caltech.

* Not to be confused with a transhumanist concept for controlling human evolution.

Abstract of Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life

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.