Engineered Protein Incorporates Silicon Into Carbon-based Molecules

A new study has shown how natural organisms can be used to make silicon-carbon bonds, something only chemists had done before.

Scientists at California Institute of Technology (Caltech) in San Diego bred a new bacterial protein called cytochrome c, to manufacture synthetic bonds that would link silicon and carbon.

The finding that has applications in several industries. Molecules with silicon-carbon, or organosilicon, compounds are found in pharmaceuticals as well as in many other products, including agricultural chemicals, paints, semiconductors, and computer and TV screens.

Currently, these products are made synthetically, since the silicon-carbon bonds are not found in nature.

Science-fiction?

The study’s lead author, Jennifer Kan, a postdoctoral scholar, said:

“No living organism is known to put silicon-carbon bonds together, even though silicon is so abundant, all around us, in rocks and all over the beach.”

This work is also the first to demonstrate that nature can in fact adapt to incorporate silicon into carbon-based molecules, the building blocks of life. Scientists have long wondered if life on Earth could have evolved to be based on silicon instead of carbon.

Science-fiction authors likewise have imagined alien worlds with silicon-based life, like the lumpy Horta creatures portrayed in an episode of the 1960s TV series Star Trek.

Carbon and silicon are chemically very similar. They both can 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.

“We decided to get nature to do what only chemists could do–only better,”

says Frances Arnold, Caltech’s Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry, and principal investigator of the new research,

Directed Evolution

organosilicon

Artist rendering of organosilicon-based life. Credit: Lei Chen and Yan Liang (BeautyOfScience.com) for Caltech

The researchers used a method called directed evolution, developed by Arnold in the early 1990s, in which 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.

“It’s like breeding a racehorse,” says Arnold. “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 perfect racehorse stud turned out to be a protein from a bacterium 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.

Could life ever evolve to use silicon on its own?

Arnold says that is up to nature:

“This study shows how quickly nature can adapt to new challenges,” she says. “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. Nature could have done this herself if she cared to.”

S. B. Jennifer Kan, Russell D. Lewis, Kai Chen, Frances H. Arnold
Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life
Science 25 Nov 2016: Vol. 354, Issue 6315, pp. 1048-1051 DOI: 10.1126/science.aah6219

Top Image: Dr. Richard Feldmann. Cytochrome C