Directed Evolution Teaches Nature the Unnatural, Brings Silicon to Life
Caltech researchers have achieved a spectacular demonstration that living organisms can be persuaded to make silicon-carbon bonds. The study is the first to show that nature can adapt to incorporate silicon into carbon-based molecules, the building blocks of life. This breakthrough could have en important impact on how medicines and other chemicals are made in the future, and open new horizons to synthetic biology.
Carbon-Silicon (Organosilicon) compounds have important applications in pharmaceuticals, agricultural chemicals, paints, semiconductors, computer and TV screens, and other industrial products. These products are made synthetically by chemists in the lab, since silicon-carbon bonds are not found in nature. The Caltech scientists demonstrated that biology can instead be used to manufacture silicon-carbon bonds, in ways that are more environmentally friendly and potentially much less expensive.
Lead researcher Frances Arnold, a Caltech Professor of Chemical Engineering, Bioengineering and Biochemistry, said:
“We decided to get nature to do what only chemists could do – only better.”
Earlier this year, Arnold was awarded the Millennium Technology Prize – the world’s most prominent award for technological innovations that enhance the quality of people’s lives – for her “directed evolution” method, which creates new and better proteins in the laboratory using principles of evolution. The directed evolution technique, used to achieve the new results, enlists the help of nature’s design process – evolution – to come up with better enzymes, which are molecules that catalyze, or facilitate, chemical reactions. “In the same way that breeders mate cats or dogs to bring out desired traits, scientists use directed evolution to create desired enzymes,” noted the Caltech press release about Arnold’s award.
The research is published in Science with the title “Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life.” A companion review by independent researchers at the Technical University of Berlin, titled “Teaching nature the unnatural,” is also published in Science.
The researchers discovered that a protein from a bacterium that grows in hot springs in Iceland, called cytochrome c, which normally shuttles electrons to other proteins, acts like an enzyme to create silicon-carbon bonds. The scientists used directed evolution techniques to mutate the DNA coding for the protein and create an enzyme that can make silicon-carbon bonds 15 times more efficiently than the best catalyst invented by chemists, and with fewer unwanted byproducts.
“Silicon is found in nature in many inorganic forms, some of which are constructed by living organisms. Yet, no known biological molecule contains a carbon–silicon (C–Si) bond, and no biological processes to form C–Si bonds have been identified,” note the Berlin reviewers, adding that the beauty and value of the new research lie in the enzyme-promoted formation of an unnatural bond. “This closes a crucial gap between biological and chemical catalysis,” conclude the reviewers.
“The impact is unforeseeable, but it seems that we are a big step closer to potentially facilitating industrially relevant reactions such as alkene hydrosilylation with biomolecules.”
Toward New Life-Silicon Interfaces and Organosilicon-Based Life Forms?
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. However, life as we know it is based on carbon, and no silicon-based forms of life have been found on Earth.
“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,” says lead author Jennifer Kan, a postdoctoral scholar in Arnold’s lab.
The researchers colclude that the in-vitro and in-vivo examples of carbon–silicon bond formation shown in the study, using an enzyme and Earth-abundant iron, “affirm the notion that nature’s protein repertoire is highly evolvable and poised for adaptation.”
With only a few mutations, existing proteins can be repurposed to efficiently forge chemical bonds not found in biology and grant access to areas of chemical space that living systems have not explored.”
The Caltech breakthrough shows that life can be persuaded to incorporate silicon into its basic components, a research result that could open the way to new synthetic biology-based industrial manufacturing techniques – and perhaps to the possibility to create next-generation interfaces between carbon life and silicon hardware, or even new forms of organosilicon-based life, similar to the artist rendering in the cover image.
“This study shows how quickly nature can adapt to new challenges,” added 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. Nature could have done this herself if she cared to.”
Images from Lei Chen and Yan Liang/Caltech. Video from Caltech.