Scientists Hack Cellular Machinery, Create First Artificial Ribosome
Scientists at the University of Illinois at Chicago and Northwestern University have created an artificial ribosome that works like a natural one. The ribosome is the cellular complex of proteins and RNA molecules that synthesizes proteins in living cells. The development could open the way to creating custom designer proteins.
The artificial ribosome, called Ribo-T, was created in the laboratories of Alexander Mankin, director of the UIC College of Pharmacy’s Center for Biomolecular Sciences, and Northwestern’s Michael Jewett, assistant professor of chemical and biological engineering.
The research is published in a Nature article titled “Protein synthesis by ribosomes with tethered subunits,” with a review titled “Synthetic biology: Ribosomal ties that bind.” Both Nature papers are paywalled, but Nature News has a summary titled “Hacked molecular machine could pump out custom proteins.”
Hacking the Protein Synthesis Machine to Create Designer Proteins
Ribosomes read molecular instructions encoded in RNA templates transcribed from DNA, and assemble amino acids into proteins according to the instructions in a process called translation. Natural ribosomes have two subunits, one large and one small, which come together to build a protein and separate from each other once the target protein is complete. Each subunit later joins another matching subunit to build another protein.
Previous effort to create functional synthetic ribosomes with new properties – such as the ability to build designer proteins – were complicated by artificial ribosome subunits coming together with natural ones, reducing the cell’s ability to produce normal proteins. In the engineered ribosome Ribo-T, two artificial subunits are permanently linked together by a molecular tether. In the image, two polyadenine RNA tethers (red) link Ribo-T’s two engineered ribosomal subunits, small (left) and large (right).
It was previously believed that the ability of the two ribosomal subunits to separate was required for protein synthesis, but the research results show that it isn’t. Ribo-T could build proteins in a test-tube, and it was able to build enough protein in bacterial cells that lacked natural ribosomes to keep the bacteria alive.
“What we were ultimately able to do was show that by creating an engineered ribosome where the ribosomal RNA is shared between the two subunits and linked by these small tethers, we could actually create a dual translation system,” said Jewett.
Our new protein-making factory holds promise to expand the genetic code in a unique and transformative way, providing exciting opportunities for synthetic biology and biomolecular engineering.
“This is an exciting tool to explore ribosomal functions by experimenting with the most critical parts of the protein synthesis machine, which previously were ‘untouchable,'” added Mankin.
The research development could allow scientists to better understand protein synthesis, explore how antibiotics work and convert cells into custom chemical factories. The researchers will further study what the system can do for synthetic biology, perhaps producing new antibiotics or unnatural polymers. “We’re just at the leading edge,” said Jewett.
Images from Nature, University of Illinois at Chicago, and Northwestern University.