This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Every cell relies on ribosomes, the molecular machines that read genetic instructions and use them to assemble proteins. A cell needs thousands of types of proteins at any one time, so ribosomes must be generalists, capable of using instructions to produce any protein.
Researchers at the University of Illinois Chicago have engineered a different kind of ribosome: one dedicated to making a single type of protein. The study, published in Nature, introduces a new platform for synthetic biology that is currently in the development stage. But it could someday be used to create designer peptide-based drugs, the authors said.
The platform, called Ribo-M, physically links a ribosome to messenger RNA, the genetic instructions for making a specific protein. "Natural ribosomes need to look around the cell to find the blueprint or the recipe for any of the hundreds of proteins to synthesize," said study author Kasra Alizadeh, a Ph.D. graduate of the Retzky College of Pharmacy and a postdoctoral fellow in the College of Engineering. That's highly effective for normal cellular life, but it can be limiting for biotechnology applications that require cells to produce unusual proteins, therapeutic molecules or other engineered products.
"We decided to overcome this problem by incorporating the message into the ribosome itself," said Alexander Mankin, distinguished professor in the Retzky College of Pharmacy and corresponding author of the study. "Our engineered ribosomes are specialized," Alizadeh said. "They always carry with them the recipe for one specific protein and only focus on making that protein without having to waste time looking around." The project required years of trial and error.
The team generated tens of thousands of ribosome variants and screened thousands of bacterial colonies in search of a functional design, Alizadeh said. Once they found one, the researchers demonstrated that Ribo-M could successfully produce several different proteins, including a protein that creates green fluorescence, an antibiotic-resistance protein and a light-producing enzyme. The researchers say they have created a new framework for engineering protein production.
"A good analogy is with physicians," Mankin said. "You have a general physician, who has to know a little bit about every single disease. But if you need to have brain surgery, you better go to the one who has specialized in this particular task." Like a specialist trained for a specific job, specialized ribosomes could be optimized to produce proteins with properties not found in nature.
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