Synthetic ribosome

Despite the controversial wording, this definition reflects the main features of our organisms and other living beings: the protein nature and the constant need for material for effective protein biosynthesis.

Molecular and cellular biology are relatively young branches of science, but breakthrough developments in the field of biotechnology in recent years are associated with them. The Human Genome project helped develop methods for rapid sequencing and computer analysis of nucleotide sequences. Geneticists have learned the language of DNA, learned to read and even adjust the plan of intracellular protein synthesis, but working with the code is just the beginning.

The biosynthesis of proteins itself can be controlled only when we move from understanding the templates for their release to recreating all stages of the production process itself. Therefore, a detailed study of the mechanisms of protein translation and the creation of ribosomes from scratch is now of key interest.

Ribosomes are the main intracellular protein factory. The structure of these organoids has been known in general terms for a long time, but no one knew how to replace them with a molecular machine. Creating a specialized ribosome from scratch for the production of exotic polypeptides seemed like a task of the distant future. Each ribosome consists of two subunits having different weights. For protein synthesis, both subunits combine and slide along the matrix RNA, performing the assembly of the polypeptide according to the program written on it.

In the video below, the mRNA is represented by a yellow thread. It is released through the pores of the nucleus into the cytoplasm of the cell. There it is first joined by a small subunit of the ribosome (light blue), and then by a large one (purple). The resulting complex receives aminoacyl-tRNA (green) molecules that supply different amino acids for protein synthesis. Soon, a red thread separates from the ribosome – a synthesized polypeptide.

The artificial ribosome, called Ribo-T, is arranged a little differently. If it were also made up of two parts, then synthetic subunits would be able to move through the endothelial matrix and enter into competitive relations with natural ones, blocking them. As a result, the cell would simply die, losing the ability to synthesize proteins.

Therefore, the authors of the study decided to combine the artificial ribosome subunits in advance, leaving enough space between them for the matrix RNA to slide. Such an immobilized structure shows less impressive results in terms of speed, but the main thing is that it works inside a living E.coli cell. Bacteria survive and continue to synthesize a given protein even after replacing all the original ribosomes with synthetic ones.

"The rate of protein biosynthesis on Ribo-T turns out to be about twice as low as that of natural ribosomes, but the structure of the latter has been improved over billions of years of evolution, and our development is only a year old," comments Alexander Mankin, co–author of the study.

Since the early eighties of the last century, bacteria (mainly E. Coli) with a modified genome have been used for the industrial synthesis of insulin, somatotropin, interferons and other complex proteins. With the help of an artificial ribosome, the authors expect to make any proteins even easier.

So far, each Ribo-T is capable of synthesizing only proteins of a certain class, but this is more than enough for the proof-of-concept level. The next stage in the development of biotechnologies will be the creation of a universal synthetic ribosome capable of assembling any proteins to order. These can be components with any biological activity – safe vaccines containing no pathogen, peptide hormones, components of selective medicines, new cosmetics and food products.

"In their work, the authors overcame the main obstacle to creating fully synthetic ribosomes with the desired properties," notes Karissa Sanbonmatsu, a researcher at Los Alamos National Laboratory, "they laid the foundation for dramatic changes."

A similar assessment is given by Yale University biologist Farren Isaacs: "This research will be the key to the production of completely new classes of exotic proteins," he says in an interview with The Verge.

A year ago, the Scripps Research Institute (TSRI) created a new genetic alphabet with a couple of additional coding molecules not found in nature. Now it can be tested on an artificial ribosome.

The recombinant proteins obtained until today were completely identical to those formed naturally. They always contained the remnants of a standard set of twenty or less L-alpha amino acids. Combining the augmented genetic code with the capabilities of artificial ribosomes, it is theoretically possible to start the biosynthesis of 172 amino acids and create completely different proteins on an industrial scale.

Like any scientific development, artificial ribosomes can become a dual-use technology. If we solve the problem of their delivery to the cells of a living organism, then Ribo-T can be used to treat ricin poisoning. This protein poison has no specific antidotes. It dissociates ribosome subunits, blocking protein biosynthesis. The artificial ribosome is already resistant to the effects of ricin, since its subunits are initially interconnected.

On the other hand, with the help of Ribo-T, new toxins can be synthesized – absolutely unknown to a potential enemy and much more suitable for sabotage than ricin and other natural poisons.