She repeated Recent studypublished on September 11 in the journal Nature Biotechnology, writes the genetic alphabet with the aim of creating new proteins that do not exist in nature using innovative techniques. The study was conducted by scientists at the American Scripps Research Institute, led by Egyptian researcher Ahmed Badran, an assistant professor in the institute’s Department of Structural and Integrative Computational Biology.
He says Matthew HartmanProfessor of organic chemistry in the Department of Chemistry at Virginia Commonwealth University in the United States, said in a statement obtained by Al Jazeera Net: “The beauty of the concept presented in this study is that it is easy to integrate into many types of processes because it only requires thoughtful design of genes.
Triple genetic code
The living cell functions according to a mechanism that boils down to its production of specific proteins through which it performs its functions and interacts with its environment. Insulin, for example, is a protein secreted by pancreatic cells into the blood to maintain sugar levels. This protein is formed inside the beta cells of the pancreas through a general mechanism used by the majority of cells in the body and by the cells of other living organisms to perform their various functions.
Proteins are present in our body, from the building blocks of our muscles to the tiniest structures operating in small cells. To build them, the cell translates a specific part of the genetic code (DNA) contained in its nucleus into amino acids, which are the primary units that make up the protein, and these acids are linked together to form one of the known proteins.
To understand the problem, imagine that an exciting movie is now on your friend’s computer. You ask his permission to get it via a finger-sized storage device (flash memory), and then play it on your computer. If the text on the storage device is written in a special language, your computer translates it, and the movie appears on the screen.
This is, to some extent, what happens in protein synthesis in our body, where amino acids are synthesized via a triple code, i.e. consisting of only 3 letters, known as a codon. Each codon is a designated code for a specific amino acid. For example, the amino acid tryptophan in its place is translated using a three-letter codon consisting of the three letters “UGG”. Similarly, methionine can be called using “AUG”. thus making each sequence and change in the arrangement of the four basic chemical letters – A, U, G and C – in the codon to build a different amino acid.
Rewriting the genetic alphabet
Badran and his team have managed to rewrite the triple genetic alphabet designed to use the 20 essential amino acids, and make it quaternary. The goal is simply to use additional non-essential amino acids. This will increase biodiversity by creating proteins that did not already exist in nature.
Badran says, in exclusive statements to Al Jazeera Net: “We have discovered principles that can be easily designed and applied to messenger RNA to improve the way the ribosome reads quaternary base sequences. By incorporating many different unconventional amino acids into the same protein, we will be able to produce proteins with good chemistry ‘beyond those available in nature.'”
The team performed a process known as “codon compression,” which involves placing “highly used” triplet codons around quadruplet codons in a way that dramatically improves decoding efficiency. This helped the ribosome (a subcellular particle involved in this process) correctly read the quaternary codons, allowing the desired unconventional amino acids to be successfully incorporated.
The term “high frequency” codon refers to a codon that is frequently used by a living cell to encode specific amino acids during protein synthesis. These codons are preferred because they improve the efficiency of the amino acid translation process, meaning that the ribosome is able to read them more easily and quickly, leading to a more efficient protein production process.
The researchers observed a cellular preference for highly used codons when they come immediately after quaternary codons. This observation prompted them to pursue an artificial genetic recoding approach, in which they used a highly used codon for each amino acid in the protein-coding elements of the genetic table, so that there was a triplet codon for each of the 20 standard amino acids and a quadcodon for each unconventional amino acid. With additional effort, the team was able to incorporate 47 unique nonessential amino acids into the proteins.
A new world of innovative proteins
“I’ve been excited about the potential of new proteins and peptides in nature for some time, and I believe that improving the way we access chemically diverse molecules will allow researchers to develop a new generation of therapeutics,” Badran says. “This new study, which I hope will be the first of many, is strongly consistent with this belief.”
To demonstrate the utility of this approach in cells, the team focused their work on the biosynthesis of “programmable macrocyclic peptides” because of their high stability; this is an important property of chemical compounds, and the Scripps Institute researchers succeeded in incorporating three distinct non-traditional amino acids into biologically manufactured macrocyclic proteins, which successfully altered their chemical properties.
“The real strength of our technology is its simplicity compared to previous models,” Badran says. “We are not the first group to explore quadruple decoding. Professor Chen and Peter Schultz at Scripps Research were pioneers in this field, and we are. Building on their previous work, our long-term vision is to develop “This approach creates chemically diverse macrocyclic proteins with novel activities.”
Badran grew up in the Egyptian city of Tanta and immigrated to the United States during his high school years. Since then, he has studied biochemistry and molecular biology at the University of Arizona, as well as biochemistry and directed evolution at Harvard University, and applied synthetic biology at MIT/Broad Institute.
“During that time, I lived in many parts of the world and saw how scientific progress could benefit all of humanity, and that ideal shaped my approach to science,” Badran says. “For example, I grew up in Egypt and lived in Arizona. The United States was a force.” “My lab’s work on mitigating climate change through protein engineering is motivated by the fact that these parts of the world are most at risk from rising global temperatures.”