Can only 20 amino acids be used in life? British scientists break the deadlock

Biology textbooks tell us that the proteins of all living organisms on earth are composed of only 20 amino acids. Theoretically, the types of amino acids can be extremely large, but why do only these 20 amino acids appear in living organisms? Scientists have been exploring this problem for a long time and trying to use other amino acids to build proteins.

On January 10, the research team of the Molecular Biology Laboratory (LMB) of the British Medical Research Council reported in the journal Nature that they had developed an effective method to induce bacteria to add structurally unusually unusual amino acids to proteins, and have succeeded in four amino acids.

In terms of chemical structure, the 20 common amino acids used by organisms are called α-amino acids. In addition, there are unique twists and turns of β-amino acids and γ-amino acids in the molecular main chain. The cheapest way to make proteins is to design living cells to produce proteins. Synthetic chemists have mixed dozens of non-standard alpha amino acids into proteins to synthesize a new life form, but a large number of amino acids with more strange structures have not been successful.

There are two key steps in protein synthesis: transcription and translation – first, short-chain transport RNA (tRNA) transports amino acids to the cell’s protein assembler – in the ribosome, each tRNA can encode specific amino acids and connect amino acids to the appropriate tR through aminoacyl tRNA synthase. NA; Secondly, the tRNA carrying amino acids binds to the long chain of messenger RNA (mRNA) containing all genetic information to complete the replication of genetic information. With the movement of the ribosome, the amino acid is continuously transported to this long chain.

Alexandria Deliz Liang, a chemist at the University of Zurich, compares protein manufacturing to an assembled train: first, train carriages must be loaded, and then these carriages must be connected together. In order to produce new types of protein, researchers must let these two steps work at the same time. Jason Chin, a chemist at LMB, added: “If any of them doesn’t work, the system will fail.”

In the first step, the 20 amino acids used by living organisms have their corresponding aminoacyl tRNA synthase, which can specifically identify the side chain and tRNA of amino acids. It is precisely because of the existence of such a monotological enzyme that the genetic information of mRNA can be accurately reflected in the amino acid sequence of the protein.

Researchers took this as a breakthrough to create millions of alternative versions that may bind to foreign amino acids through the gene of mutated amino tRNA synthase. Then, they insert these enzymes into E. coli to see if the ribosome can successfully bind these foreign amino acids to proteins. Results Eight enzymes successfully loaded with foreign amino acids were found, of which four of which could be combined into the growing protein chain by the natural ribosome of E. coli, including 3 β-amino acids and 1 α-α-amino acid.

“We broke the deadlock.” Chin said.

Chang Liu, a chemist at the University of California, Irvine, who did not participate in the study, said: “It is a great achievement to convert these new categories of amino acids into proteins.” Samuel Gellman, a chemist at the University of Wisconsin-Madison, said that although this is only proof of the principle, it is likely to have a significant impact on the future. First of all, this method helps pharmaceutical companies design protein drugs that are resistant to enzymes in vivo. Secondly, because the shape of these uncommon amino acids is different from the standard version, this method can also be used to improve industrial catalysts.

However, this research still depends on whether the ribosome can accept unusual amino acids. Therefore, the research team is also trying to change the ribosom itself, hoping to enable it to recognize tRNA encodings that are not available in nature and accept amino acids with unusual shapes through systematic mutations. Chin said that with the advancement of research, it is believed that the team can transform bacteria to produce protein polymer materials with new characteristics composed entirely of very common amino acids. 

Related information:https://www.nature.com/articles/s41586-023-06897-6