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22nd Amino Acid Reflects Genetic Versatility 22nd Amino Acid Reflects Genetic Versatility 22nd Amino Acid Reflects Genetic Versatility

May 23, 2002 — Scientists once believed the genetic code of living organisms carried the blueprint for making only 20 amino acids, the building blocks of proteins that carry out the functions of every living cell. But a 21st amino acid was identified in 1986. And in the May 24, 2002 issue of the journal Science, scientists report discovering a 22nd amino acid.

The discovery by Ohio State University researchers indicates that life’s genetic code is richer than once thought and that scientists may be able to manipulate the code to make new industrial enzymes – proteins that speed chemical reactions, University of Utah geneticists say in a commentary also published in Science.

“It suggests we can intervene and genetically engineer amino acids to produce designer enzymes for industrial purposes,” said Ray Gesteland, distinguished professor of human genetics and vice president for research at the University of Utah. “The chemical industry uses enzymes a lot for making complex chemicals that are difficult to make synthetically.”

The discovery of a 22nd genetically encoded, natural amino acid means “there is unexpected versatility in the readout of hereditary information to synthesize proteins,” including enzymes, said John F. Atkins, a research professor of human genetics at the university. “Hereditary information is crucial to all life, and its translation into useful proteins is essential for life. So finding unexpected versatility in this process is very interesting.”

In their “Perspective” commentary column in Science, Atkins and Gesteland wrote that the discovery “reflects the greater richness of the genetic code than is apparent from the standard textbook account.”

Discovery of the 22nd amino acid – named pyrrolysine – was reported in two studies in Science led by Joseph Krzycki and Michael Chan at Ohio State University.

Genes are composed of DNA, a molecule made of pairs of chemicals called bases or nucleotides and known by the letters A, C, G and T. When the hereditary instructions in a gene are carried out, the DNA’s code is “transcribed” into RNA, which is made of bases known as A, C, G and U. The code within the RNA is “read” – three bases at a time – to make the proteins that carry out every function in a living cell.

When RNA’s instructions are “read” to make a protein, three bases order production to start, and three bases – known as a “stop codon” – signal that the protein is complete. The Ohio State researchers found that the three RNA bases UAG don’t always act to signal that a protein is complete, but instead can be reprogrammed to act as the genetic blueprint for the 22nd amino acid, pyrrolysine.

They found the genetic code for pyrrolysine in microbes named Methanosarcina barkeri, which produce methane or natural gas. The microbes belong to the group of organisms known as Archaea, which are single-celled organisms that tend to live in extreme environments such as hot springs and are distinct from bacteria, plants, animals, fungi and other forms of life.

In their commentary, Atkins and Gesteland note that many rare “nonstandard” amino acids are found in nature beyond the 20 “standard” ones. But they are not made by instructions contained in the genetic code of living organisms. Instead, they are made when amino acids in a protein are modified chemically after the protein already has been made according to genetic instructions.

The 1986 discovery of selenocysteine represented the 21st “genetically encoded natural amino acid,” and pyrrolysine is the 22nd.

“The implication is that the genetic code itself can be modified through evolution to encode more stuff – new amino acids,” Gesteland said.

That, in turn, implies that scientists may be able to manipulate the genetic code to make even more amino acids and thus produce new enzymes for industry. Enzymes are proteins that speed or catalyze chemical reactions, and they are widely used in making cheese, beer, laundry detergents, animal feed, baked goods, paper, soft drinks, textiles and many other products.

Gesteland said discovery of the 22nd genetically encoded amino acid raises the bigger question of how life’s genetic code is reprogrammed to do new things, and also suggests “there may be other surprises out there. Are there yet other amino acids?”

The 21st and 22nd natural amino acids likely evolved because they increase the activity of the enzymes of which they are building blocks. In the case of pyrrolysine, the Ohio State researchers believe it may help Methanosarcina barkeri produce methane.

Discovery of new, genetically encoded amino acids is only one type of example of versatility in life’s genetic code, said Atkins, who also is affiliated with the Dublin-based Science Foundation Ireland.

For 16 years, Atkins and Gesteland have studied how the different proteins may be produced if “frame shifting” occurs. A protein normally is produced when its chemical bases are read three at a time, as in 1-2-3, 1-2-3 and so on. But a different protein may result if the “reading frame” is shifted so the chemical bases are read 2-3-1, 2-3-1 and so on.