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The first microorganisms that both produce a nonnatural amino acid and incorporate it into proteins have been created by authors. The modified Escherichia coli bacteria synthesize proteins using a 21st amino acid, p-aminophenylalanine, in addition to the 20 amino acids common to all other life forms. "We have effectively removed a billion-year constraint on our ability to manipulate the structure and function of proteins. The additional genes that make this possible are encoded on plasmids, circular pieces of DNA that the researchers inserted into the bacteria. But authors note that the genes could potentially be incorporated directly in the E. coli genome. Nonnatural proteins produced by modified microorganisms could prove useful as reagents, sensors, molecular probes, and drugs. Such microorganisms could also be useful for studying fundamental evolutionary questions about the number of amino acids used in protein synthesis. "Why did life stop with 20, and why these 20?" A few natural organisms do produce unusual amino acids beyond the common 20 (such as selenocysteine and pyrrolysine) and incorporate them into proteins, but this is rare. In earlier studies, researchers have inserted nonnatural amino acids into proteins in the laboratory and have found ways to make microorganisms express nonnatural proteins. But the team's new study is the first in which free-living microorganisms have been induced to biosynthesize their own nonnatural amino acid and incorporate it into proteins. To accomplish this, the researchers added three items to the bacteria: Part of a genetic pathway from another microorganism, which enables the E. coli to biosynthesize p-aminophenylalanine; A tRNA that recognizes a uridine-adenine-guanine (UAG) stop codon on mRNA; and A modified synthetase that catalyzes addition of the nonnatural amino acid to the tRNA. T he modified bacteria can incorporate p-aminophenylalanine into myoglobin "with fidelity and efficiency rivaling those of the common 20 amino acids," the scientists note. The bacteria seem to suffer no ill effects from the modifications. To ensure that the modified microorganisms wouldn't turn into little Frankensteins, authors disabled them: The altered E. coli can only survive under carefully designed lab conditions and thus can't escape into the wild. |
| UPDATE | 01.03 |
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