Unnatural biochemistry: bacteria make and use an alien amino acid.

Almost all organisms assemble proteins from the same 20 natural building blocks, known as amino acids. But now, in a feat of genetic engineering, researchers have for the first time constructed an organism that synthesizes and incorporates a 21st amino acid into its proteins.

The modified version of the common bacterium Escherichia coli could be valuable to scientists investigating why life operates with 20 amino acids, rather than, say, 19 or 21, remarks Ryan Mehl, a member of the team that created the bacterium at the Scripps Research Institute in La Jolla, Calif.

The work could also lead to biotech organisms that manufacture new materials from nonstandard amino acids. Instead of chemical plants, "we could have bacteria generating our polymers," says Mehl, who last September moved from Scripps to Franklin & Marshall College in Lancaster, Pa. He and his coworkers describe their organism in the Jan. 29 Journal of the American Chemical Society.

Hung-wen (Ben) Liu of the University of Texas at Austin rates the work as "beautiful." The research solves a technically challenging problem and potentially has many practical uses, he adds.

Researchers previously had coerced bacteria to take up extra amino acids from laboratory dishes and use them to make proteins (SN: 6/3/00, p. 360). But until now, no one had altered a bacterium so that it could synthesize a 21st amino acid and then incorporate it into proteins along with the standard amino acids.

The Scripps team, led by Peter Schultz, gave E. coli genetic instructions for making a nonstandard amino acid--one produced by another bacterium as part of a defensive chemical but not naturally integrated into proteins. All the modified E. coli requires to construct the new amino acid is salt, water, and a carbon source, such as glucose.

The scientists also genetically modified the organism's biochemical machinery so it would integrate the alien amino acid into proteins. To avoid inflicting any harm on the bacterium, the researchers made it use the extra amino acid in the construction of the oxygen-carrying protein called myoglobin--a protein not naturally found in E. coli.

The work "achieves something that most of us have dreamed of," says Jack Kirsch of the University of California, Berkeley. "It's sensational."

The Scripps scientists have begun testing whether E. coli that make 21 amino acids fare better than their conventional cousins under stressful conditions, such as extreme temperatures and poor nutrition, says Mehl.