A newly engineered bacterium has a chemistry unlike anything found in nature. The bug manufactures an amino acid not made by any other living thing and uses it to construct its proteins, the molecules that carry out the lion's share of cellular chemistry.
Most organisms pick and choose from 20 naturally occurring amino acids to build their proteins. But 2 years ago, a team led by Peter Schultz, a chemist at the Scripps Research Institute in La Jolla, California, engineered the genes of an Escherichia coli bacterium to incorporate a 21st amino acid into its proteins. The basic machinery that makes proteins starts with trios of nucleotide bases, called codons, that make up DNA. Each codon directs a particular amino acid to be added to a protein chain. Schultz's team co-opted a little-used codon--known as the amber stop codon--and reengineered the cellular enzymes to add a new amino acid, O-methyl-L-tyrosine, whenever it saw that codon. But to get the bug to make proteins with the unnatural amino acid, the researchers had to feed the amino acid to the bacterium.
Now, in the 29 January issue of the Journal of the American Chemical Society, Schultz's team reports going one step further by engineering an E. coli that can manufacture a new amino acid on its own. They followed the same approach as before with a different amino acid, p-aminophenylalanine, but also spliced a trio of enzyme-producing genes from a strain of Streptomyces bacteria into the E. coli. Together with another enzyme already present in E. coli, these enzymes enabled the bugs to turn a common compound in E. coli called chorismate into p-aminophenylalanine. To find out what difference this unusual chemistry makes, Schultz and colleagues plan to see whether these E. coli fare better than the 20-amino-acid variety in response to food shortages and other challenges.
"These results are very exciting," in part because they provide researchers with a new way to explore evolution, says David Liu, a chemist and specialist in molecular evolution at Harvard University in Cambridge, Massachusetts. "It's tantalizing to ask how can this organism evolve, now that it is equipped with a method for not only using a nonnatural building block but also for creating that building block," says Liu.