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New amino acid discovered in Methanosarcina barkeri


The discoverers of a new amino acid report that a stop sign is not always a stop sign. The amino acid, called pyrrolysine, is genetically encoded by a nucleotide sequence that normally halts the translation of mRNA—a stop codon. But during the assembly of certain proteins, the researchers found, cells override the stop codon, incorporate pyrrolysine, and continue to synthesize protein.

Detail from a ribbon diagram of the MtmB hexamer. View full

Pyrrolysine is found in at least one bacterium and certain species of Archaea—the domain of life separate from plants, animals, and bacteria. It was discovered by Joseph A. Krzycki and Michael K. Chan of the Ohio State University in Columbus and their colleagues, who were trying to understand how an Archaeon called Methanosarcina barkeri produces methane.

"We know now that genomes have the potential to hold real surprises," says Krzycki. Based on the fact that pyrrolysine is not present in most bacteria or Archaea, Krzycki hypothesizes that the amino acid was transferred from one species to another during evolution.

Interest in methane-producing microbes—known as methanogens—is high; four Archaeal species have been sequenced in recent years. Krzycki and colleagues are searching the genome databases of these and other species in search of pyrrolysine. They will try to understand how often the 'UAG' stop codon is overridden during protein synthesis rather than recognized as a stop sign.

There are twenty standard amino acids encoded in the genomes of all organisms. In 1986, researchers discovered a nonstandard amino acid, called selenocysteine, which is also encoded by the UGA stop codon. The great majority of nonstandard amino acids are created through the chemical modifications of standard amino acids after translation.

The initial analyses of pyrrolysine suggested that it was amino acid lysine. But structural studies of the protein containing pyrrolysine, done in the laboratory of Michael Chan, indicated that it was the twenty-second amino acid. The findings appear in two papers in today's issue of Science.

"This is an example of researchers getting an interesting early result and then pushing hard to find the answer," says Chan. "The answer could have been mundane—it might have been lysine. But in the end it turned out to be exciting."

The new discovery "reflects the greater richness of the genetic code than is apparent from the standard textbook account," write John F. Atkins and Ray Gesteland of the University of Utah, Salt Lake City, in a commentary in Science.

See related GNN articles
»Key player in global warming: M. acetivorans is sequenced
»The genome of the hyperthermophile Methanopyrus kandleri

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Atkins, J.F. & Gesteland, R. The 22nd amino acid. Science 296, 1409-1410 (May 24, 2002).
Hao, B. et al. A new UAG-encoded residue in the structure of a methanogen methyltransferase. Science 296, 1462-1466 (May 24, 2002).
Srinivasan, G. et al. Pyrrolysine encoded by UAG in Archaea: Charging of a UAG-decoding specialized tRNA. Science 296, 1459-1462 (May 24, 2002).

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