Pyrrolysine, the 22nd amino acid, discovered in 2002, might lay claim to being the 21st following the discovery by Ohio State University researchers that, like the twenty canonical amino acids, it is translated by the genetic code using a natural tRNA synthetase-tRNA pair.1 Pyrrolysine is the first new amino acid discovered since selenocysteine in 1986, but the latter results from modification of serine after attachment to its tRNA.

Microbiologist Joseph Krzycki and chemist Michael Chan discovered pyrrolysine, encoded by stop codon UAG, in certain methyltransferases of the methanogenic anaerobe Methanosarcina barkeri. Krzycki says there were suspicions that pyrrolysine results from a postactivation modification of lysine, but his latest collaboration with Chan reveals that a specific tRNA is charged directly with pyrrolysine.

By expressing the pyrrolysine-specific synthetase and tRNA and the M. barkeri methyltransferase in Escherichia coli, Krzycki and Chan showed that pyrrolysine added to the culture became...

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