Discovery of a new actor in protein translation adds to our understanding of one aspect of protein biosynthesis. While determining the structure of a bacterial enzyme, members of the New York Structural Genomics Research Consortium found a previously unknown metabolite—carboxy-S-adenosyl-l-methionine (Cx-SAM) (Nature 2013, DOI: 10.1038/nature12180). Cx-SAM turns out to play a role in modifying uridine bases in bacterial transfer RNAs. Such modifications extend tRNA’s ability to recognize codons, which signal which amino acid to make during protein synthesis. The metabolite may be formed through an unusual intermediate, according to the biosynthetic pathway proposed by the team, led by structural biologists Steven C. Almo and Jungwook Kim of Albert Einstein College of Medicine, in New York City. One enzyme produces Cx-SAM by catalyzing the transfer of a carboxyl group from prephenate to SAM, a reaction that proceeds through a ylide intermediate that acts as a carboxyl acceptor. Ylides have been suggested to mediate biochemical transformations, but no evidence so far confirms their participation. Another enzyme then recognizes Cx-SAM and uses it to convert 5-hydroxyuridine into 5-oxyacetyl uridine.