Detecting the Elusive ‘Ylide’ — Ylides, molecules containing two opposing charges on adjacent atoms, have been proposed as intermediates in biochemical reactions, but until now there was little evidence supporting this theory. In a study appearing in Nature’s May 15 online edition, Drs. Jungwook Kim and Steven Almo, and colleagues describe a ylide intermediate — formed from the biomolecule SAM (S-adenosylmethionine) — during biosynthesis of the newly identified metabolite Cx-SAM. The group subsequently demonstrated that Cx-SAM is used to generate the modified nucleotide5-oxyacetyl uridine (cmo5U) on bacterial tRNAs, which is required for efficient processing of the genetic code. While determining the X-ray crystal structure of an enzyme required for the biosynthesis of cmo5U, the researchers discovered Cx-SAM — a SAM molecule with a carboxylate (CO2-) group attached, in the enzyme’s active site. They theorized that this metabolite was generated from SAM via a series of biochemical reactions involving the formation of a ylide, and then tested several compounds that led to their discovery that prephenate (an aromatic amino acid precursor) generated Cx-SAM, thereby providing compelling evidence for the existence of the ylide intermediate. Dr. Kim is an associate of biochemistry and Dr. Almo is professor of biochemistry and of physiology & biophysics. Dr. Almo holds the Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology.
Posted on: Thursday, July 18, 2013