The Two Faces of SAM

An unusual radical mechanism enables ribosome methylation in bacteria. The word “radical” ( 1 ) is often associated with highly energetic species (atoms or molecules) that chemically react with, and modify or destroy, molecules that they encounter. All organisms devote considerable metabolic effort to “control” radicals, such as reactive oxygen and nitrogen species (for example, the hydroxyl radical and nitric oxide), and to repair the damage that they inflict on macromolecules and small molecules alike. Radical-based reactions, however, also play an important role in metabolism. Evolution has produced mechanisms that harness radicals' reactivity to carry out difficult chemical transformations with exquisite specificity. For instance, while the common cellular compound called S -adenosylmethionine (SAM) is well known to play a role in the methylation of nucleophiles by a typical substitution reaction, in seminal work, Knappe and Schmitt ( 2 ) demonstrated that SAM mediates radical chemistry in organisms grown anaerobically (see the figure). Since then, investigators have implicated SAM in many unusual and diverse radical-based transformations.