Synthesizing heme and some vitamin and antibiotic compounds requires enzymes that mediate radical chemistry. But enzymes must carefully control radical compounds, lest they escape and wreak havoc within a cell. A study suggests a new role for an iron-sulfur cluster in one superfamily of 100,000 enzymes that use S-adenosylmethionine (SAM) to catalyze radical reactions. Researchers knew from earlier studies that the cluster cleaves SAM to produce 5′-deoxyadenosyl radical (5′-dAdo•). Now, they have discovered that the cluster also binds 5′-dAdo through an Fe–C bond (Science 2016, DOI: 10.1126/science.aaf5327). A team led by Joan B. Broderick of Montana State University and Brian M. Hoffman of Northwestern University trapped a reaction intermediate of pyruvate formate-lyase activating enzyme, which uses SAM to generate a glycyl radical on the target lyase. They used electron nuclear double resonance spectroscopy to study the intermediate and found that it is an organometallic species, with a covalent link between the 5′-C of 5′-dAdo and an iron atom of the cluster. Although it is unclear whether other radical SAM enzymes follow the same mechanism, this scheme echoes that of enzymes that use vitamin B-12 (adenosylcobalamin) to conduct radical chemistry.