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<jats:title>Itaconate brings metalloenzyme to a halt</jats:title> <jats:p> Controlled radicals enable unusual enzymatic transformations, but radical generation and management require dedicated systems. Ruetz <jats:italic>et al.</jats:italic> investigated how the immunometabolite itaconate might undermine these intricate systems to inhibit propionate metabolism, a crucial metabolic pathway in pathogenic <jats:italic>Mycobacterium tuberculosis</jats:italic> (Mtb) (see the Perspective by Boal). They found that the coenzyme A (CoA) derivative of itaconate can irreversibly inhibit the enzyme methylmalonyl-CoA mutase (MCM), which uses the radical-generating cofactor adenosylcobalamin, or coenzyme B <jats:sub>12</jats:sub> . Itaconyl-CoA derails the normal radical reaction catalyzed by MCM, forming a long-lived, biradical species, which is incapable of completing the catalytic cycle and cannot be recycled by the endogenous coenzyme B <jats:sub>12</jats:sub> regeneration machinery. Itaconate blocks Mtb growth on propionate, and this inhibition mechanism may be relevant to how macrophages resist Mtb infection. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6465" page="589" related-article-type="in-this-issue" vol="366" xlink:href="10.1126/science.aay0934">589</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6465" page="574" related-article-type="in-this-issue" vol="366" xlink:href="10.1126/science.aaz4540">574</jats:related-article> </jats:p>