<jats:title>Golden Regulator</jats:title> <jats:p> <jats:italic>Staphylococcus aureus</jats:italic> is a common cause of intractable infections that are exacerbated by an array of toxins and virulence factors. The <jats:italic>agr</jats:italic> pheromone has been thought to represent the master regulator of virulence in this pathogen, but it is not always expressed and is also found in many nonpathogenic cocci. A strictly conserved, nonribosomal peptide synthetase has now been found by <jats:bold> Wyatt <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="294" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1188888">294</jats:related-article> , published online 3 June) by genome mining. The enzyme assembles valine and tyrosine into cyclic dipeptides called aureusimines that are expressed by all sequenced strains of <jats:italic>S. aureus</jats:italic> , including the “superbug” MRSA (Methicillin-resistant <jats:italic>Staphylococcus aureus</jats:italic> ). Microarray analysis showed a striking effect of mutation in the synthetase locus on the production of immunomodulators, hemolysins, and other exotoxins by the pathogen. Indeed, mice infected systemically with the mutant strain showed a restricted spread of infection compared with the wild type.