Biologists at the Washington University in St. Louis are using comparative metabologenomics to try to uncover what may be “silencing” Streptomyces (the bacteria responsible for the first bacterial antibiotics to treat tuberculosis back in the 1940s) and preventing it from producing desirable compounds encoded by its genes. The study highlights comparative metabologenomics as a powerful approach to expose the features that differentiate strong antibiotic producers from weaker ones.