Griselimycin was discovered in two Streptomyces bacteria strains in 1960, but the peptide-based bacteria killer never quite gained a foothold in the clinic because of its poor pharmacokinetics. Although a methyl analog showed promise as a weapon against Mycobacterium tuberculosis, the causative agent of tuberculosis, it was too quickly metabolized in humans, among other problems, to be able to launch an effective attack on the pathogen. A team led by Rolf Müller of the Helmholtz Institute for Pharmaceutical Research Saarland, in Germany, has now modified griselimycin with a cyclohexyl group on a proline ring to give it a longer half-life and revive the molecule as an antibiotic candidate (Science 2015, DOI: 10.1126/science.aaa4690). Beyond developing the synthesis of the modified peptide, the researchers discovered that the bacterial target of griselimycin is a protein called DNA polymerase sliding clamp, which is involved in DNA replication and repair. They also crystallized the DNA-griselimycin complex to locate the hydrophobic pocket where the antibiotic chokes its target.