Although there are a large number of antibiotics currently in clinical use, many of them are becoming less effective as a result of drug resistance developed by some pathogenic strains of bacteria.1 One such antibiotic is rifampin (rifampicin), an antituberculosis drug derived from rifamycins, which exhibits its antibacterial activity through inhibition of the bacterial RNA polymerase.2 Mutations affecting the â subunit of RNA polymerase can confer bacterial resistance to rifampin.3 In our effort to search for new bacterial RNA polymerase inhibitors that may be used as broad-spectrum antibiotics, we have chemically investigated the bioactive organic extract of the liquid culture of a Streptomyces strain (NRRL 21611) isolated from a soil sample collected in DeSoto Falls, GA. The polymerase inhibitory component in this extract was found to be salinamide A (1), a recently-reported4 unusual bicyclic depsipeptide from a Streptomycete that was found on the surface of a marine jellyfish. From the extract of this Georgia soil strain, we also isolated a new cyclohexapeptide, which we gave the name desotamide (2). In this paper, we report the bioactivity of salinamide A and the structure elucidation of desotamide.