- Antimycins are made by Streptomyces bacteria and inhibit the final stage in electron transport by inhibiting the mitochondrial cytochrome c oxidase. This makes them bioactive against a wide range of organisms but they have also recently been shown to be potent and specific inhibitors of the Bcl-2/BclxL family of anti-apoptotic proteins which are over-produced in drug-resistant cancers. We recently cloned and characterised the gene cluster that encodes antimycin biosynthesis from Streptomyces albus S4 and showed that it is encoded by four operons, antAB, antCDE, antFG and antHIJKLMNO. The antA gene encodes a unique RNA polymerase sigma factor that is dedicated to regulating biosynthesis of the unusual precursor for antimycin bioasynthesis by activating expression of the antFGHIJKLMNO genes. AntA is encoded by all seven known antimycin biosynthetic gene clusters and the antFG and antHIJKLMNO promoters of all seven clusters contain AntA binding sites, suggesting a conserved regulatory mechanism. Although only seven clusters have been identified more than 40 antimycins are known and production of antimycins is widespread in Streptomyces species. Given the recent interest in antimycins as anti-cancer agents we are planning to isolate more antimycin gene clusters and examine the diversity of these biosynthetic pathways and products in different streptomycetes. This is likely to lead to the discovery of new antimycins with increased anti-cancer activities and to facilitate pathway engineering to develop modified antimycins.