The bacterium Streptomyces coelicolor M145 reacts to transition-metal-ion stress with myriad growth responses, leading to different phenotypes. In particular, in the presence of Co 2 + ions (0.7 mm) S. coelicolor consistently produced a red phenotype. This phenotype, when compared to the wild type, differed strongly in its production of volatile compounds as well as high molecular weight secondary metabolites. LC-MS analysis revealed that in the red phenotype the production of the prodigiosins, undecylprodigiosin and streptorubin B, was strongly induced and, in addition, several intense signals appeared in the LC-MS chromatogram. Using LC-MS/MS and NMR spectroscopy, two new prodigiosin derivatives were identified, that is, coeligiosin A and B, which contained an additional undecylpyrrolyl side chain attached to the central carbon of the tripyrrole ring system of undecylprodigiosin or streptorubin B. This example demonstrates that environmental factors such as heavy metal ion stress can not only induce the production of otherwise not observed metabolites from so called sleeping genes but alter the products from well-studied biosynthetic pathways.In their natural environment, microorganisms such as Actinomyces have to cope with changing and sometimes adverse conditions. Microorganisms not only rapidly adapt under evolutionary pressure [1] but their genomes contain a great repertoire of secondary metabolite genes [2] that can ensure their survival.Actinomyces are most well-known for their secondary metabolites, such as polyketides or non-ribosomal peptides, many of which turned out to be of invaluable pharmaceutical use, for example, as antibiotics. [3] The variation of fermentation conditions has been intensively used in order to optimize the production of secondary metabolites in biotechnological processes.[4] Bode et al. systematically varied growth conditions in order to induce the formation of diverse secondary metabolites in a selected Streptomyces strain and termed their approach OSMAC (one strain many compounds).[5] With the genome sequencing of many Actinomyces such as the model Streptomycete Streptomyces coelicolor A3(2), [6] it became evident that these antibiotic producers comprise a lot more secondary metabolite gene clusters than secondary metabolites that have been identified from them. [2,7] Clearly, the maintenance of secondary metabolite gene clusters and their formation is costly for the producing strains.[8] In contrast to laboratory cultivation under optimized growth conditions, in their natural environment microorganisms have to cope with biotic and abiotic stress factors, for example, competition for space and nutrients. In such scenarios secondary metabolites are likely specifically and flexibly produced to ensure survival under varying and challenging growth conditions. In nature, therefore, microorganisms most likely produce secondary metabolites from "silent gene clusters" to react to their environment. Biotic and abiotic factors influence the microorganisms, leading to morpholo...