Currently the rate of discovering commercially relevant bioactive small molecules from common actinomycete sources has decreased as this practice frequently leads to the re-isolation of previously described secondary metabolites (1). Therefore, during the last years the selective isolation of rare and uncommon actinomycetes from extreme and neglected environments has become the centre of attention of microbial drug discovery programs. Underexplored habitats, such as marine ecosystems, deep-sea sediments and insect-associated actinomycetes represent a rich source of novel strains with the capacity to biosynthesise new/novel microbial metabolites (2, 3). Fifty actinomycete isolates belonging to three taxonomic families of the order Actinomycetales and isolated from the wood-feeding termite Coptotermes lacteus were subjected to phylogenetic and chemical investigations. The isolates were first tested for their ability to produce bioactive metabolites using small-scale fermentation conditions. Ten different liquid cultures conditions were tested in order to determine the best condition that triggers the production of secondary metabolites with new chemical structures. Based on the fermentation outcomes a dereplication strategy for the analysis of the actinomycete metabolome was developed using HPLC-LCMS-NMR based approaches. Chemical profiling of the extracts identified five strains producing unique secondary metabolome fingerprints. Large-scale fermentations as well as co-cultivation methods (where the strains are paired against each other to reveal possible changes in metabolite production) are being performed on these selected isolates. The generated crude extracts are being examined for the presence of new structurally diverse microbial natural products.