Marine Actinomyceten als neue Quelle für die Entdeckung von Medikamenten in der Krebstherapie

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The long-term goal of this research project is to identify novel agents for the treatment of cancer. The overall objective of this extension proposal is to continue and finish the isolation and structure elucidation of new natural products from previous activity-screened actinomycetes, which were isolated from ocean sediments. These plentiful, yet virtually unexplored, organisms have evolved to produce collections of chemically unique, bioactive metabolites. The central hypothesis is that groups of evolutionarily-related marine actinomycetes (phylotypes) produce related suites of molecules (chemotypes). This hypothesis could be substantiated during the last month by extensively studies of strain extracts derived from marine actinomycetes. Obtaining and explore new phylotypes in culture is an effective method for natural product discovery. Genome sequencing on these phylotypes reveals a complex secondary metabolome even beyond the observed chemotypes1. Our subsequent hypothesis is that stimulated activation of silent gene clusters will lead to production of so far not observed secondary metabolites. If both hypotheses prove to be true based upon the isolation of new natural products from these phylotypes, this research could dramatically increase the efficiency of microbial natural products discovery.