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

这个研究项目的长期目标是找出治疗癌症的新药物。本扩展提案的总体目标是继续并完成从海洋沉积物中分离出的活性筛选放线菌的新天然产物的分离和结构阐明。这些数量众多，但实际上尚未开发的生物已经进化到产生化学上独特的生物活性代谢物。核心假设是进化相关的海洋放线菌群（种型）产生相关的分子套件（化学型）。在过去的一个月里，对从海洋放线菌中提取的菌株进行了广泛的研究，证实了这一假设。在培养中获得和探索新的种型是发现天然产物的有效方法。这些种型的基因组测序揭示了一个复杂的次级代谢组，甚至超出了观察到的化学型1。我们随后的假设是，受刺激的沉默基因簇的激活将导致迄今未观察到的次生代谢物的产生。如果这两个假设都被证明是正确的，基于从这些种型中分离出新的天然产物，本研究将大大提高微生物天然产物的发现效率。

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.