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

海洋放线菌作为癌症治疗药物发现的新来源

• 批准号: 61929451
• 负责人: Professorin Dr. Sandra Lösgen
• 金额: --
• 依托单位: Whitney Laboratory for Marine Bioscience
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/61929451?language=en
• 关键词: Marine; Actinomyceten; als; neue; Quelle

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.

该研究项目的长期目标是寻找治疗癌症的新药。该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先前活性筛选的放线菌中新天然产物的分离和结构阐明。这些丰富但几乎未经探索的生物体已经进化产生化学上独特的生物活性代谢物的集合。中心假设是，进化相关的海洋放线菌群（系统型）产生相关的分子套件（化学型）。这一假设可以在上个月通过对海洋放线菌菌株提取物的广泛研究得到证实。在培养物中获得和探索新的系统发育型是发现天然产物的有效方法。对这些系统型的基因组测序揭示了复杂的次级代谢组，甚至超出了观察到的化学型1。我们随后的假设是，沉默基因簇的刺激激活将导致迄今为止未观察到的次生代谢物的产生。如果基于从这些系统型中分离出新的天然产物，这两个假设被证明是正确的，那么这项研究可以极大地提高微生物天然产物的发现效率。