DFG-NSF-Antrag: Using the marine natural product psymberin as a discovery template for biosynthetic engineering and biosynthetic product investigation

DFG-NSF 应用：使用海洋天然产物薄荷素作为生物合成工程和生物合成产品研究的发现模板

• 批准号: 28792386
• 负责人: Professor Dr. Jörn Piel
• 金额: --
• 依托单位: Institut für Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/28792386?language=en
• 关键词: DFG; NSF; Antrag; Using; marine

There is overwhelming evidence that many bioactive natural products isolated from marine invertebrates are synthesized by as-yet unculturable bacterial symbionts. However, the elusive lifestyle of these microbes has so far precluded the systematic exploration of their pharmacological potential. With a set of newly developed metagenomic techniques, this collaborative project aims to contribute to a better understanding of natural product symbiosis. We will study the chemical ecology, evolution and genetics of the producer of psymberin, a highly promising anticancer agent with selective activity against solid tumor cells. Psymberin, isolated from a Psammocinia sp. sponge, is a member of the pederin family of polyketides found in beetles and sponges. Our contribution to this collaboration is the isolation of genomic regions carrying the psymberin biosynthesis genes from the sponge metagenome, guided by sequence data from previous studies on the symbiotic pederin and onnamide producers. The genes will then be analyzed to deduce evolutionary and taxonomic information and finally heterologously expressed in a culturable host to generate a sustainable psymberin source.

有压倒性的证据表明，许多从海洋无脊椎动物中分离出来的生物活性天然产物是由尚未培养的细菌共生体合成的。然而，迄今为止，这些微生物难以捉摸的生活方式阻碍了对其药理潜力的系统探索。该合作项目旨在利用一套新开发的宏基因组技术，为更好地理解天然产物共生做出贡献。psyberin是一种非常有前途的抗癌药物，对实体肿瘤细胞具有选择性活性，我们将研究psyberin的化学生态学、进化和遗传学。从沙马属海绵中分离出来的灵菊素是甲虫和海绵中发现的聚酮类pederin家族的一员。我们对这次合作的贡献是在先前对共生的pederin和onnamide产生物的研究序列数据的指导下，从海绵宏基因组中分离出携带psyberin生物合成基因的基因组区域。然后对这些基因进行分析，以推断进化和分类信息，并最终在可培养的宿主中异种表达，以产生可持续的心理素来源。