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

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，到目前为止，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。通过一套新开发的元基因组学技术，这一合作项目旨在帮助更好地理解天然产品的共生。我们将研究psymberin的化学生态、进化和遗传学，psymberin是一种非常有前途的抗癌药物，对实体瘤细胞具有选择性活性。Psymberin，分离自一株Psammocinia sp.海绵，是甲虫和海绵中发现的聚酮的Pederin家族的成员。我们对这一合作的贡献是从海绵元基因组中分离出携带psymberin生物合成基因的基因组区域，并以先前关于共生pederin和onnamide生产者的序列数据为指导。然后对这些基因进行分析，以推断进化和分类信息，最后在可培养的宿主中异源表达，以产生可持续的psymberin来源。

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.