Exploitation and total synthesis of new microbial sphingolipid-type signaling molecules (EXSPHINGO)

我们的目标是进行一个多学科的研究方法的结构和功能分析的新的化学介质，这是参与特定的微生物-宿主相互作用的调制。在这个项目的框架中，我们的具体目标是详细的化学表征的未开发类的细菌鞘脂和磺脂类分离的拟杆菌门的成员，已被发现，以调节发病的发展在一个最接近的生活亲属的动物，choanoflagellate Salpingoeca rosetta。我们将应用最先进的有机和天然产物化学方法来（1）通过新的，模块化和原子经济的全合成来证明分离的前所未有的微生物鞘脂和磺脂的结构分配，（2）使合成获得功能化衍生物，（3）促进从预选的细菌菌株中分离新型鞘脂和磺脂，以及（4）与其他小组合作，基于生态学和药理学相关的分析，对合成和分离的化合物进行功能分析。我们的研究受益于不同研究主题之间的强大协同作用。我们将建立新的和有效的合成程序，第一次全合成迄今未报道的细菌磺酰脂质，并使用已建立的S.基于Rosetta细胞的测定。从长远来看，我们的方法将深入了解细菌鞘脂的内在和生态作用，促进更好地了解真核生物可以感知和响应细菌小分子信号的机制，也可能为新的医疗干预措施的发展提供信息。

Our objective is to perform a multidisciplinary research approach for the structural and functional analysis of novel chemical mediators, which are involved in the modulation of specific microbe-host interactions. In frame of this project, we specifically aim for a detailed chemical characterization of the unexplored class of bacterial sphingo- and sulfonolipids isolated from members of the Bacteroidetes phylum, which have been found to regulate an onset of development in one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. We will apply state-of-the-art methodologies of organic and natural product chemistry to (1) proof the structural assignment of isolated unprecedented microbial sphingo- and sulfonolipids by a new, modular and atom-economic total synthesis, (2) enable synthetic access to functionalized derivatives, (3) promote the isolation of novel sphingo- and sulfonolipids from preselected bacterial strains, and (4) perform a functional analysis of synthesized and isolated compounds based on ecological and pharmacological-relevant assays in collaboration with other groups. Our research benefits from strong synergies between different research topics. We will establish new and efficient synthetic procedures, the first total synthesis of so far unreported bacterial sulfonolipids, and an extensive structure-function analysis of sulfonolipids and derivatives using an established S. rosetta cell-based assays. In the long-term, our approach will provide insights into the intrinsic and ecological roles of bacterial sphingolipids, promote a better understanding of the mechanisms by which eukaryotes can perceive and respond to small molecule signals from bacteria, and may also inform the development of new medical interventions.