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

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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.