Ribosomal natural products from the human oral microbiome

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The project deals with the characterization of new natural products from the human oral microbiomeDuring the survey and characterization of the human microbiome a lot of bacterial genomes were sequenced. In the search for gene clusters for new natural products, in two genomes of members of the actinomycetales, several gene clusters encoding for different ribosomal synthezised natural products (lantipeptides, lasso peptides, linaridins) were found. The putative lasso peptide gene cluster shows unusual features: Up to twelve, but at least five precursor peptides are encoded next to each other, adjacent to a processing enzyme, an asparagine synthetase. This enzyme thus seems to have a great substrate promiscuity. In the course of this project, as many as possible of the up to 17 predicted natural products should be characterized and their structure elucidated. This should be done initially with mass spectrometric methods as Nano-DESI-MS. The Moore and Dorrestein labs have lots of experience with the mass-spectrometry based characterization of peptides combined with bioinformatic methods. Interesting candidates should be tested against different biological targets and their structure should be fully elucidated with NMR spectroscopy. Additionally, the putatively promiscuous asparagine synthetase should be further characterized and the promiscuity should be exploited, to synthesize new unnatural natural products. Another part of the project deals with the characterization of the symbioses of the human oral microbiome bacteria: The metabolic interactions of bacterial strains should be elucidated by cocultivations and subsequent MALDI imaging mass spectrometry and molecular networking analysis. Additionally, more of the sequenced genomes of the oral microbiome should be searched systematically for further natural product gene clusters and possibly missing biosynthetic pathways from the primary metabolism to further characterize the symbioses.