Investigating natural product biosynthetic pathways in the microbiomes associated with long-lived aquatic vertebrates

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It has recently been recognized that the important contribution of beneficial microbiomes to the prolonged lifespan of their animal hosts. In our efforts to identify key bacteria, metabolites and biosynthetic genes that may contribute to the longevity of aquatic animals, we initially obtained bacterial isolates from long-lived animals, such as chitons (lifespan ~40 years) and a Japanese rockfish (lifespan >90 years). We isolated and purified metagenome from each chiton sample. Subsequent PCR-cloning and sequencing led to the detection of a biosynthetically promising bacterium in the metagenome from two of five studied chiton samples. We isolated ~430 bacterial strains from different parts of individual chitons and tested them for antibiotic resistance. It was found that ~109 bacterial strains showing resistance to certain antibiotics, which were subsequently subjected to PCR-cloning to detect strains with biosynthetic potential. These screening efforts to identify biosynthetically promising bacteria are still on going. This is in collaboration with the Lab of Prof. Joern Piel (ETH Zurich) to complement with their work on the bacterial chemistry. Using known sponge-derived compounds, we optimized the screening protocol for testing the ability of compounds to stimulate lifespan extension in the organism model Saccharomyces cerevisiae. This was based on monitoring proteasome activity of yeast lysates after being treated with tested compounds in comparison with the positive control (proteasome-stimulating compounds) and the negative control (proteasome inhibitor).