Genome Mining of the Tumor Microbiome Reveals Biosynthetic Diversity and Potential Tumor-modulating Metabolites
Human tumor-associated microbes -- the tumor microbiome -- have demonstrated an increasingly important role in human health due to their relevance to cancer progression and treatment response. While the metabolism at the host-microbiota interface, such as in the human gut, has been extensively investigated in recent years, the specialized metabolites from the tumor microbiome remain uncharted…
Human tumors harbor a diverse community of microbes, collectively known as the tumor microbiome. While research on the gut microbiome's metabolism has advanced, the tumor microbiome's specialized metabolites are still largely unknown. To explore this, scientists analyzed metagenome-assembled genomes from 3,526 human tumors, discovering 624 biosynthetic gene clusters that could produce tumor-relevant metabolites.
The research unveiled several known metabolites and potentially novel ones, spanning various biosynthetic classes. One standout finding involved a conserved family of biosynthetic genes from the Fusobacterium genus, known to play a role in cancer. By expressing these genes, researchers uncovered a new group of long-chain fatty acyl amides.
They then focused on one of these compounds, oleoyl {gamma}-aminobutyric acid, and discovered that it exhibits immunomodulatory properties and acts as a partial agonist for G-protein-coupled receptors. This suggests that such metabolites from Fusobacterium may influence tumor progression. These results provide a foundation for future studies on how tumor microbiome-derived metabolites might impact cancer.
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