Waters Award for Excellence in Natural Products Innovation: Dealing with dark matter(s) in the ocean: Challenges and opportunities

Abstract

Due to longer evolutionary history, highly competitive environments with complex ecological interactions and unsurpassable biological diversity, marine organisms have proven to be outstanding sources for potent and chemically diverse molecules for discovery of drugs and functional ingredients. However, these efforts are severely hampered due to low supply, legal and physical access issues and chemical complexity of marine natural products for rapid dereplication and/or full structure elucidation. Another major problem for the exploitation of marine natural products (MNPs) is the ambiguity of their metabolic (natural) source. Although most MNPs are reported from marine invertebrates, 16 of the 20 MNPs that are or were recently undergoing clinical trials against cancer have their origin in (symbiotic) microorganisms [1]. However, less than 1% of the estimated microbial diversity is cultivable, and many biosynthetic gene clusters within this 1% largely remain silent or underexpressed in artificial laboratory conditions [2]. As a result, vast majority of marine secondary metabolites escape detection/annotation and their potential for discovery remain in total darkness. Hence, efficient marine biodiscovery requires innovative approaches and a great analytical chemistry infrastructure. This presentation will describe our efforts for identification of metabolic and microbiome profile of deep-sea organisms and some aquacultured shellfish species. Our on-going studies to promote chemical diversity of marine microbes by employing OSMAC and co-culturing techniques and visualization/localization of MNPs by chemical imaging will also be highlighted.