The chemical origins of biological interactions: an evolutionarily refined approach for natural products discovery

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One of the greatest challenges we currently face is the development of antibiotic-resistance in human pathogens. In the past, scientists have harvested a large number of antibacterial and antifungal molecules from microbes found in the soil. These molecules that are isolated from natural sources are referred to as natural products. Because many natural products are structurally complex, they often have useful bioactive properties. Indeed, the structures of natural products form the inspiration for the majority of successful drug candidates. However, both the pharmaceutical industry and academia have realized that searching for natural products using standard procedures (e.g. isolating soil microbes) is labour-intensive and often leads to rediscovery of known compounds. In this proposed research, we will develop novel techniques to identify new biologically-active drug-like molecules from natural sources at a lower cost and higher success rate. To achieve this goal, we will study multiple microbes isolated from the same biological environment (e.g. the human gut, the hives of social insects) where they have naturally grown and been in competition with each other for the same resources. We will develop a test in the lab to see which microbes can most successfully kill off other microbes isolated from the same source, and then determine which natural products are responsible for this killing activity. This work is extremely important for providing new developments in drug discovery and antibiotics resistance research. The new molecules we find will serve as targets for other chemists to synthesize and modify; the molecules will also serve as drug leads for biochemists, microbiologists and pharmacologists to further test and explore. If our new natural products show promising biological activity, we will patent the compounds before pursuing commercial development. The anticipated outcomes of this research would promote not only the scientific community of Canada, but also its economic interests. Successful development of any new natural products into usable drugs would have a global impact and ultimately benefit the general public.