Marine microbial natural product discovery

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Summary The impact of natural products on modern society is indisputable given their importance to medicine. As one example, 42% of anticancer and 47% of anti-infective agents introduced over the past 25 years are natural products. While remarkable discoveries have been made, the rate of natural product discovery has declined in recent years, profoundly affecting the development of new therapeutics and the related pharmaceutical and biotechnology industries. The general aim of this proposal is to conduct basic research in natural products chemistry and associated microbiology to develop innovative methods to improve natural product discovery. Microbes (bacteria and fungi) will be the source of our natural products investigations and will be obtained from marine environments. Microbes are of great interest as they can generally be readily fermented to produce required amounts of natural product. The marine environment represents an underexplored resource for microbial natural product discovery thus improving the likelihood of isolating new compounds. While there has been substantial effort in natural product discovery for applications in human health, there has been much less effort in veterinary medicine. This project aims to identify new marine natural products with applications as antimicrobial agents for use in livestock animals, companion animals and horses. For ethical reasons, ‘last resort’ antimicrobials such as vancomycin are reserved solely for the treatment of MRSA infections in humans and are not to be used in animals; therefore, a pressing need exists in veterinary medicine for the discovery of novel antibiotics to treat infections caused by emergent drug-resistant pathogens. Overall, the proposal seeks to develop new methods for the isolation of marine-derived microbes thus allowing access to new sources of natural products. Further, it aims to develop new methods to induce natural product production in microbial fermentation and seeks to develop a new chemical tool to efficiently identify new natural products from large sets of complex mixtures. Lastly, antimicrobial assays of relevance to veterinary medicine will be used to guide the isolation and characterization of new natural products. Overall, this research program will develop research methods that will greatly enhance the rate of discovery of new bioactive natural products.