New Ways to Discover, Investigate, and Detect Bacterial Natural Products and their Biosynthetic Pathways

November 13, 2015

Charles Melancon

     Natural products – structurally complex, naturally-occurring organic molecules that often possess useful bioactivities – are critical as a source of new drugs and drug leads for the treatment of microbial and viral infections and cancers, and of probes for interrogating cellular pathways. With the rise of multi-drug resistant microbial pathogens, deadly viruses, and cancer cells lines that are recalcitrant to treatment posing serious threats to human health, it is critical that we continue to discover new natural product drugs to combat these diseases.
     However, standard methods for discovering, producing, and elucidating the mechanisms of action of natural products have a number of limitations, including high compound rediscovery rates, an inability to access cryptic compounds, and a lack of convenient assays that report directly on drug-target interactions. Continued advances in our understanding of both the biosynthesis and mechanisms of action of natural products, when coupled with the emergence of the fields of genomics and synthetic biology, offer tremendous opportunities to overcome these limitations and accelerate progress in natural product discovery through integrated multi-disciplinary and holistic approaches.
    Over the past 5 years, my group has undertaken an ambitious and multi-disciplinary research program aimed at developing new tools and methods for 1) discovering natural products and the biosynthetic gene clusters responsible for their production, 2) investigating the enzymological details of natural product biosynthesis, and 3) detecting and quantifying the effects of interactions between natural products and their targets. Advances we have made in each of these three research directions as well as ongoing work and future plans will be discussed.