Innovations in strain prioritization to streamline natural product discovery

Natural products remain the best sources of drugs and drug leads and serve as outstanding small-molecule probes to dissect fundamental biological processes.  A great challenge for the natural product community it to discover novel natural products efficiently and cost effectively.  Traditional natural product discovery programs are not sustainable, demanding too much time, effort, and resources.  In spite of the rapid advances in DNA sequencing technologies and bioinformatics, sequencing all strains and annotating all genomes within a collection is not a practical means to discover new natural products.  As the size of strain collections continues to grow, innovations in strains prioritization are clearly needed.  Resources could then be devoted preferentially to the strains that hold the highest promise in producing novel natural products.  Rapid strain prioritization could fundamentally change how microbial natural products are discovered.  The connection between natural products and the genes encoding their biosynthesis has now been well recognized, and genes, as well as chemistry, are increasingly being exploited to categorize known natural products and discover new ones.  Selected examples from our current efforts in developing methods to prioritize actinomycetals, thereby identifying the most promising strains for targeted discovery of novel natural products will be discussed.