Why Natural Products?

Natural products (NPs) have been exquisitely tailored via evolution to elicit potent and unique biological activities, rendering them unrivaled in structural complexity and diversity.  Accordingly, NPs have served as drug leads for the pharmaceutical industry, affording antibiotics and anticancer compounds, greatly improving the quality of life for humanity.  Of the FDA-approved small molecule therapeutics, 67% of anti-infective and 83% of anti-cancer drugs are NPs, NP derivatives, or inspired by NPs.  Additionally, NPs have a good track record for uncovering new biology relevant to drug discovery.  They are uniquely biased to bind protein folds, and as such, NPs and their derivatives have provided unique chemical matter for disrupting protein-protein interactions.  The targets and mechanism for NPs are often novel and unanticipated.  Phenotypic or high content screens are best positioned to detect agents of such unanticipated mechanism, the rationale being that these formats offer the full complement of cellular components that might be used in a novel NP mechanism.

Bacteria and fungi are prolific resources of NPs.  Among the half million of NPs known to date, ~70,000 of them are of bacterial and fungal origin, with approximately half (~33,500) have been shown to be bioactive.  Of the 70,000 total, ~30,000 are from fungi and ~40,000 have been isolated from bacteria, of which about half (~20,000) are from actinobacteria.

Chart of natural product drugs

Since the launch of the Natural Products Library Initiative (NPLI) at The Scripps Research Institute (TSRI) in 2011, we have now assembled one of the largest known collections of NP producing microbial strains in the world.  This resource provides an outstanding opportunity to identify new leads in biologically active chemical space and serves as the inspiration to launch the Natural Products Discovery Ceneter (NPDC) at Scripps Research.