Our library of ~50,000 (and growing) natural product extracts (NPEs) contains unmatched chemical diversity available for screening by drug discovery researchers in the United States and worldwide. The library is gnomically and chemically mapped and incorporated into our chemoinformatic platform for rapid deconvolution and discovery. The NPE library is prepared using a data-intensive 14-step process called the "E-PurE: Extracts to Pure Entity" approach, which includes:
- Microbial isolation from diverse geographical sources and growth media conditions to maximize chemical diversity
- Extraction of NPEs using high-grade organic solvents and specialized in-situ resin capture methodology to capture a wide range of drug-like molecules
- Chromatographic fractionation of crude NPEs into four sub-fractions to enrich bioactive molecules and remove nuisance compounds
- Formatting of NPEs and fractions into barcoded 384-well plates for high-throughput screening
- Acquisition of LC-MS/MS chemical profiles for all NPEs to enable dereplication of known compounds and identification of novel chemotypes
- Integration of NPE chemical profiles with microbial genome sequencing data to pair bioactive NPEs with their encoding biosynthetic gene clusters.
- Deposition of NPE plates and associated metadata into screening collections for broad access by the scientific community
The E-PurE approach provides an efficient and reproducible workflow to convert microbial cultures into enhanced NPE libraries amenable to modern high-throughput screening and cheminformatic approaches to accelerate natural product-based drug discovery.
