The Nautilus Microbial Natural Product Discovery Process

Microbes are isolated from diverse geographic locations ranging from the tropics (e.g. Barbados and The Bahamas) to Canada's Arctic. To maximize the diversity of microbes within our collection, at each geographic location microbes are isolated from invertebrates, such as sponges and coral tissue, algae and sediment. A taxonomic dereplication step is utilized to ensure the microbial library contains unique organisms, thus increasing the value of the MNPB.

Microbes are cultured using a minimum of four proprietary conditions designed to upregulate natural product biosynthesis. Culture extracts are assessed in a UPLC-HRMS screening / dereplication step designed to rapidly identify fractions containing known natural products and ones that likely contain novel chemistry.Invertebrates are extracted and fractionated over C18 to generate six fractions which are stored in standardized amounts in 96-well plates and are also evaluated in our UPLC-HRMS screen. The invertebrate fraction library and microbial culture extracts are also evaluated in preliminary bioactivity screening in a wide panel of antimicrobial assays. When necessary, scale-up of fermentations can provide access to increased amounts of active natural products for additional biological characterization. Active fractions are subjected to activity-guided purification and pure natural products characterized using modern spectroscopic methods. A secure, web based data management system facilitates organization and searching of collection, taxonomy, chemical profiling and biological assays. Complete or partial access is available to partners. The MNPB has been established to work in partnership to develop products in defined sectors.