SBIR Phase I: A Natural Product Drug Discovery Platform Based on High-Throughput Elicitor Screening (HiTES)

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The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project will be the development of a novel, small-molecule drug discovery platform that triggers the production of cryptic microbial metabolites for use as new pharmaceuticals with the potential to target a range of diseases. This technology will address pain points associated with the development of new drugs, such as long timelines and high costs. By using a proprietary process and established collection of elicitor molecules, microorganisms can be compelled to generate natural products that offer biological activities that may be impossible with synthetic molecules. The proposed technology is the only screening platform that is free of genetics and cloning, focusing on bioactivity first, and enabling rapid and efficient biomolecule discovery. Initially the platform will be used to target the antibiotic/antiviral market, with future applications for anti-tumor and immunosuppressant drugs. This project has the potential to improve the health of the American public by providing a steady stream of novel drug candidates to address a range of unmet medical needs. This Small Business Innovation Research (SBIR) Phase I project aims to develop a novel, small-molecule drug discovery platform based on High-Throughput Elicitor Screening (HiTES), a rapid, simple method for triggering production of microbial cryptic metabolites and interrogating their activities without the need for genome sequencing, cloning, or genetics. There is a large untapped store of natural products in the form of ‘cryptic’ biosynthetic gene clusters encoded in microbial genomes that are not expressed under laboratory conditions. The technical objectives are to increase output/throughput of the platform, assess and optimize chemical diversity, and expand the platform to new antibiotic-resistant pathogens of public health concern. Silent genes across multiple bacterial species will be activated to generate cryptic metabolites with the goal of producing 5,000 induced metabolomes, which will be characterized using mass spectrometry. A workflow will be created that integrates bioactivity assays against multiple pathogens with HiTES screening. Finally, in-house software will be updated to include prioritization in terms of novel chemistry, desired bioactivity, and lack of cytotoxicity. Successful Phase I completion will demonstrate the ability to implement and use HiTES multiplexed with bioactivity studies and software to identify chemically-novel and unique compounds with promising bioactivities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.