Bioinformatics-driven discovery of novel compounds using metabolomics and CRISPR
A cutting-edge approach combining bioinformatics, metabolomics, and CRISPR technology to discover novel compounds by analyzing biosynthetic gene clusters (BGCs). This method aims to identify and activate silent BGC pathways, advancing compound discovery and potential applications.
Overview
This innovative approach leverages the integration of bioinformatics, metabolomics, and CRISPR technology to discover novel compounds through the analysis of biosynthetic gene clusters (BGCs). By comparing BGCs from target strains with known sequences and related strains, this method identifies potential novel compounds. The approach further explores the activation of silent BGC pathways using digital-RTPCR and CRISPR editing, with options for heterologous expression to overcome challenges in pathway expression.
Technical specifications
- Bioinformatics and Database Utilization: Utilizes a comprehensive graph database of sequenced proteins, BGCs, and species to hypothesize likely products and identify novel "singletons."
- Metabolomics Integration: Employs untargeted metabolomics to detect unique masses in co-cultures and identify analogs using GNPS.
- CRISPR Technology: Develops CRISPR tools for BGC manipulation in non-model bacteria, including BGC knockout and regulator manipulation.
- Activation of Silent Pathways: Uses digital-RTPCR for culture condition screening and CRISPR strategies for BGC activation.
- Heterologous Expression: Offers fallback option for expressing pathways from novel bacteria.
Technology readiness level
The technology is currently at TRL 2, indicating that the concept and application have been formulated, with ongoing development and validation efforts to advance its readiness for practical applications.
About University of Wisconsin, Madison
The University of Wisconsin–Madison is the state’s flagship public research university, a comprehensive institution with a large research enterprise and broad disciplinary breadth. Industry engages through shared instrumentation, pilot‑scale testbeds, and co-located core facilities that support prototyping and scale-up. An affiliated research and technology park hosts startups and corporate R&D, while integration with a major hospital system enables clinical translation; a statewide extension network connects campus advances to companies and communities across Wisconsin. Research is sustained by competitive federal funding from agencies such as NIH, NSF, DOE, USDA, and DoD, alongside state and industry partnerships. Dedicated commercialization support—through an affiliated foundation and campus offices—provides IP management, licensing, startup mentoring, and flexible, industry-friendly agreements.
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