Varigen Biosciences Corp

Multi-omics and Synbio Enabled Discovery of Antifungal Fernene Triterpenes - Project Summary. a New Functional Metabologenomics Approach Is Proposed for the Development of a Second Generation of Fernene-based Antifungal Terpenes. Our Team Led by Mead (varigen), Keller (university of Wisconsin) and Kelleher (northwestern University) Explore the Diversity of This Unique Family of Triterpenes Using a Fusion of Technologies That Unites Genomics With Metabolomic Understanding of Fungal Terpene Synthesis. We Begin by Applying a Genome Mining-driven Approach to Find New Natural Analogs of Enfumafungin. the Resulting Data Are Then Integrated With Metabolomic Analysis and Antifungal Bioactivity Assay Data to Establish the Putative Enfumafungin-like Metabolites Encoded by Diverse Strains and Ultimately Chart the Structure-activity Relationship Space Within This Potent Class of Antifungals. in Parallel, Our Team Is Constructing a Modular Platform Capable of Generating Hundreds of Different Analogs in Functional Amounts. Here, We Will Heterologously Express the Enfumafungin-like Pathways From Fungal Strains in an Engineered Aspergillus Nidulans Host. the Sequence- Specific Cloning and Heterologous Expression of Lead Molecules Discovered in This Program Will Establish Methods to Conduct Targeted Swapping of Cyclase Genes Across Multiple Species to Generate New Antifungal Fernene-like Scaffolds. the Long-term Goal, Requiring Additional Resources, Is to Advance a Second Generation of Triterpene Antifungal Analogs Into the Research and Clinical Market Place. Overall, This Program Provides an Important Next Step Towards Establishing Functional Metabologenomics as a Viable Tool to Go From Genome to Functional Therapeutic. as a Testbed, We Turn to a Natural Product Family With a Recent History of Clinical Utility for the Development of New Analogs and Technologies to Access Them.