Synthetic biology platform for enhancing microbial natural product yields

Overview

Varigen Biosciences has developed a proprietary synthetic biology platform focused on capturing, manipulating, and expressing large biosynthetic gene clusters (BGCs) from microbial genomes. This technology enables rapid identification and production of novel natural product metabolites and peptides with bioactive properties, including activity against viral and microbial pathogens affecting plants and insects. By mining over 1,200 sequenced Bacillus genomes, Varigen is unlocking access to an enormous repository of evolutionarily selected compounds that remain inaccessible through traditional culture-based screening methods.

The platform addresses a critical bottleneck in natural product discovery by enabling two complementary approaches: sequence-based analysis of genomic DNA followed by CRISPR/Cas9-mediated precision cloning and inducible expression of pathways, and functional testing of compounds produced by individual clones of metagenomic libraries. This dual capability accelerates the de-orphaning of product metabolites and their associated biosynthetic pathways.

Technical specifications

Core capabilities:

• Capture and expression of large biosynthetic gene clusters spanning 13-110 kb
• CRISPR/Cas9-mediated precision cloning for pathway manipulation
• Inducible expression systems for controlled metabolite production
• Bioinformatic mining of over 1,200 sequenced Bacillus genomes
• Functional screening of metagenomic library clones
• Pathway engineering for enhanced production yields
• Metabolite modification capabilities

Current portfolio:

• Nine BGCs currently being expressed for diverse bioactive functions
• Over 100 natural product pathways cloned and expressed for dozens of customers
• Focus on metabolites and peptides active against viral and microbial pathogens of plants and insects

Applications:

• Agricultural pathogen control
• Novel antimicrobial discovery
• Bioactive peptide production
• Pathway optimization for industrial-scale production

Technology readiness level

The platform has been validated through the successful cloning and expression of 100 natural product pathways for multiple customers, demonstrating commercial viability and reproducibility. Varigen is currently mining over 1,200 sequenced Bacillus genomes and actively expressing nine biosynthetic gene clusters spanning 13-110 kb for diverse bioactive functions. Future validation efforts include collaborative work with an industry partner to identify priority pathways for metabolite production and engineer these pathways for overproduction or modification. The technology is positioned for partnership-driven advancement toward agricultural and pharmaceutical applications.