Abstract
The biosynthetic gene cluster (BGC) for penicillin was the first BGC to be discovered, over 30 years ago. It revealed the evolutionary principle of clustering microbial genes involved in secondary metabolite/natural product synthesis. Conservative estimates suggest the existence of over a million BGCs in the fungal kingdom alone. The immense therapeutic potential of this evolutionarily refined wellspring of potent, cell-permeant small molecules urges investment into its characterization. However, the sheer number of BGCs combined with their cryptic expression patterns present two rate-limiting challenges. The first is the accurate and comprehensive identification of diverse fungal BGCs (which can contain tens of genes) that encode therapeutically relevant molecules with activity against clinically validated targets. The second is the high-throughput capacity to forcibly express BGCs to produce the natural products encoded within. Hexagon Bio has built a world-leading platform to overcome these challenges and deliver valuable human medicines inspired by potent metabolites encoded within the Earth’s metagenome. This platform leverages extensive microbial genome sequencing, proprietary algorithms that predict the human and fungal protein targets of natural products, and high-throughput heterologous expression systems to produce fungal metabolites.
Published Version
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