Heterologous expression of fungal biosynthetic gene clusters (BGCs) for production of secondary metabolites
The discovery of novel natural compounds (secondary metabolites) remains a central goal in biotechnology and fungi are particularly prolific producers of these compounds. Many of natural products are encoded by biosynthetic gene clusters (BGCs), which provide a roadmap for discovering and producing new natural products. Yet, with only about 10% of fungal species described and even fewer cultured, our capacity to uncover their full potential remains limited. To address this gap, novel approaches are urgently needed to unlock and harness the wealth of novel natural products produced by fungi.
The innovation of this project lies in combining several axes into a single integrated approach: genomics, to localize genes that encode interesting natural products; genome engineering, to modify the host and drive the production of metabolites previously identified as promising; and metabolomics, to identify and characterize the resulting compounds, linking genetic information to actual metabolite profiles. In short, this project proposes to establish a bioprospecting platform through the heterologous expression of entire BGCs in a genetically tractable host (chassis).
This project seeks to develop new approaches for producing fungal natural products, with the potential to reveal novel structures and functions that could drive future applications. Once produced, fungal metabolites can be systematically screened for antimicrobial or pharmaceutical activity. Promising candidates may then be developed into products that deliver direct benefits: from improving agriculture to advancing human and animal health.