Synthetic biology tools for biosynthesis of small molecules

Fungi are prolific producers of bioactive small molecules known as secondary metabolites. These fungal secondary metabolites have been the source of medicines, including important clinical drugs such as the antibiotic penicillin and the cholesterol-lowering statins. Recent genome sequencing efforts have revealed a large number of gene clusters encoding unknown secondary metabolite biosynthetic pathways in fungi. Thus, there are immense opportunities for discovery of novel molecules from these sequenced fungal genomes for application in medicine and agriculture.

At the same time, there is increasing interest in engineering microbes as chemical factories for sustainable production of pharmaceutical drugs, fine chemicals and fuels. This will involve constructing and engineering novel pathways in the microbial cells in a way that will maximise production, but with minimum impact on cell growth.

The production of secondary metabolites in fungi involves orchestrating multiple genes encoding various biosynthetic enzymes, and often orthogonally, in response to specific environmental signals. The translated biosynthetic enzymes then come together to catalyse a series of biochemical reactions required to make the desired molecules.

Can we learn from fungi to develop better tools for engineering microbes?

By learning from fungi, we hope to hijack the genetic circuits of fungal secondary metabolite pathways as tools for engineering eukaryotic cells (yeast and filamentous fungi), for production of useful chemicals and for discovery of novel molecules from fungal genomes.

For more background information, see the suggested readings below.