Background
My research aims to combine bacterial genomics and chemical biology to guide natural product discovery and engineering. The vast and expanding databases of bacterial genomes provides an exciting opportunity to understand the evolution and diversity of natural products, providing novel insights into their biosynthesis.
Bacteria often group their genes together based on related functions such as the biosynthesis of specialised metabolites, known as biosynthetic gene clusters (BGCs). We can predict the presence of BGCs on bacterial genome, which acts as a gateway to further analyse their prevalence, distribution, and diversity using bioinformatic software.
My research encapsulates two tandem avenues: discovery and engineering:
Genome-guided discovery of natural products
Using a technique known as genome mining, we can exploit 100,000s of bacterial genomes to explore the diversity of related BGCs based on a small subset of previously characterised BGCs. This allows us to identify and characterise novel versions of these BGCs that leads to to discovery of novel natural products. The bioactive properties of these compounds can be investigated to determine the efficacy as antimicrobials, anti-cancer agents, and biopesticides.
Evolution-guided engineering of natural products
The same BGC is often found in multiple strains of the same species, or even multiple species of the same genus. By analysing hundreds of versions of the same BGC we can find natural splice variations in their genes that have occurred through recombination events. Excitingly, these gene splice variants encode for functional enzymes that biosynthetise variants of the original compound. We aim to explore these natural recombination events with the aim of replicating them in the lab to engineer novel variants of bioactive compounds of interest with enhanced efficacy.
