Exploring nature`s silent pharmacy

Kate de Mattos-Shipley 1,2 Katherine Williams 2 Trong Tuan Dao 1 Ian Prosser 2 Christine Willis 1 Andrew Bailey 2
1School of Chemistry, University of Bristol, Bristol, UK
2School of Biological Sciences, University of Bristol, Bristol, UK

The medicinal properties of fungi have been known about for millennia and were exploited for the benefit of humans by many ancient civilisations, including those in Ancient China, Eastern Europe, Mesoamerica and Africa. Moving forward in time to the 20th century, scientific advances allowed the health benefits of fungi to be utilised in a more complex and sophisticated manner, with fungal natural products being developed into life-changing medicines such as the penicillins and cephalosporins.

Even more recent developments, particularly in the fields of synthetic biology and genomics, have further opened up the field of natural product research. In particular, sequencing of fungal genomes has revealed that fungi house a surprisingly large number of biosynthetic gene clusters, many of which appear to be silent or inactive under typical culturing conditions. This suggests that there are many beneficial products yet to be discovered and exploited. Of particular interest would be novel antibacterial compounds, which could contribute to the fight against growing antibiotic resistance.

The ongoing research project, ‘Exploring Nature`s Silent Pharmacy’, aims to design a production pipeline that will allow high throughput investigation of uncharacterised biosynthetic gene clusters and analysis of novel bioactive molecules. The fungal isolates selected for this study have been chosen to span a range of differing lifestyles, including insect, fungal and plant pathogens, marine fungi and soil fungi, in an attempt to discover as much chemical diversity as possible.

We will show progress towards automating this discovery pipeline, including the use of advanced in silico tools, liquid-handling robotics coupled with yeast-based recombination to build refactored gene clusters for expression in Aspergillus oryzae, and subsequent chemical analysis for product characterisation.