Nature's silent pharmacy; exploring fungal genomes for hidden antibiotics
Fungi have proven to be an important source of bioactive compounds in the past, with penicillins, cephalosporins and statins amongst the best examples. This project seeks to reveal the many beneficial products yet to be discovered which may include new classes of antibiotics.
What is the problem?
Discovery programmes for new antibiotics are urgently needed to help address the escalating problem of AMR and drug-resistant infections.
Fungi have long been known to produce useful bioactive compounds, but genome sequencing has revealed far more metabolic potential than has been realised from simple chemical screening, suggesting there is great potential for further exploitation of these organisms in the hunt for new antibiotics.
A potential solution
A team led by by Dr Andy Bailey (School of Biological Sciences) are developing a high throughput pipeline to re-factor the clusters of genes revealed from genome sequencing. This will allow their expression in the lab-friendly fungus Aspergillus oryzae and thus reveal this "silent pharmacy". Novel compounds will be purified and assessed for antibiotic and other pharmaceutically relevant activities.
Outcome and next steps
The team have designed a production pipeline, aided by the use of high throughput robots, that are allowing them to investigate every candidate gene cluster from an initial group of ten selected fungi. The 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. This will help to inform future choice of strains for a wider scale analysis in a second round of screening. The team are currently focusing on the interesting gene clusters and promising compounds found, so far.
- Dr Andy Bailey (School of Biological Scences)
- Prof Gary Foster (School of Biological Sciences)
- Prof Chris Willis (School of Chemistry)
- Dr Paul Race (School of Biochemistry)
- Dr Colin Lazarus (School of Biological Sciences)
- Dr Jim Spencer (School of Cellular and Molecular Medicine)
- Prof Matthew Avison (School of Celluar and Molecular Medicine)
- 'Tackling AMR - A Cross Council Initiative' Theme 2: Accelerating therapeutic and diagnostics development. MRC-led with the BBSRC, ESRC and EPSRC
Dr Andy Bailey
Tel: +44 (0)117 39 41171