Fungi are one of the world’s primary organisms. Ecologically, they have the capacity to both facilitate and destroy crop production, while their fruiting bodies and hyphae often have beneficial medicinal properties. However the true potential of mushrooms remained untapped until scientists from the University of Bristol developed novel techniques for manipulating their genetic structure.

Mushrooms and toadstools, or Basidiomycota, have a complex genetic composition which has historically defied detailed experimentation. Since 1998, researchers from Bristol’s internationally renowned School of Biological Sciences have been pioneering new approaches.

Novel techniques

In 1998, Professor Gary Foster and Dr Andy Bailey realised that in order to analyse and then manipulate the gene expression of Basidiomycota, a new technique was needed.

By 2005, they had created the Basidio Molecular Toolkit, which has subsequently enabled the global agricultural and pharmaceutical industry to make dramatic breakthroughs in crop production and antibiotic research.

The Toolkit works by identifying and testing foreign genes which can be used to modify basidiomycetes, either by silencing or increasing the degree to which a target gene is expressed. The kit also contains a range of ready-to-use DNA vehicles developed by Foster and Bailey, with easily interchangeable components that can carry the foreign DNA into the fungus.

“Mushrooms have long been known as a vital resource, not only as a food source, but also as invaluable mine for enzymes used within industry and biotechnology, roles within traditional medicine, as well as playing a crucial role within the wider environment. With the development of this Toolkit and its availability to the wider scientific community, the full potential of mushrooms can now be reached” said Foster.

Medicinal purposes

One of the most far-reaching collaborations to emerge from Bristol’s work was a 12-year project funded by the pharmaceutical firm GlaxoSmithKlein (GSK). From 2005, Foster and Bailey helped GSK to investigate the genomic potential of the organism Clitopilus passeckerianus, which produces a natural antibiotic called pleuromutilin.

Pleuromutilin is one of the few antibiotics that are effective against the superbug Staphylococcus aureus (MRSA). Using the Basidio Molecular Toolkit, it was found that individual genes could be modified in C. passeckerianus so as to stimulate the production of pleuromutilin.

Not only did the toolkit greatly advance the search for new antibiotics, it saved GSK costly R&D time that would otherwise have been spent on more labour intensive investigations. GSK subsequently used the molecular toolkit to help validate another antibiotic, Altargo/Altabax, which was approved for use in the EU in 2007.

The toolkit has also enabled researchers to bolster the production of compounds of interest from medicinal mushrooms that are known to have anti-cancer effects. Bristol’s toolkit has been used to increase the production of a range of compounds to commercially viable levels.

Crop production

Improvements in agriculture have also been facilitated by the Basidio toolkit. In 2007, the Bristol team began working with the US Department of Agriculture (USDA) and with the Royal Horticultural Society (RHS) to analyse and genetically manipulate the honey fungus, Armillaria mellea, a major problem for horticulture and a parasite with the capacity to reduce the lifespan of walnut and almond trees from 30 to ten years. As a result, two of California’s most significant exports face less of a risk.

From a purely scientific perspective, the research underpinning the development of the Basidio toolkit contributed to efforts by an international cohort of researchers to publish the full genome of the world’s most cultivated mushroom, Agaricus bisporus. The information could prove invaluable in developing disease-resistant varieties of button mushrooms, with further benefits for the agricultural industry.