In a new study published in Scientific Reports, scientists have combined embryology, mycology and chemistry to test secondary metabolites from >10,000 species of fungi for biological activity.1
Our global population is aging. It's also growing. It's also afflicted by a wide variety of illnesses, some of which we lack a cure or even symptomatic treatment for. Now, possibly more than ever, novel drug compound discovery is pertinent.
Despite advances in the production of chemically synthesized drugs throughout the twentieth century, most of the drugs that are currently used in the clinic are derived from natural products. As biologically active compounds are often chemically related to one another, it's crucial that we continue to search for novel compounds.
Do fungi hold the key for the future of biologics?
A team of researchers from the Hubrecht Institute, in collaboration with scientists from the Westerdijk Institute and Utrecht University, have turned to fungi, which they deem to be an "underexplored resource", to search for biologically active compounds.
Fungi have been a component of traditional medicine throughout history. However, it was Alexander Fleming's accidental discovery of penicillin in 1928 that really emphasized the potential to extract active biological compounds from fungi to create therapeutics.2 "Every year new compounds produced by fungi are identified, but so far we have only investigated a very small subset of all existing fungi. This suggests that many more biologically active compounds remain to be discovered," says Jelmer Hoeksma, researcher at the Hubrecht Institute.
The largest fungi collection in the world
In the new study, the scientists utilized the Westerdijk Institute's largest collection of live fungi in the world to create a library of filtrates derived from >10,000 different species of fungi. A filtrate refers to all the metabolite products that a fungus excretes.
The researchers chose to investigate the effects of filtrate on zebrafish embryos, a vertebrate that is physiologically similar to humans and is commonly adopted in pharmacological testing. The embryos develop and mature in a matter of days, enabling swift detection of the activity of the fungal metabolites.
From the filtrate sample, 1526 filtrates were found to contain biologically active compounds that demonstrated a physiological effect on the zebrafish embryos. The scientists opted to focus on 150 filtrates for further analysis, from which they isolated 34 known compounds. Included in these compounds was the cholesterol lowering drug lovastatin, which was produced by the fungus Resinicium furfuraceum – this was previously unknown.
Of further interest was the finding that certain compounds induced pigmentation in the zebrafish embryos. As pigmentation can play a crucial role in the development of skin cancer, this is a notable find in the study, and the scientists are currently working to isolate the active compounds causing this pigmentation in the model.
The researchers believe that this study emphasizes the importance of further investigating the biological compounds produced by fungi in the pursuit for novel biological drugs. Hoeksma concludes: "The large library of fungal filtrates that we have set up can also be tested in many other systems, such as models for antibiotic resistance in bacteria and tumor development, making this study only the tip of the iceberg.
1. Hoeksma et al. 2019. A new perspective on fungal metabolites: identification of bioactive compounds from fungi using zebrafish embryogenesis as read-out. Scientific Reports. DOI: https://doi.org/10.1038/s41598-019-54127-9.
2. Tan and Tatsumura. 2019. Alexander Fleming (1881–1955): Discoverer of penicillin. Singapore Medical Journal. DOI: 10.11622/smedj.2015105.