Secondary Metabolites of Fungi: Friend and Foe

Carla J. Harper
Latest posts by Carla J. Harper (see all)

There are old mushroom hunters, and there are bold mushroom hunters. There are no old, bold mushroom hunters.

Disclaimers: This post discusses some of the toxic mushrooms found in Ireland. This should not be used as a guide. Do not consume wild mushrooms – it can be very easy for beginners and seasoned mushroom hunters/foragers to confuse species or look-alikes. Be smart and be safe.

Moreover, this post discusses recent findings and information on mental health, depression, anxiety, and other related mood disorders. For individuals and concerned loved ones who are seeking support and information about managing depression, anxiety or other related mood disorders please see the TCD College Counselling service (https://www.tcd.ie/Student_Counselling/) Other websites: https://www.mentalhealthireland.ie or https://www.aware.ie/support/support-line/

Cover image credit: adege from Pixabay

The foe

COVID-19 has fundamentally changed our daily lives. Given this change, more people are going outside and enjoying the simple pleasure of walking. Along these walks people are coming across things that have likely always been there, but were previously ignored or unnoticed, such as mushrooms. A couple of questions that typically come to mind when finding a mushroom are (1) what is it? and (2) can I eat it?

The answer to the latter question is – if you are unsure whether a wild mushroom is edible, then do not eat it. It’s important to bear in mind that several people are poisoned each year in Ireland by consuming toxic mushrooms. For example, in September 2019 a man needed a liver transplant after consuming Amanita virosa also known as the ‘destroying angel’ and a further 24 people had confirmed mushroom poisoning by the end of November 2019 [1]. Some of the most toxic native Irish species include Amanita phalloides (the death cap), Amanita virosa (destroying angel), Cortinarius speciosissimus (web cap), and the Clitocybe rivulosa (fool’s funnel) – but there are many more.

Figure 1. Examples of native toxic mushrooms in Ireland. (A) Amanita virosa (destroying angel). (B) Amanita phalloides (the death cap) © Archenzo; permissions GFDL and Cc-by-sa-2.5,2.0,1.0 (C) Cortinarius speciosissimus (web cap), © Eric Steinert; permissions GFDL and Cc-by-sa-2.5,2.0,1.0. (D) Clitocybe rivulosa (fool’s funnel) © 2020 Wild Food UK.

One of the most frequently asked questions to a mycologist is – why do mushrooms produce toxins? Or as ecologists and evolutionary biologists, we ask – what selective advantage do these compounds confer to the mushrooms? [2]

The short answer is: we really don’t know [3]. There is, however, a growing body of evidence that suggests certain toxins, or secondary metabolites, are produced by some fungi to prevent them from being eaten by other organisms (mycophagy, fungivory) that would consume the fruiting bodies before they can sporulate. It’s interesting to note that certain organisms have resistance to alpha-amanitin, the principal toxic secondary metabolite produced by the genus Amanita, such as the fruit fly Drosophila [4]. Mitchell et al. (2015) [5] have further suggested that since Drosophila do not consume the Amanita mushrooms in nature, the alpha-amanitin resistance may have evolved as a result due to previous pesticide exposure.

Another possible ecological function of alpha-amanitin is protection against fungus-consuming gastropods such as slugs. There has been little research concerning alpha-amanitin sensitivity or resistance in gastropods. Some investigators have suggested that snails are approximately 200 times more tolerant to alpha-amanitin than humans [6]. It has been purported with little supporting evidence that other organisms, including vertebrates such as pigs, skunks, deer, that show at least some resistance to alpha-amanitin [2]. The only vertebrates indisputably sensitive to orally ingested amatoxins, such as alpha-amanitin, are humans and dogs.

Figure 2. (A) Alpha-amanitin structure. (B) Amanita phalloides (the death cap).

Back to the original question – why do mushrooms produce toxins? Walton (2018) [2] stated it best “…For the amatoxins, the simplest explanation is that they provide defense against mycophagous insects and perhaps gastropods. Insects and slugs probably exert stronger evolutionary pressure on mushrooms than mammals and reptiles simply because they are so much more numerous. …An alternate but not mutually exclusive hypothesis is that the toxins might induce a learned food aversion by causing gastrointestinal distress. Because mammals are presumed to be better learners than invertebrates, this hypothesis seems more applicable to mammals.”

The potential friend

In addition to the impact on physical health, COVID-19 has been shown to have an impact on mental health. A study by Hyland et al. (2020) showed that generalized anxiety disorder (GAD) and depression were a common experience in the population of the Republic of Ireland during the initial phase of the COVID-19 pandemic [7].

An exciting study led by Trinity researchers demonstrates the potential use of psilocybin (a secondary metabolite produced by, but not restricted to, certain Psilocybe mushrooms) therapy for various psychiatric disorders in post-COVID-19 clinical psychiatry [8]. It should be noted that this is not the first study to explore the therapeutic potential of psilocybin for various mental health disorders, in fact it has a long and complex history [9,10]. Moreover, in the Republic of Ireland as of 31 January 2006, it is illegal to possess or supply psilocybin mushrooms in a dried or prepared state [11].

There are a few species of hallucinogenic fungi in Ireland, Amanita muscaria, or the fly agaric, and the psilocybin producing Psilocybe semilanceata, also known as the ‘liberty cap’. Ecologically, P. semilanceata typically grows in grasslands and is a saprotrophic species on decaying grass roots. The species is found all around Ireland and is typically most abundant in the autumn [12]. Hallucinogenic fungi also have a long history with ancient Ireland [13]. Here, the question comes up again – why do mushrooms produce hallucinogenic compounds?

Figure 3. (A) Psilocybin structure. (B) Psilocybe semilanceata (the liberty cap).

The answer is likely similar as to why fungi produce toxic secondary metabolites, to deter insects and other organisms from consuming the mushrooms. A study by Reynolds et al. (2018) [14] demonstrated that psilocybin producing mushrooms have a cluster of five genes in common to produce the enzymes necessary to create psilocybin. Moreover, they seem to have transferred these genes from species to species, via horizontal gene transfer, as a group.

In the simplest terms, in humans, psilocybin causes hallucinations by suppressing a particular neurotransmitter. But in insects, suppression of this neurotransmitter has a different effect – it dampens appetite [15].

Irrespective of the effect, e.g., life threatening such as alpha-amanitin or possibly life-enhancing such as the therapeutic potential of psilocybin, secondary metabolites of fungi can have a profound impact on our lives. The study of fungal secondary metabolites is one of the most exciting areas of mycology for potential discoveries not only in pharmacology but also their ecological importance, such as animal-fungus interactions. For example, could there be novel uses for fungal secondary metabolites found in Irish bogs? See the exciting new project, “Unlocking Nature’s Pharmacy from Bogland Species” led by TCD’s own Dr. Helen Sheridan [16]. This post highlights only two examples of fungal secondary metabolites, but this is only the hyphal tip of the mycelium.

For a list, albeit incomplete, of poisonous and ‘best avoided’ mushrooms in Ireland see Dowding, P. and Smith, L., 2008. Forest fungi in Ireland. National Council for Forest Research and Development (COFORD).

FREE PDF: http://www.coford.ie/media/coford/content/publications/ForestFungiinIreland2008160919.pdf


[1] Hamilton D., Meagher, G. 2020. Mushroom poisoning, a public health issue. Epi Insight 21(1) https://ndsc.newsweaver.ie/epiinsight/wygqxzz6k6j1hu4itv9mdt?a=1&p=56221600&t=17517774

[2] Walton J. (2018) Ecology and Evolution of the Amanita Cyclic Peptide Toxins. In: The Cyclic Peptide Toxins of Amanita and Other Poisonous Mushrooms. Springer, Cham. https://doi.org/10.1007/978-3-319-76822-9_6

[3] Interview with Tom Bruns (University of California, Berkley) 2013. Why are mushrooms poisonous?  https://www.thenakedscientists.com/articles/interviews/why-are-mushrooms-poisonous

[4] Jaenike, J., Grimaldi, D. A., Sluder, A. E., & Greenleaf, A. L. (1983). α-Amanitin tolerance in mycophagous Drosophila. Science221(4606), 165-167.

[5] Mitchell, C. L., Yeager, R. D., Johnson, Z. J., D’Annunzio, S. E., Vogel, K. R., & Werner, T. (2015). Long-term resistance of Drosophila melanogaster to the mushroom toxin alpha-amanitin. PLoS One10(5), e0127569.

[6] Wieland T (1986) Peptides of poisonous Amanita mushrooms. Springer, Berlin.

[7] Hyland, P., Shevlin, M., McBride, O., Murphy, J., Karatzias, T., Bentall, R.P., Martinez, A. and Vallières, F., 2020. Anxiety and depression in the Republic of Ireland during the COVID‐19 pandemic. Acta Psychiatrica Scandinavica142(3), pp.249-256.

[8] Kelly, J.R., Crockett, M.T., Alexander, L., Haran, M., Baker, A., Burke, L., Brennan, C. and O’Keane, V., 2020. Psychedelic science in post-COVID-19 psychiatry. Irish journal of psychological medicine, pp.1-6.

[9] Garcia-Romeu, A., Kersgaard, B. and Addy, P.H., 2016. Clinical applications of hallucinogens: A review. Experimental and clinical psychopharmacology24(4), p.229.

[10] Carhart-Harris, R.L., Bolstridge, M., Rucker, J., Day, C.M., Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard, J.A., Forbes, B., Feilding, A. and Taylor, D., 2016. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry3(7), pp.619-627.

[11] Government bans sale of ‘magic’ mushrooms. https://www.drugsandalcohol.ie/11230/

[12] Species detail Liberty cap (Psilocybe semilanceata).  https://maps.biodiversityireland.ie/Species/150629

[13] Buckler N. The mysterious and lost magic mushroom rituals of the ancient Celts. The genuinely Irish Old Moore’s Almanac. https://oldmooresalmanac.com/the-mysterious-and-lost-magic-mushroom-rituals-of-the-ancient-celts/ 

[14] Reynolds, H.T., Vijayakumar, V., Gluck‐Thaler, E., Korotkin, H.B., Matheny, P.B. and Slot, J.C., 2018. Horizontal gene cluster transfer increased hallucinogenic mushroom diversity. Evolution Letters2(2), pp.88-101.

[15] Starr, M. 2018. Scientists have found the reason why magic mushrooms evolved to be so ‘magical’. Science alert. https://www.sciencealert.com/magic-mushrooms-psilocybin-evolved-deter-predators-horizontal-gene-transfer

[16] O’Shea, C. 2020. Unlocking the therapeutic and commercial potential of Ireland’s historic boglands. https://www.tcd.ie/news_events/articles/unlocking-the-therapeutic-and-commercial-potential-of-irelands-historic-boglands/

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