From basic to applied research, prototypes and products

Fungi have both good and bad facets (Pointing and Hyde 2001). They are essential for nutrient cycling because of their ability to degrade cellulose and lignin (Pointing et al. 2001). On the other hand, they cause serious human, animal and plant diseases and have numerous negative aspects on human life (Hyde et al. 2018a). Fungi are, however, also relatively understudied, but are an essential, fascinating and biotechnologically useful group of organisms with an incredible biotechnological potential for industrial exploitation. In this paper, we detail 50 ways in which we can potentially exploit fungi. We provide notes and examples for all potential exploitations and give examples from our own work and the work of others. We also provide a flow chart that can be used to convince funding bodies just how important fungi are and their potential for biotechnological research and potential products.

While several of our chapters are dealing with marketed products that even include blockbuster pharmaceuticals, such as the beta-lactam antibiotics, the statins and cyclosporine, others are dedicated to newly upcoming areas that still remain to be explored. Other chapters treat relatively small market segments that may expand in the future. For example, the consumers around the world now increasingly prefer natural compounds over synthetic chemicals and even in the industrial sectors that produce commodity chemicals, there is now an increased interest in development of sustainable biotechnological processes, in order to obtain new natural products that can eventually replace traditional synthetics. As compared to other biological sources, in particular plants, fungi have the great advantage that they can be grown in large bioreactors at an industrial scale, and suitable processes for their cost-efficient fermentation have been available for many decades, e.g. for production of certain organic acids, enzymes and antibiotics. As exemplified by the recent studies of the Thai mycobiota, modern polyphasic taxonomic approaches are constantly revealing a plethora of new and undescribed species even in the fairly well-known genera of fungi like Agaricus (Hyde et al. 2018b). Even the majority of the known species in the fungal kingdom are virtually untapped with regard to potential applications, also because they were never cultured and studied for their growth characteristics and physiology. New methods and protocols have to be developed for this purpose, and this implies that substantial basic research must be carried out before the exploitation of the novel organisms can be envisaged.

Although fungi have so many potential uses, research on their potential applications is in general poorly funded and much of the research that is being carried out in academia is fundamental, even in areas that belong to the fields of biotechnology and applied mycology. For example, screening fungi for production of antibiotics by antagonistic culture testing has often been reported, but is unlikely to lead to industrial projects. Often, it will take over a decade even to bring a given project based on a novel fungal metabolite into the preclinics, and even this is only possible by joint, interdisciplinary efforts of biologists, biotechnologists, pharmacists and chemists. Moreover, the Big Pharma industry has recently downsized their capacities for in-house research, meaning that the academic sector (sometimes supported by smaller companies or organisations like the Bill and Melinda Gates Foundation and the Wellcome Trust) has become more and more involved in the preclinical evaluation of new compounds. Investing in basic research may seem, at first sight, a costly affair. However, there are numerous examples of the past demonstrating why investing in basic research pays off in the long run, and even more reasons, why it is today more important than ever to renew an interest in basic research on fungi. But how to convince funders, in particular from the private sector, to invest into researchers doing basic research on fungi?

There are, no doubt, areas of research, which are of utmost importance to the entire world, yet are considered valueless to the pharmaceutical industry. One of these is the search for novel anti-infectives, as the world is running out of antibiotics (Hesterkamp 2017; WHO report 2017). It has long been seen as a tedious process to obtain novel antibiotics from living organisms.

However, the focus in the past has been on the same bacterial and fungal genera, such as Streptomyces in the Actinobacteria and common soil moulds like Aspergillus and Penicillium in the filamentous fungi (Karwehl and Stadler 2017). Since almost no novel carbon skeletons have been discovered from these common soil microbes in the past 20 years, it makes much more sense to study the numerous species that are constantly being discovered and shown to belong to new phylogenetic groups.

In our review, we present fungi, in particular Basidiomycota, as a still underexplored, highly promising source of anti-infectives, immunosuppressants, and other pharmaceuticals (see Badalyan et al. 2019; Sandargo et al. 2019a) that is nowhere near dried up. We give examples on recent developments of turning fungal natural products into commercial drugs and give an overview of the current state of applied research in this field.

In the past, fungal natural products have also led to some blockbusters and various developmental candidate compounds for the agrochemical industry (Bills and Gloer 2016). However, the uncontrolled usage of such fungal pesticides has led to the development of more and more resistances against these agrochemicals (Lucas et al. 2015). A more controlled approach of crop protection is therefore advisable. More basic research is needed to understand natural processes, and thereby allow for the search of natural control agents. In the entries dealing with “Strategies against plant disease”, we show the great potential of fungi as biocontrol agents. We give examples of how fungal biocontrol agents can help save the Agro sector tremendous amounts of money, if companies are given the opportunity to produce cost efficient biocontrol agents. In a likewise manner, the part on “Enhancing crops and forestry” deals with the current research on ectomycorrhiza and their potential application as natural biofertilizers.

With the new trend to a more sustainable, health-oriented living, and constant reports of hazardous chemicals found in food and cosmetics, the demand for more ecological, more “natural” alternatives is high. This is again, where fungi can step in. In the entries on “Food and beverages from fungi” and “Commodities”, we present examples of how basic research on fungi has made its way into the food and beverage, but also the textile and flavour industry. Finally, in the part on “Saving the planet” we illustrate the great potential of fungi towards a more sustainable living and how fungi can assist to cope with some potential future challenges that are threatening human civilisation.

Strategies against human disease

The scientific community recently celebrated the 90th anniversary of Sir Alexander Fleming’s discovery of penicillin, which marked the starting point of the era of antibiotic chemotherapy. As outlined by Karwehl and Stadler (2017), among the numerous antibiotics that were discovered over the next 50 years, relatively few compound classes were derived from fungi. The latter include the cephalosporins (Newton and Abraham 1955), which belong to the same class as the penicillins, i.e. the beta glucan antibiotics, as well as fusidic acid (Godtfredsen et al. 1962) and pleuromutilin (Novak and Shlaes 2010; Sandargo et al. 2019a). Most other commercial antibiotics are actually derived from Streptomyces species and other actinobacteria, or even from other prokaryotes. For details of the history of research on antibiotics, we refer to the review by Mohr et al. (2017). As we cannot cover the entire field in this paper, we will give a brief overview on antibacterials, antimycotics and biofilm inhibitors and illustrate their usages with some examples of marketed drugs as well as
other compounds that have recently been discovered.

The amazing potential of fungi: 50 ways we can exploit fungi industrially

Strategies against human disease

1. Antibacterial antibiotic

2. Antimycotics and fungicides

3. Biofilm inhibitors

4. Anti-cancer agents

5. Anti-diabete

6. Improving nerve functioning

7. Fungi in Traditional Chinese Medicine

8. Cardiovascular disease control by fungi

9. Antiviral agents

10. Immunosuppressive and immunomodulatory agents from fungi

Strategies against plant disease

11. Biocontrol of plant disease using endophytes

12. Biocontrol of insects using fungi

13. Biocontrol of nematodes and fungal nematicides

14. Biocontrol of weeds and herbicides from fungi

15. Fungal antagonists used in post-harvest disease control

16. Biocontrol of rusts and smuts by antagonistic fungi

Enhancing crops and forestry

17. Biofertilizers

18. Arbuscular mycorrhizae as biofertilizers

19. Application of ectomycorrhizal fungi in forestry

20. Use of orchid mycorrhizae and endophytes in biotechnology

21. Growth promoting hormones from fungi

22. Mitigating abiotic stress in plants: the endophyte method

Food and beverages from fungi

23. Growing mushrooms in composts

24. Growing mushrooms in bags

25. Growing mushrooms in the field

26. Modern mushroom production: an automated factory process

27. New edible mushrooms

28. Agaricus subrufescens

29. Using fungi to enhance food value

30. Food colouring from filamentous fungi

31. Food flavouring

32. What is mushroom stock? Products, processes and flavours

33. Fungi used in making tea

34. Wine, beer and spirits

35. Functional foods and nutraceuticals

36. Harvesting the untapped probiotic potential of fungi

Saving the planet

37. Agricultural waste disposal

38. Mycoremediation: Fungi to the rescue

39. Mycofumigation using the genus Muscodor

40. Biomass to biofuel: unmasking the potential of lesser-known fungi

41. Packed-bed bioreactor for mycomaterial production

42. Fungal degradation of plastics: A hidden treasure for green environment

43. Polycyclic aromatic hydrocarbon degradation by basidiomycetes

44. Can fungi help modify the sustainable soil enhancer biochar?

Commodities

45. Fungi and cosmetics

46. Agarwood

47. Fungal enzymes

48. Preservatives

49. Organic acids

50. Textile dyes

 

Source: Hyde, K.D., Xu, J., Rapior, S. et al. The amazing potential of fungi: 50 ways we can exploit fungi industrially. Fungal Diversity97, 1–136 (2019). https://doi.org/10.1007/s13225-019-00430-9