Ten decadal advances in fungal biology leading towards human well-being

Abstract

Fungi are an understudied resource possessing huge potential for developing products that can greatly improve human well-being. In the current paper, we highlight some important discoveries and developments in applied mycology and interdisciplinary Life Science research. These examples concern recently introduced drugs for the treatment of infections and neurological diseases; application of -OMICS techniques and genetic tools in medical mycology and the regulation of mycotoxin production; as well as some highlights of mushroom cultivaton in Asia. Examples for new diagnostic tools in medical mycology and the exploitation of new candidates for therapeutic drugs, are also given. In addition, two entries illustrating the latest developments in the use of fungi for biodegradation and fungal biomaterial production are provided. Some other areas where there have been and/or will be significant developments are also included. It is our hope that this paper will help realise the importance of fungi as a potential industrial resource and see the next two decades bring forward many new fungal and fungus-derived products.

Keywords: Biomaterial; CRISPR; Drug development; Morel cultivation; Mushroom cultivation; Mycotoxin biosynthesis; Plastic degradation.

Fig. 1

Fungi-derived natural immunosuppressants

Fig. 2

Stromata of Ophiocordyceps khonkaenensis. Kindly provided by Artit Khonsanit

Fig. 3

Mechanism of phosphorylation of sphingosine and fingolimod via sphingosine kinase 2 (Strader et al. 2011)

Fig. 4

Clinical manifestation of a and b invasive fungal diseases caused by Aspergillus and c and d zoonotic dermatomycosis due to species from Trichophyton benhamiae clade. a A magnetic resonance image of the head showing an abscess (indicated with white arrow) in the left temporo-occipital area of 17-year-old boy with chronic granulomatous disease. b Chest computed tomography image showing lesion (white arrow) consistent with acute invasive pulmonary aspergillosis in a cancer patient. c Dermatophytosis localized on the bearded areas. d Infection localized on the neckline and face of 9-year-old girl contracted from guinea pig

Fig. 5

Antimyotic agents approved or under development for treatment of fungal infections. Fungal metabolites are printed in red and metabolites from Actinobacteria are printed in blue; the others are of synthetic origin

Fig. 6

Reannotated enfumafungin biosynthetic gene cluster (efu) and hypothesized core step of the enfumafungin biosynthesis

Fig. 7

Development of ibrexafungerp (4) and comparison of chemical structures 1–4. By modifying the chemical entities at C-2, C-3 and C-25 (illustrated by colored boxes), a series of semi-synthetic conversions culminated in the development of 4

Fig. 8

Chemical structures of pleuromutilin and its derivatives

Fig. 9

Diagram of signal transduction pathway of fungal carbohydrate antigens by the human immune system. Bcl B-cell lymphoma protein 10, CARD9 caspase recruitment domain-containing protein 9, IFN interferon, IL interleukin, MALT1 mucosa-associated lymphoid tissue lymphoma translocation protein 1, NF-kB nuclear factor kappa-light-chain-enhancer of activated B cells, P phosphor, SYK tyrosine-protein kinase, Th T-helper cell. CARD9/Bcl10/MALT1 is a central proinflammatory signalosome in innate immune cells. Modified after Drummond et al. (2011)

Fig. 10

Global production of mushrooms and truffles from 1961 to 2019 (Food and Agriculture Organization Statistical 2019a). Aggregate global data may include official, semi-official, estimated, or calculated data

Fig. 11

Production share (A) and top 10 producers (B) of mushrooms and truffles. Average production was calculated by the aggregate data of mushroom and truffle trade and production from 1961 to 2019. Aggregate global data may include official, semi-official, estimated or calculated data (Food and Agriculture Organization Statistical 2019a)

Fig. 12

Annual change of quantity and value of mushroom products. A export quantity of canned and fresh mushrooms, B Export value of canned and fresh mushrooms, C Import quantity of canned and fresh mushrooms, D Import value of canned and fresh mushrooms. Fresh mushroom products comprise both mushrooms and truffles in the FAO database (Food and Agriculture Organization Statistical 2019b)

Fig. 13

Relative contribution of the three major sectors (cultivated edible mushrooms, medicinal mushrooms, and wild harvested mushrooms) to the global mushroom market (A), generated using data from Royse et al. (2017); and the mushroom value chain highlighting the key sectors within the mushroom industry, and the feedback loops between these sectors (B)

Fig. 14

Schematic steps of the synthesis process of mycelium-based composite with key steps and possible variations in processes

Fig. 15

Applications of mycelium-based materials in different fields. a, b Packaging. c Leather. d–f Construction materials. g, h Others

Fig. 16

a Production of morels in China from 2010 to 2019, b Morel production in different provinces of China in 2019. Data sources: http://bigdata.cefa.org.cn/index.html (Accessed date: 21 Mar. 2022)

Fig. 17

Morel spawn. a mother culture. b mother spawn. c, d final spawn with numerous sclerotia. e white stout mycelia of morels in the final spawn

Fig. 18

The morel cultivation protocol. a land preparation. b bedding and ditching. c, d spawning, casing, and watering. e exogenous nutrition aiding. f, g primordium. h nascent fruiting bodies. i, j mature fruiting bodies. k harvesting. l commercial morels

Fig. 19

Symptoms of fungal disease on Morchella sextelata (b-d). Colony of fungal disease on PDA medium that isolated from infected morels (e-i). a Healthy fruiting bodies. b Diseased fruiting body infected Cladobotryum mycophilum. c, d Diseased fruiting body infected Diploöspora longispora. e Diploöspora longispora. f Cladobotryum mycophilum. g Clonostachys rosea. h Fusarium sp. i Fusarium sambucinum

Fig. 20

Proposed model of gliotoxin disruption of 7SK snRNP, causing release of P-TEFb and activation of the latent HIV-1 LTR via release of CDK9 from the 7SK snRNP complex. Free P-TEFb is then recruited to the HIV-1 Tat-TAR axis, leading to phosphorylation of RNA Pol II and subsequent stimulation of transcription elongation. CDK9 cyclin-dependent kinase 9; DSIF 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole sensitivity inducing factor, CTB non-toxic B-subunit of cholera toxin, HEXIM hexamethylene bis-acetamide inducible 1; LARP La ribonucleoprotein domain family, LTR latency reversal, MEPCE methylphosphate capping enzyme, NELF negative elongation factor, Pol polymerase, snRNP small nuclear ribonucleic protein, TAR trans-activation response, Tat trans-activation of transcription, TEF transcription elongation factor; Modified after Stoszko et al. (2020)