Medicinal mushrooms/macrofungi

During a mycological survey of the Democratic Republic of the Congo, a fungal specimen that morphologically resembled the American species Hypoxylon papillatum was encountered. A polyphasic approach including morphological and chemotaxonomic together with a multigene phylogenetic study (ITS, LSU, tub2, and rpb2) of Hypoxylon spp. and representatives of related genera revealed that this strain represents a new species of the Hypoxylaceae. However, the multi-locus phylogenetic inference indicated that the new fungus clustered with H. papillatum in a separate clade from the other species of Hypoxylon. Studies by ultrahigh performance liquid chromatography coupled to diode array detection and ion mobility tandem mass spectrometry (UHPLC-DAD-IM-MS/MS) were carried out on the stromatal extracts. In particular, the MS/MS spectra of the major stromatal metabolites of these species indicated the production of hitherto unreported azaphilone pigments with a similar core scaffold to the cohaerin-type metabolites, which are exclusively found in the Hypoxylaceae. Based on these results, the new genus Parahypoxylon is introduced herein. Aside from P. papillatum, the genus also includes P. ruwenzoriense sp. nov., which clustered together with the type species within a basal clade of the Hypoxylaceae together with its sister genus Durotheca.

New meroterpenoids bis-heimiomycins A-D (1-4) and heimiomycins D and E (5 and 6) were isolated from solid rice cultures of Heimiomyces sp., while new calamene-type sesquiterpenoids heimiocalamene A (7) and B (8) were isolated from shake cultures, respectively. Structures of the metabolites were elucidated by 1D and 2D NMR in addition to HRESIMS data. While relative configurations were assigned by ROESY data, absolute configurations were derived from the structurally related, previously described calamenes, which we herein name heimiocalamenes C-E (9-11). A plausible biosynthetic pathway was proposed for 1-6, with a radical reaction connecting their central para-benzoquinone building block to calamene-sesquiterpenoids. Based on the assumption of a common biosynthesis, we reviewed the structure of the known nitrogen-containing derivative 11, calling the validity of the originally proposed structure into question. Subsequently, the structure of 11 was revised by analysis of HMBC and ROESY NMR data. Only heimiomycin D (5) displayed cytotoxic effects against cell line KB3.1.

Protein microarray screenings identified fungal natural products from the azaphilone family as potent inhibitors of SARS-CoV-2 spike protein binding to host ACE2 receptors. Cohaerin F, as the most potent substance from the cohaerin group, led to more than 50% less binding of ACE2 and SARS-CoV-2 spike protein. A survey for structurally related azaphilones yielded the structure elucidation of six new multiformins F-J (11-15) and the revision of the stereochemistry of the multiformins. Cohaerin and multiformin azaphilones (1-5, 8, 12) were assessed for their activity in a cell-based infection assay. Calu-3 cells expressing human ACE2 receptor showed more than 75% and 50% less infection by SARS-CoV-2 pseudotyped lentivirus particles after treatment with cohaerin C (1) and cohaerin F (4), respectively. Multiformin C (8) and G (12) nearly abolished the infection of cells. OOur data show that multiformin-type azaphilones prevent the binding of SARS-CoV-2 to the cell entry receptor ACE2.

Mahesh C.A. Galappaththi, Nimesha M. Patabendige, Bhagya M. Premarathne, Kalani K. Hapuarachchi, Saowaluck Tibpromma, Dong-Qin Dai, Nakarin Suwannarach, Sylvie Rapior, Samantha C. Karunarathna. A review of Ganoderma triterpenoids and their bioactivities. Biomolecules, Special Issue Fungal Metabolism - Enzymes and Bioactive Compounds II, 13 (1), 24 (2023). doi:10.3390/biom13010024. hal-03912698 ___ For centuries, Ganoderma has been used as a traditional medicine in Asian countries to prevent and treat various diseases. Numerous publications are stating that Ganoderma species have a variety of beneficial medicinal properties, and investigations on different metabolic regulations of Ganoderma species, extracts or isolated compounds have been performed both in vitro and in vivo. However, it has frequently been questioned whether Ganoderma is simply a dietary supplement for health or just a useful "medication" for restorative purposes. More than 600 chemical compounds including alkaloids, meroterpenoids, nucleobases, nucleosides, polysaccharides, proteins, steroids and triterpenes were extracted and identified from Ganoderma, with triterpenes serving as the primary components. In recent years, Ganoderma triterpenes and other small molecular constituents have aroused the interest of chemists and pharmacologists. Meanwhile, considering the significance of the triterpene constituents in the development of new drugs, this review describes 495 compounds from 25 Ganoderma species published between 1984 and 2022, commenting on their source, biosynthetic pathway, identification, biological activities and biosynthesis, together with applications of advanced analytical techniques to the characterization of Ganoderma triterpenoids.

Plant disease associated fungi are of concern to plant pathologists, plant breeders, post harvest disease experts, quarantine officials and farmers in Thailand. Checklists with sound morphological identification are paramount to work by these specialists. In recent years molecular techniques have been applied to species identification and many species have been shown to comprise numerous cryptic species. In this paper, the need for modern systematic treatments of several important phytopathogenic genera are highlighted and a recommendation for future research of plant pathogens in Thailand is discussed.

Two common types of glutinous rice, Khao Niew Dam (KK) and Khao Niew Kiew Ngu (KN), found in Chiang Rai, Thailand were selected to study the feasibility to be the raw material for vinegar production. The malting process is a key role to gain the sufficient sugar content for wort preparation which is used as the substrate for the vinegar fermentation. In this work, the effect of malting temperature (25, 30 and 35 ºC) on amylolytic enzyme profile (α- and β-amylase) which is the key enzyme during the malting process were focused. The results showed that both α- and β-amylase showed the highest specific activity at 35 ºC. The maximum specific activity of α-amylase was 2.33 U/mgprotein found in KK and β-amylase was 2.82 U/mgprotein found in KN. The moisture content at malting temperature of 30 ºC was highest (63.25% and 64.10% found in KK and KN, respectively) on day 7 of incubation. Total carbohydrate content and % malting loss were demonstrated as substrate consumption during amylolytic enzyme hydrolysis. The maximum total carbohydrate content of KK and KN at a malting temperature of 30 ºC was 13.82 g/L and 9.57 g/L on day 7 and 4 of incubation, respectively. The highest malting loss (50.94%) was found in KN at 30 ºC. Generally, the product of amylolytic enzymes hydrolysis is reducing sugar. The maximal amount of reducing sugar and the productivity (QP,max) derived from KK and KN were 178.64 g/L and 161.14 g/L and 27.66 g/L.d and 24.90 g/L.d, respectively. In conclusion, the temperature affected the enzyme profile to provide the sugar production in different rice varieties. The optimal malting temperature for the germinated rice grains was 30 °C found in both varieties and the Khao Niew Dam (KK) provided high reducing sugar production during germination. Therefore, this species has the feasibility to be used as the substrate for wort production.

Bacterial cellulose (BC) is widely used in various applications. To apply in biomedical use, the natural BC and low-cost production should be considered. The aim of this study was to apply the spent coconut water (SCW) as supplement in the culture medium to produce high yield of BC. An acetic acid bacterium, Komagataeibacter nataicola (formerly Acetobacter sp. TISTR 975), was producer. The culture medium was modified from Watanabe and Yamanaka (1995) in which the molasses was used as carbon source. The culture was performed statically in 600-mL plastic boxes containing 200 mL culture medium at 30 C for 14 days. The effect of 50% (v/v) SCW and 50% (v/v) fresh coconut water (FCW) supplemented in the culture medium containing an initial total carbohydrate at 43.4±15.9 g/L as carbon source were studied. Besides, the control conditions including 100% (v/v) SCW and 50 g/L sucrose as a sole carbon source, respectively, were also investigated. The results showed that the addition of 50% (v/v) FCW showed the maximum BC concentration (CP), BC productivity (QP) and % Yield at 13.5±0.1 g/L, 1.8±0.0 g/L d and 23.7±0.1%, respectively. Interestingly, the results were not different significantly (p  0.05) with the addition of 50% (v/v) SCW. The maximum CP, QP and % Yield were 12.5±0.1 g/L, 1.6±0.0 g/L d and 31.9±4.7%, respectively. Undoubtedly, both supplements provided the greater yield than the controls. Thus, the SCW could be an alternative supplement in the culture medium containing molasses as carbon source to promote the BC production by K. nataicola.

Neurotrophins such as nerve growth factor (ngf) and brain-derived neurotrophic factor (bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for the treatment of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. In this study, we investigated the neurotrophic properties of triterpenes isolated from fruiting bodies of Laetiporus sulphureus and a mycelial culture of Antrodia sp. MUCL 56049. The structures of the isolated compounds were elucidated based on nuclear magnetic resonance (NMR) spectroscopy in combination with high-resolution electrospray mass spectrometry (HR-ESIMS). The secondary metabolites were tested for neurotrophin (ngf and bdnf) expression levels on human astrocytoma 1321N1 cells. Neurite outgrowth activity using rat pheochromocytoma (PC-12) cells was also determined. Twelve triterpenoids were isolated, of which several potently stimulated the expression of neurotrophic factors, namely, ngf (sulphurenic acid, 15α-dehydroxytrametenolic acid, fomefficinic acid D, and 16α-hydroxyeburicoic acid) and bdnf (sulphurenic acid and 15α-dehydroxytrametenolic acid), respectively. The triterpenes also potentiated ngf-induced neurite outgrowth in PC-12 cells. This is, to the best of our knowledge, the first report on the compound class of lanostanes in direct relation to bdnf and ngf enhancement. These compounds are widespread in medicinal mushrooms; hence, they appear promising as a starting point for the development of drugs and mycopharmaceuticals to combat neurodegenerative diseases. Interestingly, they do not show any pronounced cytotoxicity and may, therefore, be better suited for therapy than many other neurotrophic compounds that were previously reported.

Neurotrophins such as nerve growth factor (ngf) and brain derived neurotrophic factor (bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for treatment of neurodegerative diseases including Alzheimer's disease and Parkinson's disease. In this study, we investigated the neurotrophic properties of triterpenes isolated from fruiting bodies of Laetiporus sulphureus and a mycelial culture of Antrodia sp. MUCL 56049. The structures of the isolated compounds were elucidated based on nuclear magnetic resonance (NMR) spectroscopy in combination with high-resolution Electrospray mass spectrometry (HR-ESIMS). The secondary metabolites were tested for neurotrophin (ngf and bdnf) expression levels on human astrocytoma 1321N1 cells. Neurite outgrowth activity using rat pheochromocytoma (PC-12) cells was also determined. Twelve triterpenoids were isolated, of which several potently stimulated the expression of neurotrophic factors namely, ngf (sulphurenic acid, 15α-dehydroxytrametenolic acid, fomefficinic acid D and 16α-hydroxyeburicoic acid) and bdnf (sulphurenic acid and 15α-dehydroxytrametenolic acid), respectively. The triterpenes also potentiated ngf-induced neurite outgrowth in PC-12 cells. This is, to the best of our knowledge, the first report on the compound class of lanostanes in direct relation to bdnf and ngf enhancement. These compounds are widespread in medicinal mushrooms; hence, they appear promising as starting point for development of drugs and mycopharmaceuticals to combat neurodegenerative diseases. Interestingly, they do not show any pronounced cytotoxicity and may therefore be better suited for therapy than many other neurotrophic compounds that were previously reported.

The monotypic "bulbilliferous hyphomycete" genus Taxomyces was erected in 1993 for a fungal endophyte isolated from the Yew tree Taxus brevifolia and named Taxomyces andreanae. This fungus was reported to produce the plant-derived anti-cancer drug taxol. The original description of the fungus was not conclusive as to its taxonomic position because no sporulation or other salient morphological features were reported. Consequently, the taxonomic affinities of this fungus have remained obscure. However, a full genome sequence of this strain was generated by a German research group in 2013, in an unsuccessful attempt to detect the biosynthesis genes encoding for taxol. This prompted us to search for phylogenetic marker genes and compare those with the data that recently have become available from state-of-the-art polyphasic taxonomic studies. Surprisingly, the strain turned out to belong to the phlebioid clade of wood-destroying Basidiomycota as inferred from a comparison of its partial ITS, the 28S rDNA (LSU), the RNA polymerase II largest subunit (rpb1), the RNA polymerase II second largest subunit (rpb2), and the translation elongation factor 1-α (tef1) sequences. A multi gene genealogy based on these loci revealed that the closest relative is Ceriporiopsis (syn. Mycoacia) gilvescens. Even though such wood-destroying Basidiomycota are regularly encountered among the endophytic isolates after surface-disinfection of plant organs, the vast majority of the reported endophytic fungi belong to the Ascomycota. Nevertheless, the data available now allow for synonymizing Taxomyces with Ceriporiopsis, and the necessary new combination is made.

Seven sesquiterpenoids, named nebucanes A-G (1-7), featuring a rare alliacane scaffold with unprecedented furan or pyrrole functions, were isolated from the fermentation broth of Clitocybe nebularis. Their structures were established on the basis of 1D/2D NMR spectroscopic analyses, HR-(+)-ESIMS spectra, and comparison of measured and calculated CD spectra for determination of the absolute configuration. Assessing the biological activities, nebucane D (4) exhibited antifungal effects against Rhodotorula glutinis, while nebucane G (7) displayed significant cytotoxicity against MCF-7 and A431 cell lines.

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.

Five new drimane-type sesquiterpenoids were isolated from cultures of the tropical basidiomycetes, Perenniporia centrali-africana (originating from Kenya) and Cerrena sp. nov. (originating from Thailand). A new pereniporin A derivative (1), a new drimane-type sesquiterpene lactam (2), and the new 6,7-Dehydro-isodrimenediol (3) were isolated from P. centrali-africana. In parallel, the two new drimane-type sesquiterpene lactams 5 and 6 were isolated together with known isodrimenediol (4) from Cerrena sp. This is the first report of drimane-type sesquiterpene lactams from basidiomycetes. The structures were elucidated based on 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data, in combination with high-resolution electrospray mass spectrometric (HR-ESIMS) data. The compounds were devoid of significant antimicrobial and cytotoxic activities

Hericium is a well-known genus that comprises edible and medicinal mushrooms with fleshy, distinctive white spines that hang from a tough, unbranched clump, and grows on dying or dead wood. In preparation for the artificial cultivation of these mushrooms in Thailand, an optimization of mycelial growth on different agar culture media, for various conditions (including temperature, pH, cereal grains, and agricultural waste, carbon sources, nitrogen sources, and the ratio of media components) was carried out. For this study, three strains of H. erinaceus (MFLUCC 21-0018, MFLUCC 21-0019, and MFLUCC 21-0020) were favorably grown on OMYA medium, at 25°C and at a pH of 4-4.5, while one strain of H. erinaceus (MFLUCC 21-0021) grew favorably on CDA medium, at 25°C and pH 5.5. The favorable condition for H. coralloides (MFLUCC 21-0050) growth was MYPA medium, at 30°C and pH 5.5. All five strains presented higher mycelial growth on wheat grain. Carbon and nitrogen sources promoted higher rates using molasses and yeast extract respectively, and a ratio of these media components of 10:1 resulted in higher growth rates. The data presented provide growth requirements that will be useful in the future development of the cultivation of Hericium mushrooms.

In our continued search for biologically active metabolites from cultures of rare Basidiomycota species, we found eight previously undescribed cyathane-xylosides from submerged cultures of Dentipellis fragilis, which were named dentifragilins A–H. In addition, the known cyathane deriv-atives striatal D and laxitextine A were isolated. All compounds were characterized by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) as well as by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. Several of the compounds exhibited significant activities in standardized cell-based assays for the determination of antimicrobial and cytotoxic effects. The discovery of cyathanes in the genus Dentipellis has chemotaxonomic implications, as this class of diterpenoids has already been shown to be characteristic for mycelial cultures of the related genera Hericium and Laxitextum, which are classified as Dentipellis in the family Heri-ciaceae.

Le ganoderme luisant est considéré, en Asie, dès les dynasties mythiques puis impériales chinoises comme une panacée, d’une part à cause de sa rareté, mais aussi grâce à ses nombreuses vertus décrites dans les anciens ouvrages. L’identification et les recherches sur ce champignon ont été longtemps difficiles à cause de sa rareté dans la nature. Cependant, les nouvelles méthodes de culture découvertes au XXe siècle ont permis aux chercheurs d’approfondir les recherches sur ce champignon. Dans le cadre de cette thèse, nous étudions ce champignon des points de vue de la médecine chinoise traditionnelle et de la médecine moderne chinoise. En effet, en médecine chinoise traditionnelle, ce champignon est apprécié pour ses nombreuses vertus en accord avec la théorie des cinq éléments, qui permettent de cibler plusieurs maladies. Pour conforter l’utilisation du ganoderme en médecine moderne chinoise, des études récentes ont permis de mettre en évidence plusieurs propriétés intéressantes comme les activités immunomodulatrices, antitumorales, anti-oxydantes et antiinflammatoires. Le défi majeur, à ce jour, pour les chercheurs, consisterait à prouver l’efficacité de ce champignon grâce à de nouveaux outils comme le Q-Marker afin de lui donner enfin une véritable place dans l’arsenal thérapeutique et en particulier dans le domaine de l’oncologie. _______ Mots clés : Ganoderma lucidum (lingzhi), médecine chinoise traditionnelle, théorie des cinq éléments, taxonomie, polypores, triterpènes, polysaccharides, activités thérapeutiques, complément alimentaire

A mycelial culture of the African basidiomycete Echinochaete cf. brachypora was studied for biologically active secondary metabolites, and four compounds were isolated from its crude extract derived from shake flask fermentations, using preparative high-performance liquid chromatography (HPLC). The pure metabolites were identified using extensive nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). Aside from the new metab-olites 1-methoxyneomarinone (1) and (E)-3-methyl-5-(-12,13,14-trimethylcyclohex-10-en-6-yl)pent-2-enoic acid (4), the known metabolites neomarinone (2) and fumaquinone (4) were obtained. Such compounds had previously only been reported from Actinobacteria but were never isolated from the cultures of a fungus. This observation prompted us to evaluate whether the above metabolites may actually have been produced by an endosymbiontic bacterium that is associated with the ba-sidiomycete. We have indeed been able to characterize bacterial 16S rDNA in the fungal mycelia, and the production of the metabolites stopped when the fungus was sub-cultured on a medium containing antibacterial antibiotics. Therefore, we have found strong evidence that compounds 1-4 are not of fungal origin. However, the endofungal bacterium was shown to belong to the genus Ralstonia, which has never been reported to produce similar metabolites to 1-4. Moreover, we failed to obtain the bacterial strain in pure culture to provide final proof for its identity. In any case, the current report is the first to document that polyporoid Basidiomycota are associated with endosymbionts and constitutes the first report on secondary metabolites from the genus Echinochaete.

Badalyan S.M., Barkhudaryan A. et Rapior S. Medicinal macrofungi as cosmeceuticals: A review. International Journal of Medicinal Mushrooms, 24 (4), 1-13 (2022). doi:10.1615/IntJMedMushrooms.2022043124. hal-03633501 _____Macrofungi (mushrooms) have been studied for their nutritional value and medicinal properties. However, progress in the biotechnological application of macrofungi in the cosmetic industry as cosmeceuticals and nutricosmetics remains slow. Currently, the cosmetic industry is in a constant search for valuable natural ingredients or extracts with relevant bioactive properties (e.g., antiaging, anticollagenase, antielastase, antihyaluronidase, antipigmentation, anti-inflammatory, antioxidant, and antityrosinase) to design formulations. Edible medicinal mushrooms are an unlimited source of nutraceuticals and pharmaceuticals. They can be used as a source of ingredients to develop organic cosmeceuticals, nutriceuticals, and nutracosmetics for topical and oral administration.

The genus Morchella has gone through turbulent taxonomic treatments. Although significant progress in Morchella systematics has been achieved in the past decade, several problems remain unresolved and taxonomy in the genus is still in flux. In late 2019, a paper published in the open-access journal Scientific Reports raised serious concerns about the taxonomic stability of the genus, but also about the future of academic publishing. The paper, entitled “High diversity of Morchella and a novel lineage of the esculenta clade from the north Qinling Mountains revealed by GCPSR-based study” by Phanpadith and colleagues, suffered from gross methodological errors, included false results and artifactual phylogenies, had misapplied citations throughout, and proposed a new species name invalidly. Although the paper was eventually retracted by Scientific Reports in 2021, the fact that such an overtly flawed and scientifically unsound paper was published in a high-ranked Q1 journal raises alarming questions about quality controls and safekeeping procedures in scholarly publishing. Using this paper as a case study, we provide a critical review on the pitfalls of Morchella systematics followed by a series of recommendations for the delimitation of species, description of taxa, and ultimately for a sustainable taxonomy in Morchella. Problems and loopholes in the academic publishing system are also identified and discussed, and additional quality controls in the pre- and post-publication stages are proposed.

An investigation of the chemical components of the fermentation extract of two cultures of Amylosporus cf. graminicola and Amylosporus cf. campbelii from Cuba and Zimbabwe, respectively, led to the isolation of seven previously undescribed secondary metabolites for which we proposed the trivial names amylosporanes A−G (1−7) along with the known compounds orsellinic acid (11), colletorin D acid (12), colletorin B (13), colletochlorin B (14), and the β-lactam cyclo-(S-Pro-R-Leu) (15). Three additional compounds (8−10) previously unknown from a fungal source were also characterized for the first time, and two of them were assigned the trivial names amylosporanes H−I (8−9) while the other was identified as cannabigerorcinic acid (10). The structures of the isolated compounds were determined based on their high-resolution electrospray ionization mass spectrometry (HR-ESIMS) spectra and an extensive analysis of their 1D and 2D NMR spectroscopic data. Based on literature searches, we hypothesized that a majority of the isolated metabolites have orsellinic acid (11) as a biosynthetic precursor following a combined route of mevalonate-associated and orsellinic acid-associated pathways. Colletochlorin B (14), the only compound possessing chlorine in its structure, exhibited significant activity against Bacillus subtilis (minimum inhibitory concentration, 2 μg/mL), stronger than that of oxytetracycline, and significant cytotoxicity against A431 cells with an IC 50 value of 4.6 μM.

Coprinoid fungi from the clade Coprinellus (Agaricomycetes, Psathyrellaceae) are ecologically flexible, possibly fimicolous, often lignicolous and grassland species. Species can be distinguished from other coprini by morphological characteristics of basidiomes and mycelia. The sterile Ozonium (dark orange-rust hyphal strands) and asexually sporulating morphotypes (anamorph name Hormographiella) in the life cycle of Coprinellus species are described as taxonomically significant characters. Several Coprinellus species are also able to easily develop mature fruiting bodies in vitro. Morphological characteristics of dikaryons of the Coprinellus species disseminatus, domesticus, ellisii, xanthothrix and aff. radians were studied on two media (MEA, YMGT) at different temperatures (from 4 to 42oC) and cardinal temperatures established. All strains grow generally denser on the nutrient-rich YMGT, as compared with the less rich MEA. However, average growth rates (GRavr) were higher on MEA. Hyphal clamps were only observed in C. disseminatus dikaryons. Hormographiella oidiation (formation of dry arthrospores) was present in all species, except of C. disseminatus. All strains produced ozonium strands on MEA but colors and densities were influenced by temperatures. Ozonium production by the mesophilic species was best at 25-30oC on both media under best growth conditions (GRavrs between 6.5 to 12.5 mm/d) but relatively poor at 37-40oC and below 25oC. Most strains grow very slowly (0.8-1.7 mm/d) at 4oC, except of C. ellisii and C. aff. radians with <1.0 mm growth around inocula after 25 days at 4oC. All strains did not grow at 42oC. Growth of C. xanthothrix and C. domesticus at 40°C was irregular on both media (2.2 and 2.5 mm/d) indicating stress effects, while C. aff. radians (7.1 and 6.6 mm/d), C. ellisii (4.6 and 3.6 mm/d), and C. xanthothrix 398 (3.5 and 3.7 mm/d) grow relatively well at 40oC. Only C. disseminatus did not grow at 37°C and 40oC on both media. Strains grow similar well at the optimum temperature 26°C (6.4 and 6.1 mm/d on MEA, 6.7 and 6.1 mm/d on YMG/T), although one strain reacts in fruiting on temperature by not producing brown basidiospores at warmer weather (>20°C) and very few at colder temperatures (<15°C). In summary, the study showed that combined sexual and asexual cultural characteristics (clamps, ozonium, oidiation, and fruiting in cultures for C. aff. radians and C. ellisii) can assist species identification, while growth rates and cardinal temperatures are of limited value and fail as sole/revealing criteria for proper species/strain identification by overall too similar behaviours.

Hericium is a genus of edible mushroom with proven medicinal efficacy. The mycelium and basidiomata contain many nutrients and bioactive compounds with therapeutic uses. Recent and emerging evidence has shown that Hericium is helpful to various diseases with medicinal properties, such as anti-oxidant, anti-cancer, anti-diabetic, anti-hyperglycemic, hypolipidemic properties, anti-inflammatory, anti-microbial, anti-viral, and hepatoprotective. Over the past decade, many studies have been done on Hericium cultivation to produce enough basidiomata for culinary and medical purposes, due to its rarity in natural habitat. The purpose of this review is to provide the cultivation methods including indoor-outdoor cultivations and submerged culture methods, health-enhancing applications, economic importance, and industrial applications of Hericium mushroom.

The genus Agaricus contains many edible and medicinal mushrooms; and some of them are used for commercial purposes. Most Agaricus species have been described from temperate geographic areas, but their occurrence in the tropfuics is still underexplored. The present study describes the successful cultivation of two wild strains from Thailand, A. flocculopsipes and A. campestroides for the first time. The optimal conditions for mycelial growth have been evaluated for both strains, formation of basidiomata on compost could only be observed for A. campestroides. In the present study, mycelial growth and mushroom production conditions were optimized. The temperature range of 25-30 °C with 80-90% humidity was assessed as preferred conditions for primordia and basidiomata formation in a compost rice straw medium with sandy-soil casing layer. Blazeispirols (blazeispirol A and D), a family of triterpenoids that is known to act as selective agonists of Liver X receptor alpha with beneficial effects in vivo in a murine model, were detected in crude extracts from submerged cultures of A. campestroides and A. flocculosipes.

Schizophyllum commune est un champignon basidiomycète faisant partie de la famille des Schizophyllaceae. Il possède une large répartition géographique due, d’une part, au grand nombre de substrats ligneux sur lesquels il peut se développer, et d’autre part, à sa grande résistance aux stress environnementaux et à sa xéro-tolérance découlant de sa morphologie unique. Même si ce champignon est connu depuis plus de 300 ans, ce n’est que très récemment, en 1960, que son métabolite principal, le schizophyllane, a été découvert. C’est un β-D-glucane ayant de nombreuses propriétés pharmacologiques entrainant de multiples possibilités quant à son utilisation comme futur médicament. L’objectif de ce travail est de recenser dans la littérature les différentes facettes et caractéristiques de Schizophyllum commune : sa classification, sa répartition géographique, son mode de vie, sa reproduction, ses caractéristiques morphologiques, sa composition nutritionnelle et sa culture. Il sera également étudié les impacts néfastes de S. commune comme phytopathogène mais également en santé humaine comme agent fongique à l’origine d’infections chez l’homme. Il sera aussi abordé le schizophyllane, son métabolite principal, dont on décrira la structure, ses activités antitumorale, antivirale, antibactérienne et antifongique ainsi que cicatrisante. Ses différentes applications possibles que ce soit dans les industrie alimentaires, pharmaceutiques ou cosmétiques seront décrites même si de plus amples recherches sont nécessaires pour espérer leur mise en place. Mots clés : Schizophyllum commune, Basidiomycète, schizophyllane, β-D-glucane. Contact: sylvie.rapior@umontpellier.fr

This is a habilitation thesis. The contents have also been published in the following review: Stadler M 2011 – Importance of secondary metabolites in the Xylariaceae as parameters for assessment of their taxonomy, phylogeny, and functional biodiversity. Current Research in Environmental & Applied Mycology 1(2), 75-133, Doi 10.5943/cream/1/2/1

Morphological characters and multi-gene phylogenetic analyses were used to identify Retiboletus specimens collected in northern Thailand. Retiboletus brevibasidiatus is described as new to science, whereas R. fuscus and R. nigrogriseus are reported for the first time from Thailand. Retiboletus brevibasidiatus produces medium-sized basidiomes, with a dark blonde to clay pileus and densely reticulate stipe mostly on the upper part with pale yellow to chrome yellow basal mycelium. It is difficult to separate R. brevibasidiatus from other closely related species on the basis of macroscopic characters. However, the new species can be distinguished by microscopic characters, mostly the shorter basidia. The macro- and micro-morphology of the R. fuscus and R. nigrogriseus collections from Thailand fit well with the previous descriptions of materials from China and Japan. Detailed descriptions, molecular phylogeny, and illustrations of the three species are provided.

A recent find of a Marasmius species in Northern Thailand led to the isolation of five unprecedented derivatives of the carotane antibiotic fulvoferruginin (1), fulvoferruginins B-F (2-6). The structures of these sesquiterpenoids were elucidated using HRESIMS, 1D and 2D NMR, as well as CD spectroscopy. Assessing the bioactivity, fulvoferruginin emerged as a potent cytotoxic agent of potential pharmaceutical interest.

Badalyan S.M. et Rapior S. Agaricomycetes mushrooms (Basidiomycota) as potential neuroprotectants. Italian Journal of Mycology, 50, 30-43 (2021). doi:10.6092/issn.2531-7342/12542 _______ The edible and medicinal agaricoid and polyporoid mushrooms (phylum Basidiomycota, order Agaricomycetes) have long been known by humans as valuable food and medicines. They are producers of different groups of high- and lowmolecular weight bioactive compounds (alkaloids, phenolics, polysaccharides, proteins, terpenoids, vitamins etc.) with around 130 therapeutic effects, including neuroprotective. Mushroom-derived biotech products are reported as effective neuroprotectants, however their potential to prevent or mitigate several neurodegenerative pathologies, such as Alzheimer and Parkinson diseases, epilepsy, depression and others has not been fully explored. This review discusses the neuroprotective potential of Agaricomycetes fungi and possibilities for their application as natural neuroprotectants.

Macrofungi production and economic value have been increasing globally. The demand for macrofungi has expanded rapidly owing to their popularity among consumers, pleasant taste, and unique flavors. The presence of high quality proteins, polysaccharides, unsaturated fatty acids, minerals, triterpene sterols, and secondary metabolites makes macrofungi an important commodity. Macrofungi are well known for their ability to protect from or cure various health problems, such as immunodeficiency, cancer, inflammation, hypertension, hyperlipidemia, hypercholesterolemia, and obesity. Many studies have demonstrated their medicinal properties, supported by both in vivo and in vitro experimental studies, as well as clinical trials. Numerous bioactive compounds isolated from mushrooms, such as polysaccharides, proteins, fats, phenolic compounds, and vitamins, possess strong bioactivities. Consequently, they can be considered as an important source of nutraceuticals. Numerous edible mushrooms have been studied for their bioactivities, but only a few species have made it to the market. Many species remain to be explored. The converging trends and popularity of eastern herbal medicines, natural/organic food product preference, gut-healthy products, and positive outlook towards sports nutrition are supporting the growth in the medicinal mushroom market. The consumption of medicinal mushrooms as functional food or dietary supplement is expected to markedly increase in the future. The global medicinal mushroom market size is projected to increase by USD 13.88 billion from 2018 to 2022. The global market values of promising bioactive compounds, such as lentinan and lovastatin, are also expected to rise. With such a market growth, mushroom nutraceuticals hold to be very promising in the years to come.

This mini-review is dedicated to the summary of results of the EU-funded Project “Golden Mycological Triangle” (acronym GoMyTri), which was carried out in collaboration of three research infrastructures in Germany, the Netherlands and Thailand during the years 2014-2018. The cooperation explored the mycological and microbiological biodiversity of Europe and Southeast Asia with regard to the search for the badly needed new antibiotics and other biologically active secondary metabolites. The project was conducted to foster international collaboration networks, know-how exchange and interdisciplinary training of young scientists. The first two years of the project were mainly dedicated to field work, and several hundreds of fungal cultures have been isolated from material mostly collected in Thailand. These fungal strains were characterized by morphological and molecular phylogenetic methods and several new taxa were discovered. The cultures underwent screening for antimicrobial and nematicidal metabolites and a number of bioactive metabolites have already been found, isolated and characterized. Several large phylogenetic studies have already been published that resulted from the project work. The results were also brought to the attention to the scientific community as well as the general public through various dissemination events. Based on the tremendous success of this project, a follow-up project application including additional partners from Africa and further European countries has recently been filed and approved, and the international, interdisciplinary collaboration will now continue in the new RISE-MSCA-Project (acronym “Mycobiomics”²)

Several edible and medicinal Agaricomycetes mushrooms possess biologically active compounds with different therapeutic effects, such as anti-oxidative, anti-inflammatory, hypocholesterolemic, hypoglycemic, anti-hypertensive, fibrinolytic, thrombolytic, potentially used as cardioprotective remedies. Previous studies have shown that mushrooms possessing cardioprotective effect (CPE) contain a high amount of vitamins and minerals, low contents of fat which makes them applicable as supplementary dietary and functional food for prevention and treatment of a variety of cardiovascular disease (CVD). The current review is directed to the evaluation of resource value of 31 edible and non-edible medicinal Agaricomycetes mushrooms with potential CPE growing in the territory of Armenia and discusses the future perspectives of their usage in biotechnology and biomedicine. Contacts: s.badalyan@ysu.am; sylvie.rapior@umontpellier.fr

Badalyan S.M. et Rapior S. Agaricomycetes medicinal mushrooms with potential potential neuroprotective activity growing in rmenia. Proceedings of the Yerevan State University, Chemistry and Biology, 54 (3), 196-203 (2020). hal-03090953 _____ The Agaricomycetes mushrooms (phylum Basidiomycota) are recognised sources of valuable food and medicines. They are producers of bioactive compounds (phenolics, polysaccharides, proteins, steroids, terpenoids, etc.) possessing around 130 therapeutic effects (antimicrobial, anti-inflammatory, antioxidant, immunomodulatory, etc.). Mushrooms are also reported as potential neurotrophic and neuroprotective agents. Seventeen edible and inedible agaricomycetous species from different taxonomic and ecological groups have been reported in Armenia to possess neuroprotective activity. Evaluation resource value and biotechnological potential of Armenian agaricomycetous mushrooms will assist further development of novel myco-pharmaceuticals to prevent and mitigate different disorders, including neurodegenerative.

We selected seven wild Basidiomycota and Ascomycota mushrooms to evaluate their antibacterial activity: Cyclocybe aegerita, Cortinarius traganus, Gyroporus castaneus, Neoboletus luridiformis, Rubroboletus lupinus, Gyromitra esculenta, and Helvella crispa. Four mushrooms, three of which have not been tested to date, displayed antibacterial potential, with a minimal inhibition concentration (MIC) of ≤ 125 µg/mL against at least one Gram-positive bacterial strain. Cyclohexanic extract of G. esculenta possessed the strongest antibacterial activity, with an MIC of 31 µg/ mL against two strains of Staphylococcus aureus. ____ Morel S., Vitou M., Masnou A., Jumas-Bilak E., Rapior S. et Licznar-Fajardo P. Antibacterial activity of wild mushrooms from Ascomycota and Basidiomycota divisions. International Journal of Medicinal Mushrooms, 23 (1), 79-89 (2021). doi:10.1615/IntJMedMushrooms.2020037443. contact: sylvie.morel@umontpellier.fr

Badalyan S.M. et Rapior S. The neurotrophic and neuroprotective potential of macrofungi. In: Medicinal Herbs and Fungi – Neurotoxicity vs. Neuroprotection. Agrawal D.C. et Dhanasekaran M. (Eds). Publisher Springer. Chapter 2: 37-78 (2021). doi:10.1007/978-981-33-4141-8_2 ____ Diversity of wild and cultivated macrofungi as edible and medicinal mushrooms has long been known by humans as a source of valuable food and medicines used by tradipraticians. In the fungal kingdom, macrofungi taxonomically belong to two phyla, the Basidiomycota (class Agaricomycetes) and Ascomycota (class Pezizomycetes). Macrofungi have been used in traditional Asian and European Medicines, and based on 90,000 known worldwide distributed mushroom species, are considered an important resource for modern clinical and pharmacological research. They are regarded as a source of high- and low-molecular-weight bioactive compounds (alkaloids, lipids, phenolics, polysaccharides, proteins, steroids, terpenoids, etc.) with more than 130 therapeutic effects (anti-inflammatory, antimicrobial, antioxidant, antitumor, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, etc.). There is also scientific evidence of using macrofungi as neuroprotectants, that is, Agaricus blazei (= Agaricus subrufescens), Ganoderma lucidum, Grifola frondosa, Hericium erinaceus, Pleurotus ostreatus, and Trametes versicolor. However, their neuroprotective effects have not been fully explored. This review discusses recent advances in research on the neuroprotective potential of macrofungi and perspectives for their application as neuroprotectants in biomedicine to prevent, support, or cure neurodegenerative disorders. Corresponding authors: s.badalyan@ysu.am, sylvie.rapior@umontpellier.fr

The oudemansielloid/xeruloid taxa Hymenopellis, Mucidula, Oudemansiella, and Xerula are genera of Basidiomycota that constitute an important resource of bioactive compounds. Numerous studies have shown antimicrobial, anti-oxidative, anti-cancer, anti-inflammatory and other bioac-tivities of their extracts. The bioactive principles can be divided into two major groups: (a) hydrophilic polysaccharides with relatively high molecular weights and (b) low molecular medium polar secondary metabolites, such as the antifungal strobilurins. In this review, we summarize the state of the art on biodiversity, cultivation of the fungi and bioactivities of their secondary metabolites and discuss future applications. Although the strobilurins are well-documented, with commercial applications as agrochemical fungicides, there are also other known compounds from this group that have not yet been well-studied. Polysaccharides, dihydro-citrinone phenol A acid, scalusamides, and acetylenic lactones such as xerulin, also have potential applications in the nutraceutical, pharmaceutical and medicinal market and should be further explored. Further studies are recommended to isolate high quality bioactive compounds and fully understand their modes of action. Given that only few species of oudemansielloid/xeruloid mushrooms have been explored for their production of secondary metabolites, these taxa represent unexplored sources of potentially useful and novel bioactive metabolites.

Diallo I., Morel S., Vitou M., Michel A., Rapior S., Traoré L., Poucheret P. et Fons F. Ergosterol and amino acids contents of culinary-medicinal Shiitake from various culture conditions. Proceedings (ISSN 2504-3900), 70, 78 (2021). doi:10.3390/foods_2020-07702 ; hal-03088931. ====> Abstract: Lentinus edodes (Shiitake) is an edible mushroom cultivated and marketed due to its nutritional and medicinal values. L. edodes is appreciated for its unique fragrant taste and its high dietetic potential. Its bioactive molecules explain its interest as medicinal mushroom. This mushroom can be grown using various substrates and culture conditions. Thus, our work focused on the comparison of chemical constituents (i.e., amino acids and ergosterol) of L. edodes fruit bodies cultivated in organic or nonorganic growing conditions in the French region of Occitanie. Sequential extraction was performed on freeze-dried fungal materials. Quantitative evaluation of amino acids was done using high performance thin layer chromatography. Assay of ergosterol was carried out using high performance liquid chromatography. For both ergosterol and amino acids, differences were highlighted between extracts (depending on the nature of the solvents) and between growing conditions (organic versus nonorganic). Extracts from organic producer contained the highest content of ergosterol, isoleucine and alanine. In conclusion, this work demonstrated that culture conditions influence the chemical profile of L. edodes as for ergosterol and amino acids, which could improve nutrition and human health.

Submerged cultures of the edible mushrooms Phlebopus portentosus and Phlebopus spongiosus were screened for their secondary metabolites by HPLC-UV/Vis and HR-LC-ESI-MS. Two new compounds, 9′-hydroxyphenyl pulvinone (1), containing an unusual pulvinone structure, and phlebopyron (2), together with the seven known pigments, atromentic acid (3), xerocomic acid (4), variegatic acid (5), methyl atromentate (6), methyl isoxerocomate (7), methyl variegatate (8), and variegatorubin (9) were isolated from the cultures. Their structures were assigned on the basis of extensive 1D/2D NMR spectroscopic analyses, as well as HR-ESI-MS, and HR-ESI-MS/MS measurements. Furthermore, the isolated compounds were evaluated for their anti-microbial and cytotoxic properties. 9′-hydroxyphenyl pulvinone (1), xerocomic acid (4), and methyl variegatate (8) exhibited weak to moderate cytotoxic activities against several tumor cell lines. The present paper provides a comprehensive characterization of pigments from the class of pulvinic acids that are present in the basidiomes of many edible bolete species.

Melleolides and armillyl orsellinates are protoilludene-type aryl esters that are synthesized exclusively by parasitic fungi of the globally distributed genus Armillaria (Agaricomycetes, Physalacriaceae). Several of these compounds show potent antimicrobial and cytotoxic activities, making them promising leads for the development of new antibiotics or drugs for the treatment of cancer. We recently cloned and characterized the Armillaria gallica gene Pro1 encoding protoilludene synthase, a sesquiterpene cyclase catalyzing the pathway-committing step to all protoilludene-type aryl esters. Fungal enzymes representing secondary metabolic pathways are sometimes encoded by gene clusters, so we hypothesized that the missing steps in the pathway to melleolides and armillyl orsellinates might be identified by cloning the genes surrounding Pro1. Here we report the isolation of an A. gallica gene cluster encoding protoilludene synthase and four cytochrome P450 monooxygenases. Heterologous expression and functional analysis resulted in the identification of protoilludene-8α-hydroxylase, which catalyzes the first committed step in the armillyl orsellinate pathway. This confirms that ∆-6-protoilludene is a precursor for the synthesis of both melleolides and armillyl orsellinates, but the two pathways already branch at the level of the first oxygenation step. Our results provide insight into the synthesis of these valuable natural products and pave the way for their production by metabolic engineering. Key points • Protoilludene-type aryl esters are bioactive metabolites produced by Armillaria spp. • The pathway-committing step to these compounds is catalyzed by protoilludene synthase. • We characterized CYP-type enzymes in the cluster and identified novel intermediates.

True fungi (Fungi) and fungus-like organisms (e.g. Mycetozoa, Oomycota) constitute the second largest group of organisms based on global richness estimates, with around 3 million predicted species. Compared to plants and animals, fungi have simple body plans with often morphologically and ecologically obscure structures. This poses challenges for accurate and precise identifications. Here we provide a conceptual framework for the identification of fungi, encouraging the approach of integrative (polyphasic) taxonomy for species delimitation, i.e. the combination of genealogy (phylogeny), phenotype (including autecology), and reproductive biology (when feasible). This allows objective evaluation of diagnostic characters, either phenotypic or molecular or both. Verification of identifications is crucial but often neglected. Because of clade-specific evolutionary histories, there is currently no single tool for the identification of fungi, although DNA barcoding using the internal transcribed spacer (ITS) remains a first diagnosis, particularly in metabarcoding studies. Secondary DNA barcodes are increasingly implemented for groups where ITS does not provide sufficient precision. Issues of pairwise sequence similarity-based identifications and OTU clustering are discussed, and multiple sequence alignment-based phylogenetic approaches with subsequent verification are recommended as more accurate alternatives. In metabarcoding approaches, the trade-off between speed and accuracy and precision of molecular identifications must be carefully considered. Intragenomic variation of the ITS and other barcoding markers should be properly documented, as phylotype diversity is not necessarily a proxy of species richness. Important strategies to improve molecular identification of fungi are: (1) broadly document intraspecific and intragenomic variation of barcoding markers; (2) substantially expand sequence repositories, focusing on undersampled clades and missing taxa; (3) improve curation of sequence labels in primary repositories and substantially increase the number of sequences based on verified material; (4) link sequence data to digital information of voucher specimens including imagery. In parallel, technological improvements to genome sequencing offer promising alternatives to DNA barcoding in the future. Despite the prevalence of DNA-based fungal taxonomy, phenotype-based approaches remain an important strategy to catalog the global diversity of fungi and establish initial species hypotheses.

Medicinal mushrooms of the genus Hericium are known to produce secondary metabolites with homeostatic properties for the central nervous system. We and others have recently demonstrated that among these metabolites cyathane diterpenoids and in particular erinacine C possess potent neurotrophin inducing properties in astrocytic cells. Yet, the signaling events downstream of erinacine C induced neurotrophin acitivity in neural-like adrenal phaeochromocytoma cells (PC12) cells have remained elusive. Similar, signaling events activated by erinacine C in astrocytic cells are unknown. Using a combination of genetic and pharmacological inhibitors we show that erinacine C induced neurotrophic activity mediates PC12 cell differentiation via the TrkA receptor and likely its associated PLCγ-, PI3K-, and MAPK/ERK pathways. Furthermore, a small library of transcriptional activation reporters revealed that erinacine C induces transcriptional activation mediated by DNA consensus binding sites of selected conserved transcription factor families. Among these, transcription is activated from an ETS consensus in a concentration dependent manner. Interestingly, induced ETS-consensus transcription occurs in parallel and independent of neurotrophin induction. This finding helps to explain the many pleiotropic functions of cyathane diterpenoids. Moreover, our studies provide genetic access to cyathane diterpenoid functions in astrocytic cells and help to mechanistically understand the action of cyathanes in glial cells.

Lentinus edodes (Shiitake) is an edible mushroom cultivated and marketed due to its nutritional and medicinal values (1). L. edodes is appreciated for its unique fragrant taste, its high dietetic potential is valuable for health and its bioactive molecules explain its interest as medicinal mushroom (1). This mushroom can be grown using various substrates and culture conditions (2). Our work focused on the comparison of nutraceutical compounds (i. e., amino acids and ergosterol) of L. edodes fruit bodies cultivated in organic or non-organic growing conditions in the French Occitanie region (2). Sequential extraction was performed on freeze dried fungal materials. Quantitative evaluation of amino acids was done using HP-TLC, dosage of ergosterol was carried out using HPLC. For both nutraceutics, differences were highlighted between extracts (depending on the nature of the solvents) and between growing conditions (organic versus non-organic). For example, extracts from non-organic producers have the highest levels of alanine and the lowest contents of isoleucine. Extracts from organic producer contain a significantly higher content of ergosterol. This work demonstrated that culture conditions influence the chemical profile of mushrooms (in our case, Lentinus edodes), particularly nutraceutics compounds which could improve nutrition and human health. Poster : Diallo I., Morel S., Vitou M., Michel A., Rapior S., Traoré L., Poucheret P. et Fons F. 2020. Nutraceutical components of culinary-medicinal Shiitake from various culture conditions. 1st International Electronic Conference on Food Science and Functional Foods, Section: Nutraceuticals and Functional Foods (10-25/11/2020, online), Poster Submission ID sciforum-036831

Badalyan S.M. et Rapior S. Perspectives of biomedical application of macrofungi. Current Trends in Biomedical Engineering & Biosciences, 19 (5), 556024 (2020). doi:10.19080/CTBEB.2020.19.556024 Current Trends in Biomedical Engineering & Biosciences (ISNN 2572-1151)______ Macrofungi (mushrooms) have widely been appreciated all over the world for their nutritional values and medicinal properties. They have been used in traditional medicine for more than 3000 years for prevention and treatment of different diseases. Modern scientific research shows that macrofungi are producers of a broad spectrum of high- and low-molecular-weight bioactive compounds, i.e., alkaloids, polysaccharides, proteins, phenolics, terpenoids, polyketides, cyclic peptides, lectins and ribosome-inactivating proteins. They have various therapeutic effects as antidiabetic, anti-inflammatory, antimicrobial, antioxidant, antitumor, antiviral, cardioprotective, hepatoprotective, hypocholesterolemic, hypotensive, immunomodulatory, neuroprotective and regenerative, and possess promising pharmacological potential. Development of fungal biotechnological cultivation industry will support production of macrofungi-derived biotech products, healthy food and mycopharmaceuticals pharmaceuticals. Further advances in fungal biology and biotechnology, genomics and proteomics will assist biomedical research and application of macrofungi.

In an investigation of stromatic Xylariales in Thailand, several specimens of Daldinia were discovered. Three novel species (D. flavogranulata, D. phadaengensis and D. chiangdaoensis) were recognised from a molecular phylogeny based on concatenated ITS, LSU, RPB2 and TUB2 sequence data, combined with morphological characters and secondary metabolite profiles based on high performance liquid chromatography coupled to diode array detection and mass spectrometry (HPLC-MS). The major components detected were cytochalasins (in D. flavogranulata and D. chiangdaoensis and daldinin type azaphilones (in D. phadaengensis). In addition, D. brachysperma, which had hitherto only been reported from America, was found for the first time in Asia. Its phylogenetic affinities were studied, confirming previous suspicions from morphological comparisons that the species is closely related to D. eschscholtzii and D. bambusicola, both common in Thailand. Daldinia flavogranulata, one of the new taxa, was found to be closely related to the same taxa. The other two novel species, D. phadaengensis and D. chiangdaoensis share characters with D. korfii and D. kretzschmarioides, respectively.

Three previously undescribed compounds named heimiomycin A−C (1−3), featuring a unique scaffold with calamenene connected to a hydroxystyryl-pyranone moiety, along with the new calamenene derivatives 4 and 5 and phenanthridine derivative (6) were obtained from a culture of a Heimiomyces sp. This is the first report of the occurrence of calamenene-type terpenoids in fungi. Compound 3 exhibited antimicrobial activity against Gram-positive bacteria and Mucor hiemalis. Compounds 1 and 3 displayed moderate cytotoxicity against KB 3.1 and L929 cell lines, respectively.

Lentinus edodes (= Lentinula edodes) is an edible mushroom grown and marketed for centuries due to its nutritional and medicinal properties. L. edodes has multiple pharmacological activities as antioxidant and anti-inflammatory. Few studies were performed taking into account the influence of culture conditions to optimize the biological properties of L. edodes on human health. Our work focused on the comparison of antioxidant capacity and anti-inflammatory activity of L. edodes fruit bodies cultivated by three mushroom producers in the French Occitanie region using the same strain in various growing conditions (organic and nonorganic). Sequential extraction was performed on freeze dried fungal materials. All extracts have a quantifiable but moderate antioxidant activity using the DPPH and ORAC tests. The antiinflammatory activity of the ethanol and aqueous extracts was evaluated on a model of inflammatory macrophages. The ethanol extracts inhibit NO production in a dose-dependent manner when the cells are pre-treated for 4 h with a 24 h stimulation time. _______KEY WORDS: Lentinus edodes, anti-inflammatory, antioxidant, DPPH, food health benefit, J774.A1 macrophages, medicinal mushrooms, nitric oxide, ORAC, pharmacology._____ Corresponding author: francoise.fons@umontpellier.fr

Six saprobic fungal isolates were assayed for the in vitro antimicrobial activity against nine pathogenic microorganisms. The results showed that four fungal isolates including Clonostachys rosea MFLU10-0261, Fusicoccum aesculi MFLU10-0260, MFLU10-0266, and Ophioceras cf. leptosporum MFLU10-0281 were effective inhibitors against some test microorganisms. Of these, Ophioceras cf. leptosporum MFLU 10-0281 and Fusicoccum aesculi MFLU10-0260 exhibited a maximum inhibition zone of 15 ± 1 mm and 11 ± 1.6 mm against Staphylococcus aureus TISTR 1466 and Candida albicans TISTR 5779, respectively. These fungi also act as strong decomposers on leaves of Magnolia liliifera during the decay process from previous study. The results suggest that saprobic fungi could be a promising resource of useful bioactive compounds.

Macrolepiota dolichaula, an edible white spored gilled mushroom, is widely distributed in tropical and temperate countries. In this study, nutritional quality of M. dolichaula strain MFLUCC-13-0579 cultivated in compost was investigated. Proximate analysis of dry weight of M. dolichaula showed a composition of 25.53% protein, 44.37% carbohydrate, 14.17% fiber, 1.17 % lipid and 5.19% ash with energy of 299.06 kJ/g mushroom. In addition, the antimicrobial activities from fresh mushroom, dry mushroom and mycelial extracts showed significant activities against Micrococcus luteus and Staphylococcus aureus. Based on this study, it can be concluded that M. dolichaula is a good source of nutrients and posses some antimicrobial activities.

Rhopalostroma species were collected from Northern Thailand and subjected to morph-molecular analysis. One species possessed small, clavate stromata, with short and stout stipes, asci with an amyloid apical apparatus and ellipsoidal, dark ascospores with germ slits. Morphology and combined phylogenetic analysis of ITS, LSU, β-tubulin and RPB2 sequence data, showed it to be a new Rhopalostroma species introduced herein as R. brevistipitatum. A nodulisporium-like asexual morph was produced in culture. A morphological description and photographs of R. brevistipitatum are provided in this paper, with amendments to the generic description.

Three new species of Hypoxylon (Hypoxylaceae, Xylariales) are described based on a polyphasic approach that included morphological examination, molecular phylogeny and chemotaxonomic studies of specimens collected in Panama. Specifically, we compared the sexual morph (stromata, asci, and ascospores) of the specimens collected with known species of Hypoxylon and inferred a phylogeny of this genus based on a Randomized Axelerated Maximum Likelihood (RAxML) analysis of partial β-tubulin (TUB2) DNA sequences and the internal transcribed spacer regions (ITS). Hypoxylon baruense sp. nov. is phylogenetically related to H. subgilvum but differs in the shape of stromata, and by having larger ascospores and a smooth perispore. Hypoxylon bellicolor sp. nov. is phylogenetically well differentiated, featuring effused-pulvinate stromata with orange granules and ostioles lower than the stromatal surface. Hypoxylon sporistriatatunicum sp. nov., is phylogenetically related to H. shearii var. minor but differs in the shape of the stromata, in having ostioles higher than the stromatal surface, and in having larger ascospores. The secondary metabolite profiles of these species were studied by HPLC-DAD-MS and these correspond to the results of the morphological and phylogenetic studies. Additionally, we also report Amphirosellinia evansii, H. howeanum, H. cinnabarinum and Stilbohypoxylon quisquiliarum from Panama for the first time and Citrus sinensis as a new host of H. cinnabarinum. With this work, the number of species of Xylariales and Hypoxylon reported from Panama have increased to 103 and 18, respectively.

Medicinal mushrooms have been used for several hundred years, mainly in Asian countries, for the treatment of various pathologies. More recently, they have been used in the treatment of cancer. As part of this thesis, we are particularly interested in the lingzhi mushroom (Ganoderma lucidum) also called immortality fungus, for its anticancer properties. We therefore reported on the mechanisms of action of both the total extracts of Ganoderma lucidum and the two main bioactive molecules groups, i.e., polysaccharides and triterpenes. Their efficiencies have been demonstrated through in vitro tests and clinical studies. Although these natural compounds have been shown to be effective as a standard therapy treatment in the treatment of cancer (used as monotherapy or in combination with radiotherapy or chemotherapy) in Japan and China for over 30 years, it is fundamental to mention that they can also have significant side effects requiring advices of uses for human health. RESUME : Les champignons médicinaux sont utilisés depuis plusieurs centaines d'années, principalement dans les pays asiatiques, pour le traitement de différentes pathologies. Plus récemment, ils ont été utilisés dans le traitement du cancer. Dans le cadre de cette thèse, nous nous sommes particulièrement intéressés au ganoderme luisant (Ganoderma lucidum) également appelé champignon de l’immortalité, pour ses propriétés anticancéreuses. Nous avons donc étudié les mécanismes d’action à la fois des extraits totaux de Ganoderma lucidum et des deux principaux groupes de molécules bioactives : les polysaccharides et les triterpènes. Leurs efficacités ont été mises en évidence au travers de tests in vitro et d’études cliniques. Bien que ces composés naturels aient prouvé leur efficacité en tant que traitement de support aux thérapeutiques standards dans le traitement du cancer (utilisations en monothérapie ou en association avec la radiothérapie ou la chimiothérapie) au Japon et en Chine depuis plus de 30 ans, il est fondamental de mentionner qu’ils peuvent également présenter des effets indésirables non négligeables nécessitant des conseils d’utilisations pour la santé humaine. MOTS-CLES : Cancer, Ganoderma lucidum, mécanismes d’action, polysaccharides, triterpènes

iceps e-Conference 2020 postponed to November 24-25th 2020 (Toulouse, France) _______ Poster 41: Pain, increase of body temperature, skin redness and swelling are the main symptoms of the inflammatory process. Inflammation is a well-known contributing factor to many age-related chronic diseases. Mycotherapy is one strategy to prevent or suppress inflammation. Lentinula edodes (Shiitake) is an edible mushroom grown and marketed due to its nutritional and medicinal properties [1-2]. Shiitake has multiple pharmacological activities as antitumor, antioxidant and anti-inflammatory effects [3-4]. Our work focused on the comparison of anti-inflammatory activity of Shiitake fruit bodies cultivated by three mushroom producers in the French Occitanie region using the same strain in various growing conditions (organic and non-organic). Sequential extraction was performed on freeze dried fungal materials. The anti-inflammatory activity of the ethanol and aqueous extracts was evaluated on in vitro model of murine inflammatory macrophages. Regarding results of the polar extracts tested, all ethanol extracts inhibit significantly NO and to a lesser degree TNF? productions in a concentration-dependent manner thus suggesting Shiitake potential interest in the treatment against neurogenic inflammation. On the other hand, the inhibition observed for aqueous extracts (NO and TNF? productions) remains low whatever organic and non-organic fungal materials. Regarding the growing conditions used, our study shows few significant differences in the anti-inflammatory activities among the Shiitake extracts from the three French mushroom producers [5]. However, supplementary experiments will need to be conducted before Shiitake is used for its anti-inflammatory potential to prevent and treat pain associated with inflammation. [1] Poucheret P., Fons F., Rapior S., 2006 Cryptogamie, Mycologie, 27(4), 311-333. [3] Yin Y., Fu W., Fu M., He G., Traore L., 2007. Asia Pacific Journal of Clinical Nutrition, 16(1), 258-260. [5] Diallo I., Boudard F., Morel S., Vitou M., Guzman C., Saint N., Michel A., Rapior S., Traoré L., Poucheret P., Fons F., 2020. International Journal of Medicinal Mushrooms (in press).

iceps e-conference 2020 postponed to November 24-25th 2020 (Toulouse, France) ___________ Poster 26 : Si la phytothérapie a depuis longtemps acquis ses lettres de noblesses, le champignon demeure le parent pauvre dans le domaine des soins naturels. Cependant, certaines espèces de champignons telle que le ganoderme luisant (Ganoderma lucidum) sont utilisées depuis des millénaires en Chine et au Japon comme aliments de longue vie et de jeunesse prolongée. Aujourd'hui la mycothérapie est en pleine mutation, passant d'une médecine empirique à une science basée sur des preuves scientifiques. Dans ce contexte un nombre croissant d'étude sont publiées chaque année afin de légitimer et de comprendre leurs utilisations traditionnelles mais également de leurs trouver de nouvelles propriétés pharmacologiques. Au regard de ces nombreuses preuves scientifiques, l'utilisation de la mycothérapie peut trouver sans aucun doute une place légitime en tant qu'intervention non médicamenteuse (INM) dans le parcours de soin, de santé et/ou de vie d'une personne malade ou à risque de maladie. En effet le mycothérapie peut avoir une action préventive ou thérapeutique. L'utilisation d'extraits ou de molécules bioactives isolées de Ganoderma lucidum potentialise l'action de traitements biomédicaux en améliorant par exemple l'observance des patients par une réduction notable de leurs toxicités responsables des douleurs ressenties. Toutefois l'utilisation de Ganoderma lucidum n'est pas dépourvu de toxicité. En effet des cas d'effets indésirables et d'interactions médicamenteuses ont été rapportés dans la littérature scientifique. - Ayeka P, 2018. Potential of mushroom compounds as immunomodulators in cancer immunotherapy: A review. Evidence based complementary and alternative medicine. Volume 218, article ID 7271509 - Popovic V et al., 2013. Mycotherapy of cancer : an update on cytotoxic and antitumor activities of mushrooms, bioactive principles and molecular mechanisms of their action. Curr Top Med Chem. 13(21):2791-806 - Yuen MFet al., 2004. Hepatotocixity due to a formulation of Ganoderma lucidum (lingzhi). J Hepatol; 41:686-687

In the course of our exploration of the Thai invertebrate-pathogenic fungi for biologically active metabolites, pigmentosin A (1) and a new bis(naphtho-α-pyrone) derivative, pigmentosin B (2), were isolated from the spider-associated fungus Gibellula sp. Furthermore , a new glycosylated asperfuran 3, together with one new (6) and two known (4 and 5) cyclodepsipeptides, was isolated from Cordyceps javanica. The pigmentosins 1 and 2 showed to be active against biofilm formation of Staphylococcus aureus DSM1104. The lack of toxicity toward the studied microorganism and cell lines of pigmentosin B (2), as well as the antimicrobial effect of pigmentosin A (1), made them good candidates for further development for use in combination therapy of infections involving biofilm-forming S. aureus. The structure elucidation and determination of the absolute configuration were accomplished using a combination of spectroscopy, including 1D and 2D NMR, HRMS, Mosher ester analysis, and comparison of calculated/experimen-tal ECD spectra. A chemotaxonomic investigation of the secondary metabolite profiles using analytical HPLC coupled with diode array detection and mass spectrometry (HPLC-DAD-MS) revealed that the production of pigmentosin B (2) was apparently specific for Gibellula sp., while the glycoasperfuran 3 was specific for C. javanica.

Lentinula edodes (Lentin du chêne), est un champignon comestible, cultivé en Asie, particulièrement au Japon, dans le domaine de la médecine traditionnelle. La consommation du shiitake ainsi que son utilisation médicinale se développe de plus en plus en Europe. Néanmoins, sa consommation n’est pas sans risques. Le champignon présente différents composés qui peuvent induire des effets secondaires, parfois graves, chez certains consommateurs non avertis. Dans ce travail, la description de ce champignon, ses modes de culture et sa composition chimique ont été décrits avant d’explorer plus particulièrement les effets secondaires dus à sa consommation. Ceux-ci se traduisent principalement par des dermatites flagellaires et des troubles digestifs. Face à ces réactions présentées par certains consommateurs, les différents traitements utilisés ont été rapportés. Mots clés : Dermatite flagellaire, Eritadénine, Lentinane, Lentin du chêne, Traitements, Troubles digestifs Titre en anglais : Lentinula edodes (Shiitake), an edible medicinal mushroom: cultivation types, side effects after consumption and treatments. Key-words: Digestive side effects, Eritadenine, Lentinan, Shiitake, Skin dermatitis, Treatments

During the course of screening for new metabolites from basidiomycetes, we isolated and characterized five previously unde-scribed secondary metabolites, skeletocutins M-Q (1-5), along with the known metabolite tyromycin A (6) from the fruiting bodies of the polypore Skeletocutis sp. The new compounds did not exhibit any antimicrobial, cytotoxic, or nematicidal activities. However , compound 3 moderately inhibited the biofilm formation of Staphylococcus aureus (S. aureus), while compounds 3 and 4 performed moderately in the ʟ-leucine-7-amido-4-methylcoumarin (ʟ-Leu-AMC) inhibition assay. These compounds represent the first secondary metabolites reported to occur in the fruiting bodies by Skeletocutis. Interestingly, tyromycin A (6) was found to be the only common metabolite in fruiting bodies and mycelial cultures of the fungus, and none of the recently reported skeletocutins from the culture of the same strain were detected in the basidiomes.

During the course of screening for new metabolites from basidiomycetes, we isolated and characterized five previously undescribed secondary metabolites skeletocutins M-Q ( 1 - 5 ) along with the known metabolite tyromycin A ( 6 ) from the fruiting bodies of the polypore Skeletocutis sp. The new compounds did not exhibit any antimicrobial, cytotoxic or nematicidal activities. However, compound 3 moderately inhibited the biofilm formation of Staphylococcus aureus , while compounds 3 and 4 performed moderately activity in the L -leucine-7-amido-4-methylcoumarin ( L -Leu-AMC) inhibition assay. These compounds represent the first report of secondary metabolites occurring in the fruiting bodies of Skeletocutis . Interestingly, tyromycin A was found to be the only common metabolites in fruiting bodies and mycelial cultures of the fungus, and none of the recently reported skeletocutins from the culture of the same strain was detected in the basidiomes.

Cordycepin, 3’-deoxyadenosine, is a nucleoside analog of adenosine, which was first isolated in 1950 from Cordyceps militaris. The compound possesses various biological activities including antitumor, anti-diabetic, immunomodulatory and anti-bacterial effects (1). Cordycepin is considered a chemical marker for fungi in the genus Cordyceps.

To explore the chemical diversity of metabolites from new species of Dothideomycetes, the ex-type strain of Sparticola junci was investigated. Seven highly oxygenated and functionalized spirodioxynaphthalene natural products incorporating carboxyalkylidene-cyclopentanoid (1-4), carboxyl-functionalized oxabicyclo[3.3.0]octane (5-6), and annelated 2-cyclopentenone/δ-lactone (7) units, sparticolins A-G, were isolated from submerged cultures of the fungus. Their chemical structures including their relative (and absolute) configurations were established through spectroscopic and X-ray crystallographic analyses. Sparticolin B (2) exhibited inhibitory activity against the Gram-positive bacteria Bacillus subtilis, Micrococcus luteus, and Staphylococcus aureus, while sparticolin G (7) showed antifungal activities against Schizosaccharomyces pombe and Mucor hiemalis. All other sparticolins were only weakly active against S. aureus and also showed weak activities against the nematode Caenorhabditis elegans. Compounds 2 and 7 also showed moderate cytotoxic activities against seven mammalian cell lines.

Fungi are considered one of the most diverse, ecologically significant, and economically important organisms on Earth. The edible and medicinal mushrooms have long been known by humans and were used by ancient civilizations not only as valuable food but also as medicines. Mushrooms are producers of high- and low-molecular-weight bioactive compounds (alkaloids, lectins, lipids, peptidoglycans, phenolics, polyketides, polysaccharides, proteins, polysaccharide-protein/peptides, ribosomal and non-ribosomal peptides, steroids, terpenoids, etc.) possessing more than 130 different therapeutic effects (analgesic, antibacterial, antifungal, anti-inflammatory, antioxidant, antiplatelet, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, immunosuppressive, mitogenic/regenerative, etc.). The early record of Materia Medica shows evidence of using mushrooms for treatment of different diseases. Mushrooms were widely used in the traditional medicine of many countries around the world and became great resources for modern clinical and pharmacological research. However, the medicinal and biotechnological potential of mushrooms has not been fully investigated. This review discusses recent advances in research on the pharmacological potential of mushrooms and perspectives for their clinical application. Keywords Bioactive compounds · Clinical application · Ethno-mycopharmacology · Medicinal mushrooms · Pharmacological potential Badalyan S.M., Barkhudaryan A. et Rapior S., 2019. Recent progress in research on the pharmacological potential of mushrooms and prospects for their clinical application. In: Medicinal Mushrooms: Recent Progress in Research and Development. Agrawal D.C. et Dhanasekaran M. (Eds). Publisher Springer Nature Singapore Pte Ltd, pp 1-70. https://doi.org/10.1007/978-981-13-6382-5_1. ISBN 978-981-13-6382-5

Annales de la Société d’Horticulture et d’Histoire Naturelle de l’Hérault, 145 (1), 5-8 (2005).

Fungi are an understudied, biotechnologically valuable group of organisms. Due to the immense range of habitats that fungi inhabit, and the consequent need to compete against a diverse array of other fungi, bacteria, and animals, fungi have developed numerous survival mechanisms. The unique attributes of fungi thus herald great promise for their application in biotechnology and industry. Moreover, fungi can be grown with relative ease, making production at scale viable. The search for fungal biodiversity, and the construction of a living fungi collection, both have incredible economic potential in locating organisms with novel industrial uses that will lead to novel products. This manuscript reviews fifty ways in which fungi can potentially be utilized as biotechnology. We provide notes and examples for each potential exploitation and give examples from our own work and the work of other notable researchers. We also provide a flow chart that can be used to convince funding bodies of the importance of fungi for biotechnological research and as potential products. Fungi have provided the world with penicillin, lovastatin, and other globally significant medicines, and they remain an untapped resource with enormous industrial potential. Keywords Biocontrol · Biodiversity · Biotechnology · Food · Fungi · Mushrooms

The morphological and growth characteristics of mycelial cultures of 24 xylotrophic medicinal Agaricomycetes mushrooms including 12 edible species collected in Mazandaran and Golestan Provinces of Northern Iran were studied for the first time. The morphology of colonies, growth parameters, and an ability to develop in vitro teleomorph, presence and form of hyphal clamps, cystidia, loops, asexual spores (anamorphs), crystals and other cultural characteristics of Iranian collections were observed. The obtained data can be used for taxonomic identification of mycelial cultures of studied species/strains during their biotechnological cultivation to obtain mycelial biomass and bioactive compounds.

The morphological and growth characteristics of several Armenian strains of the tinder polypore fungus Fomes fomentarius were screened on agar media at 25, 30, 35, 38°C and 40°C. The revealed taxonomically valuable mycelial characteristics can be used for identification of F. fomentarius, as well as to control the purity of cultures during their biotechnological cultivation to obtain biomass and bioactive compounds.

Fermentation of the fungal strain Skeletocutis sp. originating from Mount Elgon Natural Reserve in Kenya, followed by bioassay guided fractionation led to the isolation of twelve previously undescribed metabolites named skeletocutins A-L (1-5, 7-13) together with the known tyromycin A (6). Their structures were assigned by NMR spectroscopy complemented by HR-ESIMS. Compounds 1-6 and 11-13 exhibited selective activities against Gram-positive bacteria, while compound 10 weakly inhibited the formation of biofilm of Staphylococcus aureus. The isolated metabolites were also evaluated for inhibition of L-leucine aminopeptidase, since tyromycin A had previously been reported to possess such activities but only showed weak effects. Furthermore, all compounds were tested for antiviral activity against Hepatitis C virus (HCV), and compound 6 moderately inhibited HCV infectivity with an IC50 of 6.6µM.

Bandara A.R., Rapior S., Mortimer P.E., Kakumyan P., Hyde K.D. et Xu J. 2019. A review of the polysaccharide, protein and selected nutrient content of Auricularia, and their potential pharmacological value. Mycosphere 10 (1), 579-607. doi :10.5943/mycosphere/10/1/10_____Auricularia is a key genus among edible macrofungi, sourced as either wild or cultivated mushrooms. Auricularia species are utilized as nutrient-rich foods and medicinal resources, with particular prominence in Traditional Asian Medicine. Cultivated Auricularia species can be grown under a wide range of conditions, allowing for production volumes worldwide. Although Auricularia species are used predominantly within the food industry, there is strong potential for their use in the production of therapeutic drugs, thus making it necessary to identify relevant bioactive compounds and further our understanding of its pharmacological properties. Carbohydrates are the major nutritional constituent of edible Auricularia species in addition to proteins, fat, fiber, ashes vitamins and minerals. This review discusses polysaccharides as one of the major active compounds found in edible Auricularia species in relation to their nutritional value, extraction methods, and pharmacological properties. Current methods of evaluating the pharmacological effects of compounds derived from Auricularia include in vitro assays, in vivo animal models, as well as several human clinical trials. Potential medical applications for these compounds include the production of novel therapeutic drugs for treating diseases such as cancer, diabetes, and cardiovascular disorders.

Six new cyathane diterpenoids, cyahookerins A-F (1-6), as well as nine known analogues (7-15), were isolated from the liquid culture of the basidiomycete Cyathus hookeri. Their structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, HRESIMS, and ECD), and the absolute configurations of compounds 1 and 4 were determined by single-crystal X-ray crystallography. Compounds 1 and 2 represent the first unusual cyathane acetals featuring a dioxolane ring. Compounds 1-6 displayed differential nerve growth factor-induced neurite outgrowth-promoting activity in PC-12 cells at concentrations of 10 μM. In addition, cyahookerin B (2), cyathin E (9), cyathin B2 (12), and cyathin Q (13) showed significant nitric oxide production inhibition in Lipopolysaccharide (LPS)-activated BV-2 microglial cells with IC50 values of 12.0, 6.9, 10.9, and 9.1 μM, respectively. Similar binding modes of the four compounds were indicated by molecular-docking studies, and structure-activity relationships are discussed.

During the course of searching for new anti-infective and other biologically active secondary metabolites from Kenyan basidiomycetes, 13 previously undescribed metabolites, (6R,7S,10R)-7,10-epoxy-7,11-dimethyldodec-1-ene-6,11-diol (1) and 12 sesquiterpenes named elgonenes A−L (2−13), and the known compound P-coumaric acid (14) were isolated from a basidiomycete collected in Mount Elgon Natural Reserve. The producing organism represents a new species of the genus Sanghuangporus, which is one of the segregates of the important traditional Asian medicinal mushrooms that were formerly known as the "Inonotus linteus" complex. The structure elucidation of compounds 1−13, based on 2D NMR spectroscopy, high-resolution mass spectrometry, and other spectral methods, and their antibacterial, antifungal, and cytotoxic activities are reported.

Fungi are considered one of the most diverse, ecologically significant, and economically important organisms on Earth. The edible and medicinal mushrooms have long been known by humans and were used by ancient civilizations not only as valuable food but also as medicines. Mushrooms are producers of high- and low-molecular-weight bioactive compounds (alkaloids, lectins, lipids, peptidoglycans, phenolics, polyketides, polysaccharides, proteins, polysaccharide-protein/peptides, ribosomal and non-ribosomal peptides, steroids, terpenoids, etc.) possessing more than 130 different therapeutic effects (analgesic, antibacterial, antifungal, anti-inflammatory, antioxidant, antiplatelet, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, immunosuppressive, mitogenic/regenerative, etc.). The early record of Materia Medica shows evidence of using mushrooms for treatment of different diseases. Mushrooms were widely used in the traditional medicine of many countries around the world and became great resources for modern clinical and pharmacological research. However, the medicinal and biotechnological potential of mushrooms has not been fully investigated. This review discusses recent advances in research on the pharmacological potential of mushrooms and perspectives for their clinical application. _____Key-words: Bioactive compounds · Clinical application · Ethno-mycopharmacology · Medicinal mushrooms · Pharmacological potential.

The strophariaceous basidiomycete Cyclocybe aegerita (synonyms Agrocybe aegerita and A. cylindracea) is one of the most praised cultivated edible mushrooms and is being cultivated at large scale for food production. Furthermore, the fungus serves as a model organism to study fruiting body formation and the production of secondary metabolites during the life cycle of Basidiomycota. By studying the secondary metabolite profiles of C. aegerita, we found several terpenoids in submerged cultures. Aside from the main metabolite, bovistol (1), two new bovistol derivatives B and C (2, 3) and pasteurestin C as a new protoilludane (4) were isolated by preparative HPLC. Their structures were elucidated by mass spectrometry and NMR spectroscopy. The relative configurations of 2–4 were assigned by ROESY correlations, and 3JH,H coupling constants in the case of 4. Applying quantitative PCR for gene expression validation, we linked the production of bovistol and its derivatives to the respective biosynthesis gene clusters.

Rhodatin (1), a meroterpenoid featuring a unique pentacyclic scaffold with both spiro and spiroketal centers, and five unusual acorane-type sesquiterpenoids, named rhodocoranes A−E (2−6, respectively), are the first natural products isolated from the basidiomycete Rhodotus palmatus. Their structures were elucidated by two-dimensional NMR experiments and HRESIMS, while the absolute configuration of the substance family was determined by Mosher's method utilizing 2. Rhodatin strongly inhibited hepatitis C virus, whereas 4 displayed cytotoxicity and selective antifungal activity.

The volatiles from an isolate of the fungus Daldinia cf. childiae, obtained from a specimen collected in China, were collected by use of a closed-loop stripping apparatus and analysed by GC-MS. A total number of 33 compounds from different classes were rigorously identified by comparison of mass spectra to library spectra and of retention indices to tabulated data from the literature. For unknown compounds structural suggestions were delineated from the mass spectra and verified by chemical synthesis of reference materials. Through this approach two 2-alkylated furan derivatives were identified, demonstrating that the genus Daldinia continues to be an interesting source for the discovery of novel secondary metabolites. Feeding experiments with sodium (1,2-13C2)acetate were performed to investigate the biosynthesis of the polyketide 5-hydroxy-2-methyl-4-chromanone that are in favour of a non-enzymatic cyclisation step.

The screening of morphological and growth characteristics of mycelial collections of medicinal bracket fungus Ganoderma adspersum (Agaricomycetes, Polyporales) of different geographical origins (Armenia, Georgia, Iran) on malt-extract agar (MEA) and potato-dextrose agar (PDA) media for 6 days, as well as in submerged culture (malt-extract, ME, 200 rt min) for 14 days at different temperature (25, 30, 35, 38 °C) was performed. Species-specific mycelial macro- and micromorphological characteristics, such as white, cottony-felt, later chamois, leathery, creamy-lemon-yellowish fast-growing colonies, roundshaped hyphal clamps, hyaline, round-shaped, smooth chlamydospore-like swellings and brownish cuticular cells, numerous tetrahedral crystals were described in agar and submerged cultures. The formation of small, dense and smooth pellets, as well as hyphal swellings during submerged growth was observed. The favorable growth temperature for studied collections of G. adspersum was 25-30 °C. The revealed cultural characteristics will be used for taxonomic identification and quality control of mycelial cultures during their biotechnological cultivation.