Search

Different fungal species belonging to the Colletotrichum genus cause anthracnose disease in a range of major crops, resulting in huge economic losses worldwide. Typical symptoms include dark, sunken lesions on leaves, stems, or fruits. Colletotrichum spp. have synthesized, in vitro, a number of biologically active and structurally unusual metabolites that are involved in their host’s infection process. In this study, we applied a one strain many compounds (OSMAC) approach, integrated with targeted and non-targeted metabolomics profiling, to shed light on the secondary phytotoxic metabolite panels produced by pathogenic isolates of Colletotrichum truncatum and Colletotrichum trifolii. The phytotoxicity of the fungal crude extracts was also assessed on their primary hosts and related legumes, and the results correlated with the metabolite profile that arose from the different cultural conditions. To the best of our knowledge, this is the first time that the OSMAC strategy integrated with metabolomics approaches has been applied to Colletotrichum species involved in legume diseases.

Ascochyta blight, caused by Ascochyta fabae, poses a significant threat to faba bean and other legumes worldwide. Necrotic lesions on stems, leaves, and pods characterize the disease. Given the economic impact of this pathogen and the potential involvement of secondary metabolites in symptom development, a study was conducted to investigate the fungus's ability to produce bioactive metabolites that might contribute to its pathogenicity. For this investigation, the fungus was cultured in three substrates (Czapek-Dox, PDB, and rice). The produced metabolites were analyzed by NMR and LC-HRMS methods, resulting in the dereplication of seven metabolites, which varied with the cultural substrates. Ascochlorin, ascofuranol, and (R)-mevalonolactone were isolated from the Czapek-Dox extract; ascosalipyrone, benzoic acid, and tyrosol from the PDB extract; and ascosalitoxin and ascosalipyrone from the rice extract. The phytotoxicity of the pure metabolites was assessed at different concentrations on their primary hosts and related legumes. The fungal exudates displayed varying degrees of phytotoxicity, with the Czapek-Dox medium's exudate exhibiting the highest activity across almost all legumes tested. The species belonging to the genus Vicia spp. were the most susceptible, with faba bean being susceptible to all metabolites, at least at the highest concentration tested, as expected. In particular, ascosalitoxin and benzoic acid were the most phytotoxic in the tested condition and, as a consequence, expected to play an important role on necrosis's appearance.

[Background] Rusts and powdery mildews are severe fungal diseases of major crops worldwide, including cereals and legumes. They can be managed by chemical fungicide treatments, with negative consequences as environmental pollution and risk for human and animal health. Bioactive natural products could be the safest alternative for pest control. The family of anthraquinones, as well as analogue compounds containing an anthraquinone moiety or some modified anthraquinone rings, has been reported to exhibit certain antibiotic activity. Thus, the potential antifungal activity of some anthraquinones isolated from Ascochyta lentis, was assayed in this study for their effectiveness to reduce rust and powdery mildew diseases on pea and oat. Their effect on fungal development was macro- and microscopically assessed on inoculated leaves, and compared to the control achieved by the chemical fungicide (Tetraconazol 12.5% and Azoxystrobin 25%). In addition, the most promising compound was also tested at different concentrations in inoculated whole plants in order to evaluate its preventive and curative potential against fungal infection., [Results] All metabolites studied strongly reduced the development of rust and powdery mildews in both pea and oat, being pachybasin and lentiquinone C the most effective ones in hampering fungal spore germination and appressoria formation. Some of them also affected post-penetration events reducing colony size and number of haustoria per colony. Results were confirmed for pachybasin in whole plants assays, showing an efficacy similar to the commercial fungicide to control fungal diseases, both in preventive and curative applications. [Conclusions] Some fungal anthraquinones and close metabolites, especially pachybasin, could be very promising molecules with effective potential as antifungal agents against both rust and powdery mildew of both pea and oat. Some structure activity-relationships feature have also been evaluated. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Basic Mycology and Mycotechnology deals with the study of fungi and production of their valuable products like different metabolites, food and pharmaceuticals by using fungal system as machinery in consideration with the principles of fungal biology, bioconversion and environmental technology. The book has been designed to give a basic idea on Mycology & applied biotechnological aspects of fungi. This book is aimed to cater to students of undergraduate & post-graduate, students appearing for various competitive examinations and researchers. The Book highlights on the basics about growth behaviors and diversity of fungi, detailed cell structures of different groups of fungi, wood decaying fungi, fungal genomics, fungal phylogeny as well as evolutionary aspects of fungi under “Basic Mycology” section. Under “Mycotechnology” section, authors have tried to give an input about fungal enzyme technology, role of fungal metabolites; recent findings about fungal recombinant technology in the field of industry have been discussed. This book also covers the research information about how “Plant-Mycorrhiza” and “Plant- Plant Growth Promoting Fungi (PGPF)” interactions can be used for sustainable agriculture. Authors have discussed about the role of “Mycoremediation” and how it can be used as an alternative eco-friendly approach for sustainable management of environment.

Basic Mycology and Mycotechnology deals with the study of fungi and production of their valuable products like different metabolites, food and pharmaceuticals by using fungal system as machinery in consideration with the principles of fungal biology, bioconversion and environmental technology. The book has been designed to give a basic idea on Mycology & applied biotechnological aspects of fungi. This book is aimed to cater to students of undergraduate & post-graduate, students appearing for various competitive examinations and researchers. The Book highlights on the basics about growth behaviors and diversity of fungi, detailed cell structures of different groups of fungi, wood decaying fungi, fungal genomics, fungal phylogeny as well as evolutionary aspects of fungi under “Basic Mycology” section. Under “Mycotechnology” section, authors have tried to give an input about fungal enzyme technology, role of fungal metabolites; recent findings about fungal recombinant technology in the field of industry have been discussed. This book also covers the research information about how “Plant-Mycorrhiza” and “Plant- Plant Growth Promoting Fungi (PGPF)” interactions can be used for sustainable agriculture. Authors have discussed about the role of “Mycoremediation” and how it can be used as an alternative eco-friendly approach for sustainable management of environment.

Cytochalasans are highly complex fungal metabolites which exhibit diverse biological activities. Little is known of the chemical steps involved in the construction of the tricyclic core, which consists of an octahydro-isoindole skeleton fused to a macrocyclic ring. Here, using a directed gene knockout and complementation strategy, we show that PyiF is implicated as the proposed intramolecular [4+2] Diels-Alderase required for construction of the tricyclic core of pyrichalasin H 1. © 2020 The Royal Society of Chemistry.

Natural products research remains a fertile source for drug discovery due to the complexity, chemical diversity and biological activity of compounds discovered from nature. Verticillins are members of the epipolythiodioxopiperazine (ETP) alkaloid class of fungal metabolites and are known as potent cytotoxic agents, some with IC50 values of less than 10 nM. Studies showed that verticillin A has activity as a selective histone methyl transferases inhibitor with important anticancer properties. However, several challenges slowed the further development of this class of compounds. The goals of this project strived to address such challenges in the development of the ETP alkaloids in three ways: (1) enhancing the production of verticillins, (2) identifying and isolating new analogues of the verticillins, and (3) developing a targeted delivery approach for the verticillins. Aim 1 was achieved by analyzing different fungal strains under a suite of fermentation conditions. These studies were facilitated by the use of the droplet-liquid microjunction-surface sampling probe (droplet probe) coupled with UHPLC–PDA–HRMS/MS, which enables chemical analysis in situ directly from the surface of the cultures. These experiments showed that the production of verticillins was greatly affected by growth conditions. Using these technologies to select the best among the tested growth conditions, the production of the verticillin analogues was increased in laboratory scale fermentation. Aim 2 was achieved via using a precursor-directed biosynthesis approach that was monitored in situ via droplet probe. To characterize the generated series of “non-natural natural products”, a suite of NMR and mass spectrometry data were collected. This approach yielded novel compounds that would be difficult to generate via synthesis. Furthermore, and in a collaborative manner, the generation of new analogues was also achieved via semisynthetic approaches that generated ester, carbonate, sulfonate and carba

Weeds are undesirable vegetation directly or indirectly inferring with human welfare. Conventional methods of weed control have failed due to one or other reason. Herbicide-resistant weeds are the main problem in weed control due to the number of weed biotypes resistant to herbicides that constantly increases by the continuous use of the same products for years. Development of alternative weed control methods is needed to help decrease reliance on herbicide use. Biological weed control is an alternative option for weed problems, particularly in agriculture and forestry. It is based on the use of natural enemies, particularly insects and pathogens to control weeds, as a sustainable, low cost and more environmentally acceptable method of weed control. One of the approaches to biological weed control using fungal phytotoxin applied in similar ways to conventional herbicides. Fungal phytotoxins are natural secondary metabolites produced by plant pathogenic fungi during host–pathogen interactions. They have received considerable particular attention for elucidating disease etiology, and consequently to design strategies for disease control. Due to wide differences in their chemical structures, these toxic metabolites have different ecological and environmental roles and mechanisms of action. This review aims at summarizing the studies on the possible use of fungal phytotoxin as a lucrative, novel source of secondary phytotoxic herbicidal compounds for management of broad spectrum, noxious and pernicious weeds.

Although fungi produce highly structurally diverse metabolites, many of which have served as excellent sources of pharmaceuticals, no fungi-derived agent has been approved as a cancer drug so far. This is despite a tremendous amount of research being aimed at the identification of fungal metabolites with promising anticancer activities. This review discusses the results of clinical testing of fungal metabolites and their synthetic derivatives, with the goal to evaluate how far we are from an approved cancer drug of fungal origin. Also, because in vivo studies in animal models are predictive of the efficacy and toxicity of a given compound in a clinical situation, literature describing animal cancer testing of compounds of fungal origin is reviewed as well. Agents showing the potential to advance to clinical trials are also identified. Finally, the technological challenges involved in the exploitation of fungal biodiversity and procurement of sufficient quantities of clinical candidates are discussed, and potential solutions that could be pursued by researchers are highlighted., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

The low yields of biomass and antimicrobial metabolites obtained in fermentation processes are limiting factors for implementing biological control agents in the field -- In this context, optimization of the culture medium for the biological control agent Bacillus subtilis EA-CB0015 was conducted in submerged culture to maximize the biomass production and antifungal activity -- Additionally, the active metabolites against the phytopathogen Mycosphaerella fijiensis produced under optimized conditions were identified -- Carbon and nitrogen constituents of the culture medium were optimized using a 22 factorial design with central point followed by a multiple response optimization coupled to the desirability function approach -- The optimized medium (33.4 g/L of glucose and 32.5 g/L of yeast extract), showed significant increases in both, cell density by 3.6 folds (13.271.0 g/L) and antifungal activity by 1.2 folds (77.770.3% inhibition) -- To gain insight into the type of active compounds, they were purified and identified by mass spectrometry (MS) -- The MS analysis revealed the presence of three families of lipopeptides: surfactin, fengycin and iturin -- The high antifungal activity was associated with the novel fengycin C and with iturin -- A which were partially growth-associated with a maximum concentration of 781.4 and 355.4 mg/L at 36 h of growth, respectively -- These results indicate the potential of B. subtilis EA-CB0015 to produce high concentrations of biomass and lipopeptides that can be exploited for biotechnological application

Although fungi produce highly structurally diverse metabolites, many of which have served as excellent sources of pharmaceuticals, no fungi-derived agent has been approved as a cancer drug so far. This is despite a tremendous amount of research being aimed at the identification of fungal metabolites with promising anticancer activities. This review discusses the results of clinical testing of fungal metabolites and their synthetic derivatives, with the goal to evaluate how far we are from an approved cancer drug of fungal origin. Also, because in vivo studies in animal models are predictive of the efficacy and toxicity of a given compound in a clinical situation, literature describing animal cancer testing of compounds of fungal origin is reviewed as well. Agents showing the potential to advance to clinical trials are also identified. Finally, the technological challenges involved in the exploitation of fungal biodiversity and procurement of sufficient quantities of clinical candidates are discussed, and potential solutions that could be pursued by researchers are highlighted., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

Uranium contamination of soils and water is a worldwide problem due to geology or anthropogenic release such as mining, or use of inorganic fertilizers. In situ remediation of low and moderately contaminated sites is a complicated procedure due to the complex chemistry of uranium. This study demonstrates that at pH 3.5, a fungal strain isolated from unprocessed uranium bearing shale creates hydrochemical conditions that immobilize 97% of a total of 10 mg L-1 dissolved uranium in a 0.20 μm pore system. The redistribution occurred within 10 minutes and remained for five weeks and just 12% of the inventory was retrieved in the biomass. Size exclusion chromatography of the dissolved phase identified organic substances in the range of more than 60 kD down to 100 D as a response to time of incubation. Geochemical modeling indicates formation of uranium-organic complexes where ligand size, coordination chemistry and their tendency to agglomerate determine the redistribution.

An in silico screen of the NIH Molecular Library Small Molecule Repository (MLSMR) of 350000 compounds and confirmatory bioassays led to identification of chaetochromin A (1) as an inhibitor of botulinum neurotoxin serotype A (BoNT A). Subsequent acquisition and testing of analogues of 1 uncovered two compounds, talaroderxines A (2) and B (3), with improved activity. These are the first fungal metabolites reported to exhibit BoNT/A inhibitory activity., Published in ACS Medicinal Chemistry Letters, v3 p387-391, 2 Apr 2012.

Penicillium roqueforti, Penicillium paneum, Monascus ruber, Alternaria tenuissima, Fusarium graminearum, Fusarium avenaceum, Byssochlamys nivea and Aspergillus fumigatus have previously been identified as major fungal contaminants of Danish maize silage. In the present study their metabolite production and in vitro cytotoxicity have been determined for fungal agar and silage extracts. All 8 fungal species significantly affected Caco-2 cell viability in the resazurin assay, with large variations for each species and growth medium. The 50% inhibition concentrations (IC50) of the major P. roqueforti metabolites roquefortine C (48μg/mL), andrastin A (>50μg/mL), mycophenolic acid (>100μg/mL) and 1-hydroxyeremophil-7(11),9(10)-dien-8-one (>280μg/mL) were high. Fractionating of agar extracts identified PR-toxin as an important cytotoxic P. roqueforti metabolite, also detectable in maize silage. The strongly cytotoxic B. nivea and P. paneum agar extracts contained patulin above the IC50 of 0.6μg/mL, however inoculated onto maize silage B. nivea and P. paneum did not produce patulin (>371μg/kg). Still B. nivea infected maize silage containing mycophenolic acid (∼50mg/kg), byssochlamic acid and other metabolites, was cytotoxic. In contrast hot-spots of P. roqueforti, P. paneum, M. ruber and A. fumigatus were not more cytotoxic than uninoculated silage.

Kojic acid [5-hydroxy-2-(hydroxymethyl)-1,4-pyrone], is a fungal metabolite produced by many species of fungi Aspergillus oryzae, Acetobacter and Penicillium camembertii. It is used for inhibiting the browning effect of tyrosinase in the food and cosmetic industries. However, kojic acid is water-soluble and its instability has been a problem in cosmetic use. The improvement in oil-solubility of kojic acid through its chemical or lipase-catalyzed acylation with fatty acid has been reported and synthesis of kojic acid ester by chemical method usually results in a complex mixture. Recently, enzymatic synthesis with lipase as catalyst has been used to produce a number of commercially important esters, both by transesterification and by direct esterification. Therefore, an optimized process for high yield enzymatic synthesis of kojic acid ester would benefit manufacturers and be more appealing to consumers. The aims of this research project were set up for better understanding on the relationships between the factors (reaction time, temperature, and enzyme amount and substrate molar ratio) and the response (% molar conversion) of kojic acid esters synthesis, to determine optimal synthesis conditions for kojic acid esters by immobilized lipase using Response surface methodology (RSM) and central composite design (CCD) and to characterize the structure of the product synthesized. RSM and CCD were employed to evaluate the effects of synthesis variables, such as reaction time (24 to 48 h), temperature (30 to 60 0C), enzyme amount (0.1 to 0.4 g) and substrate molar ratio of kojic acid to oleic acid (1:1 to 5:1).The products were extracted and subjected to thin layer chromatography and gas chromatography and the structure of products were confirmed by infra red, gas chromatography-mass spectroscopy and nuclear magnetic resonance. The optimum conditions for the synthesis of kojic acid esters were achieved at 36 h, 45oC, 0.25 g of enzyme amount, mole ratio of 3 (kojic acid/oleic

[EN] Bioassay-guided fractionation of the organic extract derived from the terrestrial fungus Penicillium coalescens led to the isolation of the known mycotoxin (-)-botryodiplodin (1) and eight new structurally related analogues (2-9). The structures of the novel compounds were determined by MS and NMR studies, including 1D and 2D NMR. A likely biogenetic pathway from the aldehydic open form of 1 (C-7 unit, U1) is proposed for these metabolites. Among all the isolated metabolites, only (-)-1 showed antifungal, antibacterial, and insecticidal activity. This latter activity appears to be a new property attributed to (-)-1.

[EN] Bioassay-guided fractionation of the organic extract derived from the terrestrial fungus Penicillium coalescens led to the isolation of the known mycotoxin (-)-botryodiplodin (1) and eight new structurally related analogues (2-9). The structures of the novel compounds were determined by MS and NMR studies, including 1D and 2D NMR. A likely biogenetic pathway from the aldehydic open form of 1 (C-7 unit, U1) is proposed for these metabolites. Among all the isolated metabolites, only (-)-1 showed antifungal, antibacterial, and insecticidal activity. This latter activity appears to be a new property attributed to (-)-1.

Filamentous fungi produce asexual dispersive spores (conidia), when conditions are not suitable for apical extension growth. Conidiation (the process by which conidia produced) in genus Penicillium has attracted considerable interest because of its wide usage in different areas. In addition, several Penicillium species are pathogenic toward humans and plants, causing crop spoilage as well as decay processes. It is consequently important to understand this process since it could provide tools to inhibit or to induce conidiation in the case when fungal conidia are harmful or are useful. However, the precise mechanism by which conidiation induction is triggered has proved to be elusive. Recently, two fungal metabolites conidiagenol (1) and conidiagenone (2) were isolated from the fermentation broth of Penicillium cyclopium. They are related diterpenes, and show potent and selective conidiation inducing activity in liquid culture. 2 is believed to be the true inducer and 1 a biosynthetic precursor of 2, and its effect depends on its oxidation to 2 by the fungus. In order to initiate a structure-activity relationship study, and to obtain analogues of the natural product with similar or more potent biological activity but more readily available, three types of analogues of conidiogenone 2 were prepared. Starting from the ring A which bears all the functional groups, the simplified ring A, ring AB and tricyclic analogues were designed and synthesized. They share the same functional groups as the parent molecular but differ in size. In addition, a reasonable route towards the total synthesis of conidiogenone (2) is proposed. In the course of synthesis of the analogues, a mild method for hydrolysis of acetals in solvent-free conditions under microwave irradiation was developed, to meet the need for the selective deprotection of acetals.

[EN] New analogues of the bioactive enamides isolated from P. brevicompactum (2 and 3) have been synthesized to improve the biological activities. Two different structural modifications have been introduced: substitution of the aliphatic side chain present in the natural products (1-4) by other groups frequently found in other active compounds and use of other nitrogen-containing five-membered rings with different degrees of oxidation. In this way, the insecticidal and fungicidal activities have been improved. Thus, compound 9, which posseses a 3-pyrroline ring, exhibited important insecticidal activity against third-instar nymphs of Oncopeltus fasciatus Dallas (100% mortality at 7.5 mu g/cm(2)). Remarkable fungicidal activity was also found, and preliminary structure-activity relationships could be established.

[EN] New analogues of the bioactive enamides isolated from P. brevicompactum (2 and 3) have been synthesized to improve the biological activities. Two different structural modifications have been introduced: substitution of the aliphatic side chain present in the natural products (1-4) by other groups frequently found in other active compounds and use of other nitrogen-containing five-membered rings with different degrees of oxidation. In this way, the insecticidal and fungicidal activities have been improved. Thus, compound 9, which posseses a 3-pyrroline ring, exhibited important insecticidal activity against third-instar nymphs of Oncopeltus fasciatus Dallas (100% mortality at 7.5 mu g/cm(2)). Remarkable fungicidal activity was also found, and preliminary structure-activity relationships could be established.

[EN] Two new natural products, N-(2-methyl-3-oxodec-8-enoyl)-2-pyrroline (2) and 2-(hept-5-enyl)-3-methyl-4-oxo-6,7,8,8a-tetrahydro-4H-pyrrolo[2,1-b]-1,3-oxazine (3), have been isolated from Penicillium brevicompactum Dierckx. Compound 2 has shown an important in vivo anti-juvenile-hormone (anti-JH) activity while compound 3 has exhibited insecticidal activity against Oncopeltus fasciatus Dallas. Both products have been synthesized starting from 1,4-hexadiene, by means of a sequence of reactions which includes the preparation of 6-octenoic acid and its transformation into the corresponding acid chloride, in order to acylate Meldrum's acid. Subsequent aminolysis with pyrrolidine, followed by methylation at the activated position of the ß-oxo amide with iodomethane, introduction of a methoxy group at the pyrrolidine ring by anodic oxidation and final elimination of methanol on SiO2 led to 2 and 3. The fact that both metabolites can be prepared by the same sequence indicates that they must be biogenetically related. Based on structural similarities, compounds 2 and 3 are also closely related to the recently discovered brevioxime

[EN] Two new natural products, N-(2-methyl-3-oxodec-8-enoyl)-2-pyrroline (2) and 2-(hept-5-enyl)-3-methyl-4-oxo-6,7,8,8a-tetrahydro-4H-pyrrolo[2,1-b]-1,3-oxazine (3), have been isolated from Penicillium brevicompactum Dierckx. Compound 2 has shown an important in vivo anti-juvenile-hormone (anti-JH) activity while compound 3 has exhibited insecticidal activity against Oncopeltus fasciatus Dallas. Both products have been synthesized starting from 1,4-hexadiene, by means of a sequence of reactions which includes the preparation of 6-octenoic acid and its transformation into the corresponding acid chloride, in order to acylate Meldrum's acid. Subsequent aminolysis with pyrrolidine, followed by methylation at the activated position of the ß-oxo amide with iodomethane, introduction of a methoxy group at the pyrrolidine ring by anodic oxidation and final elimination of methanol on SiO2 led to 2 and 3. The fact that both metabolites can be prepared by the same sequence indicates that they must be biogenetically related. Based on structural similarities, compounds 2 and 3 are also closely related to the recently discovered brevioxime

[EN] Two new natural products have been isolated from culture broth of Penicillium brevicompactum Dierckx. The structures have be en assigned as N-(2-methyl-3-oxodecanoyl)pyrrole and N-(2-methyl-3-oxodec-8-enoyl)pyrrole on the basis of spectral data. Synthesis of analogues has been carried out by acylation of the pyrrole ring at Ct with different acylated Meldrum's acids. Two analogues (6b and 7b) have shown interesting insecticidal activities, and three other ones (6a, 6c, and 7a) have exhibited significant broad-spectrum fungicidal activities. These synthetic products might be considered as a starting point in the search for new pesticides.

[EN] Two new natural products have been isolated from culture broth of Penicillium brevicompactum Dierckx. The structures have be en assigned as N-(2-methyl-3-oxodecanoyl)pyrrole and N-(2-methyl-3-oxodec-8-enoyl)pyrrole on the basis of spectral data. Synthesis of analogues has been carried out by acylation of the pyrrole ring at Ct with different acylated Meldrum's acids. Two analogues (6b and 7b) have shown interesting insecticidal activities, and three other ones (6a, 6c, and 7a) have exhibited significant broad-spectrum fungicidal activities. These synthetic products might be considered as a starting point in the search for new pesticides.

Using a monoclonal antibody-based ELISA, 600 pAN7-1 plasmid-tagged mutants of Penicillium paxilli were screened for paxilline accumulation and one paxilline negative mutant, YI-20, was identified (Itoh, unpublished data). A molecular analysis of this mutant showed that pAN7-1 was inserted at a single site but was present as 4-6 copies arranged in a head-to tail tandem repeat. Rescue of flanking sequences and analysis of the corresponding genomic region revealed that YI-20 has an extensive deletion at the site of pAN7-1 integration. Probing of a CHEF gel with the same sequences showed that associated with the deletion is a rearrangement of chromosome Va. Targeted gene disruption of wild-type sequences adjacent to the site where pAN7-1 inserted, resulted in the generation of two additional paxilline-negative mutants; both were single crossovers with deletions extending outside the region mapped. Neither of these new mutants had a rearrangement of chromosome Va, suggesting that deletion of genes on this chromosome is responsible for the paxilline-negative phenotype.