No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Role of fungal metabolites in pharmaceuticals, human health, and agriculture
ResearchGate has not been able to resolve any citations for this publication.
Fungi produce several bioactive metabolites, pigments, dyes, antioxidants, polysaccharides, and industrial enzymes. Fungal products are also the primary sources of functional food and nutrition, and their pharmacological products are used for healthy aging. Their molecular properties are validated through the use of recent high-throughput genomic, transcriptomic, and metabolomic tools and techniques. Together, these updated multi-omic tools have been used to study fungal metabolites structure and their mode of action on biological and cellular processes. Diverse groups of fungi produce different proteins and secondary metabolites, which possess tremendous biotechnological and pharmaceutical applications. Furthermore, its use and acceptability can be accelerated by adopting multi-omics, bioinformatics, and machine learning tools that generate a huge amount of molecular data. The integration of artificial intelligence and machine learning tools in the era of omics and big data has opened up a new outlook in both basic and applied researches in the area of nutraceuticals and functional food and nutrition.
Key Points
•Multi-omic tool helps in the identification of novel fungal metabolites
•Intra-omic data from genomics to bioinformatics
•Novel metabolites and application in human health
Global food production faces many challenges, including climate change, a water crisis,
land degradation, and desertification. These challenges require research into non-traditional sources
of human foods. Edible mushrooms are considered an important next-generation healthy food
source. Edible mushrooms are rich in proteins, dietary fiber, vitamins, minerals, and other bioactive
components (alkaloids, lactones, polysaccharides, polyphenolic compounds, sesquiterpenes, sterols,
and terpenoids). Several bioactive ingredients can be extracted from edible mushrooms and incorporated into health-promoting supplements. It has been suggested that several human diseases can
be treated with extracts from edible mushrooms, as these extracts have biological effects including
anticancer, antidiabetic, antiviral, antioxidant, hepatoprotective, immune-potentiating, and hypocholesterolemic influences. The current study focuses on sustainable approaches for handling edible
mushrooms and their secondary metabolites, including biofortification. Comparisons between edible
and poisonous mushrooms, as well as the common species of edible mushrooms and their different
bioactive ingredients, are crucial. Nutritional values and the health benefits of edible mushrooms, as
well as different biomedical applications, have been also emphasized. Further research is needed to
explore the economic sustainability of different medicinal mushroom bioactive compound extracts
and their potential applications against emerging diseases such as COVID-19. New approaches such
as nano-biofortification are also needed to supply edible mushrooms with essential nutrients and/or
to increase their bioactive ingredients.
Naturally occurring autochthonous microbes associated with ethnic beer starters are diverse and important as they play different functional roles in beer fermentations. The study on culturable microbes from the ethnic rice beer starter “emao” of the Bodo community of Assam is limited. Here we isolated and identified the culturable fungal diversity associated with emao and screened them for beer-producing capability from glucose and starch substrates. Based on morphology and molecular characterization, the species identified were Candida glabrata (Cgla_RF2), Cyberlindnera fabianii (Cfab_RF37), Hyphopichia burtonii (Hbur_RF19), Mucor circinelloides (Mcir_RF48), Mucor indicus (Mind_RF25), Penicillium citrinum (Pcit_RF32), Rhodosporidiobolus ruineniae (Rrui_RF4 & Rrui_RF43), Saccharomyces cerevisiae (Scer_RF6), Saccharomycopsis fibuligera (Sfib_RF11), and Wickerhamomyces anomalus (Wano_RF3) among which the relative abundance (RA) of W. anomalus was the highest (24%) followed by C. glabrata and H. burtonii (16% in each). Five (Hbur_RF19, Sfib_RF11, Mind_RF25, Mcir_RF48, and Pcit_RF32) of eleven isolates showed amylase positive in the starch medium. Scer_RF6 showed the highest ethanol tolerance (14% v/v) followed by Hbur_RF19 (12% v/v), Cgla_RF2 (11% v/v) and Wano_RF3 (11% v/v). The amylase-positive strains produced beer-containing ethanol in the range of 3.17–7.3 (% v/v) from rice substrate. Although the rice beer produced by amylase-positive strains showed negligible pH difference, other parameters like ethanol, ascorbic acid, total phenol, and antioxidant properties were varied from beer to beer. Antibacterial activities shown by Mcir_RF48 and Pcit_RF32 against the test bacteria were higher with a 23–35 mm zone of inhibition than the other isolates. The present findings reveal the presence of fungi with antibacterial, amylolytic, ethanol fermenting, and antioxidant producing capacity in emao which could the source for future bioprospection.
Covering: 2002 to 2020In their natural environment, fungi must compete for resources. It has been hypothesized that this competition likely induces the biosynthesis of secondary metabolites for defence. In a quest to discover new chemical diversity from fungal cultures, a growing trend has been to recapitulate this competitive environment in the laboratory, essentially growing fungi in co-culture. This review covers fungal-fungal co-culture studies beginning with the first literature report in 2002. Since then, there has been a growing number of new secondary metabolites reported as a result of fungal co-culture studies. Specifically, this review discusses and provides insights into (1) rationale for pairing fungal strains, (2) ways to grow fungi for co-culture, (3) different approaches to screening fungal co-cultures for chemical diversity, (4) determining the secondary metabolite-producing strain, and (5) final thoughts regarding the fungal-fungal co-culture approach. Our goal is to provide a set of practical strategies for fungal co-culture studies to generate unique chemical diversity that the natural products research community can utilize.
Essential oils (EOs) are volatile and concentrated liquids extracted from different parts of plants. Bioactive compounds found in EOs, especially terpenes and terpenoids possess a wide range of biological activities including anticancer, antimicrobial, anti-inflammatory, antioxidant, and antiallergic. Available literature confirms that EOs exhibit antimicrobial and food preservative properties that are considered as a real potential application in food industry. Hence, the purpose of this review is to present an overview of current knowledge of EOs for application in pharmaceutical and medical industries as well as their potential as food preservatives in food industry.
Basidiomycetes, also known as club fungi, consist of a specific group of fungi. Basidiomycetes produce a large number of secondary metabolites, of which sesquiterpenoids, diterpenoids and triterpenoids are the primary components. However, these terpenoids tend to be present in low amounts, which makes it difficult to meet application requirements. Terpenoid biosynthesis improves the quantity of these secondary metabolites. However, current understanding of the biosynthetic mechanism of terpenoids in basidiomycetes is insufficient. Therefore, this article reviews the latest research on the biosynthesis of terpenoids in basidiomycetes and summarizes the CYP450 involved in the biosynthesis of terpenoids in basidiomycetes. We also propose opportunities and challenges for chassis microbial heterologous production of terpenoids in basidiomycetes and provide a reference basis for the better development of basidiomycete engineering.
Bakery items are a vital element of a well-balanced diet, and supermarket shelves now stock a wide range of them. Bakery items are the most popular ready-to-eat foods (REF).Objective:To assess the microbial quality of bakery foods (Bread, Cake and patties) and check the total plate count (TPC), bacterial and yeast count Methods:The analysis of the microbial quality of bakery products was determined for three different bakery products (bread, cake and patties) at ten different locations collected from a renowned bakery in Lahore, Pakistan. The samples were assessed under complete hygienic conditions by standardized plate count (TPC) and MPN method. Micro-organisms (Coliform, Fecal Coliform and Yeast) were lately confirmed by their morphological characteristics and biochemical tests Results: Among the three commodities, bread was found to be highly contaminated by micro-organisms and the total plate count recorded was 4.7 x 105cfu g-1collected from sector I9 which is not consumable. Whereas Patties showed the number of TPC as 1.6 x 105 cfu g-1also collected from sector I9. Cake was revealed as least infected bakery product i.e., 5.7 x 104 cfu g-1. The above results showed that sector I9 is highly contaminated and a threat for health. Bacterial plate count (Coliform and Fecal Coliform count) was highly measured in bread as 460 MPN g-1 taken from sector I5 where as it remains under the permissible limit determined by WHO, 1994 in remaining sectors Conclusions:In conclusion the bakery food is contaminated by the use of un-hygienic water, miss handled during the process after baking i.e., slicing, serving and packaging. To avoid a possible epidemic of food borne illness, competent authorities should conduct a stricter and more stringent inspection of REFs sold to clients in bakeries.
The long-term and excessive usage of pesticides is an enormous burden on the environment, which also increases pest resistance. To overcome this problem, research and application of entomopathogenic fungi, which are both environmentally friendly and cause lower resistance, have gained great momentum. Entomopathogenic fungi have a wide range of prospects. Apart from Bacillus thuringiensis, Beauveria bassiana is the most studied biopesticide. After invading insect hosts, B. bassiana produces a variety of toxins, which are secondary metabolites such as beauvericin, bassianin, bassianolide, beauverolides, tenellin, oosporein, and oxalic acid. These toxins help B. bassiana to parasitize and kill the hosts. This review unequivocally considers beauveria toxins highly promising and summarizes their attack mechanism(s) on the host insect immune system. Genetic engineering strategies to improve toxin principles, genes, or virulent molecules of B. bassiana have also been discussed. Lastly, we discuss the future perspective of Beauveria toxin research, including newly discovered toxins.
Significance
Fungi represent an underexploited resource for new compounds with applications in the pharmaceutical and agriscience industries. Despite the availability of >1,000 fungal genomes, our knowledge of the biosynthetic space encoded by these genomes is limited and ad hoc. We present results from systematically organizing the biosynthetic content of 1,037 fungal genomes, providing a resource for data-driven genome mining and large-scale comparison of the genetic and molecular repertoires produced in fungi, and compare to those present in bacteria.
Marine fungi are species of fungi which live in estuaries environment and marine environment. These species are found in common habitat. Marine fungi are rich in antimicrobial compounds such as anthrones, cephalosporins, peptides, steroids. These compounds which are derived mainly focused in the area of anti-inflammatory, anti-oxidant, anti-fungal, anti-microbial, anti-fouling activity. Bioactive terpene compounds are produced by marine fungi and marine derived fungi can produce sclerotides, trichoderins. Marine fungi have become the richest sources of biologically active metabolites and structurally novel in the marine environment. In a recent study the marine derived fungi dichotomomyces cejpii exhibits activity towards cannabinoid which is used to treat alzheimer dementia. Aspergillus unguis showed significant acetyl cholinesterase besides its anti-oxidant activity. These acts as a promising intent for discovery of pharmaceutically important metabolites like alkaloids, peptides. Computational (in silico) strategies have been developed and broadly applied to pharmacology advancement and testing. This review summarizes the bioactive compounds derived from marine fungi in accordance with the sources and their biological activities.
Fungi are a group of eukaryotic organisms and source of food, organic acids, alcohol, antibiotics, growth-promoting substances, enzymes, and amino acids. They include microorganisms like molds, yeasts, and mushrooms. They live on dead or living plants or animals' tissue. Fungi are very different from other living organisms ; they are the primary decomposers of substances in the ecological system. Fungi are tremendous decomposer of organic waste material and most readily attack cellulose, lignins, gums, and other organic complex substances. Fungi can act also under a wide range of soil reaction from acidic to alkaline soil reactions. Fungi conjointly play a basic role in different physiological processes as well as mineral and water uptake, chemical change, stomatal movement, and biosynthesis of compounds termed biostimulants, auxins, lignan, and ethylene to enhance the flexibility of plants to ascertain and cope environmental stresses like drought, salinity, heat, cold, and significant metals.
Trichoderma species are widely used as biofungicides for the control of fungal plant pathogens. Several studies have been performed to identify the main genes and compounds involved in Trichoderma–plant–microbial pathogen cross-talks. However, there is not much information about the exact mechanism of this profitable interaction. Peptaibols secreted mainly by Trichoderma species are linear, 5–20 amino acid residue long, non-ribosomally synthesized peptides rich in α-amino isobutyric acid, which seem to be effective in Trichoderma–plant pathogenic fungus interactions. In the present study, reversed phase (RP) high-performance liquid chromatography (HPLC) coupled with electrospray ionization (ESI) mass spectrometry (MS) was used to detect peptaibol profiles of Trichoderma strains during interactions with fungal plant pathogens. MS investigations of the crude extracts deriving from in vitro confrontations of Trichoderma asperellum and T. longibrachiatum with different plant pathogenic fungi (Fusarium moniliforme, F. culmorum, F. graminearum, F. oxysporum species complex, Alternaria solani and Rhizoctonia solani) were performed to get a better insight into the role of these non-ribosomal antimicrobial peptides. The results revealed an increase in the total amount of peptaibols produced during the interactions, as well as some differences in the peptaibol profiles between the confrontational and control tests. Detection of the expression level of the peptaibol synthetase tex1 by qRT-PCR showed a significant increase in T. asperellum/R. solani interaction in comparison to the control. In conclusion, the interaction with plant pathogens highly influenced the peptaibol production of the examined Trichoderma strains.
Mushrooms have a long history of uses for their medicinal and nutritional properties. They have been consumed by people for thousands of years. Edible mushrooms are collected in the wild or cultivated worldwide. Recently, mushroom extracts and their secondary metabolites have acquired considerable attention due to their biological effects, which include antioxidant, antimicrobial, anti-cancer, anti-inflammatory, anti-obesity, and immunomodulatory activities. Thus, in addition to phytochemists, nutritionists and consumers are now deeply interested in the phytochemical constituents of mushrooms, which provide beneficial effects to humans in terms of health promotion and reduction of disease-related risks. In recent years, scientific reports on the nutritional, phytochemical and pharmacological properties of mushroom have been overwhelming. However, the bioactive compounds and biological properties of wild edible mushrooms growing in Southeast Asian countries have been rarely described. In this review, the bioactive compounds isolated from 25 selected wild edible mushrooms growing in Southeast Asia have been reviewed, together with their biological activities. Phytoconstituents with antioxidant and antimicrobial activities have been highlighted. Several evidences indicate that mushrooms are good sources for natural antioxidants and antimicrobial agents
Synthetic chemical pesticides have been used for many years to increase the yield of agricultural crops. However, in the future, this approach is likely to be limited due to negative impacts on human health and the environment. Therefore, studies of the secondary metabolites produced by agriculturally important microorganisms have an important role in improving the quality of the crops entering the human food chain. In this review, we have compiled information about the most important secondary metabolites of fungal species currently used in agriculture pest and disease management.
The draft genome of the ascomycete fungus Xylaria flabelliformis (previously known as Xylaria cubensis ) was sequenced using Illumina paired-end technology. The assembled genome is 41.2 Mb long and contains 11,404 genes. This genome will contribute to our understanding of X. flabelliformis secondary metabolism and the organism’s ability to live as a decomposer as well as an endosymbiont.
A number of gene clusters involved in biosynthesis of secondary metabolites are presumably silent or expressed at low levels under conditions of standard laboratory cultivation, resulting in a large gap between the pool of discovered metabolites and genome capability. This work mimicked naturally occurring competition by construction of an artificial coculture of basidiomycete fungi for the identification of secondary metabolites with novel scaffolds and excellent bioactivity. Unusual linear sesterterpenes of postrediene A to C synthesized by P. ostreatus not only were promising lead drugs against human-pathogenic fungi but also highlighted a distinct pathway for sesterterpene biosynthesis in basidiomycetes. The current work provides an important basis for uncovering novel gene functions involved in sesterterpene synthesis and for gaining insights into the mechanism of silent gene activation in fungal defense.
Fungi grow in competitive environments, and to cope, they have evolved strategies, such as the ability to produce a wide range of secondary metabolites. This begs two related questions. First, how do secondary metabolites influence fungal ecology and interspecific interactions? Second, can these interspecific interactions provide a way to “see” how fungi respond, chemically, within a competitive environment? To evaluate these, and to gain insight into the secondary metabolic arsenal fungi possess, we co-cultured Aspergillus fischeri, a genetically tractable fungus that produces a suite of mycotoxins, with Xylaria cubensis, a fungus that produces the fungistatic compound and FDA-approved drug, griseofulvin. To monitor and characterize fungal chemistry in situ, we used the droplet-liquid microjunction-surface sampling probe (droplet probe). The droplet probe makes a microextraction at defined locations on the surface of the co-culture, followed by analysis of the secondary metabolite profile via liquid chromatography-mass spectrometry. Using this, we mapped and compared the spatial profiles of secondary metabolites from both fungi in monoculture versus co-culture. X. cubensis predominantly biosynthesized griseofulvin and dechlorogriseofulvin in monoculture. In contrast, under co-culture conditions a deadlock was formed between the two fungi, and X. cubensis biosynthesized the same two secondary metabolites, along with dechloro-5′-hydroxygriseofulvin and 5′-hydroxygriseofulvin, all of which have fungistatic properties, as well as mycotoxins like cytochalasin D and cytochalasin C. In contrast, in co-culture, A. fischeri increased the production of the mycotoxins fumitremorgin B and verruculogen, but otherwise remained unchanged relative to its monoculture. To evaluate that secondary metabolites play an important role in defense and territory establishment, we co-cultured A. fischeri lacking the master regulator of secondary metabolism laeA with X. cubensis. We found that the reduced secondary metabolite biosynthesis of the ΔlaeA strain of A. fischeri eliminated the organism’s ability to compete in co-culture and led to its displacement by X. cubensis. These results demonstrate the potential of in situ chemical analysis and deletion mutant approaches for shedding light on the ecological roles of secondary metabolites and how they influence fungal ecological strategies; co-culturing may also stimulate the biosynthesis of secondary metabolites that are not produced in monoculture in the laboratory.
The cycloundecapeptide cyclosporin A (CsA) was first isolated from the insect-pathogenic fungus Tolypocladium inflatum for its antifungal activity and later developed as an immunosuppressant drug. However, the full biosynthetic mechanism of CsA remains unknown and has puzzled researchers for decades. In this study, the biosynthetic gene cluster is suggested to include 12 genes encoding enzymes, including the nonribosomal peptide synthetase (NRPS) (SimA) responsible for assembling the 11 amino acid substrates of cyclosporine and a polyketide synthase (PKS) (SimG) to mediate the production of the unusual amino acid (4R)-4-[(E)-2-butenyl]-4-methyl-l-threonine (Bmt). Individual deletion of 10 genes, isolation of intermediates, and substrate feeding experiments show that Bmt is biosynthesized by three enzymes, including SimG, SimI, and SimJ. The substrate d-alanine is catalyzed from l-alanine by alanine racemase SimB. Gene cluster transcription is regulated by a putative basic leucine zipper (bZIP)-type protein encoded by the cluster gene SimL. We also found that the cluster cyclophilin (SimC) and transporter (SimD) genes contribute to the tolerance of CsA in the CsA-producing fungus. We also found that cyclosporine production could enable the fungus to outcompete other fungi during cocultivation tests. Deletion of the CsA biosynthetic genes also impaired fungal virulence against insect hosts. Taking all the data together, in addition to proposing a biosynthetic pathway of cyclosporines, the results of this study suggest that CsA produced by this fungus might play important ecological roles in fungal environment interactions.
Mosquitoes are the carriers of severe and well-known illnesses such as malaria, arboviral encephalitis, dengue, chikungunya and yellow fever, which cause significant morbidity and mortality in humans and domestic animals around the world. Entomopathogenic fungal metabolites act as a mosquito control agent and are potential alternatives to chemical control because they can be innovative and more selective than chemical insecticides. The main aim of the present study was to perform experiments on the larvicidal and pupicidal effects of the entomopathogenic fungus Beauveria bassiana (isolated from infected grasshopper) against the first to fourth instar larvae of Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti. The larval and pupal mortality were observed after 24 h of exposure. The efficacy of an ethyl acetate mycelium extract at all the tested concentrations (50, 100, 150, 200, 250 and 300 μg mL⁻¹) exhibited better activity against the 1st to 4th instar larvae of An. stephensi (LC50 = 42.82, 39.45, 25.72, and 32.66; LC90 = 254.67, 367.11, 182.27, and 199.20 μg mL⁻¹), Cx. quinquefasciatus (LC50 = 72.38, 68.11, 27.06, and 35.495; LC90 = 481.68, 254.69, 129.83, and 146.24 μg mL⁻¹) and Ae. aegypti (LC50 = 62.50, 52.89, 58.60, and 47.12; LC90 = 314.82, 236.18, 247.53, and 278.52 μg mL⁻¹), respectively. The pupicidal activity of the fungal mycelium extracts was tested against An. stephensi, Cx. quinquefasciatus and Ae. Aegypti, where the ethyl acetate extracts had different LC50 values (LC50 = 40.66, 54.06, 44.26, and LC90 = 184.02, 225.61, and 263.02 μg mL⁻¹). Based on Fourier transform infrared spectroscopy (FTIR) analysis and gas chromatography-mass spectrometry (GC-MS) analyses, the ethyl acetate mycelium extract contained six major chemical compounds identified as 9,12-octadecadienoic acid (ZZ)– (63.16%), n-hexadecanoic acid (21.28%), octadecanoic acid, phenyl methyl ester (10.45%), dehydroegosterol 3,5-dinitrobenzoate (1.86%), squalene (1.66%) and bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)prophyl]maleate (1.56%). The n-hexadecanoic acid standard was found to be better larvicidal against An. stephensi, Cx. quinquefasciatus, followed by Ae. aegypti. The HPLC analysis of the ethyl acetate mycelium extract was compared with that of the n-hexadecanoic acid standard and it was found to show a similar chromatographic peak (at a retention time of 3.383 and 3.378 min). The outcome of the present study identifies the bioactive compounds obtained from B. bassiana that can be used as effective and alternate larvicidal and pupicidal agents against the An. stephensi Cx. quinquefasciatus and Ae. aegypti mosquito vectors.
Cyclosporin A is a cyclic undecapeptide with a variety of biological activities including immunosuppressive, anti-inflammatory, antifungal, and antiparasitic properties. It is an extremely powerful immunosuppressant and is approved for the use in organ transplantation to prevent graft rejection in kidney, liver, heart, lung, and combined heart?lung transplants. As its role in transplantation surgery increases, the demand on industry for improved yields intensifies. For this reason, this chapter mainly focuses on enhanced production of cyclosporin A from microbes by different techniques.
Nowdays there is evidence that dairy propionibacteria display probiotic properties, which as yet have been underestimated. The aim of this paper is to review the recent highlights of data representing the probiotic potential of dairy propionibacteria, studied both by general selection criteria (useful for all probiotic potentials), and by more specific and innovative approach. Dairy propionibacteria show a robust nature, that makes them able to overcome technological hurdles, allowing their future use in various fermented probiotic foods. In addition to the general selection criteria for probiotics in areas such as food safety, technological and digestive stress tolerance, many potential health benefits have been recently described for dairy propionibacteria, including, production of several active molecules and adhesion capability, that can mean a steady action in modulation of microbiota and of metabolic activity in the gut; their impact on intestinal inflammation, modulation of the immune system, potential modulation of risk factors for cancer development modulation of intestinal absorption.
In this study, 23 Debaryomyces hansenii strains, isolated from cheese and fish gut, were investigated in vitro for potential probiotic properties i.e. (1) survival under in vitro GI (gastrointestinal) conditions with different oxygen levels, (2) adhesion to Caco-2 intestinal epithelial cells and mucin, and (3) modulation of pro- and anti-inflammatory cytokine secretion by human monocyte-derived dendritic cells. As references two commercially available probiotic Saccharomyces cerevisiae var. boulardii (S. boulardii) strains were included in the study. Our results demonstrate that the different D. hansenii yeast strains had very diverse properties which could potentially lead to different probiotic effects. One strain of D. hansenii (DI 09) was capable of surviving GI stress conditions, although not to the same degree as the S. boulardii strains. This DI 09 strain, however, adhered more strongly to Caco-2 cells and mucin than the S. boulardii strains. Additionally, two D. hansenii strains (DI 10 and DI 15) elicited a higher IL-10/IL-12 ratio than the S. boulardii strains, indicating a higher anti-inflammatory effects on human dendritic cells. Finally, one strain of D. hansenii (DI 02) was evaluated as the best probiotic candidate because of its outstanding ability to survive the GI stresses, to adhere to Caco-2 cells and mucin and to induce a high IL-10/IL-12 ratio. In conclusion, this study shows that strains of D. hansenii may offer promising probiotic traits relevant for further study.
The yeast Candida utilis is used as a food additive and as a host for heterologous gene expression to produce various metabolites and proteins. Reliable protocols for intracellular production of recombinant proteins are available for C. utilis and have now been expanded to secrete proteins into the growth medium or to achieve surface display by linkage to a cell wall protein. A recombinant C. utilis strain was recently shown to induce oral tolerance in a mouse model of multiple sclerosis suggesting future applications in autoimmune therapy. Whole genome sequencing of C. utilis and its presumed parent Cyberlindnera (Pichia) jadinii demonstrated different ploidy but high sequence identity, consistent with identical recombinant technologies for both yeasts. C. jadinii was recently described as an antagonist to the important human fungal pathogen Candida albicans suggesting its use as a probiotic agent. The review summarizes the status of recombinant protein production in C. utilis, as well as current and future biotechnological and medical applications of C. utilis and C. jadinii.
Endophytes, which mostly include bacteria, fungi and actinomycetes, are the endosymbionts that reside asymptomatically in plants for at least a part of their life cycle. They have emerged as a valuable source of novel metabolites, industrially important enzymes and as stress relievers of host plant, but still many aspects of endophytic biology are unknown. Functions of individual endophytes are the result of their continuous and complex interactions with the host plant as well as other members of the host microbiome. Understanding plant microbiomes as a system allows analysis and integration of these complex interactions. Modern genomic studies involving metaomics and comparative studies can prove to be helpful in unraveling the gray areas of endophytism. A deeper knowledge of the mechanism of host infestation and role of endophytes could be exploited to improve the agricultural management in terms of plant growth promotion, biocontrol and bioremediation. Genome sequencing, comparative genomics, microarray, next gen sequencing, metagenomics, metatranscriptomics are some of the techniques that are being used or can be used to unravel plant–endophyte relationship. The modern techniques and approaches need to be explored to study endophytes and their putative role in host plant ecology. This review highlights “omics” tools that can be explored for understanding the role of endophytes in the plant microbiome.
We studied here the yeast content of poultry feces, collected randomly from a French farm located in the north of the country. Thus, 81 yeast colonies were isolated and clustered into 22 distinct groups using the rep-PCR method. A single colony was taken from each group and identified using biochemical (ID 32C system) and molecular (sequencing of the D1/D2 domain of 26S rDNA and ITS1-5.8-ITS2 rDNA region) methods. Both methods led to the identification of Candida
famata species. One isolate of C.
famata strains, named strain Y5, was further studied for its cytotoxicity, adhesion, and surface properties, hemolytic activity, and its survival in simulated gastric and intestine environments. The data obtained advocate the probiotic potential of this isolate.
Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resistance processes. The review also concerns the mimicking of plant effector molecules like auxins, gibberellins and abscisic acid by fungal secondary metabolites that modulate plant growth or even can subvert the plant defense responses such as programmed cell death to gain nutrients for fungal growth and colonization. It also looks through the special secondary metabolite production and host selective toxins of some significant fungal pathogens and the plant response in form of phytoalexin production. New results coming from genome and transcriptional analyses in context of selected fungal pathogens and their hosts are also discussed.
In this study, cholesterol assimilation ratios and some probiotic characteristics of yeasts were investigated. For this purpose, yeasts were isolated from milk and foods that were naturally fermented and not containing starter culture. In vitro cholesterol assimilation properties were determined in media. The Cholesterol assimilation by yeast strains ranged between 1.36 and 73.33%. Twenty-one yeast strains showing high assimilation percentage were selected, and their acid tolerance, bile tolerance, bile salt deconjugation activity and survival in simulated gastrointestinal conditions were investigated. Among the strains assessed, 12 of them showed probiotic characteristics.
Probiotics are live microorganisms which are beneficial for the host when ingested at high enough concentrations. The methylotrophic yeast Pichia pastoris is widely used as heterologous protein production platform. However, its use as probiotic is poorly studied. The objective of this study was to evaluate some probiotic properties of the P. pastoris strain X-33 wild type. The resistance to in vitro and in vivo gastrointestinal conditions, stability in feed, safety, and antibacterial activity against Salmonella Typhimurium were evaluated. The yeast remained viable and persisted at appropriate concentration in the diet for at least 2 months, survived the stresses of the gastrointestinal tract in vitro and in vivo, caused no behavioral changes or lesions when administered to mice, inhibited the growth of S. Typhimurium in culture media, and reduced adhesion of the bacteria to the intestinal cells HCT-116. In the challenge experiment with a LD50 of virulent S. Typhimurium strain, mice supplemented with the yeast had a higher survival rate (50 % when administered by gavage and 80 % via the diet, compared with 20 and 50 %, respectively, in the control group). In addition, the S. Typhimurium concentration in the intestine of the surviving mice was lower; the score of intestinal lesions, lower; and the pathogen, not detected in the liver, spleen, and feces when compared to the control group (p < 0.05). It was concluded that the yeast Pichia pastoris X-33 has probiotic properties with remarkable antibacterial activity against S. Typhimurium.
Natural products, their derivatives or compounds based on natural product leads constitute ∼50% of clinically used pharmaceuticals. This review highlights pharmaceuticals currently used in Australia and New Zealand that have their origins in fungal metabolites, discussing the natural products chemistry and medicinal chemistry leading to their application as pharmaceuticals.
Ergot alkaloids are nitrogen-containing natural products belonging to indole alkaloids. The best known producers are fungi of the phylum Ascomycota, e.g., Claviceps, Epichloë, Penicillium and Aspergillus species. According to their structures, ergot alkaloids can be divided into three groups: clavines, lysergic acid amides and peptides (ergopeptines). All of them share the first biosynthetic steps, which lead to the formation of the tetracyclic ergoline ring system (except the simplest, tricyclic compound: chanoclavine). Different modifications on the ergoline ring by specific enzymes result in an abundance of bioactive natural products, which are used as pharmaceutical drugs or precursors thereof. From the 1950s through to recent years, most of the biosynthetic pathways have been elucidated. Gene clusters from several ergot alkaloid producers have been identified by genome mining and the functions of many of those genes have been demonstrated by knock-out experiments or biochemical investigations of the overproduced enzymes.
According to the literatures, Flammulina velutipes contains biologically active components such as dietary fiber, polysaccharide, and mycosterol, whose effects in reducing blood sugar, blood pressure, and cholesterol have been proven. This study used the active components extracted from Flammulina velutipes powder (FVP) and Flammulina velutipes extract (FVE) to investigate the impact of these active components on lipid metabolism of hamsters. The results show that the total dietary fiber content in FVP and FVE is 29.34 mg/100 g and 15.08 mg/100 g, respectively. The total mycosterol content is 46.57 ± 0.37 mg/100 g and 9.01 ± 0.17 mg/100 g, respectively. The male hamsters were subjected to lipid metabolism monitoring by adding 1, 2, and 3% FVP or FVE into their diets for a period of 8 weeks. The animal assay results show that the 3% FVP and FVE groups have the lowest concentration of TC (total cholesterol), TG (triacylglycerol), LDL (low density lipoprotein cholesterol), and LDL/HDL (high density lipoprotein cholesterol) in the serum and liver (P < 0.05). Our results demonstrate that the addition of 3% FVP or FVE has a significant effect on the lipid metabolism in hamsters whose increased level of HDL in the serum was induced by high fat diet.
An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic-"live microorganisms which when administered in adequate amounts confer a health benefit on the host"-was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.
The potential of endophytes, particularly endophytic fungi, capable of demonstrating desirable functional traits worth exploitation using red biotechnology is well established. However, these discoveries have not yet translated into industrial bioprocesses for commercial production of biopharmaceuticals using fungal endophytes. Here, we define the current challenges in transforming curiosity driven discoveries into industrial scale endophyte biotechnology. The possible practical, feasible, and sustainable strategies that can lead to harnessing fungal endophyte-mediated pharmaceutical products are discussed.
In this study, a dichloromethane fraction (DCMF) from 70% Auricularia auricula-judae ethanol extract showed the highest level of antitumor activity compared to other solvent fractions (ethyl acetate, butanol, and water). The DCMF was found to have more potent antitumor activity against broncheoalveolar cancer (half maximal inhibitory concentration = 57.2 µg/mL) and gastric cancer cells (half maximal inhibitory concentration = 73.2 µg/mL) compared to the other solvent fractions, although all fractions inhibited the proliferation of the tumor cells in a dose-dependent manner. We further analyzed the DCMF composition by gas chromatography−coupled mass spectroscopy. Based on the results of this analysis, an antitumor active component (diazane) was identified in the DCMF. However, we found that diazane alone had a lower level of antitumor activity than the DCMF. These findings indicate that other unknown components of the DCMF also are responsible for the cytotoxic effects of DCMF against tumor cells. Semiquantitative reverse transcription polymerase chain reaction analysis demonstrated that DCMF induced cytotoxicity or tumor cell apoptosis as a result of the downregulation of Bcl-2 expression and p53 overexpression. Taken together, our study results demonstrated that the DCMF may be used as a functional additive for enhancing antioxidant activities and suppressing tumor growth in the body.
Recent shift in trends of agricultural practices from application of synthetic fertilizers and pesticides to organic farming has brought into focus the use of microorganisms that carryout analogous function. Trichoderma spp. is one of the most popular genera of fungi commercially available as a plant growth promoting fungus (PGPF) and biological control agent. Exploitation of the diverse nature of secondary metabolites produced by different species of Trichoderma augments their extensive utility in agriculture and related industries. As a result, Trichoderma has achieved significant success as a powerful biocontrol agent at global level. The endorsement of Trichoderma spp. by scientific community is based on the understanding of its mechanisms of action against a large set of fungal, bacterial and in certain cases viral infections. However, it is still an agnostic view that there could be any single major mode of operation, although it is argued that all mechanisms operate simultaneously in a synchronized fashion. The central idea behind this review article is to emphasize the potentiality of applications of target specific secondary metabolites of Trichoderma for controlling phytopathogens as a substitute of commercially available whole organism formulations. With the aim to this point, we have compiled an inclusive list of secondary metabolites produced by different species of Trichoderma and their applications in diverse areas with the major emphasis on agriculture. Outlining the importance and diverse activities of secondary metabolites of Trichoderma besides its relevance to agriculture would generate greater understanding of their other important and beneficial applications apart from target specific biopesticides.
Mushrooms possess nutritional and medicinal properties that have long been used for human health preservation and that have been considered by researchers as possible sources of free radical scavengers. In this work, the antioxidant properties of water extracts from Agaricus blazei Murill, produced by maceration and decoction, are demonstrated in vitro. Resistance to oxidation is demonstrated through three mechanisms: i) inhibition of enzymatic oxidative process, with 100% inhibition of HRP (horseradish peroxidase) and MPO (myeloperoxidase); ii) inhibition of cellular oxidative stress, with 80% inhibition of the oxidative burst of polymorphonuclear neutrophils (PMNs); and iii) direct action over reactive species, with 62% and 87% suppression of HOCl and superoxide anion radical (O2 ), respectively. From the data, it was concluded that the aqueous extract of A. blazei has significant antioxidant activity, indicating its possible application for nutraceutical and medicinal purposes.
Fungal co-culture is a strategy to induce the production of secondary metabolites by activating cryptic genes. We discovered the production of a new compound, talarodone A (1), along with five known compounds 2-6 in co-culture of Talaromyces pinophilus and Paraphaeosphaeria sp. isolated from soil collected in Miyazaki Prefecture, Japan. Among them, the productions of penicidones C (2) and D (3) were enhanced 27- and sixfold, respectively, by the co-culture. The structure of 3 should be represented as a γ-pyridol form with the reported chemical shifts, but not as a γ-pyridone form, based on DFT calculation.
Covering: up to 2019
Fungi produce a remarkable diversity of secondary metabolites: small, bioactive molecules not required for growth but which are essential to their ecological interactions with other organisms. Genes that participate in the same secondary metabolic pathway typically reside next to each other in fungal genomes and form biosynthetic gene clusters (BGCs). By synthesizing state-of-the-art knowledge on the evolution of BGCs in fungi, we propose that fungal chemodiversity stems from three molecular evolutionary processes involving BGCs: functional divergence, horizontal transfer, and de novo assembly. We provide examples of how these processes have contributed to the generation of fungal chemodiversity, discuss their relative importance, and outline major, outstanding questions in the field.
One of the exciting movements in microbial sciences has been a refocusing and revitalization of efforts to mine the fungal secondary metabolome. The magnitude of biosynthetic gene clusters (BGCs) in a single filamentous fungal genome combined with the historic number of sequenced genomes suggests that the secondary metabolite wealth of filamentous fungi is largely untapped. Mining algorithms and scalable expression platforms have greatly expanded access to the chemical repertoire of fungal-derived secondary metabolites. In this Review, I discuss new insights into the transcriptional and epigenetic regulation of BGCs and the ecological roles of fungal secondary metabolites in warfare, defence and development. I also explore avenues for the identification of new fungal metabolites and the challenges in harvesting fungal-derived secondary metabolites.
Objectives: Parasitic Cordyceps fungi, such as Cordyceps sinensis, is a parasitic complex of fungus and caterpillar, which has been used for medicinal purposes for centuries particularly in China, Japan and other Asian countries. This article gives a general idea of the latest developments in C. sinensis research, with regard to the active chemical components, the pharmacological effects and the research and development of products in recent years. Key findings: The common names for preparations include DongChongXiaCao in Chinese, winter worm summer grass in English. It has many bioactive components, such as 3′-deoxyadenosine, cordycepic acid and Cordyceps polysaccharides. It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. It also can be used to treat conditions such as night sweating, hyposexuality, hyperglycaemia, hyperlipidaemia, asthenia after severe illness, respiratory disease, renal dysfunction, renal failure, arrhythmias and other heart disease and liver disease. Because of its rarity and outstanding curative effects, several mycelia strains have been isolated from natural Cordyceps and manufactured by fermentation technology, and are commonly sold as health food products. In addition, some substitutes such as C. militaris and adulterants also have been used; therefore, quality control of C. sinensis and its products is very important to ensure their safety and efficacy. Summary: Recent research advances in the study of Cordyceps, including Cordyceps mushrooms, chemical components, pharmacological functions and developmental products, has been reviewed and discussed. Developing trends in the field have also been appraised.
Two new alkylated furan derivatives, 5-(undeca-3′,5′,7′-trien-1′-yl)furan-2-ol (1) and 5-(undeca-3′,5′,7′-trien-1′-yl)furan-2-carbonate (2), were isolated from the crude extract of the plant endophytic fungus Emericella sp. XL029 associated with the leaves of Panax notoginseng. The anti-agricultural pathogenic fungal assay indicated that compound 1 displayed significant activity against all tested fungi with minimum inhibitory concentrations (MIC) values from 25 to 3.1 μg/mL, while compound 2 displayed activity against all tested fungi except for Rhizoctonia solani and Fusarium oxysporum with MIC values from 50 to 12.5 μg/mL. Furthermore, compounds 1–2 also exhibited significant inhibitory activity against eight of thirteen tested bacteria with MIC values ranging from 50 to 6.3 μg/mL.
Actinobacteria have the genetic potential for the production of wide variety of yet-to-discover secondary metabolites. They are known for their metabolic versatility that allows them to survive even under extreme environmental conditions. Further, considerable increase in the interest pertaining to the natural products originating from the saline and alkaline environments has brought haloalkaliphilic actinobacteria into the focus of intensive research. These organisms harbour huge potential for the discovery of new antibiotics and enzymes with novel properties. Besides, they have vast biosynthetic potential that remains unexplored. In the present chapter, we have evaluated the present state of research on the haloalkaliphilic actinobacteria and their unique antimicrobial properties. The highlights include the distribution of the haloalkaliphilic actinobacteria, their adaptation in different stress conditions, and mining of their unique antimicrobial and enzymatic potential. © Springer International Publishing Switzerland 2015. All rights reserved.
The possible beneficial properties of food and associated microorganisms for both human and animal health are increasingly investigated. While many bacteria have been characterised as probiotics, only one yeast variety, Saccharomyces cerevisiae var. boulardii, has been recognised to be part of this group, regardless of the importance of yeasts in the food industry. In this work, we have studied the probiotic or health-beneficial potential of 130 yeast strains isolated from food belonging to the collection of the Institute of Food Science Research CIAL (CSIC-UAM). To that end, the response of these yeasts to physiological conditions during consumption has been assessed through measuring their capacity to grow at 37 °C and to survive the gastrointestinal transit conditions. Almost 50% of the yeast analysed could thrive at the host intestine temperature, and of these, almost 37% had growth kinetic parameters higher at 37 °C than at 25 °C. In addition, about 95% of the strains could survive the exposition to conditions simulating the gastrointestinal transit. The yeast strains were also analysed for exhibiting auto-aggregation phenotype, antioxidant activity and the production of killer peptides, this only found in 8.5% of the strains analysed. These properties could be regarded as additional interesting features for selecting new probiotic strains.
The human gastrointestinal epithelium makes up the largest barrier separating the body from the external environment. Whereas invasive pathogens cause epithelial barrier disruption, probiotic microorganisms modulate tight junction regulation and improve epithelial barrier function. In addition, probiotic strains may be able to reduce epithelial barrier disruption caused by pathogenic species. The aim of the present study was to explore non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Benchmarking against established probiotic strains, we evaluated the ability of four non-pathogenic yeast species to modulate transepithelial electrical resistance (TER) across a monolayer of differentiated human colonocytes (Caco-2 cells). Further, we assessed yeast modulation of a Salmonella Typhimurium induced epithelial cell barrier function insult. Our findings demonstrate distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function. Whereas the established probiotic yeast Saccharomyces boulardii increased TER across a Caco-2 monolayer by 30%, Kluyveromyces marxianus exhibited significantly stronger properties of TER enhancement (50% TER increase). In addition, our data demonstrate significant yeast mediated modulation of Salmonella induced epithelial cell barrier disruption and identify Kluyveromyces marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
To determine the starter-culture and multifunctional potentials of yeast strains from some cereal-based Nigerian traditional fermented food products.
Yeast isolates were screened for enzymes production and identified by sequencing the D1/D2 region of 26S rDNA. Pichia kluyveri LKC17, Issatchenkia orientalis OSL11, Pichia kudriavzevii OG32, Pichia kudriavzevii ROM11 and Candida tropicalis BOM21 exhibited the highest protease, lipase and phytase activity. They were selected and further evaluated for gastrointestinal survival and adherence ability. Although strain-specific, they retained viability at 37 °C and showed survival at pH 2.0. I. orientalis OSL11 showed the highest survival at 2% bile salts concentration and P. kudriavzevii ROM11 showed the least survival. The yeast strains showed strong autoaggregation ability (81.24-91.85%) and hydrophobicity to n-hexadecane (33.61-42.30%). The highest co-aggregation ability was detected for Pichia kudriavzevii OG32 and Escherichia coli (71.57%). All the yeast strains removed cholesterol in the range of 49.03-74.05% over 48 h and scavenged for free radicals in methanol reaction system.
In this study, we isolated new yeast strains with multifunctional potentials that can be used as functional starter cultures to produce cereal-based probiotic products.
The development of probiotic yeast strains as starter culture to improve the quality attributes and confer functional value on cereal-based traditional fermented foods is beneficial. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Ergot alkaloids are well known preparations. Ergot alkaloids used in obstetrics and gynaecology are ergometrine (ergonovine; EM), methylergometrine (methergine; ME) and bromocriptine. The pharmaceutical properties of ME EM) are critical. To guarantee stability, ME and EM ampoules should be stored in a cool, dark place. ME and EM tablets are unstable in all conditions and they show an unpredictable bioavailability, which prevents oral use of the drugs for any purpose.
ME and EM are known for their strong uterotonic effect and, compared with other ergot alkaloids, for their relatively slight vasoconstrictive abilities. ME and EM do have a place in the management of the third stage of labour as they are strong uterotonics. They act differently from oxytocin and prostaglandins, and have different adverse effects. Oxytocin should be used as prophylaxis or a the drug of first choice; next, ME or EM should be used, and if none of these drugs produce the desired effects, prostaglandins should be used to control bleeding.
Ergot alkaloid use in gynaecology has been limited and today is discouraged even in essential menorrhagia. It is suggested that EM and ME be used (parenterally) only in first trimester abortion curettage, to reduce blood loss. Bromocriptine has been used for lactation suppression. However, alternatives such as cabergoline, which possess fewer adverse effects, are now available and therefore preferred for this indication.
In sum, there is no place for the prophylactic use of ME and EM in obstetrics or gynaecology. They can be used for therapeutic purposes in the third stage of labour. During use, the practitioner must be alert for adverse effects.
Yeasts are unicellular eukaryotic microorganisms with a great importance in the elaboration on many foods and beverages. In the last years, researches have focused their attention to determine the favourable effects that these microorganisms could provide to table olive processing. In this context, the present study assesses, at laboratory scale, the potential technological (resistance to salt, lipase, esterase and β-glucosidase activities) and probiotic (phytase activity, survival to gastric and pancreatic digestions) features of 12 yeast strains originally isolated from Greek natural black table olive fermentations. The multivariate classification analysis carried out with all information obtained (a total of 336 quantitative input data), revealed that the most promising strains (clearly discriminated from the rest of isolates) were Pichia guilliermondii Y16 (which showed overall the highest resistance to salt and simulated digestions) and Wickerhamomyces anomalus Y18 (with the overall highest technological enzymatic activities), while the rest of strains were grouped together in two clearly differentiated clusters. Thus, this work opens the possibility for the evaluation of these two selected yeasts as multifunctional starters, alone or in combination with lactic acid bacteria, in real table olive fermentations.
In the present study, the anticancer activity of Auricularia polytricha polysaccharides (APPs) towards A549 human lung cancer cells and its underlying mechanisms were investigated. APPs significantly inhibited the proliferation and DNA synthesis of A549 cells in a concentration-dependent manner. The compound also induced apoptosis in A549 cells by arresting cell cycle progression at the G0/G1 phase. Western blotting assay demonstrated that APPs significantly increased the expression of cyclin-dependent kinase (CDK) inhibitors p53 and p21, whereas the expression of cyclin A, cyclin D, and CDK2 were decreased by treatment with APPs. This apoptotic induction in APPs-treated A549 cells was also associated with the release of cytochrome c from mitochondria to cytosol, which in turn resulted in the activation of caspase-9 and -3, and the cleavage of poly (ADP-ribose) polymerase (PARP). Furthermore, the inhibitory effect of APPs on the growth in BALB/c-nu nude mice bearing A549 cells was also proven. These findings suggested that APPs might be a useful chemotherapeutic agent for lung cancer.
Production of d
S-threo-isocitric acid (ICA) by yeast meets serious difficulties since it is accompanied by a simultaneous production of citric acid (CA) in significant amounts that reduces the yield of desired product. In order to develop an effective process of ICA production, 60 yeast strains of different genera (Candida, Pichia, Saccharomyces, Torulopsis, and Yarrowia) were tested for their ability to produce ICA from rapeseed oil; as a result, wild-type strain Yarrowia lipolytica VKM Y-2373 and its mutant Y. lipolytica 704-UV4-A/NG50 were selected as promising ICA producers. The effects of temperature, pH, aeration, and concentrations of rapeseed oil, iron, and itaconic acid on ICA production by selected strains were studied. Under optimal conditions (pH 6.0; aeration 50–55 %; rapeseed oil concentration of 20–60 gl−1, iron ion concentration of 1.2 mg l−1, and itaconic acid amount of 30 mM), selected strains of Y. lipolytica produced predominantly ICA with a low amount of a by-product, CA.