Enhancing the Discovery of Bioactive Secondary Metabolites From Fungal Endophytes Using Chemical Elicitation and Variation of Fermentation Media (original) (raw)
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Chemical elicitation as an avenue for discovery of bioactive compounds from fungal endophytes
Frontiers in Chemistry
The present study investigated the molecular phylogeny, antimicrobial and cytotoxic activities of fungal endophytes obtained from the A*STAR Natural Organism Library (NOL) and previously isolated from Sungei Buloh Wetland Reserve, Singapore. Phylogenetic analysis based on ITS2 gene suggests that these isolates belong to 46 morphotypes and are affiliated to 23 different taxa in 17 genera of the Ascomycota phylum. Colletotrichum was the most dominant fungal genus accounting for 37% of all the isolates, followed by Diaporthe (13%), Phyllosticta (10.9%) and Diplodia (8.7%). Chemical elicitation using 5-azacytidine, a DNA methyltransferase inhibitor and suberoylanilide hydroxamic acid, a histone deacetylase inhibitor resulted in an increase in the number of active strains. Bioassay-guided isolation and structural elucidation yielded pestahivin and two new analogues from Bartalinia sp. F9447. Pestahivin and its related analogues did not exhibit antibacterial activity against Staphylococcu...
Crude metabolite extracts derived from the culture broths of endophytic fungi of five ethno-pharmacologically important plant species used by the ethnic tribes of the hill state of Meghalaya in NorthEast India were screened for the presence of toxins and secondary metabolites using agar plug paper chromatography, TLC (thin layer chromatography) and LC-MS (liquid chromatography-mass spectroscopy). The endophytic fungal isolates were found to produce a wide range of toxins, growth hormones and antibiotics upon searching in a fungal mycotoxin database. Relatedness among the fungal isolates was determined based upon their extra-cellular metabolite production pattern. The endophytic fungal isolates in the present study showed a wide range of metabolomic diversity and can be explored as potential microbial cell factories for production of a diverse range of biomolecules. Taxonomic relatedness of the endophytes based upon the snapshots of their secretomes, presented a contrasting picture in relation to their morphological identity. Rapid metabolome analysis of endophytic fungi using analytical techniques like LC-MS coupled with mass related search in fungal specific metabolite databases is bound to increase our insights about fungal chemo-taxonomy as a whole and bio-prospection of useful fungal metabolites in particular.
Isolation and Purification of Bioactive Metabolites from Fungal Endophytes– A Review
Abstract: Endophytes are the microorganisms that occur within the tissues of the plants without causing any noticeable symptoms and diseases to the host. In general, fungi and bacteria are the most common microbes exist as endophytes in plants. In recent years, endophytic fungi are known to produce several bioactive secondary metabolites, mainly used in pharmaceutical, agricultural and industrial applications. This review describes the isolation of naturally occurring bioactive compounds from endophytic microorganisms. In the recent past, a wealth of information on the isolation and purification of bioactive secondary metabolites from various endophytes have been reported. As endophytes produce these secondary metabolites in lower concentrations, it is required to employ improved isolation and purification methods of these secondary metabolites for their complete recovery.
The eurobiotech journal, 2019
Endophytic fungi associated with Nigerian plants have recently generated significant interest in drug discovery programmes due to their immense potential to contribute to the discovery of new bioactive compounds. This study was carried out to investigate the secondary metabolites of endophytic fungi isolated from leaves of Newbouldia laevis, Ocimum gratissimum, and Carica papaya. The plants were collected from Agulu, Anambra State, SouthEast Nigeria. Endophytic fungal isolation, fungal fermentation; and extraction of secondary metabolites were carried out using standard methods. The crude extracts were screened for antimicrobial activities using the agar well diffusion method, and were also subjected to high performance liquid chromatography (HPLC) analysis to identify their constituents. A total of five endophytic fungi was isolated, two from N. laevis (NL-L1 and NL-L2), one from O. gratissimum (SL-L1), and two from C. papaya (PPL-LAC and PPL-LE2). In the antimicrobial assay, the extracts of NL-L2, SL-L1, and PPL-LE2 displayed mild antibacterial activity against both Gram negative and Gram positive test bacteria. PPL-LAC extract showed mild activity only against S. aureus, while no antimicrobial activity was recorded for NL-L1 extract. All the endophytic fungal extracts showed no activity against the test fungi C. albicans and A. fumigatus. HPLC analysis of the fungal extracts revealed the presence of ethyl 4-hydroxyphenyl acetate and ferulic acid in NL-L1; ruspolinone in NL-L2; protocatechuic acid, scytalone, and cladosporin in SL-L1; indole-3-acetic acid and indole-3carbaldehyde in PPL-LE2; and indole-3-acetic acid in PPL-LAC. The findings of this study revealed the potentials possessed by these plants as source of endophytes that express biological active compounds. These endophytes hold key of possibilities to the discovery of novel molecules for pharmaceutical, agricultural and industrial applications.
Journal of Advanced Pharmacy Research, 2017
Objectives: This study aimed to point the significant rule of metabolomics tools to assess the chemistry of the bioactive metabolites produced by endophytic fungus Aspergillus chevalieri isolated from Lagerostromia tomentosa C. presl. The anticancer of crude extracts, fractions and pure compounds and antimicrobial of pure compounds were investigated as part of this study. Methods: An endophytic fungus (Aspergillus chevalieri) was isolated from the tissues of the stem of Lagerostromia tomentosa C. Presl and identified through molecular biological procedure by DNA isolation, PCR, DNA sequencing and through searching the Gene Bank. Metabolomics profiling and dereplication studies were employed to choose the optimum growth medium and conditions that yield the most significant metabolites. The crude extract of the 30-days rice culture of Aspergillus chevalieri was subjected to bioactivity and metabolomics guided isolation approach. The structure of the isolated compounds was determined on the basis of 1D, 2D NMR and mass spectrometry (HR-ESIMS) analysis. Results: four fractions were further purified to produce five pure compounds, which are Ergosterol (1), Ergosterol peroxide (2), Campesterol (3), Flavoglaucin (4) and 3-O-methyl caffeic acid (5). Multivariate data analysis highlighted the most significant metabolites contributed to the bioactivity. The pure compounds were tested for the anticancer and antimicrobial activity, compound (1) exhibited significant antitrypanosomal activity, while compounds (2, 3, 4 and 5) effectively inhibited the growth of Escherichia coli, Staphylococcus aureus and Candida albicans. Conclusion: A combination of metabolomic-and bioassay-guided approaches gives an access to a shorter and faster route to highlight the active metabolites, which are highly correlated to the bioactivity during the first stage of fractionation.
Plant associated fungal endophytes as a source of natural bioactive compounds
Mycology
Endophytes are a potent source of bioactive compounds that mimic plant-based metabolites. The relationship of host plant and endophyte is significantly associated with alteration in fungal colonisation and the extraction of endophyte-derived bioactive compounds. Screening of fungal endophytes and their relationship with host plants is essential for the isolation of bioactive compounds. Numerous bioactive compounds with antioxidant, antimicrobial, anticancer, and immunomodulatory properties are known to be derived from fungal endophytes. Bioinformatics tools along with the latest techniques such as metabolomics, next-generation sequencing, and metagenomics multilocus sequence typing can potentially fill the gaps in fungal endophyte research. The current review article focuses on bioactive compounds derived from plantassociated fungal endophytes and their pharmacological importance. We conclude with the challenges and opportunities in the research area of fungal endophytes.
Journal of Advanced Pharmacy Research
Objectives: This study aimed to point the significant rule of metabolomics tools to assess the chemistry of the bioactive metabolites produced by endophytic fungus Aspergillus chevalieri isolated from Lagerostromia tomentosa C. presl. The anticancer of crude extracts, fractions and pure compounds and antimicrobial of pure compounds were investigated as part of this study. Methods: An endophytic fungus (Aspergillus chevalieri) was isolated from the tissues of the stem of Lagerostromia tomentosa C. Presl and identified through molecular biological procedure by DNA isolation, PCR, DNA sequencing and through searching the Gene Bank. Metabolomics profiling and dereplication studies were employed to choose the optimum growth medium and conditions that yield the most significant metabolites. The crude extract of the 30-days rice culture of Aspergillus chevalieri was subjected to bioactivity and metabolomics guided isolation approach. The structure of the isolated compounds was determined on the basis of 1D, 2D NMR and mass spectrometry (HR-ESIMS) analysis. Results: four fractions were further purified to produce five pure compounds, which are Ergosterol (1), Ergosterol peroxide (2), Campesterol (3), Flavoglaucin (4) and 3-O-methyl caffeic acid (5). Multivariate data analysis highlighted the most significant metabolites contributed to the bioactivity. The pure compounds were tested for the anticancer and antimicrobial activity, compound (1) exhibited significant antitrypanosomal activity, while compounds (2, 3, 4 and 5) effectively inhibited the growth of Escherichia coli, Staphylococcus aureus and Candida albicans. Conclusion: A combination of metabolomic-and bioassay-guided approaches gives an access to a shorter and faster route to highlight the active metabolites, which are highly correlated to the bioactivity during the first stage of fractionation.
Biodiversity, Bioprospecting and Development The Future Products: Endophytic Fungal Metabolites
As far as microbial world concerned on earth, there are large number of domains has shown the potential for various applications. Fungal domain is one of them. Since the discovery of penicillin, various fungi has been harnessed for a large number of applications. Still there is a requirement of novel products for human welfare and development. So what are the fungi of next door? Are the fungal endophytes? Yes? This is the area untouched for a longer period of time. These fungi represent one of the most understudied and diverse group of organisms, are ubiquitous and occur within almost all the plants, including a broad range of hosts in various ecosystems, and therefore play an important role in the natural environment. Despite extensive work in this field, the products of these fungi remains poorly characterized. A large number of endophytic fungi such as Taxomyces, Pestalotiopsis,Muscodor, Piriformospora, Alternaria, Colletotrichum, Cryptosporiopsis, produce enormous valuable products formedicinal, agricultural and industrial importance. Some of the well-known products are taxol (Paclitaxel), serine hydrolases for polyurethane degradation, Annulene (Volatile organic compounds), Colletotric acid and Cryptocandin. So what next, are endophytic fungal metabolites are the future products? The present review explore the potential of these endophytic fungi with respect to the production of various novel secondary metabolites/products in comparison with the traditional fungi of importance.
Structurally Uncommon Secondary Metabolites Derived from Endophytic Fungi
Journal of Fungi
Among microorganisms, endophytic fungi are the least studied, but they have attracted attention due to their high biological diversity and ability to produce novel and bioactive secondary metabolites to protect their host plant against biotic and abiotic stress. These compounds belong to different structural classes, such as alkaloids, peptides, terpenoids, polyketides, and steroids, which could present significant biological activities that are useful for pharmacological or medical applications. Recent reviews on endophytic fungi have mainly focused on the production of novel bioactive compounds. Here, we focus on compounds produced by endophytic fungi, reported with uncommon bioactive structures, establishing the neighbor net and diversity of endophytic fungi. The review includes compounds published from January 2015 to December 2020 that were catalogued as unprecedented, rare, uncommon, or possessing novel structural skeletons from more than 39 different genera, with Aspergillus ...