Stilbenes: a journey from folklore to pharmaceutical innovation.

In modern times, medicine is predominantly based on evidence-based practices, whereas in ancient times, indigenous people relied on plant-based medicines with factual evidence documented in ancient books or folklore that demonstrated their effectiveness against specific infections. Plants and microbes account for 70% of drugs approved by the USFDA (U.S. Food and Drug Administration). Stilbenes, polyphenolic compounds synthesized by plants under stress conditions, have garnered significant attention for their therapeutic potential, bridging ancient wisdom with modern healthcare. Resveratrol, the most studied stilbene, initially discovered in grapes, red wine, peanuts, and blueberries, exhibits diverse pharmacological properties, including cardiovascular protection, antioxidant effects, anticancer activity, and neuroprotection. Traditional remedies, documented in ancient texts like the Ayurvedic Charak Samhita, foreshadowed the medicinal properties of stilbenes long before their modern scientific validation. Today, stilbenes are integral to the booming wellness and health supplement market, with resveratrol alone projected to reach a market value of 90 million US$ by 2025. However, challenges in stilbene production persist due to limited natural sources and costly extraction methods. Bioprospecting efforts reveal promising candidates for stilbene production, particularly endophytic fungi, which demonstrate high-yield capabilities and genetic modifiability. However, the identification of optimal strains and fermentation processes remains a critical consideration. The current review emphasizes the knowledge of the medicinal properties of Stilbenes (i.e., cardiovascular, antioxidant, anticancer, anti-inflammatory, etc.) isolated from plant and microbial sources, while also discussing strategies for their commercial production and future research directions. This also includes examples of novel stilbenes compounds reported from plant and endophytic fungi.

Endophytic Fusarium species, a unique bioresource for disaggregator of misfolded alpha-synuclein.

Aggregation of α-synuclein into toxic oligomeric structures has been implicated in the pathogenesis of Parkinson's disease via several key stages of fibrillation, oligomerization, and aggregation. Disaggregation or prevention of aggregation has garnered a lot of attention as a therapeutic strategy to prevent or delay the progression of Parkinson's disease. It has been recently established that certain polyphenolic compounds and catechins present in plants and tea extracts exhibit the potential to inhibit the α-synuclein aggregation. However, their copious supply for therapeutic development is still unsolved. Herein, we report for the first time the disaggregation potential of α-synuclein by an endophytic fungus residing in tea leaves (Camellia sinensis). Briefly, a recombinant yeast expressing α-synuclein was used for pre-screening of 53 endophytic fungi isolated from tea using anti-oxidant activity as a marker for the disaggregation of the protein. One isolate #59CSLEAS exhibited 92.4% reduction in production of the superoxide ions, which were similar to the already established α-synuclein disaggregator, Piceatannol exhibiting 92.8% reduction. Thioflavin T assay further established that #59CSLEAS decreased the oligomerization of α-synuclein by 1.63-fold. Subsequently Dichloro-dihydro-fluorescein diacetate-based fluorescence assay exhibited a reduction in total oxidative stress in the recombinant yeast in the presence of fungal extract, thereby indicating the prevention of oligomerization. Oligomer disaggregation potential of the selected fungal extract was found to be 56.5% as assessed by sandwich ELISA assay. Using morphological as well as molecular methods, the endophytic isolate #59CSLEAS was identified as Fusarium sp. The sequence was submitted in the Genbank with accession number ON226971.1.

Key insights into secondary metabolites from various Chaetomium species.

Endophytic fungi have proved to be a major source of secondary metabolites, wherein the genus Chaetomium has emerged as a source of multifarious bioactive natural compounds belonging to diverse classes such as chaetoglobosins, epipolythiodioxopiperazines, azaphilones, xanthones, anthraquinone, chromones, depsidones, terpenoids, and steroids. The objective of this review is to encapsulate recent findings on various Chaetomium strains, such as C. globosum, C. cupreum, C. elatum, C. subspirale, C. olivaceum, C. indicum, and C. nigricolor known for production of beneficial secondary metabolites, with an insight into their origin and function. A thorough literature survey was conducted for obtaining Chaetomium-derived secondary metabolites, with a scope of future application into drug development efforts. More than 100 secondary metabolites, with various beneficial properties such as antitumor, cytotoxic, antimalarial, and enzyme inhibitory activities, were enlisted. We believe this review will enhance the understanding of beneficial effects conferred by various Chaetomium-derived secondary metabolites and emphasize their potential in serving novel drug development efforts. KEY POINTS: • Identified Chaetomium-derived metabolites with potential for drug development. • More than 100 beneficial metabolites are enlisted. • Benefits include anti-cancerous, antimalarial, and anti-enzymatic properties.

Penicillium citrinum, a Drought-Tolerant Endophytic Fungus Isolated from Wheat (Triticum aestivum L.) Leaves with Plant Growth-Promoting Abilities.

Endophytic fungi have recently garnered significant attention as next-generation bioinoculants due to their plausible role in ameliorating abiotic and biotic stresses. This adaptation is achieved via various signalling molecules and mechanisms established by these symbionts with their hosts. The present study screened 61 endophytic isolates of culturable mycobiome associated with wheat variety PBW725 during their crop cycle. Three endophytic isolates exhibited a minimum reduction in their growth and maximum biomass production during the drought stress developed using polyethylene glycol 6000. Further, these isolates also exhibited plant growth promoting properties by virtue of the production of indole acetic acid, gibberellic acid and ammonia. These isolates also exhibited the propensity to solubilise phosphate and zinc, produce siderophores and further exhibit extracellular enzymatic activities, contributing to plants' adaptability to abiotic stresses. The best isolate amongst the three was #5TAKL-3a, identified as Penicillium citrinum based on multilocus phylogenetic analysis. The isolate as a bioinoculant enhances various biochemical and physiological properties in planta. Hence our studies indicate that Penicillium citrinum #5TAKL-3a is a potential candidate bioinoculant for field trials to improve the adaptability of the wheat plant under drought stress.

Inhibitory activities of grape bioactive compounds against enzymes linked with human diseases.

A quest for identification of novel, safe and efficient natural compounds, as additives in the modern food and cosmetic industries, has been prompted by concerns about toxicity and side effects of synthetic products. Plant phenolic compounds are one of the most documented natural products due to their multifarious biological applications. Grape (Vitis vinifera) is an important source of phenolic compounds such as phenolic acids, tannins, quinones, coumarins and, most importantly, flavonoids/flavones. This review crisply encapsulates enzyme inhibitory activities of various grape polyphenols towards different key human-ailment-associated enzymes: xanthine oxidase (gout), tyrosinase (hyperpigmentation), α-amylase and α-glucosidase (diabetes mellitus), pancreatic lipase (obesity), cholinesterase (Alzheimer's disease), angiotensin i-converting enzymes (hypertension), α-synuclein (Parkinson's disease) and histone deacetylase (various diseases). The review also depicts the enzyme inhibitory mechanism of various grape polyphenols and briefly discusses their stature as potential therapeutic and drug development candidates. KEY POINTS: • Nineteen major bioactive polyphenols from the grape/grape products and their disease targets are presented • Sixty-two important polyphenols as enzyme inhibitors from grape/grape products are presented • A thorough description and graphical presentation of biological significance of polyphenols against various diseases.

Effect of precursor feeding, dietary supplementation, chemical elicitors and co-culturing on resveratrol production by Arcopilus aureus.

Resveratrol is an important stilbene, initially identified from red wine possessing immense therapeutic, cosmeceutical and nutraceutical applications. In the present study, endophytic fungus Arcopilus aureus(#12VVLMP) which produces resveratrol extracellularly was selected as a candidate for epigenetic modulation using natural supplements, precursor feeding, chemical elicitors and co-culturing to enhance resveratrol production. The present study highlighted the role of natural supplements i.e. grape seed extract and grape skin extract which constitute grape pomace to enhance resveratrol production by 27.7 and 13.65% respectively. Co-culturing also impacted the resveratrol production by A. aureus, enhancing it by 9.4%. Chemical elicitors and precursor feeding did not induce significant enhancement in resveratrol production. Enhancement of anti-oxidant effect was also observed in the case of use of natural supplements assayed by DPPH and ABTS• radical scavenging assays. Similarly anti-staphylococcal and anti-candida activities were potentially higher when natural supplements were used followed by co-culturing. These findings indicate that the use of natural supplement which is a by-product of wine industry may be used as a modulator of resveratrol production by A. aureus. This shall lead to a cost-effective fermentation process of resveratrol production, the global demand of which is continuously increasing.

Marvellous Muscodor spp.: Update on Their Biology and Applications.

Nearly 20 years ago, the first report appeared on the discovery of a novel genus-Muscodor. This organism was isolated as an endophyte from a cinnamon tree that had been introduced to Honduras from Sri Lanka in the early part of the last century. Characteristically, the original Muscodor albus, and all of its species isolated since that time are non-spore producers and each one exudes a characteristic spectrum of volatile bioactive compounds. The majority have a whitish mycelium, which is sometimes coiling, intertwined and decorated with variously shaped structures. Presently, there are at least 22 type species known/documented and each has been described as an endophyte from various plant families with widely varying habitats. An enormous variety of volatile organic compounds (VOCs) are produced by Muscodor spp. and some of these include esters, acids, aldehydes, ketones, aromatics, alkanes, alcohols, nitrosamides and terpenoids. The VOCs are both inhibitory and lethal to a wide variety of fungi and bacteria including some major pathogens of plants and humans. Interestingly, in almost all cases studied, no one compound by itself can mimic the bioactivity of the complete gas mixture, suggesting that the volatiles are acting in a synergistic manner and this has been tested with individual as well as the VOCs in various mixtures and concentrations. This review will discuss some of the recent findings in all aspects of this unique fungal genus whilst at the same time pointing out some of the major questions that remain about its biology, ecology and its applications in agriculture, medicine and other sectors. Most importantly, the authors provide arguments supporting the claim that Muscodor is taxonomically distinct from Induratia, a recently proposed change to its nomenclature.

Response surface statistical optimization of fermentation parameters for resveratrol production by the endophytic fungus Arcopilus aureus and its tyrosinase inhibitory activity.

OBJECTIVE: The present investigation primarily focusses on enhancement of resveratrol production by endophytic production from the endophytic fungus, Arcopilus aureus via one variable at a time approach (OVAT) followed by statistical approach using response surface methodology (RSM). The paper also highlights the characterization of fungal resveratrol using spectroscopic techniques. Further the tyrosinase inhibitory property was also explored in this communication for its possible use as a cosmeceutical ingredient. RESULTS: Optimization of physicochemical and nutritional parameters using OVAT approach exhibited 1.23-fold enhancement in production of resveratrol when compared to initial yield, 89.1 ± 0.08 µg/mL. Further RSM resulted in 1.49-fold enhancement in resveratrol production i.e. 133.53 µg/ml. Further, 25 mg of fungal resveratrol in pure form was obtained from the spent broth of Arcopilus aureus by column chromatography using a mobile phase comprising of MeOH: DCM in a ratio of 1.75:98.25. Further its purity on TLC was checked using 5% MeOH: DCM as mobile phase. Symmetrical peak with Rt of 3.36 min using a C18 reverse phase column confirmed the homogeneity of the purified fungal resveratrol with standard resveratrol and further corroborated by 1H-NMR, 13C-NMR and HR-MS analysis. Fungal resveratrol exhibited a good tyrosinase inhibition with an IC50 of 2.654 ± 0.432 µg/mL as compared to Kojic acid (1.329 ± 0.333). CONCLUSIONS: The present study has provided sufficient lead that process optimization techniques can complement each other for optimized production of bioactive compounds by microorganisms apart from strain improvement techniques which are generally adopted in the industry. The enhancement of resveratrol production by Arcopilus aureus by process optimization further opens up avenues for strain improvement for commercial resveratrol production through fermentation for nutraceutical and cosmeceutical applications.

Isolation and enhancement of resveratrol production in Xylaria psidii by exploring the phenomenon of epigenetics: using DNA methyltransferases and histone deacetylase as epigenetic modifiers.

Resveratrol is an important stilbene which is having a high demand due to its therapeutic, cosmeceutical and nutraceutical activities. The current study mainly focuses on strategies to enhance the fungal potential to produce resveratrol via the activation of the cryptic biosynthetic pathway with their particular interest in the antioxidant application. The endophytic fungus Xylaria psidii was isolated from the surface sterilized leaf of Vitis vinifera. With the help of HPLC analysis it is found that resveratrol concentration was maximum and enhanced in case of treatment with 5 µm SAHA (52.32 µg/mL) and by 10 µm AZA (48.94 µg/mL) followed by 10 µm SAHA (41.10 µg/mL) and 5 µm AZA (37.72 µg/mL). After treatment with different concentration of epigenetic modifiers such as HDAC inhibitors (SAHA) and dMNTs (AZA) inhibitors, a significant increase in antioxidant potential was obtained. In the case of DPPH increase in scavenging potential was found as compared to wild strain. Treatment with 5 µm SAHA and by 10 µm AZA was showing strong antioxidant potential among all the epigenetic variants as compared to wild strain. In the case of TEAC also the same trend as in the case of DPPH was obtained.

Xanthine oxidase inhibitors from an endophytic fungus Lasiodiplodia pseudotheobromae.

Two new compounds, lasdiplactone (1) and lasdiploic acid (2) and one known compound 3 were isolated from the chloroform extract of cell free filtrate of the endophytic fungus Lasiosdiplodia pseudotheobromae. The structures of new compounds were determined by interplay of spectral techniques (IR, mass, 1H NMR, 13C NMR, DEPT, and 2D NMR). The absolute configuration at C-4 position of 1 was established as S using a process similar to modified Mosher's method. The absolute configuration of 2 was established by comparing its ECD spectrum with the calculated ECD spectra of all possible isomers. In the in vitro XO inhibition assay, the highest inhibition was exhibited by 3 with an IC50 of 0.38 ±â€¯0.13 µg/ml, followed by 2 with an IC50 of 0.41 ±â€¯0.1 µg/ml and the least in 1. The oxidized form of 1 also showed high XO inhibition with IC50 of 0.35 ±â€¯0.13 µg/ml.

Xylarinase: a novel clot busting enzyme from an endophytic fungus Xylaria curta.

Xylarinase is a bi-functional fibrinolytic metalloprotease isolated from the culture filtrate of endophytic fungus Xylaria curta which is monomeric with a molecular mass of ∼33.76 kDa. The enzyme displayed both plasmin and tissue plasminogen activator like activity under in vitro conditions. It hydrolyses Aα and Bß chains of the fibrinogen. Optimal fibrinolytic activity of xylarinase is observed at 35 °C, pH 8. Ca(2+) stimulated the fibrinolytic activity of xylarinase while Fe(2+) and Zn(2+) inhibited suggesting it to be a metalloprotease. The Km and Vmax values of xylarinase were 240.9 µM and 1.10 U/ml for fibrinogen and 246 µM and 1.22 U/ml for fibrin, respectively. Xylarinase was found to prolong the activated partial thromboplastin time and prothrombin time. The N-terminal sequence of xylarinase (SNGPLPGGVVWAG) did not show any homology with previously known fibrinolytic enzymes. Thus xylarinase is a novel fibrinolytic metalloprotease which could be possibly used as a new clot busting enzyme.

Benzimidazole-Based Quinazolines: In Vitro Evaluation, Quantitative Structure-Activity Relationship, and Molecular Modeling as Aurora Kinase Inhibitors.

A series of benzimidazole-based quinazoline derivatives with different substitutions of primary and secondary amines at the C2 position (1-12) were evaluated for their Aurora kinase inhibitory activities. All compounds except for 3 and 6 showed good activity against Aurora kinase inhibitors, with IC50 values in the range of 0.035-0.532 µM. The ligand efficiency (LE) of the compounds with Aurora A kinase was also determined. The structure-activity relationship and the quantitative structure-activity relationship revealed that the Aurora inhibitory activities of these derivatives primarily depend on the different substitutions of the amine present at the C2 position of the quinazoline core. Molecular docking studies in the active binding site also provided theoretical support for the experimental biological data acquired. The current study identifies a novel class of Aurora kinase inhibitors, which can further be used for the treatment of cancer.

Potential pancreatic lipase inhibitory activity of an endophytic Penicillium species.

Pancreatic lipase (PL) is considered as one of the safest target for diet-induced anti-obesity drug development. Orlistat is the only PL inhibitor approved for anti-obesity treatment till date. In the process of exploration of new PL inhibitors, we have screened culture filtrates of 70 endophytic fungi of medicinal plants using qualitative as well as quantitative in-vitro PL assays. The qualitative assays indicated potential PL inhibition in only three isolates, namely #57 TBBALM, #33 TBBALM and #1 CSSTOT. Only ethyl acetate extracts of the culture filtrates of these isolates exhibited the PL inhibition. #57 TBBLAM ethyl acetate extract of culture filtrate exhibited potential PL inhibition with an IC50 of 3.69 µg/ml which was comparable to the positive control, i.e. Orlistat exhibiting IC50 value of 2.73 µg/ml. Further molecular phylogenetic tools and morphological studies were used to identify the isolate #57 TBBALM as Penicillium species.

Endophytic Fungi: A Treasure Trove of Antifungal Metabolites.

Emerging and reemerging fungal infections are very common in nosocomial and non-nosocomial settings in people having poor immunogenic profiles either due to hematopoietic stem cell transplants or are using immunomodulators to treat chronic inflammatory disease or autoimmune disorders, undergoing cancer therapy or suffering from an immune weakening disease like HIV. The refractory behavior of opportunistic fungi has necessitated the discovery of unconventional antifungals. The emergence of black fungus infection during COVID-19 also triggered the antifungal discovery program. Natural products are one of the alternative sources of antifungals. Endophytic fungi reside and co-evolve within their host plants and, therefore, offer a unique bioresource of novel chemical scaffolds with an array of bioactivities. Hence, immense possibilities exist that these unique chemical scaffolds expressed by the endophytic fungi may play a crucial role in overcoming the burgeoning antimicrobial resistance. These chemical scaffolds so expressed by these endophytic fungi comprise an array of chemical classes beginning from cyclic peptides, sesquiterpenoids, phenols, anthraquinones, coumarins, etc. In this study, endophytic fungi reported in the last six years (2018-2023) have been explored to document the antifungal entities they produce. Approximately 244 antifungal metabolites have been documented in this period by different groups of fungi existing as endophytes. Various aspects of these antifungal metabolites, such as antifungal potential and their chemical structures, have been presented. Yet another unique aspect of this review is the exploration of volatile antifungal compounds produced by these endophytic fungi. Further strategies like epigenetic modifications by chemical as well as biological methods and OSMAC to induce the silent gene clusters have also been presented to generate unprecedented bioactive compounds from these endophytic fungi.

Evaluation of drought-tolerant endophytic fungus Talaromyces purpureogenus as a bioinoculant for wheat seedlings under normal and drought-stressed circumstances.

The present work is aimed to hypothesize that fungal endophytes associated with wheat (Triticum aestivum L.) plants can play a variety of roles in biotechnology including plant growth. Out of 67 fungal isolates, five maximum drought-tolerant isolates were used to check their various plant growth-promoting traits, antioxidants, and antifungal activities under secondary screening. Fungal isolate #8TAKS-3a exhibited the maximum drought tolerance capacity and potential to produce auxin, gibberellic acid, ACC deaminase, phosphate, zinc solubilization, ammonia, siderophore, and extracellular enzyme activities followed by #6TAKR-1a isolate. In terms of antioxidant activities, #8TAKS-3a culture also showed maximum DPPH scavenging, total antioxidant, and NO-scavenging activities. However, #6TAKR-1a exhibited maximum total flavonoid content, total phenolic content, and Fe-reducing power and also the highest growth inhibition of Aspergillus niger (ITCC 6152) and Colletotrichum sp. (ITCC 6152). Based on morphological characters and multi-locus phylogenetic analysis of the nuc rDNA internal transcribed spacer region (ITS1-5.8S-ITS2 = ITS), ß-tubulin (TUB 2), and RNA polymerase II second largest subunit (RPB2) genes, potent fungal isolate #8TAKS-3a was identified as Talaromyces purpureogenus. Under the in vitro conditions, T. purpureogenus (#8TAKS-3a) was used as a bioinoculant that displayed a significant increase in various physio-biochemical growth parameters under normal and stressed conditions (p < 0.05). Our results indicate that drought stress-tolerant T. purpureogenus can be further used for field testing as a growth promoter.

Promising drought and salinity tolerance features of Nigrospora species existing as endophytes in Oryza sativa.

In this study, we report the discovery of novel Nigrospora species isolated from the extensively cultivated PUSA 44 rice variety in Punjab, India. Out of the 120 isolates examined, 6.6% and 5% isolates exhibited tolerance to high salinity and drought stress. Isolates 6OSFR2e and 7OSFS3a exhibited the highest indole acetic acid and gibberellic acid production, with 268.32 ± 08.10 and 25.72 ± 0.04 µg/mL. Additionally, isolates 7OSFS3a, 6OSFR2e and 6OSFL4c had highest antioxidant potential with IC50 345.45 ± 11.66, 391.58 ± 10.66, and 474.529 ± 11.08 µg/mL. The isolates 6OSFR2e and 6OSFL4c also exhibited phosphate solubilisation with a PI of 1.06 ± 0.00 and 1.04 ± 0.02. The highest cellulase and laccase production with EI 1.24 ± 0.00 and 1.16 ± 0.00 was observed by isolates 6OSFR2e and 6OSFL4c. Promising results were observed in the case of ammonia production. The isolates belonged to the same phylum, Ascomycota and were identified as Nigrospora zimmermanii (6OSFR2e) and Nigrospora oryzae (7OSFS3a), and Nigrospora sphaerica (6OSFL4c) using morpho-taxonomic and molecular identification. The present study provides a critical insight into the characteristics of these Nigrospora species, which could be used to develop a bio-consortium for the rejuvenation of PUSA-44 cultivation. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03679-9.

Plant growth-promoting endophyte Nigrospora oryzae mitigates abiotic stress in rice (Oryza sativa L.).

Climate change has severely impacted crop productivity. Nascent technologies, such as employing endophytic fungi to induce crop adaptogenic changes, are being explored. In this study, 62 isolates of fungi existing as endophytes were recovered from different parts of a drought-resistant rice variety and screened for salinity and drought tolerance. Nigrospora oryzae #2OSTUR9a exhibited in vitro antioxidant potential, indole acetic acid (351.01 ± 7.11 µg/mL), phosphate solubilisation (PI 1.115 ± 0.02), siderophore (72.57% ± 0.19%) and 1-aminocyclopropane-1-carboxylate deaminase production (305.36 ± 0.80 nmol α-ketobutyrate/mg/h). To the best of our knowledge, this is the first report on salinity and drought stress mitigation in rice plants by endophytic N. oryzae. In treated plants under salinity stress, the relative water, chlorophyll, phenolic and osmolyte content increased by 48.39%, 30.94%, 25.32% and 43.67%, respectively, compared with their respective controls. A similar trend was observed under drought stress, where the above parameters increased by 50.31%, 39.47%, 32.95% and 50.42%, respectively. Additionally, the antioxidant status of the treated plants was much higher because of the enhanced antioxidant enzymes and reduced lipid peroxidation. Our findings indicate the ability of N. oryzae to effectively mitigate the impact of stress, thereby enabling the rice plant to sustain stress conditions.

In vitro evaluation of bioactive properties of banana sap.

Banana sap is currently designated as a waste subsequent to utilization of pseudo stem in pulp and paper industry as well as other applications which is contributing to the environmental pollution. In the present study, banana sap and its crude extracts were evaluated for antimicrobial, antioxidant and anticancer properties. The role of oxidized and un-oxidized banana sap for its antimicrobial potential against a microbial test panel comprising gram positive as well as gram negative bacteria and Candida albicans using in vitro micro broth dilution assay. The un-oxidized banana sap exhibited a significantly higher antibacterial potential as evident by a lower minimal inhibitory concentration (MIC) ranging between 15.625 to 62.5 mg/mL. In vitro radical scavenging activity of dichloromethane (DCM) extract of banana sap by DPPH method exhibited 54.62 ± 1.09 (µg/mL) IC50 value at the concentration of 1 mg/mL. Dichloromethane extract of banana sap showed maximum cytotoxic effect with human breast cancer (MCF-7) cell proliferation at the concentration of 100 µg/mL which was 78.37 ± 0.05% and the cytotoxic effect significantly increased with increasing concentration of banana sap extract. Furthermore, LCMS studies revealed the presence of bioactive compounds in dichloromethane extract of banana sap, such as rescinnamine derivative, dihydrorescinnamine and epimedin A. The present study suggested that banana sap is a promising source of bioactive compounds with relevant antimicrobial, antioxidant and anticancer properties.

Fungal Endophytes: A Potential Source of Antibacterial Compounds.

Antibiotic resistance is becoming a burning issue due to the frequent use of antibiotics for curing common bacterial infections, indicating that we are running out of effective antibiotics. This has been more obvious during recent corona pandemics. Similarly, enhancement of antimicrobial resistance (AMR) is strengthening the pathogenicity and virulence of infectious microbes. Endophytes have shown expression of various new many bioactive compounds with significant biological activities. Specifically, in endophytic fungi, bioactive metabolites with unique skeletons have been identified which could be helpful in the prevention of increasing antimicrobial resistance. The major classes of metabolites reported include anthraquinone, sesquiterpenoid, chromone, xanthone, phenols, quinones, quinolone, piperazine, coumarins and cyclic peptides. In the present review, we reported 451 bioactive metabolites isolated from various groups of endophytic fungi from January 2015 to April 2021 along with their antibacterial profiling, chemical structures and mode of action. In addition, we also discussed various methods including epigenetic modifications, co-culture, and OSMAC to induce silent gene clusters for the production of noble bioactive compounds in endophytic fungi.

Superoxide dismutase, protease and lipase expression in clinical isolates of Staphylococcus aureus: a tool for antimicrobial drug discovery.

The rising incidents of invasive infections due to multidrug resistant Staphylococcus aureus necessitate the exploration of newer targets for development of antibiotics. Pathogenicity of S. aureus is attributed to a wide range of virulence factors. The aim of this study was to screen the production of three virulence factors viz. extracellular protease, extracellular lipase and superoxide dismutase in human pathogenic strains of S. aureus for development of a test panel which could aid in screening of natural products of plant and microbial origin. 27 clinical isolates were compared for their enzyme expression profiles of which eight were finally selected. Sau G5 was the only protease producing organism selected in the test panel, while Sau G3 and Sau G9 were best SOD producers and Sau G16, Sau G18, Sau G22, Sau A5 and Sau A2 exhibited highest expression among different groups of clinical staphylococci.