Hidden Treasure: Halophilic Fungi as a Repository of Bioactive Lead Compounds.

The pressing demand for novel compounds to address contemporary health challenges has prompted researchers to venture into uncharted territory, including extreme ecosystems, in search of new natural pharmaceuticals. Fungi capable of tolerating extreme conditions, known as extremophilic fungi, have garnered attention for their ability to produce unique secondary metabolites crucial for defense and communication, some of which exhibit promising clinical significance. Among these, halophilic fungi thriving in high-salinity environments have particularly piqued interest for their production of bioactive molecules. This review highlights the recent discoveries regarding novel compounds from halotolerant fungal strains isolated from various saline habitats. From diverse fungal species including Aspergillus, Penicillium, Alternaria, Myrothecium, and Cladosporium, a plethora of intriguing molecules have been elucidated, showcasing diverse chemical structures and bioactivity. These compounds exhibit cytotoxicity against cancer cell lines such as A549, HL60, and K-562, antimicrobial activity against pathogens like Escherichia coli, Bacillus subtilis, and Candida albicans, as well as radical-scavenging properties. Notable examples include variecolorins, sclerotides, alternarosides, and chrysogesides, among others. Additionally, several compounds display unique structural motifs, such as spiro-anthronopyranoid diketopiperazines and pentacyclic triterpenoids. The results emphasize the significant promise of halotolerant fungi in providing bioactive compounds for pharmaceutical, agricultural, and biotechnological uses. However, despite their potential, halophilic fungi are still largely unexplored as sources of valuable compounds.

Assessment of the intrinsic bioremediation capacity of a complexly contaminated Yamuna River of India: a algae-specific approach.

Nearly 57 million people depend on Yamuna's water for their daily needs and agriculture. This is the first study of assessment of the Yamuna River for five major pollutants - Nitrate, Sulfate, Phosphate, Silicon, and Chloride, and the role of inhabitant algal species for phycoremediation. Water samples were collected from 11 different locations across three different seasons and it was found that the concentration of these pollutants varies in different locations and seasons. The concentration of Nitrate 392.93 mg/L at ITO Monsoon 2021, Phosphate 86.25 mg/L at Baghpat, Silicon 257.34 mg/L at Faridabad, Sulfate 2165.949 mg/L at ITO during winter 2020, and Chloride 4400.741 mg/L at Old bridge during Monsoon 2021 are found maximum. A significant variation (p < 0.05) in the concentrations of Nitrate, Sulfate, Phosphate, Silicon, and Chloride before and after treatment with microalgae was observed in water samples. All six algae significantly remove all the pollutants, and the maximum pollutants removed are Phosphate and Nitrite. Scenedesmus sp., removes the highest 99.21% Phosphate and 86.31% Nitrate, whereas 78.50% of Sulfate was removed by Klebsormidium sp. The highest 92.77% Silicon and 86.20% Chloride were removed by Oocystis sp. This finding suggests that out of six algae, Scenedesmus sp., in the Yamuna water has grown primarily at all the sites and reduces maximum pollutants. The outcomes from this study confirms that Yamuna River is highly contaminated at all the sites from these five major pollutants and algae are still survive in highly contaminated Yamuna water where no other plants are grown and phycoremediate the water bodies even in the presence of very high-stress condition. These algae can further be utilized for biotreatment of any contaminated water body.

This is the first study of assessment of five major pollutants and role of inhabitant algal species of Yamuna River for Phycoremediation.

Antibacterial metabolites from an unexplored strain of marine fungi Emericellopsis minima and determination of the probable mode of action against Staphylococcus aureus and methicillin-resistant S. aureus.

Increasing prevalence of drug resistance has led researchers to focus on discovering new antibacterial agents derived from the marine biome. Although ample studies have investigated marine fungi for their bioactive metabolites with hopeful prospects in drug discovery. The present study was aimed to isolate/ identify potential antimethicillin-resistant Staphylococcus aureus compounds producing marine fungal strain from the Indian marine environment. The effective anti-MRSA compound was produced by a marine fungal strain designated as D6. The D6 strain exhibited 99% similarity to Emericellopsis minima based on 18S rRNA gene analysis. The culture conditions of E. minima D6 were optimized using nutritional and environmental parameters for enhanced anti-MRSA compound production. The agar well diffusion assay was used to determine the inhibition zone diameter of the crude extract against S. aureus and methicillin-resistant S. aureus, whereas the broth microdilution method was used to determine their minimum inhibitory concentration (MIC) active fraction. MIC values of the ethyl acetate fraction ranged from 0.8 to 1 mg/mL. SEM analysis revealed that the ethyl acetate fraction induces deep craters in methicillin-resistant S. aureus. Further, GC-MS analysis confirmed the occurrence of a total of 15 major compounds in active ethyl acetate fraction. Some of the major antibacterial compounds included cyclopentanol, isothiazole, benzoic acid, pyrrolo[1,2-a] pyrazine-1,4-dione, and hexahydro. These findings suggest that the marine fungi of E. minima can be a valuable candidate for prospecting antibiotics and an alternative complementary strategy for drug-resistant bacterial infections.

Fungal Metabolites: A Potential Source of Antidiabetic Agents with Particular Reference to PTP1B Inhibitors.

Diabetes is a growing health concern worldwide because it affects people of all age groups and increases the risk of other diseases such as renal impairment and neural and cardiovascular disorders. Oral hypoglycemic drugs mainly control diabetes; however, their associated side effects limit their use in patients with other complications. PTP1B is a viable drug target to explore new antidiabetic drugs. PTP1B acts as a negative regulator of the insulin-signaling pathway, and therefore, PTP1B inhibitors display antihyperglycemic activity. Several classes of compounds from natural and synthetic sources act as PTP1B inhibitors. Fungi are comprehensive in their diversity and recognized as a valuable source for therapeutically active molecules. In recent years, researchers have reported diverse classes of fungal secondary metabolites as potent PTP1B inhibitors. Some metabolites such as 6-O-methylalaternin, fumosorinone A, nordivaricatic acid, and the divarinyl divarate showed good activity and can be taken forward as a lead to develop novel PTP1B inhibitors and antidiabetic drugs. Therefore, the present review focuses on the fungal metabolites identified in the last five years possessing PTP1B inhibitory activity. A total of 128 metabolites are reviewed. Their fungal species and source, chemical structure, and activity in terms of IC50 are highlighted.

Antidiabetic Agents from Fungi with Special Reference to α-Glucosidase Inhibitors.

The enzyme α-glucosidases (EC 3.2.1.20) catalyzes the hydrolysis of α-1,4- glucopyranoside bond in oligosaccharides and disaccharides, and thus plays an essential role in regulating glucose content and the level of postprandial hyperglycemia. The inhibition of α-glucosidases is considered a viable strategy to develop new and effective antidiabetic drugs. Many patents like ZA201905405B; US9073897B2 have been published on α- glucosidase inhibitors. In recent years, several classes of fungal metabolites possessing a varying degree of α-glucosidases inhibitory activity have been reported. The primary chemical classes include xanthone, phenanthrene, terpenoid, coumarin, isocoumarin, naphthalene, piperazine, and polyketides. Few of the identified inhibitors exhibited severalfold better activities than well-known α-glucosidases inhibitor acarbose and can be used as a lead to develop new antidiabetic drugs. The present review highlights the recent development in the identification of α-glucosidases inhibitors from various fungal sources. Their chemical class, structures, and inhibitory activity in terms of IC50 or MIC are discussed here.

Uncovering the Fungal Diversity and Biodeterioration Phenomenon on Archaeological Carvings of the Badami Cave Temples: A Microcosm Study.

The Badami Caves are a significant example of ancient Indian rock-cut architecture, dating back to the 6th century. These caves are situated in the Malaprabha River valley and are part of the candidate UNESCO World Heritage Site known as the "Evolution of Temple Architecture-Aihole-Badami-Pattadakal", which is considered to be the cradle of temple architecture in India. Our study aimed to investigate the diversity, distribution, and biodeterioration phenomena of the fungal communities present on the cave surfaces. The study also conducted a comprehensive analysis of fungal biodeterioration on the cave carvings. Utilizing specialized techniques, the dissolution of calcite, alterations in pH levels, and biomineralization capabilities of isolated fungal strains were monitored. Additionally, this study analyzed fungal acid production using high-performance liquid chromatography (HPLC). Our findings revealed that the major genera of fungi found on the cave surfaces included Acremonium, Curvularia, Cladosporium, Penicillium, and Aspergillus. These isolated fungi were observed to produce acids, leading to the dissolution of calcium carbonate and subsequent decrease in pH values. Notably, the dominant genus responsible for acid production and the promotion of biomineralization was Aspergillus. These discoveries provide valuable insight into the ecology and functions of fungi inhabiting stone surfaces, contributing to our understanding of how to preserve and protect sculptures from biodeterioration.

Hepatoprotective and Antioxidant Potential of Phenolics-Enriched Fraction of Anogeissus acuminata Leaf against Alcohol-Induced Hepatotoxicity in Rats.

Anogeissus acuminata is used to treat wounds, diarrhoea, dysentery, and skin ailments. However, its hepatoprotective effect against ethanol-induced liver damage is yet to be reported. The phenolic-enriched ethyl acetate fraction of Anogeissus acuminata (AAE) was evaluated for hepatoprotective activity against ethanol-induced liver toxicity in rats. The intoxicated animals were treated with a phenolic-rich fraction of Anogeissus acuminata (AAE) (100 and 200 mg/kg) and silymarin (100 mg/kg). The antioxidant activity of AAE was analysed. Biochemical markers (ALT, AST, ALP, GGT, and TBL) for liver injury in ethanol-administered animals resulted in higher levels of key serum biochemical injury markers, as evidenced by increased levels of ALT (127.24 ± 3.95), AST (189.54 ± 7.56), ALP (263.88 ± 12.96), GGT (91.65 ± 3.96), and TBL (2.85 ± 0.12) compared to Group I ALT (38.67 ± 3.84), AST (64.45 ± 5.97), GGT (38.67 ± 3.84), and TBL (0.53 ± 064) (p < 0.05). AAE administration decreased serum biochemical liver injury markers as manifested in Group III animals' ALT (79.56 ± 5.16), AST (151.76 ± 6.16), ALP (184.67 ± 10.12), GGT (68.24 ± 4.05), TBL (1.66 ± 0.082) (p < 0.05), and Group IV ALT (55.54 ± 4.35), AST (78.79 ± 4.88), ALP (81.96 ± 9.43), GGT (47.32 ± 2.95), TBL (0.74 ± 0.075) (p < 0.05). Group IV exhibited the most significant reduction in serum biochemical markers as compared to Group III (p < 0.05) and close to silymarin-treated Group V ALT (44.42 ± 3.15), AST (74.45 ± 5.75), ALP (67.32 ± 9.14), GGT (42.43 ± 2.54), TBL (0.634 ± 0.077). Gene expression indices and histoarchitecture were evaluated to demonstrate the potential of AAE. The bioactive fraction of Anogeissus acuminata was rich in phenolics and flavonoid content. GC−MS analysis identified gallic acid, palmitic acid, cis-10-heptadecenoic acid, 9-octadecenoic acid, epigallocatechin, 2,5-dihydroxyacetophenone, and catechin. Oral administration of AAE (100 and 200 mg/kg) lowered the elevated levels of the biochemical markers and interleukin, and enhanced the level of enzymatic antioxidant. It also downregulated the expression level of proapoptotic genes and upregulated the expression level of the antiapoptotic gene along with improved liver histopathology.

The genus Simplicillium and Emericellopsis: A review of phytochemistry and pharmacology.

The demand for novel and improved medicine from biological sources to cater to the biopharmaceutical sector has increased significantly in recent years. Among the vast and miscellaneous microbial diversity, fungi provide a prolific source of structurally unique and biologically active secondary metabolites. Natural products obtained from fungi have reformed the era of biomedicine, providing effective drugs that have diverse healing potential. In this review, we focus on the isolation, chemical structure, and bioactivity of biomolecules that have been identified and studied for the first time. Further, we also explain in substantial detail that how the vast uninvestigated Emericellopsis and Simplicillium species may serve as a potential treasure trove of chemically diverse compounds.

Recent Advances in the Discovery of Antiviral Metabolites from Fungi.

As the world manages the impact of a global pandemic caused by COVID-19, the discovery of new antiviral agents has become way more relevant and urgent. Viruses are submicroscopic infectious agents that replicate inside the living cells of different organisms. These viruses use nucleic acids (both DNA and RNA) for further replication and maturity inside the cells. Some of the viruses responsible for various human and plant diseases belong to the classes of Picornaviridae, Retroviridae, Orthomyxoviridae, Flaviviridae, Pneumoviridae, Virgaviridae, and Hepadnaviridae, and their treatment options are limited or non-existent. The consistent reemergence and resistance development in the viral strains demand the discovery and development of new antiviral drugs possessing better efficacy. Bio-active compounds isolated from fungi can be the source of new compounds with enhanced potency and new mechanisms of action. Fungi are known to produce a diverse lot of secondary metabolites due to their existence in harsh and testing climates which are often inhabitable for many organisms. Because of these unique environments, fungi produce a variety of secondary metabolites of different chemical classes like alkaloids, quinones, furanone, pyrones, benzopyranoids, xanthones, terpenes, steroids, peptides, and many acyclic compounds. Fungal metabolites are known to display a wide range of bioactive attributes, i.e., anticancer, antibacterial, antifungal, and anti-Alzheimer's, along with antiviral properties. In this review article, we report over 300 antiviral compounds from fungal sources during the period of 2009 to 2019. The source of these compounds is marine and endophytic fungi and they are arranged based on their antiviral action against different viral families. These compounds offer promise for their use and development as future antiviral drugs.

The antidiabetic potential of endophytic fungi: Future prospects as therapeutic agents.

Diabetes mellitus is one of the most common systemic diseases in the world, and it occurs when the body becomes resistant to insulin or does not make enough insulin. As described by the World Health Organization, diabetes mellitus of all types has exponentially grown in the past decades across the globe and it is estimated to be 629 million by 2045. Despite this alarming prevalence of diabetes mellitus, there is still the lack of harmless preventive medicines. Natural products and compounds obtained from plants, fungi, bacteria, and other living organisms have been used for many decades in folklore medicine to prepare a varied range of natural formulations to treat multiple diseases and illnesses. Endophytic fungi reside inside the plant while causing no harm to the host plant and are relatively less explored as the primary source for the bioactive metabolites such as anticancer, antioxidant, antimicrobial, antidiabetic, and industrial enzymes. This mini-review summarizes the potential of compounds and extracts from endophytic fungi against diabetes mellitus. Not much research has been dedicated in-depth understanding of the role of extracts of endophytic fungi and their effect on diabetes mellitus. Therefore, this article will focus on recent work and warrant further commentaries on the published articles.

Unveiling the dermatological potential of marine fungal species components: Antioxidant and inhibitory capacities over tyrosinase.

Marine fungi are a rich source of biologically active molecules, but a poorly explored bioresource for cosmeceutical products. This study evaluates the phytochemistry, antioxidant, and antityrosinase effects of the organic extracts of marine fungi isolated from various marine environments in India. Out of 35 screened fungal strains, methanol extracts of strains P2, Talaromyces stipitatus, and D4, Aspergillus terreus exhibited antityrosinase activity of 45% and 43%, respectively, at the lowest concentration of 0.5 mg/mL. The highest free radicals scavenging activity of 94% and 97% was observed at 500 mg/mL, respectively, of the same fungal extracts. The total phenolic content ranged from 8.20 to 20.30 mg/g of the dry weight of extract, expressed as gallic acid equivalent. GC-MS analysis of T. stipitatus and A. terreus extract identified seven and 10 major compounds, respectively. Some of the major compounds included azetidine, (3E)-3-[(3,5-dimethoxybenzoyl)hydrazono]-N-isobutyl butanamide, aziridine, and 3-methylcyclopentanone, 1,1-dimethylcyclohexane, cyclopentane carboxylic acid, N-allyl-4,5,6,7-tetrahydro-2-benzothiophene-1-carboxamide, cyclo(l-Pro-l-Val), and 3-phenylpropionitrile. In conclusion, this study showed abundant fungal resources in Indian marine environments. A correlation between total phenolic contents of the extracts confirmed that phenolic compounds play an important role in antioxidant as well as antityrosinase activity of the marine fungal extracts and can be viewed as new potential antityrosinase and antioxidant resources.

Ultrastructural changes in methicillin-resistant Staphylococcus aureus (MRSA) induced by metabolites of thermophilous fungi Acrophialophora levis.

Staphylococcus aureus and Methicillin-resistant S. aureus (MRSA) remains one of the major concerns of healthcare associated and community-onset infections worldwide. The number of cases of treatment failure for infections associated with resistant bacteria is on the rise, due to the decreasing efficacy of current antibiotics. Notably, Acrophialophora levis, a thermophilous fungus species, showed antibacterial activity, namely against S. aureus and clinical MRSA strains. The ethyl acetate extract of culture filtrate was found to display significant activity against S. aureus and MRSA with a minimum inhibitory concentration (MIC) of 1 µg/mL and 4 µg/mL, respectively. Scanning electron micrographs demonstrated drastic changes in the cellular architecture of metabolite treated cells of S. aureus and an MRSA clinical isolate. Cell wall disruption, membrane lysis and probable leakage of cytoplasmic are hallmarks of the antibacterial effect of fungal metabolites against MRSA. The ethyl acetate extract also showed strong antioxidant activity using two different complementary free radicals scavenging methods, DPPH and ABTS with efficiency of 55% and 47% at 1 mg/mL, respectively. The total phenolic and flavonoid content was found to be 50 mg/GAE and 20 mg/CAE, respectively. More than ten metabolites from different classes were identified: phenolic acids, phenylpropanoids, sesquiterpenes, tannins, lignans and flavonoids. In conclusion, the significant antibacterial activity renders this fungal strain as a bioresource for natural compounds an interesting alternative against resistant bacteria.

Structural deformation in pathogenic bacteria cells caused by marine fungal metabolites: An in vitro investigation.

Over the past 50 years, fungal natural products have revolutionized medicine, yielding drugs which have enormous therapeutic potential. The aim of this study was to investigate the probable effect of marine fungal natural products on various skin pathogens. Initially, seventy natural extracts obtained from 35 different marine fungal strains were analysed by the agar well diffusion and broth micro dilution assay for their antibacterial action against six human skin pathogens. The minimum inhibitory effects of all active fungal methanolic extracts on targeted pathogens were observed between 90 and 99% at the concentration of 1 mg/mL. The highest activity was recorded by fungal strains belonging to genera Penicillium, Emericellopsis and Simplicillium. Thereafter, possible effects on target bacterial cells were studied by scanning electron microscopy which show significant destruction and structural deformation in the bacterial cell wall. The results of the present study provided good evidence that the studied marine fungi can be a potential source of natural antibacterial agents against skin bacterial pathogens.

In-vitro evaluation of marine derived fungi against Cutibacterium acnes.

Cutibacterium acnes (or Propionibacterium acnes) is the main target for the prevention and medical treatment of acne vulgaris. The aim of this study was to evaluate the in vitro anti-C. acnes and anti-S. epidermidis properties of some marine fungi isolated from different Indian marine environments. Seventy fungal isolates were obtained from samples collected from the west coasts and Andaman Island, India. Methanol extracts of 35 isolates were screened for their antibacterial properties and 5 out of the 35 isolates displayed significant inhibition as compared with tetracycline. DNA was successfully extracted from these five fungal isolates and phylogenetic analysis was performed. The methanol extracts possessed antibacterial activity against C. acnes and S. epidermidis with MIC values ranged from 0.8 mg/mL to 1 mg/mL. SEM analysis revealed that the extract induces deleterious morphological changes in the bacterial cell membrane. This study has identified some fungi extracts with significant antibacterial activity. The extracts may have potential for development as an antibacterial agent in the treatment of acne vulgaris.

Nonribosomal Peptides from Marine Microbes and Their Antimicrobial and Anticancer Potential.

Marine environments are largely unexplored and can be a source of new molecules for the treatment of many diseases such as malaria, cancer, tuberculosis, HIV etc. The Marine environment is one of the untapped bioresource of getting pharmacologically active nonribosomal peptides (NRPs). Bioprospecting of marine microbes have achieved many remarkable milestones in pharmaceutics. Till date, more than 50% of drugs which are in clinical use belong to the nonribosomal peptide or mixed polyketide-nonribosomal peptide families of natural products isolated from marine bacteria, cyanobacteria and fungi. In recent years large numbers of nonribosomal have been discovered from marine microbes using multi-disciplinary approaches. The present review covers the NRPs discovered from marine microbes and their pharmacological potential along with role of genomics, proteomics and bioinformatics in discovery and development of nonribosomal peptides drugs.

The Pharmacological Potential of Non-ribosomal Peptides from Marine Sponge and Tunicates.

Marine biodiversity is recognized by a wide and unique array of fascinating structures. The complex associations of marine microorganisms, especially with sponges, bryozoans, and tunicates, make it extremely difficult to define the biosynthetic source of marine natural products or to deduce their ecological significance. Marine sponges and tunicates are important source of novel compounds for drug discovery and development. Majority of these compounds are nitrogen containing and belong to non-ribosomal peptide (NRPs) or mixed polyketide-NRP natural products. Several of these peptides are currently under trial for developing new drugs against various disease areas, including inflammatory, cancer, neurodegenerative disorders, and infectious disease. This review features pharmacologically active NRPs from marine sponge and tunicates based on their biological activities.