Search Results (1,514)

Background: The current rise in multidrug-resistant pathogens highlights the urgent need for the discovery of novel antibacterial agents with potential clinical applications. A considerable proportion of these developed resistances may be attributable to the intrinsic response of bacteria to antibiotic-induced stress conditions in the environment. Consequently, the identification and characterization of genetic alterations in physiological processes in response to antibiotics represent promising strategies for the discovery and characterization of naturally produced novel antibacterial agents. This study investigated the antimicrobial activity of an antimicrobial active isolate Actinomadura coerulea derived from a meerkat fecal sample. Methods: The production of secondary metabolites that potentially compromise bacterial cell wall integrity was confirmed by the induction of promoter activity in whole-cell biosensors in which an antibiotic-inducible promoter was fused to the luciferase cassette. During plate-based biosensor assays, we identified naturally resistant Bacillus subtilis colonies growing in the zone of inhibition around A. coerulea colonies. After these successive rounds of selection, highly resistant spontaneous B. subtilis mutants had evolved that were subjected to whole-genome sequencing. Results: Non-silent mutations were identified in pssA, which encodes a phosphatidylserine synthase; mdtR, as a gene for the repressor of multidrug resistance proteins, and yhbD, whose function is still unknown. A new cinnamycin-like molecule, coerumycin, was discovered based on the physiological role of PssA and comprehensive genomic analysis of A. coerulea. Additional experiments with cell extracts containing coerumycin as well as the cinnamycin-like compound duramycin confirmed that the interaction between coerumycin and the bacterial cell envelope is inhibited by a loss-of-function mutation in pssA. Conclusion: Our approach demonstrates that combining the exploration of niche habitats for actinomycetes with whole-cell biosensor screening and characterization of natural resistance development provides a promising strategy for identifying novel antibiotics. Full article

Marine-derived fungi have become a vital resource for the discovery of novel secondary metabolites with diverse structures and significant biological activities. This study focuses on a systematic chemical investigation of the sponge-associated fungus Talaromyces stipitatus HF05001, leading to the isolation and identification of 20 compounds, including one new marine ketal natural product (Compound 17, Talarobispiral A). These compounds were structurally elucidated using comprehensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS. All isolates were screened for their anti-inflammatory and anti-adipogenic properties. Among them, compound 4 (Secalonic acid D, SAD), 7 (Sch 725680) and 16 (bacillisporins C) demonstrated significant anti-inflammatory potential by markedly suppressing nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Notably, compound 4 showed superior inhibitory effect, with an IC₅₀ value of 0.22 μM. Additionally, compound 4 exhibited the strongest dose-dependent inhibition of lipid droplet accumulation in 3T3-L1 preadipocytes. These findings highlight the dual therapeutic potential of metabolites from Talaromyces stipitatus, identifying promising lead compounds for the development of novel treatments for inflammatory and metabolic disorders. Full article

Staphylococcus aureus is a major opportunistic pathogen responsible for a wide spectrum of human infections, including severe and difficult-to-treat cases. The emergence of multidrug-resistant strains limits the efficacy of conventional antibiotic therapies and poses a significant global public health challenge. In this context, the search for novel antibiotics has intensified, with increasing interest in marine resources, an ecosystem still largely underexplored. Marine bacteria produce a vast array of secondary metabolites with unique structures and potentially novel modes of antibacterial action. Several compounds isolated from marine bacterial strains have demonstrated promising activity against multidrug-resistant S. aureus, including antivirulence effects such as biofilm formation and Quorum-Sensing inhibition. This review explores the potential of marine bacteria as a source of new antibiotics against S. aureus, discusses both classical and advanced strategies for the discovery of bioactive molecules, and highlights the scientific and technological challenges involved in translating these findings into clinical applications. Full article

Endophytic FoRo54 was isolated from the roots of Oryza rufipogon (Dongxiang wild rice) collected in China. Based on morphological characteristics and phylogenetic analysis of the 16S rRNA gene sequence, strain FoRo54 was identified as closely related to Micromonospora rosaria. The complete genome of FoRo54 consists of a linear chromosome of 7,057,852 bp with a GC content of 73.8 mol%. Genome mining using antiSMASH revealed 27 biosynthetic gene clusters (BGCs) potentially involved in secondary metabolite biosynthesis, including those associated with kanamycin, rosamicin, and asukamycin, consistent with the antibacterial activities of the strain. Application of a combined genome mining strategy enabled further exploration of the strain’s metabolic potential. One new rosamicin derivative, N-demethyl rosamicin (1), together with three known compounds, rosamicin (2), SCH 23831 (3), and tylactone (4), were isolated from fermentation broth. Antibacterial evaluation revealed that compounds 1-4 exhibited potent inhibitory activity against Staphylococcus aureus. Furthermore, based on genomic analysis, the biosynthetic pathway and putative gene functions responsible for these metabolites were proposed. Collectively, these findings highlight the metabolic versatility of the endophytic Micromonospora rosaria FoRo54, underscoring its potential as a valuable source of novel bioactive metabolites and providing a genomic framework for future heterologous expression and functional genetic characterization. Full article

Mangrove ecosystems along the Indian Ocean coast show great biodiversity, adapting to harsh environmental conditions of high salinity and higher organic matter, and they are a host for a range of microbial communities with special features that produce unique secondary metabolites. Of this, mangrove-associated endophytic fungi, the second largest ecological group of marine fungi, show the greater potential, being a diverse pool for discovering novel bio-actives with pharmacological and biotechnological interest. This review summarizes the research findings on structural diversity and the associated pharmacological activities of secondary metabolites produced by mangrove-associated fungi along the Indian Ocean coast reported over the period of 2002–2025, based on the literature retrieved from Google Scholar. The total of 302 secondary metabolites is presented mainly from classes of polyketides (208), alkaloids (34), and terpenoids (60). Interestingly, 164 compounds were identified, as first reported in those publications. These compounds have been reported to show diverse biological activities, and the most prominent activities are cytotoxic, antibacterial, antifungal, antioxidant, enzyme inhibitory, and anti-inflammatory effects. The structural novelty and pharmacological activities of these metabolites highlight the importance of mangrove fungi as promising sources for new drug discovery and advancing industrial biotechnology. Therefore, this review highlights the insight into the possible application of these chemical compounds in the future drug industry, as well as in biotechnology for advancing human well-being. Furthermore, though significant progress has been made in exploring the fungi community from mangroves of the African and Middle Eastern coasts, the Indian coast mangrove fungi are yet to be explored more for novel discoveries. Full article

A growing body of evidence indicates that artificial manipulation of transcriptional regulation is a powerful approach to activate cryptic biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) in fungi. In this study, one mutant strain MNP-2-OE::veA was constructed by overexpressing the global transcription regulator veA in an Arctic-derived strain Aspergillus sydowii MNP-2. Chemical investigation of the mutant OE::veA resulted in the isolation of one novel polyhydroxy anthraquinone (1) together with nine known metabolites (2–10), which were unambiguously characterized by various spectroscopic methods including 1D and 2D NMR and HR-ESI-MS as well as via comparison with literature data. Biosynthetically, compounds 1 and 10 as new arising chemicals were, respectively, formed by type II polyketide synthase (T2PK) and non-ribosomal peptide synthetase (NRPS), which were silent in the wild-type (WT) strain MNP-2. A bioassay showed that only compound 3 had weak inhibitory effect on human pathogen Candida albicans, with a MIC value of 64 ug/mL, and 4 displayed in vitro weak cytotoxic activity against HCT116 cells (IC₅₀ = 44.47 μM). These results indicate that overexpression of veA effectively awakened the cryptic BGCs in fungal strains and enhanced their structural diversity in natural products. Full article

Salt stress is one of the most harmful abiotic stresses that strongly affects plant growth and crop yield, limiting agricultural production across the Mediterranean area. Consequently, there is a growing need to identify resilient crops capable of adapting to saline conditions and enhancing desirable qualitative traits through a wide spectrum of physiological, biochemical, and molecular mechanisms. Therefore, this study aimed to investigate the effects of four different NaCl concentrations (0, 12.5, 25, and 50 mM) on the growth rates, biometric and productive characteristics, leaf gas exchange, and biochemical traits of Stevia rebaudiana Bertoni plants grown hydroponically (in a floating raft system) in a glasshouse. The results showed that NaCl-treated plants exhibited reduced growth parameters and productivity and a lower content of photosynthetic pigment content compared to the control. On the other hand, an increase in antioxidant capacity was observed due to the significant accumulation of total phenols and flavonoids, especially when stevia plants were treated with 50 mM NaCl. Similarly, the leaf concentration of ascorbic acid and glutathione remarkably increased. This provides new insight into the antioxidant defense strategy of S. rebaudiana under salt stress, demonstrating that stevia plants rely mainly on non-enzymatic mechanisms to counter oxidative stress. Although the highest salinity level (50 mM NaCl) resulted in the lowest content of steviol glycosides (stevioside + rebaudioside A), plants treated with 25 mM NaCl showed both the highest rebaudioside A content and Reb A/Stev ratio, which are desirable properties for the production of high-quality natural sweeteners. Overall, these findings underline that stevia can be considered a moderately salt-tolerant species, and mild stress conditions are able to promote the biosynthesis of interesting secondary metabolites, such as polyphenols and rebaudioside A. Full article

The Xinjiang Uygur Autonomous Region, also known as Xinjiang, China, is notable for its high diversity and abundance of lichens. The purpose of this study was to examine species diversity and the distribution patterns of saxicolous lichens, family Megasporaceae, which includes the genera Aspicilia, Circinaria and Lobothallia, in Xinjiang Province. Morphology, anatomy, chemical analysis and rDNA-ITS sequences for the species were employed for their identification. As a result, 34 crustose and strictly saxicolous species belonging to three genera were found, which included 22 species of the genus Aspicilia, two of which were new to Xinjiang (A. disjecta (Zahlbr.) J.C. Wei and A. pycnocarpa Q. Ren & Lin Liu), eight common species of Circinaria, as well as four species of Lobothallia, two of which (L. determinata (H. Magn.) T.B. Wheeler and L. pruinosa Kou & Q. Ren) are new provincial records. There was a unimodal pattern with respect to lichen species richness; all specimens of the Megasporaceae family were found between 1600 and 5100 m altitude. The 30 species were collected at altitudes between 2601 and 3100 m; only four species were recorded below 2150 m, and seven were found above 4600 m. As far as the type of rocks are concerned, 24 species were found on siliceous rocks and 10 species were found on calcareous rocks. The 24 lichen species contained seven different secondary metabolites; stictic acid, substictic acid and norstictic acid were more common, whereas aspicilin, constictic acid, lecanoric acid and connorstictic acid were found in only a few lichen species. Full article

Cyanobacteria are prolific producers of specialized metabolites of growing interest for blue biotechnology, transversal to various sectors such as cosmetics, foods and pharmaceuticals. In this work, the marine cyanobacterial strain Salileptolyngbya sp. LEGE 181209, from Cabo Verde, was systematically characterized to resolve its taxonomy, pigments profile, and cytotoxicity assessment. A polyphasic workflow combining 16S rRNA gene phylogenies, 16S–23S ITS secondary structures, p-distance, morphology, and scanning electron microscopy (SEM) was used to establish the taxonomic placement of the strain as a new species of the genus. PCR assays targeting the toxin biosynthetic genes mcyA and anaC, and cytotoxicity assays in HaCaT keratinocytes showed low-to-absent cytotoxicity, supporting a safety-forward profile for downstream use. A sequential extraction with solvents of different polarities yielded complementary pigment fractions profiled by HPLC-PDA and spectrophotometry. Total carotenoids reached 72.7 µg mg⁻¹ of dry extract (DE), the profile being dominated by β-carotene and zeaxanthin (≈42 and 8 µg mg⁻¹ of DE, respectively); chlorophyll-a was also very representative, reaching 85.6 µg mg⁻¹ of DE. Phycobiliproteins dominated the polar fraction, with phycocyanin reaching 150 µg mg⁻¹, followed by sugars (19.7 µg of glucose equivalents mg⁻¹) and phenols (8.8 µg of gallic acid equivalents mg⁻¹). Full article

Cytospora chrysosperma is a common opportunistically parasitic fungus that mainly infects forest trees, severely restricting the development of the fruit and forest industry. Surfactin is a secondary metabolite produced by Bacillus species and exhibits antifungal activity; Although the core antifungal mechanism of surfactin against plant pathogens has been extensively studied, our study found that surfactin can target the tricarboxylic acid cycle of C. chrysosperma. This study aimed to investigate the potential mechanism underlying the inhibitory effect of surfactin on C. chrysosperma. The results showed that surfactin had a significant inhibitory effect on C. chrysosperma, with a half-maximal effective concentration of 0.787 ± 0.045 mg/mL and a minimum inhibitory concentration of 2 mg/mL. Morphological observations revealed that surfactin significantly disrupted the morphology and ultrastructure of C. chrysosperma hyphae. FDA/PI staining indicated that surfactin affected the cell membrane integrity of C. chrysosperma, while DCFH-DA fluorescent staining and antioxidant enzyme activity assays demonstrated the accumulation of reactive oxygen species in hyphal cells following surfactin treatment. Additionally, the reduction in adenosine triphosphate content, as well as the decreased activities of ATPase and succinate dehydrogenase, suggested that energy production might be inhibited. Finally, MDC staining showed the occurrence of autophagosomes in C. chrysosperma hyphae after surfactin treatment, which may lead to hyphal death. Transcriptome analysis revealed that surfactin impaired the normal biosynthesis of the C. chrysosperma cell membrane and interfered with the tricarboxylic acid cycle by binding to citrate synthase, resulting in intracellular energy metabolism disorders. This study provides new insights into the potential mechanism by which surfactin inhibits hyphal growth of C. chrysosperma. Full article

The limited cultivability of Actinomycetota strains restricts the exploration of their novel antibiotics, highlighting the need for improved isolation techniques. This study employed a helper strain-assisted cultivation method which utilizes culture supernatants from helper strains to isolate diverse members of the Actinomycetota from millipedes and compared its efficacy with a standard method. Using a preliminary dual-layer solid media assay and subsequent confirmation experiments, eight helper strains (M3, M9, M13, N3, N4, N6, N8, and N9) were identified, whose supernatants promoted the growth of Actinomycetota and other microbes. Application of this method to millipede samples established a novel cultivation strategy based on co-cultivation with helper strains. The new method enabled the isolation of 233 bacterial species in total, of which 143 were species of the phylum Actinomycetota, including 49 novel species. In contrast, the standard method yielded only 42 total bacterial species and 29 species of Actinomycetota, with merely 8 novel species. Comparative diversity analysis revealed that the helper strain-assisted method yielded Actinomycetota strains from 85 genera, which was 3.5 times higher than the standard method. This demonstrates that the helper strain-assisted approach is a highly effective strategy for accessing diverse and novel microbial majority. Among the isolated Actinomycetota strains, 75 strains predicted to have high biosynthetic gene clusters (BGCs) numbers or expected to be novel species were screened for antibacterial activity. Fourteen strains (17%) exhibited inhibitory effects against at least one indicator bacterium. One novel strain, Streptomyces sp. N8-31, was selected for whole-genome sequencing. AntiSMASH analysis predicted 40 biosynthetic gene clusters in N8-31, with 60% showing less than 70% similarity to known clusters; among these, 20 clusters showed less than 50% similarity. These findings indicate that strain N8-31 is a rich reservoir of novel genetic resources, and its broad-spectrum antibacterial activity is likely linked to these unique secondary metabolite gene clusters. Critically, this study confirms that helper strain-assisted cultivation is a powerful tool for unlocking the hidden biosynthetic potential of previously inaccessible Actinomycetota. Full article

Fusarium verticillioides (F. verticillioides) is an important fungal pathogen known to infect a variety of economically critical crops, particularly maize, causing substantial yield reductions and economic losses worldwide. In addition to its direct damage to agricultural productivity, F. verticillioides threatens public health by producing/secreting potent compounds, including well-known fumonisins (FUMs), which pose significant health threats to both livestock and humans due to their toxicity and carcinogenicity. However, current knowledge of the materials secreted/produced by F. verticillioides, such as secreted proteins and additional secondary metabolites, remains limited. In the present study, we conducted an integrated secretome analysis of F. verticillioides at the exponential growth stage by using proteomic and metabolomic technologies. The results of the present study showed that proteomic analysis identified 185 proteins, including 138 fungus-specific proteins. GO enrichment of these 138 fungus-specific proteins yielded 24 significant terms spanning carbohydrate/polysaccharide and aminoglycan metabolic/catabolic processes, extracellular and membrane-anchored components, and hydrolase/peptidase activities. Meanwhile, KEGG analysis identified starch and sucrose metabolism as the sole significantly enriched pathway. Metabolomic analysis of medium supernatant showed that a total of 2352 metabolites were identified, with 110 unique to the medium supernatant of the fungal group, including fumonisins (A1, B2, B3, B4), fatty acids, and other bioactive compounds. KEGG pathway enrichment highlighted key metabolic pathways, including the TCA cycle, unsaturated fatty acid biosynthesis, and arachidonic acid metabolism. These findings provide new insights into the pathogenic mechanisms of F. verticillioides, suggesting candidates for virulence-associated functions and metabolic adaptations that potentially contribute to its pathogenicity. Full article

Fungal phytopathogens cause significant global crop losses and remain a constant obstacle to sustainable food production. Biological control has become a vital alternative to synthetic fungicides, supported by the wide variety of antifungal molecules produced by bacteria, fungi, yeasts, and plants. This review consolidates current knowledge on the main classes of microbial secondary metabolites—particularly cyclic lipopeptides and polyketides from Bacillus, Pseudomonas, Streptomyces, Trichoderma, and related generа. It emphasizes their structural diversity, biosynthetic pathways, regulatory networks, and antifungal mechanisms. These molecules, including iturins, fengycins, surfactins, syringomycins, candicidins, amphotericin analogs, peptaibols, and epipolythiodioxopiperazines, target fungal membranes, mitochondria, cell walls, and signaling systems, offering broad activity against damaging pathogens such as Fusarium, Botrytis, Magnaporthe, Colletotrichum, Phytophthora, and Rhizoctonia. The plant-derived antifungal metabolites include essential volatile compounds that complement microbial agents and are increasingly important in eco-friendly crop protection. Recent progress in genomics, metabolic engineering, and synthetic biology has accelerated strain improvement and the discovery of new bioactive compounds. At the same time, global market analyses indicate rapid growth in microbial biofungicides driven by regulatory changes and consumer demand. Full article

Mining bioactive secondary metabolites from microorganisms originating from deep-sea cold seep holds significant potential for discovering novel drug lead compounds. In this study, three known indole derivatives (1–3) were isolated from cold-seep-derived Halomonas meridiana OUCLQ22-B7. Subsequently, two-new indole dimers, meribisindole A (4) and meribisindole B (5), with nine known metabolites (6–14) were obtained via indole precursor feeding strategy. The structure of these compounds was elucidated via a combination of spectroscopic methods and circular dichroism (CD) measurement. Antimicrobial assays revealed that compounds 4, 7 and 8 exhibited potent inhibitory activity against Fusarium oxysporum CICC 41029 with minimal inhibitory concentrations (MICs) of 0.39−12.5 μg/mL, and compound 11 showed significant growth inhibition against Staphylococcus aureus CCARM 3090 with MIC value at 0.098 μg/mL. Full article

Cancer remains one of the leading causes of death worldwide, and resistance to conventional therapies underscores the need for the discovery of novel antitumor agents. The ongoing search for novel natural sources offers promising avenues for discovering unique anticancer compounds with new mechanisms of action. One of these natural sources is represented by fungi, a prolific group of endophytic and non-endophytic eukaryotes able to produce bioactive secondary metabolites, many of which exhibit potent antitumor properties. These natural compounds display diverse chemical structures including polyketides, terpenoids, alkaloids, amino acid-derived compounds, phenols, etc. Their mechanisms of action are equally varied, ranging from induction of apoptosis and cell cycle arrest to inhibition of angiogenesis and metastasis. In this review we describe some potential antitumor compounds of fungal origin, together with the characteristics and biosynthesis of three representative types of antitumor compounds produced by filamentous fungi: squalene-derived sterol-type antitumor agents, prenylated diketopiperazine antitumor metabolites and meroterpenoid antitumor compounds. The ongoing scientific debate regarding the presence of paclitaxel biosynthetic genes in fungi is also discussed. As drug resistance remains a challenge in cancer therapy, fungal compounds offer a valuable reservoir for the development of new chemotherapeutic agents with novel modes of action. Full article