Search Results (841)

In this paper, we present a novel class of hybrid polyketides, tenuazamines A–H (1–8), which exhibit a unique tautomeric equilibrium from Alternaria alternata FL7. The elucidation of the structures was achieved through a diverse combination of NMR, HR-ESIMS, and ECD methods, with a focus on extensive spectroscopic data analysis. Notably, compounds 1, 4, 8–9 exhibited potent toxic effects on the growth of Arabidopsis thaliana. This research expands the structural diversity of tenuazonic acid compounds derived from endophytic fungi and provides potential hit compounds for the development of herbicides. Full article

Fungi have played a pivotal role in human history, from the dangers of fungal toxins to the revolutionary discovery of penicillin. Fungal secondary metabolites (SMs), such as polyketides (PKs) and terpenes, have attracted considerable interest due to their diverse biological activities. Botrytis deweyae, an endophytic fungus, exhibits behaviors that are notably distinct from those of its necrotrophic relatives within the genus Botrytis. This study explores the importance of terpenes and PK gene clusters and their conservation between species. In addition, new putative biosynthetic gene clusters corresponding to those families were identified. Consequently, the new PKS BdPKS22-26 were also identified in other Botrytis species and other fungi. In addition, those new gene clusters identified in this work show differences in the degree of conservation and are phylogenetically closely related to some of the 21 PKSs previously described in the reference strain Botrytis cinerea B05.10. Moreover, a new gene cluster related to terpenes in B. deweyae B1 and B. cinerea B05.10 was also identified that had never been detected before. This new gene cluster is well conserved among other Botrytis species in many phylogenetically distant fungal lineages. Understanding the genetic basis and conservation of these putative biosynthetic gene clusters sheds light on the metabolic potential and ecological roles of B. deweyae and related fungal species. Full article

Cancer remains a leading cause of death worldwide. Also threatening the public is the emergence of antibiotic resistance to existing medicines. Despite the challenge to produce viable natural products to market, there continues to be a need within public health to provide new chemotherapeutic drugs such as those exhibiting cytotoxicity and tumor cell growth-inhibitory properties. As marine genomic research advances, it is apparent that marine-derived sediment harbors uniquely potent bioactive compounds compared to their terrestrial counterparts. The Streptomyces genus in particular produces more than 30% of all secondary metabolites currently approved for human health, thus harboring unexplored reservoirs of chemotherapeutic and antibiotic agents to combat emerging disease. The present study identifies the presence of Streptomyces hygroscopicus and rapamycinicus in environmental sediment at locations within the U.S. Stellwagen Bank National Marine Sanctuary (SBNMS) from 2017 to 2022. Sequencing and bioinformatics methods catalogued biosynthetic gene clusters (BGCs) that drive cytotoxic and antibiotic biochemical processes in samples collected from sites permittable and protected to fishing activity. Poisson regression models confirmed that Sites 1 and 3 had significantly higher occurrences of rapamycinicus than other sites (p < 0.01). Poisson regression models confirmed that Sites 1, 2 and 3 had significantly higher occurrence for Streptomyces hygroscopicus across sites (p < 0.05). Interestingly, permitted fishing sites showed a greater prevalence of both species. Statistical analyses showed a significant difference in aligned hits with polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) by site and between species with hygroscopicus showing a greater quantity than rapamycinicus among Streptomyces spp. (p < 0.05; F = 4.7 > F crit). Full article

Finding new molecules to prevent the growth of antimicrobial resistance is a hot topic for scientists worldwide. It has been reported that some raw bioproducts containing Monascus polyketides have antimicrobial activities, but extensive studies on this effect have not been conducted. In this context, our studies aimed to evaluate the antimicrobial properties of six raw bioproducts containing three classes of microbial polyketides biosynthesized by three Monascus strains through solid-state biosynthesis. As a methodology, we performed in silico predictions using programs such as PyMOL v3.0.4 and employed ESI-MS techniques to provide evidence of the presence of the six studied compounds in our bioproducts. The results obtained in silico were validated through in vitro studies using the Kirby-Bauer diffusion method on bacteria and fungi. The test performed in silico showed that Monascorubramine has the highest affinity for both Gram-positive and Gram-negative bacteria, followed by yellow polyketides such as Ankaflavin and Monascin. The estimated pharmacokinetic parameters indicated high gastrointestinal absorption and the potential to cross the blood-brain barrier for all studied compounds. However, the compounds also inhibit most enzymes involved in drug metabolism, presenting some level of toxicity. The best in vitro results were obtained for S. aureus, with an extract containing yellow Monascus polyketides. Predictions made for E. coli were validated in vitro for P. aeruginosa, S. enterica, and S. marcescens, as well as for fungi. Significant antibacterial properties were observed during this study for C. albicans, S. aureus, and fungal dermatophytes for crude bioproducts containing Monascus polyketides. In conclusion, the antimicrobial properties of Monascus polyketides were validated both in silico and in vitro. However, due to their potential toxicity, these bioproducts would be safer to use as topical formulations. Full article

Bibenzyl compounds are one of the most important bioactive components of natural medicine. However, Dendrobium officinale as a traditional herbal medicine is rich in bibenzyl compounds and performs functions such as acting as an antioxidant, inhibiting cancer cell growth, and assisting in neuro-protection. The biosynthesis of bibenzyl products is regulated by bibenzyl synthase (BBS). In this study, we have cloned the cDNA gene of the bibenzyl synthase (DoBS1) from D. officinale using PCR with degenerate primers, and we have identified a novel type III polyketide synthase (PKS) gene by phylogenetic analyses. In a series of perfect experiments, DoBS1 was expressed in Escherichia coli, purified and some catalytic properties of the recombinant protein were investigated. The molecular weight of the recombinant protein was verified to be approximately 42.7 kDa. An enzyme activity analysis indicated that the recombinant DoBS1-HisTag protein was capable of using 4-coumaryol-CoA and 3 malonyl-CoA as substrates for dihydroresveratrol (DHR) in vitro. The Vmax and Km of the recombinant protein for DHR were 3.57 ± 0.23 nmol·min⁻¹·mg⁻¹ and 0.30 ± 0.08 mmol, respectively. The present study provides further insights into the catalytic mechanism of the active site in the biosynthetic pathway for the catalytic production of dihydroresveratrol by bibenzylase in D. officinale. The results can be used to optimize a novel biosynthetic pathway for the industrial synthesis of DHR. Full article

Fusarium species are commonly found in soil, water, plants, and animals. A variety of secondary metabolites with multiple biological activities have been recently isolated from Fusarium species, making Fusarium fungi a treasure trove of bioactive compounds. This mini-review comprehensively highlights the newly isolated secondary metabolites produced by Fusarium species and their various biological activities reported from 2019 to October 2024. About 276 novel metabolites were revealed from at least 21 Fusarium species in this period. The main metabolites were nitrogen-containing compounds, polyketides, terpenoids, steroids, and phenolics. The Fusarium species mostly belonged to plant endophytic, plant pathogenic, soil-derived, and marine-derived fungi. The metabolites mainly displayed antibacterial, antifungal, phytotoxic, antimalarial, anti-inflammatory, and cytotoxic activities, suggesting their medicinal and agricultural applications. This mini-review aims to increase the diversity of Fusarium metabolites and their biological activities in order to accelerate their development and applications. Full article

Aeruginosins (AERs) are one of the most common classes of cyanobacterial peptides synthesised through a hybrid non-ribosomal peptide synthase/polyketide synthase pathway. They have been found in Microcystis, Nodularia spumigena, Oscillatoria/Plantothrix, and Nostoc. The presence of AER in Aphanizomenon isolated from the Curonian Lagoon was reported for the first time in our previous work. Here, the structure of aeruginosin 525 (AER525), isolated from Aphanizomenon sp. KUCC C2, was characterised based on high-resolution mass spectrometry. This new AER variant shows potent activity against thrombin. It also inhibits trypsin and carboxypeptidase A but has no effect on elastase and chymotrypsin. In terms of the N-terminal residue and biological activity, AER525 displaces some similarity to dysinosins, which belongs to the most potent inhibitors of thrombin among AERs. The findings underline the potential of AER525 as a new anticoagulant agent. Full article

Priestia megaterium (P. megaterium PH3) is an endophytic bacterium isolated from peanuts. It has natural resveratrol production ability and shows potential application value. This study analyzed its genetic function and metabolic mechanism through whole-genome sequencing and found that the genome size is 5,960,365 bp, the GC content is 37.62%, and 6132 genes are annotated. Functional analysis showed that this strain contained 149 carbohydrate active enzyme genes, 7 secondary metabolite synthesis gene clusters, 509 virulence genes, and 273 drug-resistance genes. At the same time, this strain has the ability to regulate salt stress, low temperature, and hypoxia. Genomic analysis reveals a stilbene-synthase-containing type III polyketide synthase gene cluster that contributes to resveratrol synthesis. A safety assessment showed that the strain is non-hemolytic, does not produce amino acid decarboxylase, and is not resistant to multiple antibiotics. In the mouse model, P. megaterium PH3 did not have significant effects on body weight, behavior, or physiological indicators. These results provide important basic data and theoretical support for its industrial application and the research and development of plant protection agents. Full article

Banana is an important fruit and food crop in tropical and subtropical regions worldwide. Banana production is seriously threatened by Fusarium wilt of banana (FWB), a disease caused by Fusarium oxysporum f. sp. cubense, and biological control is an important means of curbing this soil-borne disease. To reveal the effects of biocontrol agents on inhibiting FWB and altering the soil bacterial community under natural ecosystems, we conducted experiments at a banana plantation. The control efficiency of a compound microbial agent (CM), Paenibacillus polymyxa (PP), Trichoderma harzianum (TH), and carbendazim (CA) on this disease were compared in the field. Meanwhile, the alterations in structure and function of the rooted soil bacterial community in different treatments during the vigorous growth and fruit development stages of banana were analyzed by microbiomics method. The results confirmed that the different biocontrol agents could effectively control FWB. In particular, CM significantly reduced the incidence of the disease and showed a field control efficiency of 60.53%. In terms of bacterial community, there were no significant differences in the richness and diversity of banana rooted soil bacteria among the different treatments at either growth stage, but their relative abundances differed substantially. CM treatment significantly increased the ratios of Bacillus, Bryobacter, Pseudomonas, Jatrophihabitans, Hathewaya, and Chujaibacter in the vigorous growth stage and Jatrophihabitans, Occallatibacter, Cupriavidus, and 1921-3 in the fruit development stage. Furthermore, bacterial community function in the banana rooted soil was affected differently by the various biocontrol agents. CM application increased the relative abundance of multiple soil bacterial functions, including carbohydrate metabolism, xenobiotic biodegradation and metabolism, terpenoid and polyketide metabolism, lipid metabolism, and metabolism of other amino acids. In summary, our results suggest that the tested biocontrol agents can effectively inhibit the occurrence of banana Fusarium wilt and alter the soil bacterial community in the field. They mainly modified the relative abundance of bacterial taxa and the metabolic functions rather than the richness and diversity. These findings provide a scientific basis for the use of biocontrol agents to control banana Fusarium wilt under field conditions, which serves as a reference for the study of the soil microbiological mechanisms of other biocontrol agents. Full article

The aim of the present study was to comprehensively analyze and identify the metabolites of different varieties of raw peanut, as well as provide a reference for the utilization of different varieties of peanuts. In this study, three varieties of peanuts, namely ZKH1H, ZKH13H, and CFD, were investigated via ultrahigh-performance liquid chromatography (UPLC) and widely targeted metabolomics methods based on tandem mass spectrometry (MS) and solid-phase microextraction-gas chromatography–mass spectrometry (SPME-GC–MS). In total, 417 nonvolatile and 55 volatile substances were detected. The nonvolatile substances were classified into the following 10 categories: organic acids and derivatives (28.9%); organic oxygen compounds (21.9%); lipids and lipid-like molecules (12.6%); organoheterocyclic compounds (9.9%); nucleosides, nucleotides, and analogues (9.4%); benzenoids (7.8%); phenylpropanoids and polyketides (6.1%); organic nitrogen compounds (2.7%); lignans, neolignans, and related compounds (0.5%); and alkaloids and their derivatives (0.3%). The volatile compounds (VOCs) were classified into the following eight categories: organic oxygen compounds (24.1%); organic cyclic compounds (20.4%); organic nitrogen compounds (13%); organic acids and their derivatives (13%); lipids and lipid-like molecules (11.2%); benzenoids (11.1%); hydrocarbons (3.7%); and homogeneous non-metallic compounds (3.7%). Differentially abundant metabolites among the different peanut varieties (ZKH13H vs. CFD, ZKH1H vs. CFD, and ZKH1H vs. ZKH13H) were investigated via multivariate statistical analyses, which identified 213, 204, and 157 nonvolatile differentially abundant metabolites, respectively, and 12, 11, and 10 volatile differentially abundant metabolites, respectively. KEGG metabolic pathway analyses of the differential non-VOCs revealed that the most significant metabolic pathways among ZKH13H vs. CFD, ZKH1H vs. CFD, and ZKH1H vs. ZKH13H were galactose metabolism, purine metabolism, and aminoacyl-tRNA, while the nitrogen metabolism pathway was identified as a significant metabolic pathway for the VOCs. The present findings provide a theoretical foundation for the development and utilization of these three peanut species, as well as for the breeding of new peanut varieties. Full article

Plants cultivated on the Qinghai-Tibet Plateau (QTP) are exposed to high ultraviolet radiation intensities, so they require effective mechanisms to adapt to these stress conditions. UV-B radiation is an abiotic stress factor that affects plant growth, development, and environmental adaptation. Elymus sibiricus is a common species in the alpine meadows of the QTP, with high-stress resistance, large biomass, and high nutritional value. This species plays an important role in establishing artificial grasslands and improving degraded grasslands. In this study, UV-B radiation-tolerant and UV-B radiation-sensitive E. sibiricus genotypes were subjected to simulated short-term (5 days, 10 days) and long-term (15 days, 20 days) UV-B radiation stress and the metabolite profiles evaluated to explore the mechanism underlying UV-B radiation resistance in E. sibiricus. A total of 699 metabolites were identified, including 11 primary metabolites such as lipids and lipid-like molecules, phenylpropanoids and polyketides, organic acids and their derivatives, and organic oxygen compounds. Principal component analysis distinctly clustered the samples according to the cultivar, indicating that the two genotypes exhibit distinct response mechanisms to UV-B radiation stress. The results showed that 14 metabolites, including linoleic acid, LPC 18:2, xanthosine, and 23 metabolites, including 2-one heptamethoxyflavone, glycyrrhizin, and caffeic acid were differentially expressed under short-term and long-term UV-B radiation stress, respectively. Therefore, these compounds are potential biomarkers for evaluating E. sibiricus response to UV-B radiation stress. Allantoin specific and consistent expression was up-regulated in the UV-B radiation-tolerant genotype, thereby it can be used to identify varieties resistant to UV-B radiation. Different metabolic profiles and UV-B radiation response mechanisms were observed between the UV-B radiation-tolerant and UV-B radiation-sensitive E. sibiricus genotypes. A model for the metabolic pathways and metabolic profiles was constructed for the two genotypes. This metabolomic study on the E. sibiricus response to UV-B radiation stress provides a reference for the breeding of new UV-B radiation-tolerant E. sibiricus cultivars. Full article

Background: Lactiplantibacillus plantarum is a species found in a wide range of ecological niches, including vegetables and dairy products, and it may occur naturally in the human gastrointestinal tract. The precise mechanisms underlying the beneficial properties of these microbes to their host remain obscure. Although Lactic acid bacteria are generally regarded as safe, there are rare cases of the emergence of infections and antibiotic resistance by certain probiotics. Objective: An in silico whole genome sequence analysis of putative probiotic bacteria was set up to identify strains, predict desirable functional properties, and identify potentially detrimental antibiotic resistance and virulence genes. Methods: We characterized the genomes of three L. plantarum strains (54B, 54C, and 55A) isolated from Ethiopian traditional cottage cheese. Whole-genome sequencing was performed using Illumina MiSeq sequencing. The completeness and quality of the genome of L. plantarum strains were assessed through CheckM. Results: Analyses results showed that L. plantarum 54B and 54C are closely related but different strains. The genomes studied did not harbor resistance and virulence factors. They had five classes of carbohydrate-active enzymes with several important functions. Cyclic lactone autoinducer, terpenes, Type III polyketide synthases, ribosomally synthesized and post-translationally modified peptides-like gene clusters, sactipeptides, and all genes required for riboflavin biosynthesis were identified, evidencing their promising probiotic properties. Six bacteriocin-like structures encoding genes were found in the genome of L. plantarum 55A. Conclusions: The lack of resistome and virulome and their previous functional capabilities suggest the potential applicability of these strains in food industries as bio-preservatives and in the prevention and/or treatment of infectious diseases. The results also provide insights into the probiotic potential and safety of these three strains and indicate avenues for further mechanistic studies using these isolates. Full article

Four new polyketides, heterocornol Y (1), stemphyindan (2), pestalospirane C (3), and stemphyspyrane (4), along with five known ones (5–9) were isolated from the endophytic fungus Stemphylium globuliferum 17035 (SG17035) based on the One Strain Many Compounds (OSMAC) strategy allied with an LC-MS approach. These structures were elucidated through extensive spectroscopic analyses, single-crystal X-ray diffraction, and ¹³C NMR-DP4 analysis. Pestalospirane C (3) and stemphyspyrane (4) featured unprecedented spiroketal skeletons. In addition, the putative biosynthetic logic for compounds 1–4 was proposed. Antibacterial and cytotoxic activities of compounds 1–9 were evaluated. Stemphyspyrane (4) displayed promising antibacterial activity against different pathogens, especially against Staphylococcus aureus, Porphyromonas gingivalis, and methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 3.125 μM, 6.25 μM, and 12.5 μM, respectively. It is promising as an antibacterial agent for further optimization. Full article

Astragalus, a group of legume plants, has a pronounced rhizosphere effect. Many species of Astragalus with limited resource reserves are distributed in the high-altitude area of northern Yunnan, China. Although some of these plants have high medicinal value, the recognition of them is still at a low level. The aim of this research is to explore the species diversity of cultivable rhizofungi derived from Astragalus acaulis, A. forrestii and A. ernestii growing in a special high–cold environment of northwest Yunnan and discover anti-infective components from these fungi. A total of 93 fungal strains belonging to 38 species in 18 genera were isolated and identified. Antibacterial and antimalarial screening yielded 10 target strains. Among them, the ethyl acetate crude extract of the fermented substrate of the rhizofungus Aspergillus calidoustus AA12 derived from the plant A. acaulis showed broad-spectrum antibacterial activity and the best antimalarial activity. Further chemical investigation led to the first discovery of seven compounds from the species A. calidoustus, including sesterterpine 6-epi-ophiobolin G; three sesquiterpenes, penicisochroman A, pergillin and 7-methyl-2-(1-methylethylethlidene)-furo [3,2-H]isoquinoline-3-one; and three polyketides, trypacidin, 1,2-seco-trypacidin and questin. Among them, the compound 6-epi-ophiobolin G exhibited moderate to strong antibacterial activity against six Gram-positive pathogens with the minimum inhibitory concentration (MIC) ranging from 25 to 6.25 μg/mL and a prominent inhibitory effect on the biofilm of Streptococcus agalactiae at an MIC value of 3.125 μg/mL. This compound also displayed potent antimalarial activity against Plasmodium falciparum strains 3D7 and chloroquine-resistant Dd2 at the half-maximal inhibitory concentration (IC₅₀) values of 3.319 and 4.340 µmol/L at 72 h, respectively. This study contributed to our understanding of the cultivable rhizofungi from characteristic Astragalus plants in special high–cold environments and further increased the library of fungi available for natural anti-infectious product screening. Full article

An investigation of ×19 soil samples collected under the auspices of the Australian citizen science initiative, Soils for Science, returned ×559 chemically dereplicated microbial isolates, of which ×54 exhibited noteworthy anthelmintic activity against either the heartworm Dirofilaria immitis microfilaria and/or the gastrointestinal parasite Haemonchus contortus L1–L3 larvae. Chemical (GNPS and UPLC-DAD) and cultivation (MATRIX) profiling prompted a detailed chemical investigation of Streptomyces sp. S4S-00196A10, which yielded new anthelmintic polyketide goondapyrones A–J (1–10), together with the known actinopyrones A (11) and C (12). Structures for 1–12 were assigned on the basis of detailed spectroscopic and chemical analysis, with preliminary structure activity relationship analysis revealing selected γ-pyrones >50-fold and >13-fold more potent than isomeric α-pyrones against D. immitis mf motility (e.g., EC₅₀ 0.05 μM for 1; EC₅₀ 2.7 μM for 5) and H. contortus L1–L3 larvae development (e.g., EC₅₀ 0.58 μM for 1; EC₅₀ 8.2 μM for 5), respectively. Full article