Dataset Information

Integrating Activity-Guided Strategy and Fingerprint Analysis to Target Potent Cytotoxic Brefeldin A from a Fungal Library of the Medicinal Mangrove Acanthus ilicifolius.

ABSTRACT: Mangrove-associated fungi are rich sources of novel and bioactive compounds. A total of 102 fungal strains were isolated from the medicinal mangrove Acanthus ilicifolius collected from the South China Sea. Eighty-four independent culturable isolates were identified using a combination of morphological characteristics and internal transcribed spacer (ITS) sequence analyses, of which thirty-seven strains were selected for phylogenetic analysis. The identified fungi belonged to 22 genera within seven taxonomic orders of one phyla, of which four genera Verticillium, Neocosmospora, Valsa, and Pyrenochaeta were first isolated from mangroves. The cytotoxic activity of organic extracts from 55 identified fungi was evaluated against human lung cancer cell lines (A-549), human cervical carcinoma cell lines (HeLa), human hepatoma cells (HepG2), and human acute lymphoblastic leukemia cell lines (Jurkat). The crude extracts of 31 fungi (56.4%) displayed strong cytotoxicity at the concentration of 50 μg/mL. Furthermore, the fungus Penicillium sp. (HS-N-27) still showed strong cytotoxic activity at the concentration of 25 µg/mL. Integrating cytotoxic activity-guided strategy and fingerprint analysis, a well-known natural Golgi-disruptor and Arf-GEFs inhibitor, brefeldin A, was isolated from the target active strain HS-N-27. It displayed potential activity against A549, HeLa and HepG2 cell lines with the IC₅₀ values of 101.2, 171.9 and 239.1 nM, respectively. Therefore, combining activity-guided strategy with fingerprint analysis as a discovery tool will be implemented as a systematic strategy for quick discovery of active compounds.

SUBMITTER: Wang CF

PROVIDER: S-EPMC9315649 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundAcanthus is a unique genus consisting of both true mangrove and terrestrial species; thus, it represents an ideal system for studying the origin and adaptive evolution of mangrove plants to intertidal environments. However, little is known regarding the two respects of mangrove species in Acanthus. In this study, we sequenced the transcriptomes of the pooled roots and leaves tissues for a mangrove species, Acanthus ilicifolius, and its terrestrial congener, A. leucostachyus, to illustrate the origin of the mangrove species in this genus and their adaptive evolution to harsh habitats.ResultsWe obtained 73,039 and 69,580 contigs with N50 values of 741 and 1557 bp for A. ilicifolius and A. leucostachyus, respectively. Phylogenetic analyses based on four nuclear segments and three chloroplast fragments revealed that mangroves and terrestrial species in Acanthus fell into different clades, indicating a single origin of the mangrove species in Acanthus. Based on 6634 orthologs, A. ilicifolius and A. leucostachyus were found to be highly divergent, with a peak of synonymous substitution rate (Ks) distribution of 0.145 and an estimated divergence time of approximately 16.8 million years ago (MYA). The transgression in the Early to Middle Miocene may be the major reason for the entry of the mangrove lineage of Acanthus into intertidal environments. Gene ontology (GO) classifications of the full transcriptomes did not show any apparent differences between A. ilicifolius and A. leucostachyus, suggesting the absence of gene components specific to the mangrove transcriptomes. A total of 99 genes in A. ilicifolius were identified with signals of positive selection. Twenty-three of the 99 positively selected genes (PSGs) were found to be involved in salt, heat and ultraviolet stress tolerance, seed germination and embryo development under periodic inundation. These stress-tolerance related PSGs may be crucial for the adaptation of the mangrove species in this genus to stressful marine environments and may contribute to speciation in Acanthus.ConclusionsWe characterized the transcriptomes of one mangrove species of Acanthus, A. ilicifolius, and its terrestrial relative, A. leucostachyus, and provided insights into the origin of the mangrove Acanthus species and their adaptive evolution to abiotic stresses in intertidal environments.

Project description:A high diversity of culturable foliar endophytic fungi is known from various mangrove plants, and the core taxa include species from Colletotrichum, Pestalotiopsis, Phoma, Phomopsis, Sporomiella, among others. Since a small fraction of fungi is able to grow in culture, this study investigated the diversity of fungi associated with leaves of Acanthus ilicifolius var. xiamenensis using both isolation and metabarcoding approaches. A total of 203 isolates were cultured from surface-sterilized leaves, representing 47 different fungal species: 30 species from the winter samples (104 isolates), and 26 species from the summer samples (99 isolates). Ascomycota was dominant in both types of leaf samples, while Basidiomycota was isolated only from the summer samples. Drechslera dematioidea (10.58%, percentage of occurrence), Colletotrichum sp. 3 (7.69%) and Alternaria sp. (7.69%) were dominant in the winter samples; Fusarium oxysporum (13.13%), Diaporthe endophytica (10.10%) and Colletotrichum sp. 1 (9.09%) in the summer samples. Overall, Corynespora cassiicola (6.90%), F. oxysporum (6.40%) and Guignardia sp. (6.40%) had the highest overall percentage of occurrence. In the metabarcoding analysis, a total of 111 operational taxonomic units (OTUs) were identified from 17 leaf samples: 96 OTUs from the winter and 70 OTUs from the summer samples. Sequences belonging to Ascomycota and Basidiomycota were detected in both samples but the former phylum was dominant over the latter. Based on read abundance, taxa having the highest percentage of occurrence included Alternaria sp. (3.46%), Cladosporium delicatulum (2.56%) and Pyrenochaetopsis leptospora (1.41%) in the winter leaves, and Aureobasidium sp. (10.72%), Cladosporium sp. (7.90%), C. delicatulum (3.45%) and Hortaea werneckii (3.21%) in the summer leaves. These latter four species also had the highest overall percentage of occurrence. Combining the results from both methods, a high diversity of fungi (at least 110 species) was found associated with leaves of A. ilicifolius var. xiamenensis. Many of the fungi identified were plant pathogens and may eventually cause diseases in the host.

Project description:Mangroves are one of the most productive and biologically diverse ecosystems, with unique plants, animals, and microorganisms adapted to the harsh coastal environments. Although fungi are widely distributed in the mangrove ecosystem and they are playing an important role in the decomposition of organic matter, their genomic profiles are still poorly understood. In this study, we isolated seven Ascomycota fungi (Westerdykella dispersa F012, Trichoderma lixii F014, Aspergillus tubingensis F023, Penicillium brefeldianum F032, Neoroussoella solani F033, Talaromyces fuscoviridis F034, and Arthrinium marii F035) from rhizospheres of two mangroves of Kandelia obovata and Acanthus ilicifolius. We sequenced and assembled the whole genome of these fungi, resulting in size ranging from 29 to 48 Mb, while contig N50 from 112 to 833 Kb. We generated six novel fungi genomes except A. tubingensis, and the gene completeness and genome completeness of all seven genomes are higher than 94%. Comparing with non-mangrove fungi, we found Carbohydrate-Binding Modules (CBM32), a subfamily of carbohydrate active enzymes, only detected in two mangrove fungi. Another two subfamilies, Glycoside Hydrolases (GH6) and Polysaccharide Lyases (PL4), were significantly different in gene copy number between K. obovata and A. ilicifolius rhizospheres (P-value 0.041 for GH6, 0.047 for PL4). These findings may indicate an important influence of mangrove environments or hosts on the ability of decomposition in rhizosphere fungi. Secondary metabolite biosynthesis gene clusters were detected and we found the mangrove fungi averagely contain 18 Type I Polyketide (t1pks) synthase, which was significantly higher than 13 in non-mangrove fungi (P-value 0.048), suggesting their potential roles in producing bioactive compounds that important for fungi development and ecology. We reported seven mangrove-associated fungal genomes in this study and compared their carbohydrate active enzymes and secondary metabolites (SM) genes with those of non-mangrove fungi, and the results suggest that there are differences in genetic information among fungi in different habitats.

Project description:Acanthus ilicifolius is an important medicinal plant in mangrove forests, which is rich in secondary metabolites with various biological activities. In this study, we used transcriptomic analysis to obtain differentially expressed genes in the flavonoid metabolic pathway and metabolomic methods to detect changes in the types and content in the flavonoid metabolic synthesis pathway. The results showed that DEGs were identified in the mature roots vs. leaves comparison (9001 up-regulated and 8910 down-regulated), mature roots vs. stems comparison (5861 up-regulated and 7374 down-regulated), and mature stems vs. leaves comparison (10,837 up-regulated and 11,903 down-regulated). Furthermore, two AiCHS genes and four AiCHI genes were up-regulated in the mature roots vs. stems of mature A. ilicifolius, and were down-regulated in mature stems vs. leaves, which were highly expressed in the A. ilicifolius stems. A total of 215 differential metabolites were found in the roots vs. leaves of mature A. ilicifolius, 173 differential metabolites in the roots vs. stems, and 228 differential metabolites in the stems vs. leaves. The metabolomic results showed that some flavonoids in A. ilicifolius stems were higher than in the roots. A total of 18 flavonoid differential metabolites were detected in the roots, stems, and leaves of mature A. ilicifolius. In mature leaves, quercetin-3-O-glucoside-7-O-rhamnoside, gossypitrin, isoquercitrin, quercetin 3,7-bis-O-β-D-glucoside, and isorhamnetin 3-O-β-(2″-O-acetyl-β-D-glucuronide) were found in a high content, while in mature roots, di-O-methylquercetin and isorhamnetin were the major compounds. The combined analysis of the metabolome and transcriptome revealed that DEGs and differential metabolites were related to flavonoid biosynthesis. This study provides a theoretical basis for analyzing the molecular mechanism of flavonoid synthesis in A. ilicifolius and provides a reference for further research and exploitation of its medicinal value.

Project description:BackgroundAcanthus ilicifolius, a mangrove medicinal plant, is traditionally used to treat a variety of diseases. The aim of this research is to assess the chemoprotective outcomes of A. ilicifolius ethanolic extract against azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) in rats.Methodology/principal findingsIn our study, rats were arranged in to five groups. Rats in the normal control group were given subcutaneous injections of normal saline once weekly for 2 weeks. The AOM control, reference and treatment groups were given subcutaneous injection of AOM, 15 mg/kg body weight, once weekly for 2 weeks each. The reference group was treated with 35 mg/kg 5-Fluorouracil via intraperitoneal injection once weekly for 8 weeks, and the treatment groups were administered by gavage with 250 and 500 mg/kg A. ilicifolius extract daily for 8 weeks. Both normal and AOM control groups received the vehicle; 10% Tween-20 only. Rats treated with 250 mg/kg and 500 mg/kg of A. ilicifolius extracts showed a decrease in the mean number of ACF by 65% and 53%, respectively. Those fed with A. ilicifolius showed significantly decreased multiplicity of ACF formations when compared with the results from the AOM control group. The 250 mg/kg A. ilicifolius treatment group showed significant decreases in lipid peroxidation MDA levels when compared with the AOM control group. In immunohistochemistry staining, the proliferating nuclear cell antigen (PCNA)-positive cells were significantly higher in the AOM control group than in the A. ilicifolius-treated groups. RT-PCR showed that A. ilicifolius caused a change in the regulation of apoptosis-related genes expression.Conclusion/significanceThe results of the current study show that AOM-treated rats receiving oral exposure to A. ilicifolius demonstrated a significant decrease in the number of ACF in the colon when compared to AOM-treated rats receiving vehicle only. A ilicifolius may be an effective herbal approach for the prevention of AOM-induced ACF in the rat colon.

Dataset Information

Integrating Activity-Guided Strategy and Fingerprint Analysis to Target Potent Cytotoxic Brefeldin A from a Fungal Library of the Medicinal Mangrove Acanthus ilicifolius.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets