RESUMO
A novel actinobacterium, strain ZYX-F-186T, was isolated from marine sediment sampled on Yongxing Island, Hainan Province, PR China. Based on the results of 16S rRNA gene sequence analysis, strain ZYX-F-186T belongs to the genus Phytohabitans, with high similarity to Phytohabitans kaempferiae KK1-3T (98.3â%), Phytohabitans rumicis K11-0047T (98.1â%), Phytohabitans flavus K09-0627T (98.1â%), Phytohabitans houttuyneae K11-0057T (97.9â%), Phytohabitans suffuscus K07-0523T (97.7â%), and Phytohabitans aurantiacus RD004123T (97.7â%). Phylogenetic analysis of 16S rRNA gene sequences showed that the strain formed a single subclade in the genus Phytohabitans. The novel isolate contained meso-diaminopimelic acid, d-glutamic acid, glycine, d-alanine, and l-lysine in the cell wall. The whole-cell sugars were xylose, arabinose, ribose, and rhamnose. The predominant menaquinones were MK-9(H8), MK-9(H6), and MK-9(H4). The characteristic phospholipids were phosphatidylethanolamine, phosphatidylinositol, phosphatidylmethylethanolamine, phosphatidylglycerol, and an unknown phospholipid. The major fatty acids (>5â%) were iso-C16â:â0, anteiso-C17â:â0, and iso-C18â:â0. Genome sequencing showed a DNA G+C content of 71.9âmol%. Low average nucleotide identity, digital DNA-DNA hybridization, and average amino acid identity values demonstrated that strain ZYX-F-186T could be readily distinguished from its closely related species. Based on its phylogenetic, chemotaxonomic, and physiological characteristics, strain ZYX-F-186T represents a novel species of the genus Phytohabitans, for which the name Phytohabitans maris sp. nov. is proposed. The type strain is ZYX-F-186T (=CGMCC 4.8025T=CCTCC AA 2023025T=JCM 36507T).
Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Sedimentos Geológicos/microbiologia , RNA Ribossômico 16S/genética , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos , Vitamina K 2/análogos & derivados , Vitamina K 2/análise , Vitamina K 2/química , Hibridização de Ácido Nucleico , Parede Celular/químicaRESUMO
Seven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 8.60 ± 0.53 µM. Compound 17 showed significant α-glucosidase inhibitory activity with IC50 value of 19.96 ± 0.32 µM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages.
Assuntos
Diterpenos , Penicillium , Diterpenos/química , Anti-Inflamatórios/química , Macrófagos , Indóis/química , Penicillium/química , Estrutura MolecularRESUMO
Five new cytochalasins, diaporchalasins A-E (1-5), together with 14 known congeners (6-19) were isolated from the endophytic fungus Diaporthe sp. BMX12, which was isolated from the branches of Aquilaria sinensis. The structures of the new compounds were elucidated by extensive spectroscopic analyses including high-resolution electron spray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR). Their absolute configurations were assigned by theoretical electronic circular dichroism (ECD) calculations. Compounds 11 and 12 featuring a keto carbonyl at C-21 displayed cytotoxicity toward K562, BEL-7402, SGC-7901, A549, and HeLa cell lines with IC50 values ranging from 4.4 to 47.4â µM.
Assuntos
Ascomicetos , Citocalasinas , Ensaios de Seleção de Medicamentos Antitumorais , Thymelaeaceae , Citocalasinas/química , Citocalasinas/farmacologia , Citocalasinas/isolamento & purificação , Humanos , Thymelaeaceae/química , Thymelaeaceae/microbiologia , Ascomicetos/química , Ascomicetos/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Conformação Molecular , Sobrevivência Celular/efeitos dos fármacosRESUMO
Six undescribed capnosane-type macrocyclic diterpenes sarcocrassolins A-F (1-6) and one related known analog pavidolide D (7) were isolated from Sarcophyton crassocaule, a soft coral collected off the Nansha Islands, in the South China Sea. Their complete structures, relative configurations and absolute configurations were established through comprehensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance (QM-NMR) and single-crystal X-ray diffraction. Sarcocrassolins D (4) and E (5) showed inhibitory activity against lipopolysaccharide (LPS)-stimulated inflammatory responses in RAW264.7 cells with IC50 values of 76.8 ± 8.0 µM and 93.0 ± 3.8 µM, respectively.
Assuntos
Antozoários , Diterpenos , Animais , Espectroscopia de Ressonância Magnética , Antozoários/química , Diterpenos/farmacologia , Diterpenos/química , China , Lipopolissacarídeos/farmacologia , Estrutura MolecularRESUMO
Two undescribed p-terphenyl derivatives, asperterphenylcins A-B (1-2), and two undescribed diphenyl ether derivatives, asperdiphenylcins A-B (3-4), together with three previously described p-terphenyl derivatives-4â³-deoxyterprenin (5), terphenyllin (6), and 3â³-hydroxyterphenyllin (7)-were obtained from the solid-rice culture of the marine-derived fungus Aspergillus candidus HM5-4, which was isolated from sponges from the South China Sea. Their structures were elucidated by HRESIMS data and NMR spectroscopic analysis. Compound 1 showed a strong inhibitory effect on Neoscytalidium dimidiatum, with an inhibition circle diameter of 31.67 ± 2.36 mm at a concentration of 10.0 µg/disc. Compounds 5 and 7 displayed cytotoxic activity against human chronic myeloid leukemia cells (K562), human liver cancer cells (BEL-7402), human gastric cancer cells (SGC-7901), human non-small cell lung cancer cells (A549) and human HeLa cervical cancer cells, with IC50 values ranging from 3.32 to 60.36 µM, respectively. Compounds 2, 6 and 7 showed potent inhibitory activity against α-glucosidase, with IC50 values of 1.26 ± 0.19, 2.16 ± 0.44 and 13.22 ± 0.55 µM, respectively.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Aspergillus , FungosRESUMO
NAC is a class of plant-specific transcription factors that are widely involved in the growth, development and (a)biotic stress response of plants. However, their molecular evolution has not been extensively studied in Malvales, especially in Aquilaria sinensis, a commercial and horticultural crop that produces an aromatic resin named agarwood. In this study, 1502 members of the NAC gene family were identified from the genomes of nine species from Malvales and three model plants. The macroevolutionary analysis revealed that whole genome duplication (WGD) and dispersed duplication (DSD) have shaped the current architectural structure of NAC gene families in Malvales plants. Then, 111 NAC genes were systemically characterized in A. sinensis. The phylogenetic analysis suggests that NAC genes in A. sinensis can be classified into 16 known clusters and four new subfamilies, with each subfamily presenting similar gene structures and conserved motifs. RNA-seq analysis showed that AsNACs presents a broad transcriptional response to the agarwood inducer. The expression patterns of 15 AsNACs in A. sinensis after injury treatment indicated that AsNAC019 and AsNAC098 were positively correlated with the expression patterns of four polyketide synthase (PKS) genes. Additionally, AsNAC019 and AsNAC098 were also found to bind with the AsPKS07 promoter and activate its transcription. This comprehensive analysis provides valuable insights into the molecular evolution of the NAC gene family in Malvales plants and highlights the potential mechanisms of AsNACs for regulating secondary metabolite biosynthesis in A. sinensis, especially for the biosynthesis of 2-(2-phenyl) chromones in agarwood.
Assuntos
Malvales , Thymelaeaceae , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Filogenia , Thymelaeaceae/genética , Thymelaeaceae/química , Genes de PlantasRESUMO
Cucurbitacins, oxygenated tetracyclic triterpenoids that are found mainly in the Cucurbitaceae family, play essential roles as defensive compounds, serving as allomones against herbivores and pathogens and as signals for insect-parasite recognition. These compounds also exhibit various pharmacological effects. The biosynthesis of cucurbitacins is largely regulated by the bitter (Bi) gene, encoding an oxidosqualene cyclase, which catalyzes the conversion of 2,3-oxidosqualene into cucurbitadienol, a common precursor for cucurbitacin synthesis. Previous studies focused on uncovering the Bi gene clusters in Cucurbitaceae, but their presence in other cucurbitacin-producing plants remained unexplored. Here, the evolutionary history of Bi genes and their clusters were investigated in twenty-one plant genomes spanning three families based on chemotaxonomy. Nineteen Bi genes were identified in fourteen Cucurbitaceae, four Begoniaceae, and one Aquilaria species. Phylogenetic analysis suggested that the genome of Aquilaria sinensis contained the earliest Bi gene clusters in this dataset. Moreover, the genomic analysis revealed a conserved microsynteny of pivotal genes for cucurbitacin biosynthesis in Cucurbitaceae, while interspersed Bi gene clusters were observed in Begoniaceae, indicating rearrangements during plant Bi gene cluster formation. The bitter gene in A. sinensis was found to promote cucurbitadienol biosynthesis in the leaves of Nicotiana benthamiana. This comprehensive exploration of plant Bi genes and their clusters provides valuable insights into the genetic and evolutionary underpinnings of cucurbitacin biosynthesis. These findings offer prospects for a deeper understanding of cucurbitacin production and potential genetic resources for their enhancement in various plants.
RESUMO
BACKGROUND: Diabetic kidney disease (DKD) is a microvascular complication of diabetes mellitus, contributing to end-stage renal disease with limited treatment options. The development of DKD is attributed to podocyte injury resulting from abnormal podocyte autophagy. Consequently, the restoration of podocyte autophagy is deemed a practicable approach in the treatment of DKD. METHODS: Diabetic mice were induced by streptozotocin and high-fat diet feeding. Following 8 weeks of "QN" agarwood treatment, metrics such as albuminuria, serum creatinine (Scr), and blood urea nitrogen (BUN) were evaluated. Renal histological lesions were evaluated by H&E, PAS, Masson, and Sirius red staining. Evaluation of the effects of "QN" agarwood on renal inflammation and fibrosis in DKD mice through WB, q-PCR, and IHC staining analysis. Cytoscape 3.7.1 was used to construct a PPI network. With the DAVID server, the gene ontology (GO) functional annotation and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the target enrichment were performed. Molecular docking and binding affinity calculations were conducted using AutoDock, while PyMOL software was employed for visualizing the docking results of active compounds and protein targets. RESULTS: The results of this study show that "QN" agarwood reduced albuminuria, Scr, and BUN in DKD mice, and improved the renal pathological process. Additionally, "QN" agarwood was observed to downregulate the mRNA and protein expression levels of pro-inflammatory and pro-fibrotic factors in the kidneys of DKD mice. Network pharmacology predicts that "QN" agarwood modulates the epidermal growth factor receptor (EGFR) signaling pathway. "QN" agarwood can increase the expression of LC3B and Nphs1 in DKD mice while reducing the expression of EGFR. CONCLUSION: The present study demonstrated that "QN" agarwood ameliorated renal injury in DKD by targeting EGFR and restoring podocyte autophagy.
RESUMO
Objective: To study secondary metabolites from endophytic fungus Colletotruchum sp. HK-08 originated from the leaves of Nerium indicum. Methods: The compounds were isolated by various column chromatographic techniques, and their structures were elucidated by spectroscopic techniques [high resolution electrospray ionization mass spectroscopy (HRESIMS), one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance spectroscopy (NMR)], as well as comparison with literature data. The Ellman method was used to determine the acetylcholinesterase (AChE) inhibitory activity. Results: Four indole derivatives were identified from Colletotruchum sp. HK-08, including 6'-hydroxymonaspiloindole (1), 2-(2-oxoindolin-3-yl)ethyl 2-(4-hydroxyphenyl) acetate (2), 2-(2-oxoindolin-3-yl)ethyl 2-(2-hydroxyphenyl)acetate (3), and monaspiloindole (4). Compound 4 presented weak AChE inhibitory activity with IC50 value of (69.30 ± 6.27) µmol/L [tacrine as the positive control, with IC50 value of (0.61 ± 0.07) µmol/L]. Conclusion: Compounds 1-3 were new compounds, and compound 4 had weak AChE inhibitory activity.
RESUMO
Rubber tree (Hevea brasiliensis) is reproduced by bud grafting for commercial planting, but significant intraclonal variations exist in bud-grafted clones. DNA methylation changes related to grafting may be partly responsible for intraclonal variations. In the current study, whole-genome DNA methylation profiles of grafted rubber tree plants (GPs) and their donor plants (DPs) were evaluated by whole-genome bisulfite sequencing. Data showed that DNA methylation was downregulated and DNA methylations in CG, CHG, and CHH sequences were reprogrammed in GPs, suggesting that grafting induced the reprogramming of DNA methylation. A total of 5,939 differentially methylated genes (DMGs) were identified by comparing fractional methylation levels between GPs and DPs. Transcriptional analysis revealed that there were 9,798 differentially expressed genes (DEGs) in the DP and GP comparison. A total of 1,698 overlapping genes between DEGs and DMGs were identified. These overlapping genes were markedly enriched in the metabolic pathway and biosynthesis of secondary metabolites by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Global DNA methylation and transcriptional analyses revealed that reprogramming of DNA methylation is correlated with gene expression in grafted rubber trees. The study provides a whole-genome methylome of rubber trees and an insight into the molecular mechanisms underlying the intraclonal variations existing in the commercial planting of grafted rubber trees.
RESUMO
2-(2-Phenylethyl) chromone (PEC) and its derivatives are markers of agarwood formation and are also related to agarwood quality. However, the biosynthetic and regulatory mechanisms of PECs still remain mysterious. Several studies suggested that type III polyketide synthases (PKSs) contribute to PEC biosynthesis in Aquilaria sinensis. Furthermore, systematic studies on the evolution of PKSs in A. sinensis have rarely been reported. Herein, we comprehensively analyzed PKS genes from 12 plant genomes and characterized the AsPKSs in detail. A unique branch contained only AsPKS members was identified through evolutionary analysis, including AsPKS01 that was previously indicated to participate in PEC biosynthesis. AsPKS07 and AsPKS08, two tandem-duplicated genes of AsPKS01 and lacking orthologous genes in evolutionary models, were selected for their transient expression in the leaves of Nicotiana benthamiana. Subsequently, PECs were detected in the extracts of N. benthamiana leaves, suggesting that AsPKS07 and AsPKS08 promote PEC biosynthesis. The interaction between the promoters of AsPKS07, AsPKS08 and five basic leucine zippers (bZIPs) from the S subfamily indicated that their transcripts could be regulated by these transcription factors (TFs) and might further contribute to PECs biosynthesis in A. sinensis. Our findings provide valuable insights into the molecular evolution of the PKS gene family in A. sinensis and serve as a foundation for advancing PEC production through the bioengineering of gene clusters. Ultimately, this contribution is expected to shed light on the mechanism underlying agarwood formation.
Assuntos
Evolução Molecular , Thymelaeaceae , Thymelaeaceae/genética , Thymelaeaceae/enzimologia , Filogenia , Família Multigênica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Nicotiana/genética , Nicotiana/enzimologia , Nicotiana/metabolismo , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismoRESUMO
Four new ansamycin derivatives, named 1,19-epithio-geldanamycin A (1), 17-demethoxylherbimycin H (2), herbimycin M (3), and seco-geldanamycin B (4), together with eight known ansamycin analogues (5-12) were isolated from the solid fermentation of marine-derived actinomycete Streptomyces sp. ZYX-F-97. The structures of new compounds were elucidated by extensive spectroscopic analysis as well as nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculations. All the compounds were assayed for their antibacterial activity. Among them, compounds 4, 8, and 12 exhibited remarkable inhibition against Listeria monocytogenes with minimum inhibitory concentrations (MIC) values ranging from 8 µg·mL-1 to 64 µg·mL-1, and displayed moderate inhibition against methicillin-resistant Staphylococcus aureus (MRSA) with MIC value of 64 µg·mL-1. Compounds 4, 8, 9, and 12 showed moderate inhibition activities against both Staphylococcus aureus and Bacillus subtilis with MIC values ranging from 32 µg·mL-1 to 128 µg·mL-1.
Assuntos
Benzoquinonas , Staphylococcus aureus Resistente à Meticilina , Streptomyces , Lactamas Macrocíclicas , Streptomyces/química , Estrutura Molecular , Antibacterianos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade MicrobianaRESUMO
Six new dimeric 2-(2-phenylethyl)chromones (1-6) were successfully isolated from the ethanol extract of agarwood of Aquilaria filaria from Philippines under HPLC-MS guidance. Compounds 1-6 are all dimers formed by linking 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and flindersia 2-(2-phenylethyl)chromone via a single ether bond, and the linkage site (C5-O-C8'') of compound 2 is extremely rare. A variety of spectroscopic methods were used to ascertain their structures, including extensive 1D and 2D NMR spectroscopic analysis, HRESIMS, and comparison with literature. The in vitro tyrosinase inhibitory and anti-inflammatory activities of each isolate were assessed. Among these compounds, compound 2 had a tyrosinase inhibition effect with an IC50 value of 27.71 ± 2.60 µM, and compound 4 exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with an IC50 value of 35.40 ± 1.04 µM.
Assuntos
Anti-Inflamatórios , Monofenol Mono-Oxigenase , Óxido Nítrico , Thymelaeaceae , Madeira , Células RAW 264.7 , Animais , Thymelaeaceae/química , Camundongos , Estrutura Molecular , Madeira/química , Óxido Nítrico/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/química , Monofenol Mono-Oxigenase/antagonistas & inibidores , Filipinas , Cromonas/isolamento & purificação , Cromonas/farmacologia , Cromonas/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , FlavonoidesRESUMO
Twelve undescribed 2-(2-phenethyl)chromone dimers (1-12) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria in the Philippines, guided by a UHPLC-MS analysis. Their structures were elucidated by 1D NMR, 2D NMR, and HR-ESI-MS spectra. The absolute configuration of 2-(2-phenylethyl)chromone dimers was determined by single-crystal X-ray diffraction analysis and comparison of the experimental and calculated ECD spectra. Compounds 1, 2, 5 and 9-12 exhibited potent to moderate anti-inflammatory activity with IC50 values in the range of 22.43 ± 0.86 to 53.88 ± 4.06 µM.
Assuntos
Cromonas , Thymelaeaceae , Madeira , Thymelaeaceae/química , Filipinas , Cromonas/química , Cromonas/isolamento & purificação , Cromonas/farmacologia , Estrutura Molecular , Madeira/química , Animais , Relação Estrutura-Atividade , Camundongos , Relação Dose-Resposta a Droga , Cristalografia por Raios X , FlavonoidesRESUMO
Lanostane-type triterpenoids are the main characteristic constituents in Ganoderma mushrooms. Phytochemical analysis on the ethanol extract of the fruiting bodies of Ganoderma amboinense led to isolation and identification of twelve previously undescribed lanostane triterpenoids (1-12). Their chemical structures were determined by HR-ESI-MS, IR, and NMR spectroscopic analysis, NMR calculation, as well as X-ray crystallography. All isolates were evaluated for the α-glucosidase inhibitory and anti-inflammatory activities. Compounds 1, 5, 6, and 11 showed significant α-glucosidase inhibitory activity with IC50 values ranging from 33.5 µM to 96.0 µM. Moreover, compound 12 showed anti-inflammatory activity with IC50 value of 21.7 ± 2.1 µM.