49 results on '"Xiachang Wang"'
Search Results
2. Endophytic Microbes from Medicinal Plants in Fenghuang Mountain as a Source of Antibiotics
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Aiping Yang, Yu Hong, Fengjuan Zhou, Ling Zhang, Youjuan Zhu, Chang Wang, Yang Hu, Li Yu, Lihong Chen, and Xiachang Wang
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antibiotics ,endophyte ,medicinal plant ,strain diversity ,Streptomyces ,Penicillium ,Organic chemistry ,QD241-441 - Abstract
One of the largest concerns with world health today is still antibiotic resistance, which is making it imperative to find efficient alternatives as soon as possible. It has been demonstrated that microbes are reliable sources for the creation of therapeutic antibiotics. This research intends to investigate the endophytic microorganisms from several medicinal plants in Fenghuang Mountain (Jiangsu Province, China) and to discover new antibiotics from their secondary metabolites. A total of 269 endophytic strains were isolated from nine distinct medicinal plants. Taxonomic analysis revealed that there were 20 distinct species among these endophytes, with Streptomyces being the most common genus. Three of the target strains were chosen for scale-up fermentation after preliminary screening of antibacterial activities and the metabolomics investigation using LC-MS. These strains were Penicillium sp. NX-S-6, Streptomyces sp. YHLB-L-2 and Streptomyces sp. ZLBB-S-6. Twenty-three secondary metabolites (1–23), including a new sorbicillin analogue (1), were produced as a result of antibacterial activity-guided isolation. Through spectroscopic analysis using MS and NMR, the structures of yield compounds were clarified. According to antibacterial data, S. aureus or B. subtilis were inhibited to varying degrees by sorrentanone (3), emodic acid (8), GKK1032 B (10), linoleic acid (14), toyocamycin (17) and quinomycin A (21). The most effective antimicrobial agent against S. aureus, B. subtilis, E. coli and A. baumannii was quinomycin A (21). In addition, quinomycin A showed strong antifungal activity against Aspergillus fumigatus, Cryptococcus neoformans, and two clinical isolated strains Aspergillus fumigatus #176 and #339, with MIC as 16, 4, 16 and 16 µg/mL, respectively. This is the first time that bioprospecting of actinobacteria and their secondary metabolites from medicinal plants in Fenghuang Mountain was reported. The finding demonstrates the potential of endophytic microbes in medical plants to produce a variety of natural products. Endophytic microbes will be an important source for new antibiotics.
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- 2023
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3. Gypenosides Synergistically Reduce the Extracellular Matrix of Hepatic Stellate Cells and Ameliorate Hepatic Fibrosis in Mice
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Han Li, Hanghang Wang, Aiping Yang, Mingzhen Xue, Junyang Wang, Qi Lv, Jian Liu, Lihong Hu, Yinan Zhang, and Xiachang Wang
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gypenoside ,liver fibrosis ,PP2Cα ,extracellular matrix ,synergistic effect ,Organic chemistry ,QD241-441 - Abstract
Liver fibrosis resulting from chronic liver damage is becoming one of the major threats to health worldwide. Active saponin constituents isolated from Gynostemma pentaphyllum were found to possess a protective effect in liver diseases. Here, we obtained a naturally abundant gypenoside, XLVI, and evaluated its liver protection activity in both animal and cellular models. The results showed that it ameliorated acute and chronic liver injuries and lightened the process of fibrogenesis in vivo. XLVI can inhibit TGF-β-induced activation of hepatic stellate cells and ECM deposition in vitro. The underlying mechanism study verified that it upregulated the protein expression of protein phosphatase 2C alpha and strengthened the vitality of the phosphatase together with a PP2Cα agonist gypenoside NPLC0393. These results shed new light on the molecular mechanisms and the potential therapeutic function of the traditional herb Gynostemma pentaphyllum in the treatment of liver fibrosis.
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- 2023
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4. Editorial: Bioactive Natural Products from Microbes: Isolation, Characterization, Biosynthesis and Structure Modification
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Xiachang Wang, Yuanyuan Lu, Khaled A. Shaaban, Guojun Wang, Xuekui Xia, and Youjuan Zhu
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microbes ,natural product ,structure elucidation and modification ,activity evaluation ,biosynthesis ,Chemistry ,QD1-999 - Published
- 2022
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5. Huoshanmycins A‒C, New Polyketide Dimers Produced by Endophytic Streptomyces sp. HS-3-L-1 From Dendrobium huoshanense
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Youjuan Zhu, Yichao Kong, Yu Hong, Ling Zhang, Simin Li, Shurong Hou, Xiabin Chen, Tian Xie, Yang Hu, and Xiachang Wang
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huoshanmycin ,polyketide ,Streptomyces ,Dendrobium huoshanense ,endophyte ,Chemistry ,QD1-999 - Abstract
Three new polyketide dimers named huoshanmycins A‒C (1–3) were isolated from a plant endophytic Streptomyces sp. HS-3-L-1 in the leaf of Dendrobium huoshanense, which was collected from the Cultivation base in Jiuxianzun Huoshanshihu Co., Ltd. The dimeric structures of huoshanmycins were composed of unusual polyketides SEK43, SEK15, or UWM4, with a unique methylene linkage. Their structures were elucidated through comprehensive 1D-/2D-NMR and HRESIMS spectroscopic data analysis. The cytotoxicity against MV4-11 human leukemia cell by the Cell Counting Kit-8 (CCK8) method was evaluated using isolated compounds with triptolide as positive control (IC50: 1.1 ± 0.4 μM). Huoshanmycins A and B (1, 2) displayed moderate cytotoxicity with IC50 values of 32.9 ± 7.2 and 33.2 ± 6.1 μM, respectively.
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- 2022
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6. The Anti-colitis Effect of Schisandra chinensis Polysaccharide Is Associated With the Regulation of the Composition and Metabolism of Gut Microbiota
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Lianlin Su, Chunqin Mao, Xiachang Wang, Lin Li, Huangjin Tong, Jing Mao, De Ji, Tulin Lu, Min Hao, Ziyan Huang, Chenghao Fei, Kewei Zhang, and Guojun Yan
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Schisandra chinensis ,polysaccharide ,ulcerative colitis ,gut microbiota ,short chain fatty acid ,inflammation ,Microbiology ,QR1-502 - Abstract
Background: The pathogenesis of inflammatory bowel disease (IBD) is linked to an intricate association of environmental, microbial, and host-related factors. Polysaccharide affects host immunity by regulating the composition and metabolism of gut microbiota is the common mechanism of disease resistance. However, the efficacy and mechanism of Schisandra chinensis polysaccharide (SCP) in the treatment of inflammatory bowel disease have not been studied.Objective: To explore the effect and mechanism of SCP on dextran sodium sulfate (DSS) - induced ulcerative colitis (UC) in mice.Materials/Methods: In this study, we established a mouse model of UC, and used SCP for treatment intervention. The biochemical indexes related to inflammation were determined by ELISA kit, and the therapeutic effect of SCP on UC was clarified. Then, 16S rDNA sequencing was used to study the effect of SCP on the composition and diversity of gut microbiota. At the same time, GC-MS was used to determine the content of short chain fatty acids in intestinal contents. Finally, the relationship among gut microbiota, short chain fatty acids and inflammatory factors was analyzed, and to comprehensively explain the effect and mechanism of SCP on UC.Results: The results showed that SCP could significantly improve the physiological state of UC mice and regulate the level of inflammatory factors to normal levels. Meanwhile, SCP could significantly regulate the imbalance of gut microbiota and increase the content of SCFAs. In addition, the results of the correlation between gut microbiota and SCFAs showed that butyric acid, isobutyric acid and valeric acid had the highest correlation with gut microbiota.Conclusion: In conclusion, this research showed that SCP can inhibit inflammatory bowel disease by regulating the composition and metabolism of gut microbiota, and indicating that SCP may be used as adjuvant therapy for IBD patients.
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- 2020
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7. Rapid evaluation of Radix Paeoniae Alba and its processed products by near-infrared spectroscopy combined with multivariate algorithms
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Jiuba Zhang, Yu Li, Bin Wang, Jiantao Song, Mingxuan Li, Peng Chen, Zheyuan Shen, Yi Wu, Chunqin Mao, Hui Cao, Xiachang Wang, Wei Zhang, and Tulin Lu
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Biochemistry ,Analytical Chemistry - Published
- 2023
8. Sinoflavonoids NJ and NK, anti-inflammatory prenylated flavonoids from the fruits of Podophyllum hexandrum Royle
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Junyang Wang, Han Li, Yanhui Li, Aiping Yang, Sheng Bao, Yuntian Zhang, Qing Du, Zongping Zheng, and Xiachang Wang
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Organic Chemistry ,Plant Science ,Biochemistry ,Analytical Chemistry - Abstract
Two new prenylated flavonoids named sinoflavonoids NJ and NK (1–2), along with ten known compounds were isolated from the fruits of Podophyllum hexandrum Royle. The chemical structures were determined through NMR spectroscopic data and MS analysis. Sinoflavonoid NJ (1) with an unusual 5,11-dioxabenzo[b]fluoren-10-one skeleton was firstly reported from Berberidaceae. The isolated flavonoids were tested with LPS-induced RAW 264.7 mouse macrophages model for their anti-inflammatory activity. Sinoflavonoid NJ (1) showed the most potent inhibition on nitric oxide production with IC50 value as 0.06 μM.
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- 2023
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9. The crystal structure of <scp>AbsH3</scp> : A putative flavin adenine dinucleotide‐dependent reductase in the abyssomicin biosynthesis pathway
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Jon S. Thorson, Wenlong Cai, George N. Phillips, Yanyan Zhu, Steven G. Van Lanen, Jonathan A. Clinger, Mitchell D. Miller, Chang-Guo Zhan, and Xiachang Wang
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Flavin adenine dinucleotide ,chemistry.chemical_classification ,0303 health sciences ,Natural product ,biology ,030302 biochemistry & molecular biology ,Flavin group ,Reductase ,biology.organism_classification ,Biochemistry ,Streptomyces ,03 medical and health sciences ,chemistry.chemical_compound ,Biosynthesis ,chemistry ,Structural Biology ,Oxidoreductase ,Gene cluster ,Molecular Biology ,030304 developmental biology - Abstract
Natural products and natural product-derived compounds have been widely used for pharmaceuticals for many years, and the search for new natural products that may have interesting activity is ongoing. Abyssomicins are natural product molecules that have antibiotic activity via inhibition of the folate synthesis pathway in microbiota. These compounds also appear to undergo a required [4 + 2] cycloaddition in their biosynthetic pathway. Here we report the structure of an flavin adenine dinucleotide-dependent reductase, AbsH3, from the biosynthetic gene cluster of novel abyssomicins found in Streptomyces sp. LC-6-2.
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- 2020
10. Structure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated Streptomyces
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Bruce E. Hatcher, Gregory C. Copley, Jon S. Thorson, Xiachang Wang, James C. Hower, Yang Liu, Madan K. Kharel, Qing-Bai She, Steven G. Van Lanen, Larissa V. Ponomareva, Khaled A. Shaaban, Sherif I. Elshahawi, S. Randal Voss, and Qing Ye
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Antifungal Agents ,Pharmaceutical Science ,Quinolones ,Gram-Positive Bacteria ,01 natural sciences ,Streptomyces ,Article ,Analytical Chemistry ,Cell Line, Tumor ,Drug Discovery ,Humans ,Deoxynyboquinone ,Cytotoxicity ,Pharmacology ,Molecular Structure ,biology ,Strain (chemistry) ,010405 organic chemistry ,Chemistry ,Spectrum Analysis ,Regeneration (biology) ,Organic Chemistry ,Translation (biology) ,biology.organism_classification ,Anti-Bacterial Agents ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,Biochemistry ,Cell culture ,Molecular Medicine ,Phosphorylation ,Drug Screening Assays, Antitumor - Abstract
We report the isolation and characterization of three new nybomycins (nybomycins B–D, 1–3) and six known compounds (nybomycin, 4; deoxynyboquinone, 5; α-rubromycin, 6; β-rubromycin, 7; γ-rubromycin, 8; and [2α(1E,3E),4β]-2-(1,3-pentadienyl)-4-piperidinol, 9) from the Rock Creek (McCreary County, KY) underground coal mine acid reclamation site isolate Streptomyces sp. AD-3-6. Nybomycin D (3) and deoxynyboquinone (5) displayed moderate (3) to potent (5) cancer cell line cytotoxicity and displayed weak to moderate anti-Gram-(+) bacterial activity, whereas rubromycins 6–8 displayed little to no cancer cell line cytotoxicity but moderate to potent anti-Gram-(+) bacterial and antifungal activity. Assessment of the impact of 3 or 5 cancer cell line treatment on 4E-BP1 phosphorylation, a predictive marker of ROS-mediated control of cap-dependent translation, also revealed deoxynyboquinone (5)-mediated downstream inhibition of 4E-BP1p. Evaluation of 1–9 in a recently established axolotl embryo tail regeneration assay also highlighted the prototypical telomerase inhibitor γ-rubromycin (8) as a new inhibitor of tail regeneration. Cumulatively, this work highlights an alternative nybomycin production strain, a small set of new nybomycin metabolites, and previously unknown functions of rubromycins (antifungal activity and inhibition of tail regeneration) and also provides a basis for revision of the previously proposed nybomycin biosynthetic pathway.
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- 2019
11. Enzymatic C
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Zheng, Cui, Han, Nguyen, Minakshi, Bhardwaj, Xiachang, Wang, Martin, Büschleb, Anke, Lemke, Christian, Schütz, Christian, Rohrbacher, Pierre, Junghanns, Stefan, Koppermann, Christian, Ducho, Jon S, Thorson, and Steven G, Van Lanen
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Biological Products ,Molecular Structure ,Leucine ,Peptide Synthases ,Arginine ,Peptides ,Article - Abstract
Muraymycins are peptidyl nucleoside antibiotics that contain two C(β)-modified amino acids, (2S,3S)-capreomycidine and (2S,3S)-β-OH-Leu. The former is also a component of chymostatins, which are aldehyde-containing peptidic protease inhibitors that—like muraymycin—are derived from nonribosomal peptide synthetases (NRPSs). Using feeding experiments and in vitro characterization of twelve recombinant proteins, the biosynthetic mechanism for both nonproteinogenic amino acids is now defined. The formation of (2S,3S)-capreomycidine is shown to involve an FAD-dependent dehydrogenase:cyclase that requires an NRPS-bound pathway intermediate as a substrate. This cryptic dehydrogenation strategy is both temporally and mechanistically distinct in comparison to the biosynthesis of other capreomycidine diastereomers, which has previously been shown to proceed by C(β)-hydroxylation of free l-Arg catalyzed by a member of the non-heme Fe(2+)- and α-ketoglutarate (αKG)-dependent dioxygenase family and (eventually) a dehydration-mediated cyclization process catalyzed by a distinct enzyme(s). Contrary to our initial expectation, the sole non-heme Fe(2+)- and αKG-dependent dioxygenase candidate Mur15 encoded within the muraymycin gene cluster is instead demonstrated to catalyze specific C(β) hydroxylation of the Leu residue to generate (2S,3S)-β-OH-Leu that is found in most muraymycin congeners. Importantly, and in contrast to known l-Arg-C(β)-hydroxylases, the Mur15-catalyzed reaction occurs after the NRPS-mediated assembly of the peptide scaffold. This late-stage functionalization affords the opportunity to exploit Mur15 as a biocatalyst, proof of concept of which is provided.
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- 2021
12. Huoshanmycins A‒C, New Polyketide Dimers Produced by Endophytic
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Youjuan, Zhu, Yichao, Kong, Yu, Hong, Ling, Zhang, Simin, Li, Shurong, Hou, Xiabin, Chen, Tian, Xie, Yang, Hu, and Xiachang, Wang
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Three new polyketide dimers named huoshanmycins A‒C (
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- 2021
13. Baraphenazines A–G, Divergent Fused Phenazine-Based Metabolites from a Himalayan Streptomyces
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Sherif I. Elshahawi, Khaled A. Shaaban, Larissa V. Ponomareva, Jon S. Thorson, Xiachang Wang, Steven G. Van Lanen, Muhammad Abbas, S. Randal Voss, Imran Sajid, Yinan Zhang, and Zheng Cui
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Stereochemistry ,Metabolite ,Phenazine ,Pharmaceutical Science ,01 natural sciences ,Streptomyces ,Article ,Analytical Chemistry ,chemistry.chemical_compound ,Quinoxalines ,Drug Discovery ,Pharmacology ,chemistry.chemical_classification ,Molecular Structure ,biology ,010405 organic chemistry ,Extramural ,Organic Chemistry ,biology.organism_classification ,Bacterial strain ,Anti-Bacterial Agents ,0104 chemical sciences ,Amino acid ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,chemistry ,Phenazines ,Molecular Medicine - Abstract
The structures and bioactivities of three unprecedented fused 5-hydroxyquinoxaline/alpha-keto acid amino acid metabolites (baraphenazines A–C, 1–3), two unique diastaphenazine-type metabolites (baraphenazines D and E, 4 and 5) and two new phenazinolin-type (baraphenazines F and G, 6 and 7) metabolites from the Himalayan isolate Streptomyces sp. PU-10A are reported. This study highlights the first reported bacterial strain capable of producing diastaphenazine-type, phenazinolin-type, and izumiphenazine A-type metabolites and presents a unique opportunity for the future biosynthetic interrogation of late-stage phenazine-based metabolite maturation.
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- 2019
14. Ruthenium(<scp>ii</scp>)-catalyzed C–O/C–S cyclization for the synthesis of 5-membered O-containing and S-containing heterocycles
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Yu Wen, Yinan Zhang, Lihong Hu, Junwei Wang, Jian Liu, Xiachang Wang, Fengjun He, Lina Gao, and Liang Gao
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010405 organic chemistry ,Chemistry ,Organic Chemistry ,chemistry.chemical_element ,Substrate (chemistry) ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,Ruthenium ,chemistry.chemical_compound ,Furan ,Functional group ,Organic synthesis ,Thiazole ,Oxazole - Abstract
An efficient and convenient method for the synthesis of oxazole derivatives from enamides has been established via a ruthenium-catalyzed C–O cyclization. This protocol allows for a wide functional group compatibility, broad substrate scope and ease of operation. This catalytic method is also applicable to other 5-membered O-containing and S-containing heterocyclic systems involving thiazole and furan scaffolds, thus this strategy can be broadly applied to organic synthesis and medicinal chemistry.
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- 2019
15. Terragines F–G produced by endophytic Bacillus sp. SH-1.2-ROOT-18 from Dendrobium officinale
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Xiachang Wang, Jingyi Meng, Huimin Zhao, Li Shiyang, Yichao Kong, Xiabin Chen, Youjuan Zhu, Yuanzhuo Hu, and Shurong Hou
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Natural product ,biology ,010405 organic chemistry ,Stereochemistry ,Metabolite ,Organic Chemistry ,Plant Science ,Bacillus sp ,biology.organism_classification ,01 natural sciences ,Biochemistry ,Endophyte ,0104 chemical sciences ,Analytical Chemistry ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Dendrobium officinale ,chemistry ,Succinimide ,Base (exponentiation) ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Two new terragine analogs (1‒2) with special succinimide and aminopentane moieties were isolated from the fermentation broth of Bacillus sp. SH-1.2-ROOT-18, an endophyte previously discovered from the root of Dendrobium officinale. The structures were elucidated base on comprehensive 1 D/2D NMR and MS data analysis. Complete NMR assignments for the first reported naturally occurring metabolite 3 was also provided.
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- 2021
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16. The triterpenoid sapogenin (2α-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling
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Sheng Bao, Xinwen Zhang, Xiachang Wang, Chen-dong Zhou, Wei Liu, Shui-mei Sun, Jing-Ya Li, Jia Li, Haowen Jiang, Lihong Hu, Jia Liu, Yinan Zhang, Dakai Chen, and Zhifu Xie
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Male ,Taurocholic Acid ,Cancer Research ,Metabolite ,Immunology ,Drug development ,Pharmacology ,Gut flora ,Diet, High-Fat ,Article ,Mice ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Glucagon-Like Peptide 1 ,RNA, Ribosomal, 16S ,medicine ,Animals ,Secretion ,lcsh:QH573-671 ,Metabolic Syndrome ,chemistry.chemical_classification ,Mice, Inbred ICR ,biology ,lcsh:Cytology ,Plant Extracts ,Diabetes ,RNA-Binding Proteins ,Cell Biology ,Glucagon ,medicine.disease ,biology.organism_classification ,Gastrointestinal Microbiome ,Gynostemma ,Intestines ,Mice, Inbred C57BL ,Transplantation ,Enzyme ,chemistry ,Nuclear receptor ,Drug Design ,Farnesoid X receptor ,Metabolic syndrome - Abstract
Gypenosides, extracts of Gynostemma yixingense, have been traditionally prescribed to improve metabolic syndrome in Asian folk and local traditional medicine hospitals. However, the mechanism of its action remains unclarified. In this work, our results indicated that chronic administration of 2α-OH-protopanoxadiol (GP2), a metabolite of gypenosides in vivo, protected mice from high-fat diet-induced obesity and improved glucose tolerance by improving intestinal L-cell function. Mechanistically, GP2 treatment inhibited the enzymatic activity of bile salt hydrolase and modulated the proportions of the gut microbiota, which led to an increase in the accumulation of tauro-β-muricholic acid (TβMCA) in the intestine. TβMCA induced GLP-1 production and secretion by reducing the transcriptional activity of nuclear receptor farnesoid X receptor (FXR). Transplantation of GP2-remodelled fecal microbiota into antibiotic-treated mice also increased the intestinal TβMCA content and improved intestinal L-cell function. These findings demonstrate that GP2 ameliorates metabolic syndrome at least partly through the intestinal FXR/GLP-1 axis via gut microbiota remodelling and also suggest that GP2 may serve as a promising oral therapeutic agent for metabolic syndrome.
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- 2020
17. The Crystal Structure of AbsH3: a Putative FAD-dependent Reductase in the Abyssomicin Biosynthesis Pathway
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George N. Phillips, Wenlong Cai, Chang-Guo Zhan, Xiachang Wang, Yanyan Zhu, Jonathan A. Clinger, Mitchell D. Miller, Jon S. Thorson, and Steven G. Van Lanen
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Biological Products ,Natural product ,biology ,Stereochemistry ,Crystal structure ,Reductase ,biology.organism_classification ,Streptomyces ,Cycloaddition ,Article ,Biosynthetic Pathways ,chemistry.chemical_compound ,chemistry ,Biosynthesis ,Gene cluster ,Flavin-Adenine Dinucleotide ,Oxidoreductases - Abstract
Natural products and natural product-derived compounds have been widely used for pharmaceuticals for many years, and the search for new natural products that may have interesting activity is ongoing. Abyssomicins are natural product molecules that have antibiotic activity via inhibition of the folate synthesis pathway in microbiota. These compounds also appear to undergo a required [4 + 2] cycloaddition in their biosynthetic pathway. Here we report the structure of an flavin adenine dinucleotide-dependent reductase, AbsH3, from the biosynthetic gene cluster of novel abyssomicins found in Streptomyces sp. LC-6-2.
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- 2020
18. New peptidendrocins and anticancer chartreusin from an endophytic bacterium of
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Huimin, Zhao, Xiabin, Chen, Xiaoling, Chen, Youjuan, Zhu, Yichao, Kong, Sifang, Zhang, Xingyu, Deng, Pengfei, Ouyang, Wei, Zhang, Shurong, Hou, Xiachang, Wang, and Tian, Xie
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Original Article - Abstract
BACKGROUND: Endophyte has now become a potential source for the discovery of novel natural products, as they participate in biochemical pathways of their hosts and produce analogous or novel bioactive compounds. As an epiphytic plant, Dendrobium officinale is one of precious Chinese medicines with various activities. It is well known for containing diverse endophytes, but so far not much is known about their secondary metabolites. METHODS: the plant tissues were cut and cultured on agar plates to isolate and purify the endophytic bacteria from Dendrobium officinale. Taxonomical identification of strains was performed by 16s rRNA. At the same time, the crude extracts of the strains were tested for antibacterial and cytotoxic activities to screen out one endophyte, Streptomyces sp. SH-1.2-R-15 for further study. After scale-up fermentation, isolation, purification and structure elucidation by using MS, 1D/2D-NMR spectroscopic method, secondary metabolites were identified and submitted for biological activity test. RESULTS: Fifty-eight endophytic strains representing 9 genera were obtained, with 50% of strains were Streptomyces. One of the most active strain, Streptomyces sp. 1.2-R-15, was selected for bioassay-guided isolation, which led to the discovery of two new peptide-type compounds 1 and 2, as well as a bioactive chartreusin, and four other known natural products. Their structures were determined by comprehensive spectroscopic techniques. Chartreusin showed potent cytotoxicity against Hep3B2.1-7 (IC(50) =18.19 µM) and H1299 (IC(50) =19.74 µM) cancer cell lines, and antibacterial activity against S. aureus (IC(50) =23.25 µM). CONCLUSIONS: This study highlights the endophytic bacteria from medical plant D. officinale have potential bioactivity and natural product diversity, thus implicates them as a valuable source for new anticancer and antibiotics agents.
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- 2020
19. Pyridoxal-5'-phosphate-dependent alkyl transfer in nucleoside antibiotic biosynthesis
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Xiachang Wang, Jon S. Thorson, Minakshi Bhardwaj, Zheng Cui, Xiaodong Liu, Daniel Wiegmann, Giuliana Niro, Christian Ducho, Anke Lemke, Yinan Zhang, Jonathan Overbay, and Steven G. Van Lanen
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S-Adenosylmethionine ,Alkylation ,Stereochemistry ,Biochemical Phenomena ,Disaccharide ,nucleoside ,Biosynthesis ,Article ,Phosphates ,S-adenosyl-l-methionine ,03 medical and health sciences ,chemistry.chemical_compound ,Methionine ,antibiotic ,γ-replacement ,Phosphorylation ,Molecular Biology ,Alkyl ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,030302 biochemistry & molecular biology ,Glycosidic bond ,Nucleosides ,Cell Biology ,pyridoxal-5′-phosphate ,Recombinant Proteins ,Anti-Bacterial Agents ,chemistry ,aza-addition ,Pyridoxal Phosphate ,Linker ,Nucleoside ,Alkyltransferase - Abstract
Several nucleoside antibiotics are structurally characterized by a 5″-amino-5″-deoxyribose (ADR) appended via a glycosidic bond to a high-carbon sugar nucleoside (5′S,6′S)-5′-C-glycyluridine (GlyU). GlyU is further modified with an N-alkylamine linker, the biosynthetic origin of which has yet to be established. By using a combination of feeding experiments with isotopically labeled precursors and characterization of recombinant proteins from multiple pathways, the biosynthetic mechanism for N-alkylamine installation for ADR–GlyU-containing nucleoside antibiotics has been uncovered. The data reveal S-adenosyl-l-methionine (AdoMet) as the direct precursor of the N-alkylamine, but, unlike conventional AdoMet- or decarboxylated AdoMet-dependent alkyltransferases, the reaction is catalyzed by a pyridoxal-5′-phosphate-dependent aminobutyryltransferase (ABTase) using a stepwise γ-replacement mechanism that couples γ-elimination of AdoMet with aza-γ-addition onto the disaccharide alkyl acceptor. In addition to using a conceptually different strategy for AdoMet-dependent alkylation, the newly discovered ABTases require a phosphorylated disaccharide alkyl acceptor, revealing a cryptic intermediate in the biosynthetic pathway. Rather than a typical S-adenosylmethionine-dependent alkyltransferase, the installation of the N-alkylamine linker in several nucleoside antibiotics is catalyzed via γ-replacement by a pyridoxal-5′-phosphate-dependent aminobutyryltransferase.
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- 2019
20. Enzymatic Synthesis of the Ribosylated Glycyl-Uridine Disaccharide Core of Peptidyl Nucleoside Antibiotics
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Jonathan Overbay, Xiaodong Liu, Steven G. Van Lanen, Xiachang Wang, Zheng Cui, Jon S. Thorson, Daniel Wiegmann, Anke Lemke, Wenlong Cai, Christian Ducho, and Giuliana Niro
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chemistry.chemical_classification ,010405 organic chemistry ,Ribose ,Organic Chemistry ,Pyrimidine Phosphorylases ,Glycine ,Glycosidic bond ,010402 general chemistry ,01 natural sciences ,Article ,Uridine ,Anti-Bacterial Agents ,Substrate Specificity ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Biosynthesis ,Biochemistry ,Uridine monophosphate ,Transferase ,Peptides ,Nucleoside ,Transaldolase - Abstract
Muraymycins belong to a family of nucleoside antibiotics that have a distinctive disaccharide core consisting of 5-amino-5-deoxyribofuranose (ADR) attached to 6'- N-alkyl-5'- C-glycyluridine (GlyU). Here, we functionally assign and characterize six enzymes from the muraymycin biosynthetic pathway involved in the core assembly that starts from uridine monophosphate (UMP). The biosynthesis is initiated by Mur16, a nonheme Fe(II)- and α-ketoglutarate-dependent dioxygenase, followed by four transferase enzymes: Mur17, a pyridoxal-5'-phosphate (PLP)-dependent transaldolase; Mur20, an aminotransferase; Mur26, a pyrimidine phosphorylase; and Mur18, a nucleotidylyltransferase. The pathway culminates in glycosidic bond formation in a reaction catalyzed by an additional transferase enzyme, Mur19, a ribosyltransferase. Analysis of the biochemical properties revealed several noteworthy discoveries including that (i) Mur16 and downstream enzymes can also process 2'-deoxy-UMP to generate a 2-deoxy-ADR, which is consistent with the structure of some muraymycin congeners; (ii) Mur20 prefers l-Tyr as the amino donor source; (iii) Mur18 activity absolutely depends on the amine functionality of the ADR precursor consistent with the nucleotidyltransfer reaction occurring after the Mur20-catalyzed aminotransfer reaction; and (iv) the bona fide sugar acceptor for Mur19 is (5' S,6' S)-GlyU, suggesting that ribosyltransfer occurs prior to N-alkylation of GlyU. Finally, a one-pot, six-enzyme reaction was utilized to generate the ADR-GlyU disaccharide core starting from UMP.
- Published
- 2018
21. Antibacterial Muraymycins from Mutant Strains of Streptomyces sp. NRRL 30471
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Xiachang Wang, Stefan Koppermann, Steven G. Van Lanen, Christian Ducho, Zheng Cui, and Jon S. Thorson
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Staphylococcus aureus ,Stereochemistry ,Mutant ,Pharmaceutical Science ,Mutagenesis (molecular biology technique) ,Microbial Sensitivity Tests ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Streptomyces ,Article ,Analytical Chemistry ,Drug Discovery ,Escherichia coli ,medicine ,Pharmacology ,chemistry.chemical_classification ,Aquifex aeolicus ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Fatty acid ,Nucleosides ,biology.organism_classification ,Anti-Bacterial Agents ,0104 chemical sciences ,Complementary and alternative medicine ,Molecular Medicine ,Antibacterial activity - Abstract
Muraymycins are nucleoside antibiotics isolated from Streptomyces sp. NRRL 30471 and several mutant strains thereof that were generated by random, chemical mutagenesis. Reinvestigation of two mutant strains using new media conditions led to the isolation of three new muraymycin congeners, named B8, B9, and C6 (1-3), as well as a known muraymycin, C1. Structures of the compounds were elucidated by HRMS and 1D and 2D NMR spectroscopic analyses. Complete 2D NMR assignments for the known muraymycin C1 are also provided for the first time. Compounds 1 and 2, which differ from other muraymycins by having an elongated, terminally branched fatty acid side chain, had picomolar IC50 values against Staphylococcus aureus and Aquifex aeolicus MraY and showed good antibacterial activity against S. aureus (MIC = 2 and 6 μg/mL, respectively) and Escherichia coli Δ tolC (MIC = 4 and 2 μg/mL, respectively). Compound 3, which is characterized by an N-acetyl modification of the primary amine of the dissacharide core that is shared among nearly all of the reported muraymycin congeners, greatly reduced its inhibitory and antibacterial activity compared to nonacylated muraymycin C1, which possibly indicates this modification is used for self-resistance.
- Published
- 2018
22. Mccrearamycins A-D, Geldanamycin-Derived Cyclopentenone Macrolactams from an Eastern Kentucky Abandoned Coal Mine Microbe
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Xiachang Wang, Chang-Guo Zhan, Sherif I. Elshahawi, James C. Hower, Ziyuan Zhou, Jon S. Thorson, Yinan Zhang, Sean Parkin, Bruce E. Hatcher, M. Ryan Woodcock, Larissa V. Ponomareva, Madan K. Kharel, S. Randal Voss, Qingchao Qiu, Khaled A. Shaaban, and Xiabin Chen
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Cyclopentenone ,Stereochemistry ,Cell Survival ,Lactams, Macrocyclic ,Molecular Conformation ,Kentucky ,Cyclopentanes ,010402 general chemistry ,Streptomyces ,01 natural sciences ,Catalysis ,Article ,Benzilic acid rearrangement ,chemistry.chemical_compound ,Cell Line, Tumor ,Humans ,HSP90 Heat-Shock Proteins ,Cytotoxicity ,biology ,010405 organic chemistry ,Ansamycin ,Stereoisomerism ,General Chemistry ,General Medicine ,Geldanamycin ,biology.organism_classification ,Mycothiol ,0104 chemical sciences ,Coal ,chemistry ,Chemical engineering ,Biocatalysis - Abstract
Four cyclopentenone-containing ansamycin polyketides (mccrearamycins A-D), and six new geldanamycins (Gdms B-G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD-23-14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19-hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation. In addition to standard Hsp90α binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90α modulators in a new axolotl embryo tail regeneration (ETR) assay as a potential new whole animal assay for Hsp90 modulator discovery.
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- 2017
23. Spoxazomicin D and Oxachelin C, Potent Neuroprotective Carboxamides from the Appalachian Coal Fire-Associated Isolate Streptomyces sp. RM-14-6
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Xiachang Wang, James C. Hower, Manjula Sunkara, Mark A. Prendergast, Larissa V. Ponomareva, Matthew S. Tremblay, Gregory C. Copley, Yinan Zhang, Jianjun Zhang, Madan K. Kharel, Sherif I. Elshahawi, Meredith A. Saunders, Tuan Tran, Khaled A. Shaaban, Andrew J. Morris, and Jon S. Thorson
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Antifungal Agents ,Stereochemistry ,Pharmaceutical Science ,Coal fire ,010402 general chemistry ,01 natural sciences ,Streptomyces ,Neuroprotection ,Article ,Spoxazomicin D ,Analytical Chemistry ,Phenols ,Drug Discovery ,Humans ,Cytotoxicity ,Nuclear Magnetic Resonance, Biomolecular ,Oxazoles ,Pharmacology ,Appalachian Region ,Molecular Structure ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,biology.organism_classification ,Anti-Bacterial Agents ,0104 chemical sciences ,Sodium salt ,Coal ,Neuroprotective Agents ,Complementary and alternative medicine ,Biochemistry ,Unfolded protein response ,Molecular Medicine ,Peptides ,Oligopeptides ,Two-dimensional nuclear magnetic resonance spectroscopy ,Ethers - Abstract
The isolation and structure elucidation of six new bacterial metabolites [spoxazomicin D (2), oxachelins B and C (4, 5), and carboxamides 6–8] and 11 previously reported bacterial metabolites (1, 3, 9–12a, and 14–18) from Streptomyces sp. RM-14-6 is reported. Structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spectrometry data analysis, along with direct comparison to synthetic standards for 2, 11, and 12a,b. Complete 2D NMR assignments for the known metabolites lenoremycin (9) and lenoremycin sodium salt (10) were also provided for the first time. Comparative analysis also provided the basis for structural revision of several previously reported putative aziridine-containing compounds [exemplified by madurastatins A1, B1, C1 (also known as MBJ-0034), and MBJ-0035] as phenol-dihydrooxazoles. Bioactivity analysis [including antibacterial, antifungal, cancer cell line cytotoxicity, unfolded protein response (UPR) modulation, and EtOH damage neuroprotection] revealed 2 and 5 as potent neuroprotectives and lenoremycin (9) and its sodium salt (10) as potent UPR modulators, highlighting new functions for phenol-oxazolines/salicylates and polyether pharmacophores.
- Published
- 2016
24. Jatrophacine, a 4,5-seco-rhamnofolane diterpenoid with potent anti-inflammatory activity from Jatropha curcas
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Lihong Hu, Yang Hu, Tu-Lin Lu, Qi Lv, Xiachang Wang, Huimin Zhao, Ning Ding, and Aiping Yang
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biology ,Traditional medicine ,010405 organic chemistry ,Chemistry ,medicine.drug_class ,Organic Chemistry ,Euphorbiaceae ,Plant Science ,biology.organism_classification ,01 natural sciences ,Biochemistry ,Terpenoid ,Anti-inflammatory ,0104 chemical sciences ,Analytical Chemistry ,010404 medicinal & biomolecular chemistry ,medicine ,Jatropha curcas - Abstract
A new diterpenoid named jatrophacine (1), with an unusual 4,5-seco- rhamnofolane skeleton, was isolated from the roots of Jatropha curcas, together with eleven known diterpenoids. The structure of the new compound was elucidated through a detailed analysis of its 1 D- and 2 D-NMR spectra. The X-ray structure of jatrophol (2) is also presented. Anti-inflammatory activity with LPS-induced RAW 264.7 macrophages revealed that compound 1 strongly inhibited the production of nitric oxide (IC50 = 0.53 μM).
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- 2019
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25. Puromycins B-E, Naturally Occurring Amino-Nucleosides Produced by the Himalayan Isolate Streptomyces sp. PU-14G
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Muhammad Abbas, Larissa V. Ponomareva, Imran Sajid, Xiachang Wang, Sherif I. Elshahawi, Jon S. Thorson, and Khaled A. Shaaban
- Subjects
0301 basic medicine ,Stereochemistry ,Pharmaceutical Science ,Microbial Sensitivity Tests ,Gram-Positive Bacteria ,01 natural sciences ,Streptomyces ,Article ,Analytical Chemistry ,Mycobacterium ,03 medical and health sciences ,Drug Discovery ,Pakistan ,Pharmacology ,biology ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Nucleosides ,Isolation (microbiology) ,biology.organism_classification ,0104 chemical sciences ,030104 developmental biology ,Complementary and alternative medicine ,Molecular Medicine ,Puromycin - Abstract
The isolation and structure elucidation of four new naturally occurring amino-nucleoside [puromycins B-E (1-4)] metabolites from a Himalayan isolate ( Streptomyces sp. PU-14-G, isolated from the Bara Gali region of northern Pakistan) is reported. Consistent with prior reports, comparative antimicrobial assays revealed the need for the free 2″-amine for anti-Gram-positive bacteria and antimycobacterial activity. Similarly, comparative cancer cell line cytotoxicity assays highlighted the importance of the puromycin-free 2″-amine and the impact of 3'-nucleoside substitution. These studies extend the repertoire of known naturally occurring puromycins and their corresponding SAR. Notably, 1 represents the first reported naturally occurring bacterial puromycin-related metabolite with a 3'- N-amino acid substitution that differs from the 3'- N-tyrosinyl of classical puromycin-type natural products. This discovery suggests the biosynthesis of 1 in Streptomyces sp. PU-14G may invoke a uniquely permissive amino-nucleoside synthetase and/or multiple synthetases and sets the stage for further studies to elucidate, and potentially exploit, new biocatalysts for puromycin chemoenzymatic diversification.
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- 2018
26. Anti-inflammatory octahydroindolizine alkaloid enantiomers from Dendrobium crepidatum
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Xiachang Wang, Yang Hu, Xiaoqian Ding, Hua Yang, Lihong Hu, Minyan Liu, Jian Liu, and Chaofeng Zhang
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Models, Molecular ,Circular dichroism ,Lipopolysaccharide ,Stereochemistry ,medicine.drug_class ,Anti-Inflammatory Agents ,Lung injury ,Nitric Oxide ,01 natural sciences ,Biochemistry ,Anti-inflammatory ,Nitric oxide ,Mice ,chemistry.chemical_compound ,Alkaloids ,In vivo ,Drug Discovery ,medicine ,Animals ,Molecular Biology ,010405 organic chemistry ,Chemistry ,Alkaloid ,Organic Chemistry ,Indolizines ,Stereoisomerism ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,RAW 264.7 Cells ,Enantiomer ,Dendrobium - Abstract
Six pairs of octahydroindolizine-type alkaloid enantiomers (1–6) including three new compounds [(−)-1/(+)-1, 2] were isolated from the stems of Dendrobium crepidatum. Their structures including the absolute configurations were elucidated by extensive spectroscopic analyses and comparison between the experimental and calculated electronic circular dichroism (ECD). All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells. It was found that compounds (+)-1, 2 and (+)-6 exhibited pronounced inhibition on NO production with IC50 values in the range of 3.62–16.11 µM, being more active than the positive control, dexamethasone (IC50 = 47.04 µM). In vivo, compound 6 (100, 50 and 10 mg/kg) showed protective effects against LPS-induced acute lung injury (ALI) in mice.
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- 2020
27. Frenolicin B Targets Peroxiredoxin 1 and Glutaredoxin 3 to Trigger ROS/4E-BP1-Mediated Antitumor Effects
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Yubin Guo, Larissa V. Ponomareva, Jing Chen, Luksana Chaiswing, Khaled A. Shaaban, Bradley D. Anderson, Jon S. Thorson, Markos Leggas, Xiachang Wang, Haining Zhu, Qiou Wei, Yanan Cao, Yinan Zhang, Qing Ye, Qing-Bai She, Jamie Horn, and Daret K. St. Clair
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Male ,Cell Survival ,Clinical Biochemistry ,Transplantation, Heterologous ,Mice, Nude ,Antineoplastic Agents ,Cell Cycle Proteins ,mTORC1 ,Biology ,Peroxiredoxin 1 ,Mechanistic Target of Rapamycin Complex 1 ,01 natural sciences ,Biochemistry ,Article ,chemistry.chemical_compound ,Mice ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,Animals ,Humans ,Phosphorylation ,RNA, Small Interfering ,Molecular Biology ,Protein kinase B ,Glutaredoxins ,Adaptor Proteins, Signal Transducing ,Pharmacology ,chemistry.chemical_classification ,Reactive oxygen species ,010405 organic chemistry ,Glutathione ,Peroxiredoxins ,0104 chemical sciences ,Cell biology ,chemistry ,Tumor progression ,Cancer cell ,Molecular Medicine ,RNA Interference ,Reactive Oxygen Species ,Naphthoquinones ,Signal Transduction - Abstract
Summary Peroxiredoxin 1 (Prx1) and glutaredoxin 3 (Grx3) are two major antioxidant proteins that play a critical role in maintaining redox homeostasis for tumor progression. Here, we identify the prototypical pyranonaphthoquinone natural product frenolicin B (FB) as a selective inhibitor of Prx1 and Grx3 through covalent modification of active-site cysteines. FB-targeted inhibition of Prx1 and Grx3 results in a decrease in cellular glutathione levels, an increase of reactive oxygen species (ROS), and concomitant inhibition of cancer cell growth, largely by activating the peroxisome-bound tuberous sclerosis complex to inhibit mTORC1/4E-BP1 signaling axis. FB structure-activity relationship studies reveal a positive correlation between inhibition of 4E-BP1 phosphorylation, ROS-mediated cancer cell cytotoxicity, and suppression of tumor growth in vivo. These findings establish FB as the most potent Prx1/Grx3 inhibitor reported to date and also notably highlight 4E-BP1 phosphorylation status as a potential predictive marker in response to ROS-based therapies in cancer.
- Published
- 2018
28. Self-Resistance during Muraymycin Biosynthesis: a Complementary Nucleotidyltransferase and Phosphotransferase with Identical Modification Sites and Distinct Temporal Order
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Anke Lemke, Xiaodong Liu, Jon S. Thorson, Stefan Koppermann, Christian Ducho, Steven G. Van Lanen, Xiachang Wang, Jürgen Rohr, and Zheng Cui
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0301 basic medicine ,Disaccharide ,Transferases (Other Substituted Phosphate Groups) ,Phosphotransferase ,03 medical and health sciences ,chemistry.chemical_compound ,Bacterial Proteins ,Biosynthesis ,Transferases ,Mechanisms of Resistance ,Gene cluster ,Translocase ,Pharmacology (medical) ,Nucleotide ,Phosphorylation ,Adenylylation ,Pharmacology ,chemistry.chemical_classification ,biology ,Nucleotides ,Phosphotransferases ,Nucleosides ,Nucleotidyltransferase ,Nucleotidyltransferases ,Streptomyces ,Anti-Bacterial Agents ,030104 developmental biology ,Infectious Diseases ,Biochemistry ,chemistry ,biology.protein ,Peptides - Abstract
Muraymycins are antibacterial natural products from Streptomyces spp. that inhibit translocase I (MraY), which is involved in cell wall biosynthesis. Structurally, muraymycins consist of a 5′- C -glycyluridine (GlyU) appended to a 5″-amino-5″-deoxyribose (ADR), forming a disaccharide core that is found in several peptidyl nucleoside inhibitors of MraY. For muraymycins, the GlyU-ADR disaccharide is further modified with an aminopropyl-linked peptide to generate the simplest structures, annotated as the muraymycin D series. Two enzymes encoded in the muraymycin biosynthetic gene cluster, Mur29 and Mur28, were functionally assigned in vitro as a Mg·ATP-dependent nucleotidyltransferase and a Mg·ATP-dependent phosphotransferase, respectively, both modifying the 3″-OH of the disaccharide. Biochemical characterization revealed that both enzymes can utilize several nucleotide donors as cosubstrates and the acceptor substrate muraymycin also behaves as an inhibitor. Single-substrate kinetic analyses revealed that Mur28 preferentially phosphorylates a synthetic GlyU-ADR disaccharide, a hypothetical biosynthetic precursor of muraymycins, while Mur29 preferentially adenylates the D series of muraymycins. The adenylated or phosphorylated products have significantly reduced (170-fold and 51-fold, respectively) MraY inhibitory activities and reduced antibacterial activities, compared with the respective unmodified muraymycins. The results are consistent with Mur29-catalyzed adenylation and Mur28-catalyzed phosphorylation serving as complementary self-resistance mechanisms, with a distinct temporal order during muraymycin biosynthesis.
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- 2018
29. Insights into the Target Interaction of Naturally Occurring Muraymycin Nucleoside Antibiotics
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Zheng Cui, Steven G. Van Lanen, Jannine Ludwig, Christian Ducho, Xiachang Wang, Patrick D. Fischer, Jon S. Thorson, and Stefan Koppermann
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Staphylococcus aureus ,medicine.drug_class ,Antibiotics ,Transferases (Other Substituted Phosphate Groups) ,010402 general chemistry ,medicine.disease_cause ,Crystallography, X-Ray ,01 natural sciences ,Biochemistry ,Article ,Structure-Activity Relationship ,Bacterial Proteins ,Transferases ,Drug Discovery ,medicine ,Escherichia coli ,Structure–activity relationship ,Humans ,Urea ,Nucleotide ,General Pharmacology, Toxicology and Pharmaceutics ,Escherichia coli Infections ,Pharmacology ,chemistry.chemical_classification ,010405 organic chemistry ,Nucleotides ,Organic Chemistry ,Nucleosides ,Staphylococcal Infections ,In vitro ,0104 chemical sciences ,Anti-Bacterial Agents ,Molecular Docking Simulation ,Enzyme ,chemistry ,Molecular Medicine ,Target protein ,Peptides ,Nucleoside - Abstract
Muraymycins are a subclass of antimicrobially active uridine-derived natural products. Biological data on several muraymycin analogues have already been reported, including some inhibitory in vitro activities towards their target protein, the bacterial membrane enzyme MraY. However, a structure-activity relationship (SAR) study on naturally occurring muraymycins based on such in vitro data has been missing so far. In this work, we report a detailed SAR investigation on representatives of the four muraymycin subgroups A–D using a fluorescence-based in vitro MraY assay. For some muraymycins, inhibition of MraY with IC(50) values in the low pM range was observed. These inhibitory potencies were compared with antibacterial activities and were correlated to modelling data derived from a previously reported X-ray crystal structure of MraY in complex with a muraymycin inhibitor. Overall, these results will pave the way for the development of muraymycin analogues with optimized properties as antibacterial drug candidates.
- Published
- 2018
30. Bi- and Tetracyclic Spirotetronates from the Coal Mine Fire Isolate Streptomyces sp. LC-6-2
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Xiachang Wang, James C. Hower, Jürgen Rohr, Steven G. Van Lanen, Khaled A. Shaaban, Gregory C. Copley, Sherif I. Elshahawi, Xiabin Chen, Chang-Guo Zhan, Yinan Zhang, Larissa V. Ponomareva, Sean Parkin, Wenlong Cai, and Jon S. Thorson
- Subjects
Stereochemistry ,Metabolite ,Molecular Conformation ,Pharmaceutical Science ,010402 general chemistry ,Crystallography, X-Ray ,01 natural sciences ,Streptomyces ,DNA sequencing ,Article ,Analytical Chemistry ,chemistry.chemical_compound ,Bridged Bicyclo Compounds ,Drug Discovery ,Gene cluster ,Spiro Compounds ,Nuclear Magnetic Resonance, Biomolecular ,Pharmacology ,biology ,Bicyclic molecule ,Molecular Structure ,010405 organic chemistry ,Extramural ,Organic Chemistry ,biology.organism_classification ,Bridged Bicyclo Compounds, Heterocyclic ,0104 chemical sciences ,Coal ,Complementary and alternative medicine ,chemistry ,Multigene Family ,Molecular Medicine ,Enantiomer - Abstract
The structures of 12 new “enantiomeric”-like abyssomicin metabolites (abyssomicins M–X) from Streptomyces sp. LC-6-2 are reported. Of this set, the abyssomicin W (11) contains an unprecedented 8/6/6/6 tetracyclic core, while the bicyclic abyssomicin X (12) represents the first reported naturally occurring linear spirotetronate. Metabolite structures were determined based on spectroscopic data and X-ray crystallography, and Streptomyces sp. LC-6-2 genome sequencing also revealed the corresponding putative biosynthetic gene cluster.
- Published
- 2017
31. Mullinamides A and B, New Cyclopeptides Produced by the Ruth Mullins Coal Mine Fire Isolate Streptomyces sp. RM-27-46
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Madan K. Kharel, Jon S. Thorson, Gregory C. Copley, Manjula Sunkara, Khaled A. Shaaban, Sherif I. Elshahawi, Xiachang Wang, James C. Hower, Andrew J. Morris, and Larissa V. Ponomareva
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Pharmacology ,natural product ,biology ,pharmacognosy ,Molecular Structure ,Stereochemistry ,bioprospecting ,surugamide ,Nuclear magnetic resonance spectroscopy ,Gene Expression Regulation, Bacterial ,biology.organism_classification ,Antimicrobial ,Streptomyces ,Coal Mining ,Peptides, Cyclic ,Article ,cyclopeptide ,antibiotic ,Drug Discovery ,lipids (amino acids, peptides, and proteins) ,Antibacterial activity - Abstract
Two new cyclopeptides, mullinamides A [cyclo-(-l-Gly-l-Glu-l-Val-l-Ile-l-Pro-)] and B [cyclo-(-l-Glu-l-Met-l-Pro-)] were isolated from the crude extract of terrestrial Streptomyces sp. RM-27-46 along with the three known cyclopeptides surugamide A [cyclo-(-l-Ile-d-Ile-l-Lys-l-Ile-d-Phe-d-Leu-l-Ile-d-Ala-)], cyclo-(-l-Pro-l-Phe-) and cyclo-(-l-Pro-l-Leu-). The structures of the new compounds were elucidated by the cumulative analyses of NMR spectroscopy and high resolution mass spectrometry. While mullinamides A and B displayed no appreciable antimicrobial/fungal activity or cytotoxicity, this study highlights the first reported antibacterial activity of surugamide A.
- Published
- 2014
32. Venturicidin C, A New 20-Membered Macrolide Produced by Streptomyces sp. TS-2-2
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Xiachang Wang, Manjula Sunkara, James C. Hower, Khaled A. Shaaban, Jon S. Thorson, Andrew J. Morris, Gregory C. Copley, Sherif I. Elshahawi, Madan K. Kharel, Larissa V. Ponomareva, and Shanteri Singh
- Subjects
Antifungal ,microbial ,Antifungal Agents ,Lung Neoplasms ,Magnetic Resonance Spectroscopy ,Stereochemistry ,medicine.drug_class ,natural products ,secondary metabolite ,Ferrioxamine E ,Streptomyces ,Peptides, Cyclic ,Article ,Mass Spectrometry ,Venturicidin C ,Cell Line, Tumor ,Drug Discovery ,medicine ,apoptolidin ,Humans ,Streptomycetes ,Pharmacology ,biology ,Chemistry ,Nuclear magnetic resonance spectroscopy ,biology.organism_classification ,Adenosine ,3. Good health ,Cell culture ,Venturicidins ,Macrolides ,medicine.drug - Abstract
Venturicidin C (1), a new 20-membered macrolide along with the known venturicidins A (2) and B (3) were isolated from the crude extract of the Appalachian bacterial strain Streptomyces sp. TS-2-2. Additionally, nine other known compounds namely nocardamine, dehydroxynocardamine, desmethylenlnocardamine, ferrioxamine E (FOE), adenosine, riboflavin, cyclo(d)-trans-4-OH-Pro-(d)-Phe, cyclo(d)-Pro-(d)-Phe, and N-(2-phenylethyl)-acetamide were also isolated and identified. The structure of the new macrolide 1 was elucidated by the cumulative analyses of NMR and HR-MS spectrometry data. Complete NMR assignments for the known venturicidins A (2) and B (3) are also provided, for the first time, in this report. Venturicidins A-C did not inhibit the proliferation of A549 lung cancer cell lines but all displayed potent antifungal activity.
- Published
- 2013
33. A Diastereoselective Oxa-Pictet–Spengler-Based Strategy for (+)-Frenolicin B and epi-(+)-Frenolicin B Synthesis
- Author
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Jon S. Thorson, Manjula Sunkara, Andrew J. Morris, Xiachang Wang, Qing-Bai She, Yinan Zhang, Qing Ye, and Larissa V. Ponomereva
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Frenolicin B ,Molecular Structure ,Chemistry ,Stereochemistry ,Organic Chemistry ,Diastereomer ,Total synthesis ,Stereoisomerism ,Context (language use) ,Biochemistry ,Combinatorial chemistry ,Article ,Cyclization ,Frenolicin ,Chromans ,Physical and Theoretical Chemistry ,Naphthoquinones - Abstract
An efficient diastereoselective oxa-Pictet-Spengler reaction strategy was developed to construct benzoisochroman diastereomers. The utility of the reaction was demonstrated in the context of both the total synthesis of naturally occurring pyranonaphthoquinones (+)-frenolicin B and epi-(+)-frenolicin B as well as a range of frenolicin precursor analogs. The method is versatile and offers exquisite stereocontrol and, as such, offers a synthetic advance for the synthesis of pyranonaphthoquinone analogs.
- Published
- 2013
34. Antibacterial and Cytotoxic Actinomycins Y
- Author
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Wenlong, Cai, Xiachang, Wang, Sherif I, Elshahawi, Larissa V, Ponomareva, Xiaodong, Liu, Matthew R, McErlean, Zheng, Cui, Ashley L, Arlinghaus, Jon S, Thorson, and Steven G, Van Lanen
- Subjects
Threonine ,Molecular Structure ,Proline ,Cell Survival ,Fermentation ,Dactinomycin ,Humans ,Nuclear Magnetic Resonance, Biomolecular ,Streptomyces ,Article ,Anti-Bacterial Agents - Abstract
Four new Y-type actinomycin analogues named Y6–Y9 (1–4) were isolated and characterized from the scale up fermentation of the Streptomyces sp. strain Gö-GS12, as well as actinomycin Zp (5) that was, for the first time, isolated as a natural product. Structures of the new compounds were elucidated by the cumulative analyses of NMR spectroscopy and HRMS. The 4-hydroxythreonine on the β-ring of 1 uniquely undergoes both a rearrangement by a two-fold acyl shift and an additional ring closure with the amino group of the phenoxazinone chromophore, and the α-rings of 4 and 5 contain a rare 5-methyl proline. Compounds 2–5 showed potent antibacterial activities against Gram-positive bacteria that correlated with cytotoxicity against representative human cell lines. The combination of a β-ring rearrangement and additional ring closure in 1 rendered this actinomycin significantly less potent relative to the non-rearranged comparator actinomycin Y5 and other actinomycins.
- Published
- 2016
35. Cover Feature: Insights into the Target Interaction of Naturally Occurring Muraymycin Nucleoside Antibiotics (ChemMedChem 8/2018)
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Stefan Koppermann, Zheng Cui, Jon S. Thorson, Jannine Ludwig, Steven G. Van Lanen, Patrick D. Fischer, Christian Ducho, and Xiachang Wang
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Pharmacology ,Feature (computer vision) ,Computer science ,Organic Chemistry ,Drug Discovery ,Molecular Medicine ,Cover (algebra) ,Computational biology ,General Pharmacology, Toxicology and Pharmaceutics ,Biochemistry ,Nucleoside - Published
- 2018
36. Cytotoxic Indolocarbazoles from Actinomadura melliaura ATCC 39691
- Author
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Xiachang Wang, Jon S. Thorson, Khaled A. Shaaban, Madan K. Kharel, Markos Leggas, Sherif I. Elshahawi, and Jamie Horn
- Subjects
Staphylococcus aureus ,Stereochemistry ,Metabolite ,Mycobacterium smegmatis ,Carbazoles ,Pharmaceutical Science ,Microbial Sensitivity Tests ,Saccharomyces cerevisiae ,Alkylation ,Biology ,Article ,California ,Analytical Chemistry ,Indole Alkaloids ,chemistry.chemical_compound ,Drug Discovery ,Actinomycetales ,Potency ,Humans ,Nuclear Magnetic Resonance, Biomolecular ,Soil Microbiology ,ADME ,Pharmacology ,Antibiotics, Antineoplastic ,Strain (chemistry) ,Molecular Structure ,Organic Chemistry ,Methylation ,Carbon-13 NMR ,Micrococcus luteus ,Complementary and alternative medicine ,Biochemistry ,chemistry ,Molecular Medicine ,Topoisomerase I Inhibitors ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Actinomadura melliaura ATCC 39691, a strain isolated from a soil sample collected in Bristol Cove, California, is a known producer of the disaccharide-substituted AT2433 indolocarbazoles (6-9). Reinvestigation of this strain using new media conditions led to40-fold improvement in the production of previously reported AT2433 metabolites and the isolation and structure elucidation of the four new analogues, AT2433-A3, A4, A5, and B3 (1-4). The availability of this broader set of compounds enabled a subsequent small antibacterial/fungal/cancer SAR study that revealed disaccharyl substitution, N-6 methylation, and C-11 chlorination as key modulators of bioactivity. The slightly improved anticancer potency of the newly reported N-6-desmethyl 1 (compared to 6) contrasts extensive SAR of monoglycosylated rebeccamycin-type topoisomerase I inhibitors where N-6 alkylation has contributed to improved potency and ADME. Complete 2D NMR assignments for the known metabolite BMY-41219 (5) and (13)C NMR spectroscopic data for the known analogue AT2433-B1 (7) are also provided for the first time.
- Published
- 2015
37. A divergent enantioselective strategy for the synthesis of griseusins
- Author
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Xiachang Wang, Jon S. Thorson, Qing-Bai She, Yinan Zhang, and Qing Ye
- Subjects
chemistry.chemical_classification ,Ketone ,Griseusins ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Chemistry ,Enantioselective synthesis ,Regioselectivity ,Total synthesis ,Stereoisomerism ,General Medicine ,General Chemistry ,Ring (chemistry) ,Catalysis ,Article ,Cell Line, Tumor ,Humans ,Stereoselectivity ,Griseusin C ,Naphthoquinones - Abstract
The first enantioselective total synthesis of griseusin A, griseusin C, 4′-deacetyl-griseusin A, and two non-native counterparts in 11–14 steps is reported. This strategy highlights a key hydroxy-directed C–H olefination of 1-methylene isochroman with an α,β-unsaturated ketone followed by subsequent stereoselective epoxidation and regioselective cyclization to afford the signature tetrahydro-spiropyran ring. Colorectal cancer cell cytotoxicities of the final products highlight the impact of the griseusin tetrahydro-spiropyran ring on bioactivity. As the first divergent enantioselective synthesis, the strategy put forth sets the stage for further griseusin mechanism-of-action and SAR studies.
- Published
- 2015
38. Terfestatins B and C, New p-Terphenyl Glycosides Produced by Streptomyces sp. RM-5–8
- Author
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Mark A. Prendergast, Xiachang Wang, James C. Hower, Gregory C. Copley, Khaled A. Shaaban, Andrew J. Morris, Ibrahim S. Elgumati, Anna R. Reynolds, Manjula Sunkara, Madan K. Kharel, Steven G. Van Lanen, Yinan Zhang, Sherif I. Elshahawi, Larissa V. Ponomareva, Jon S. Thorson, and Meredith A. Saunders
- Subjects
Stereochemistry ,Biochemistry ,Streptomyces ,Article ,chemistry.chemical_compound ,Glucuronides ,Glucosides ,Terphenyl ,Terphenyl Compounds ,Animals ,Glycosides ,Physical and Theoretical Chemistry ,chemistry.chemical_classification ,biology ,Molecular Structure ,Hexuronic Acids ,Organic Chemistry ,Glycoside ,Rare sugar ,biology.organism_classification ,Rats ,chemistry ,Cell culture - Abstract
Terfestatins B (1) and C (2), new p-terphenyls bearing a novel unsaturated hexuronic acid (4-deoxy-α-l-threo-hex-4-enopyranuronate), a unique β-d-glycosyl ester of 5-isoprenylindole-3-carboxylate (3) and the same rare sugar, and two new hygromycin precursors, were characterized as metabolites of the coal mine fire isolate Streptomyces sp. RM-5–8. EtOH damage neuroprotection assays using rat hippocampal-derived primary cell cultures with 1, 2, 3 and echoside B (a terfestatin C-3′-β-d-glucuronide from Streptomyces sp. RM-5– 8) revealed 1 as potently neuroprotective, highlighting a new potential application of the terfestatin scaffold.
- Published
- 2015
39. The native production of the sesquiterpene isopterocarpolone by Streptomyces sp. RM-14-6
- Author
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Shaaban, Khaled A., Shanteri Singh, Elshahawi, Sherif I., Xiachang Wang, Ponomareva, Larissa V., Sunkara, Manjula, Copley, Gregory C., Hower, James C., Morris, Andrew J., Madan K. Kharel, and Thorson, Jon S.
- Abstract
We report the production, isolation and structure elucidation of the sesquiterpene isopterocarpolone from an Appalachian isolate Streptomyces species RM-14-6. While isopterocarpolone was previously put forth as a putative plant metabolite, this study highlights the first native bacterial production of isopterocarpolone and the first full characterisation of isopterocarpolone using 1D and 2D NMR spectroscopy and HR-ESI mass spectrometry. Considering the biosynthesis of closely related metabolites (geosmin or 5-epiaristolochene), the structure of isopterocarpolone also suggests the potential participation of one or more unique enzymatic transformations. In this context, this work also sets the stage for the elucidation of potentially novel bacterial biosynthetic machinery.
- Published
- 2014
- Full Text
- View/download PDF
40. Ruthmycin, a new tetracyclic polyketide from Streptomyces sp. RM-4-15
- Author
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Yinan Zhang, Jon S. Thorson, Lei Fang, Gregory C. Copley, Sherif I. Elshahawi, Madan K. Kharel, Larissa V. Ponomareva, Chang-Guo Zhan, Xiachang Wang, James C. Hower, and Khaled A. Shaaban
- Subjects
Antifungal ,Six member ,Antifungal Agents ,biology ,Molecular Structure ,medicine.drug_class ,Chemistry ,Stereochemistry ,Organic Chemistry ,Kentucky ,Microbial Sensitivity Tests ,biology.organism_classification ,Biochemistry ,Streptomyces ,Article ,Polyketide ,Frenolicin ,Polyketides ,medicine ,Physical and Theoretical Chemistry ,Nuclear Magnetic Resonance, Biomolecular ,Bacteria ,Naphthoquinones - Abstract
The isolation and structural elucidation of a new tetracyclic polyketide (ruthmycin) from Streptomyces sp. RM-4-15, a bacteria isolated near thermal vents from the Ruth Mullins underground coal mine fire in eastern Kentucky, is reported. In comparison to the well-established frenolicin core scaffold, ruthmycin possesses an unprecedented signature C3 bridge and a corresponding fused six member ring. Preliminary in vitro antibacterial, anticancer, and antifungal assays revealed ruthmycin to display moderate antifungal activity.
- Published
- 2013
41. The native production of the sesquiterpene isopterocarpolone by Streptomyces sp. RM-14-6
- Author
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Gregory C. Copley, Shanteri Singh, Sherif I. Elshahawi, Khaled A. Shaaban, Andrew J. Morris, Madan K. Kharel, Jon S. Thorson, Larissa V. Ponomareva, Xiachang Wang, James C. Hower, and Manjula Sunkara
- Subjects
Spectrometry, Mass, Electrospray Ionization ,biology ,Molecular Structure ,Metabolite ,Organic Chemistry ,Context (language use) ,Plant Science ,Naphthols ,biology.organism_classification ,Sesquiterpene ,Biochemistry ,Streptomyces ,Geosmin ,Terpenoid ,Article ,Analytical Chemistry ,chemistry.chemical_compound ,chemistry ,Biosynthesis ,Two-dimensional nuclear magnetic resonance spectroscopy ,Nuclear Magnetic Resonance, Biomolecular ,Sesquiterpenes - Abstract
We report the production, isolation and structure elucidation of the sesquiterpene isopterocarpolone from an Appalachian isolate Streptomyces species RM-14-6. While isopterocarpolone was previously put forth as a putative plant metabolite, the current study highlights the first native bacterial production of isopterocarpolone and the first full characterization of isopterocarpolone using 1D and 2D NMR spectroscopy and HR-ESI mass spectrometry. Considering the biosynthesis of closely related metabolites (geosmin or 5-epiaristolochene), the structure of isopterocarpolone also suggests the potential participation of one or more unique enzymatic transformations. In this context, this work also sets the stage for the elucidation of potentially novel bacterial biosynthetic machinery.
- Published
- 2013
42. The native production of the sesquiterpene isopterocarpolone by Streptomyces sp. RM-14-6
- Author
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Khaled A. Shaaban, Shanteri Singh, Sherif I. Elshahawi, Xiachang Wang, Larissa V. Ponomareva, Manjula Sunkara, Gregory C. Copley, James C. Hower, Andrew J. Morris, Madan K. Kharel, Jon S. Thorson, Khaled A. Shaaban, Shanteri Singh, Sherif I. Elshahawi, Xiachang Wang, Larissa V. Ponomareva, Manjula Sunkara, Gregory C. Copley, James C. Hower, Andrew J. Morris, Madan K. Kharel, and Jon S. Thorson
- Published
- 2015
- Full Text
- View/download PDF
43. Herbimycins D-F, ansamycin analogues from Streptomyces sp. RM-7-15
- Author
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Khaled A. Shaaban, Andrew J. Morris, Manjula Sunkara, Jon S. Thorson, Madan K. Kharel, Sherif I. Elshahawi, Gregory C. Copley, Xiachang Wang, James C. Hower, and Larissa V. Ponomareva
- Subjects
Staphylococcus aureus ,Stereochemistry ,Cell Survival ,Electrospray ionization ,Saccharomyces cerevisiae ,Pharmaceutical Science ,Context (language use) ,Microbial Sensitivity Tests ,Biology ,medicine.disease_cause ,Streptomyces ,Article ,Analytical Chemistry ,Microbiology ,Drug Discovery ,medicine ,Humans ,HSP90 Heat-Shock Proteins ,Cytotoxicity ,Nuclear Magnetic Resonance, Biomolecular ,Pharmacology ,Ansamycin ,Organic Chemistry ,Salmonella enterica ,biology.organism_classification ,Antimicrobial ,Anti-Bacterial Agents ,Complementary and alternative medicine ,Rifabutin ,Molecular Medicine - Abstract
Bacterial strains belonging to the class actinomycetes were isolated from the soil near a thermal vent of the Ruth Mullins coal fire (Appalachian mountains of Eastern Kentucky). High resolution electrospray ionization mass spectrometry (HR-ESI-MS) and ultraviolet (UV) absorption profiles of metabolites from one of the isolates (Streptomyces sp. RM-7-15) revealed the presence of a unique set of metabolites ultimately determined to be herbimycins D-F (1–3). In addition, herbimycin A (4), dihydroherbimycin A (TAN 420E) (7), and the structurally distinct antibiotic bicycylomycin were isolated from the crude extract of Streptomyces sp. RM-7-15. Herbimycins A, D-F (1–3) displayed comparable binding affinities to the Hsp90α. While the new analogues were found to be inactive in cancer cell cytotoxicity and antimicrobial assays, they may offer new insights in the context of non-toxic ansamycin-based Hsp90 inhibitors for the treatment of neurodegenerative disease.
- Published
- 2013
44. Frenolicins C-G, pyranonaphthoquinones from Streptomyces sp. RM-4-15
- Author
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Yinan Zhang, Manjula Sunkara, Sherif I. Elshahawi, Khaled A. Shaaban, Jon S. Thorson, Andrew J. Morris, Xiachang Wang, James C. Hower, Madan K. Kharel, Gregory C. Copley, and Larissa V. Ponomareva
- Subjects
Frenolicin B ,Spectrometry, Mass, Electrospray Ionization ,Stereochemistry ,Electrospray ionization ,Pharmaceutical Science ,Streptomyces ,Article ,Analytical Chemistry ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,Organic chemistry ,Humans ,Scandium chloride ,Pharmacology ,Appalachian Region ,Natural product ,biology ,Strain (chemistry) ,Molecular Structure ,Chemistry ,Organic Chemistry ,Chemical modification ,biology.organism_classification ,Actinobacteria ,Complementary and alternative medicine ,Pyrones ,Molecular Medicine ,Fermentation ,Drug Screening Assays, Antitumor ,Naphthoquinones - Abstract
Appalachian active coal fire sites were selected for the isolation of bacterial strains belonging to the class actinobacteria. A comparison of high resolution electrospray ionization mass spectrometry (HR-ESI-MS) and ultraviolet (UV) absorption profiles from isolate extracts to natural product databases suggested Streptomyces sp. RM-4-15 to produce unique metabolites. Four new pyranonaphthoquinones, frenolicins C–F (1–4), along with three known analogues, frenolicin (6), frenolicin B (7), and UCF76-A (8), were isolated from the fermentation of this strain. An additional new analogue frenolicin G (5) along with two known compounds, deoxyfrenolicin (9) and UCF 13 (10), were isolated from the fermentation supplied with 18 mg/L of scandium chloride - the first example, to the best of our knowledge, wherein scandium chloride supplementation led to the confirmed production of new bacterial secondary metabolites. Structures 1–5 were elucidated on the basis of spectral analysis and chemical modification. While frenolicins are best known for their anticoccidial activity, the current study revealed compounds 6–9 to exhibit moderate cytotoxicity against the human lung carcinoma cell line (A549) and thereby extends the anticancer SAR for this privileged scaffold.
- Published
- 2013
45. The native production of the sesquiterpene isopterocarpolone by Streptomyces sp. RM-14-6
- Author
-
Khaled A. Shaaban, Shanteri Singh, Sherif I. Elshahawi, Xiachang Wang, Larissa V. Ponomareva, Manjula Sunkara, Gregory C. Copley, James C. Hower, Andrew J. Morris, Madan K. Kharel, Jon S. Thorson, Khaled A. Shaaban, Shanteri Singh, Sherif I. Elshahawi, Xiachang Wang, Larissa V. Ponomareva, Manjula Sunkara, Gregory C. Copley, James C. Hower, Andrew J. Morris, Madan K. Kharel, and Jon S. Thorson
- Published
- 2014
- Full Text
- View/download PDF
46. Jatrophalactam, a novel diterpenoid lactam isolated from Jatropha curcas
- Author
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Zong-Ping Zheng, Lihong Hu, Xiachang Wang, and Xianwen Gan
- Subjects
biology ,Lactams ,Molecular Structure ,Chemistry ,Stereochemistry ,Organic Chemistry ,Molecular Conformation ,Jatropha ,biology.organism_classification ,Crystallography, X-Ray ,Biochemistry ,Plant Roots ,Terpenoid ,chemistry.chemical_compound ,Lactam ,Humans ,Physical and Theoretical Chemistry ,Diterpenes ,Drug Screening Assays, Antitumor ,Jatropha curcas ,Nuclear Magnetic Resonance, Biomolecular - Abstract
Jatrophalactam (1), a novel diterpenoid lactam possessing an unprecedented 5/13/3 tricyclic skeleton, was isolated from the roots of Jatropha curcas. The structure and relative configuration of jatrophalactam (1) were elucidated by extensive spectroscopic analysis and further determined by a single-crystal X-ray diffraction.
- Published
- 2009
47. A New Dolabrane-type Diterpene from Ceriops tagal
- Author
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Xiao-Wei Ouyang, Lihong Hu, Qing-Xi Yue, and Xiachang Wang
- Subjects
Pharmacology ,biology ,Stereochemistry ,Plant composition ,Rhizophoraceae ,Plant Science ,General Medicine ,biology.organism_classification ,HeLa ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,Ceriops tagal ,Drug Discovery ,Botany ,Cervical carcinoma ,Diterpene ,Cancer cell lines - Abstract
A new dolabrane-type diterpene named tagalsin O 1, together with six known analogues 2-7, were isolated from the aerial part of the mangrove plant Ceriops tagal. The structures and relative configurations were elucidated on the basis of their spectroscopic data. Cytotoxicity of the isolated compounds against HeLa human cervical carcinoma cancer cell line was evaluated.
- Published
- 2010
48. Guaiane Sesquiterpenoids from Jatropha curcas
- Author
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Lihong Hu, Jing-Han Liu, Xiachang Wang, and Shi-Ping Ma
- Subjects
Pharmacology ,biology ,Chemistry ,Chemical structure ,Plant composition ,Plant Science ,General Medicine ,biology.organism_classification ,Complementary and alternative medicine ,Drug Discovery ,Botany ,Medicinal plants ,Chemical composition ,Jatropha curcas - Abstract
Two new guaiane sesquiterpenoids named jatrophaols A and B (1, 2), along with three known analogues, were isolated from the roots of Jatropha curcas. Their structures were determined by spectroscopic methods, including 1D and 2D NMR spectroscopy, HR-EI-MS, HR-ESI-MS, and X-ray diffraction, as well as by comparison of their spectral data with those of related compounds.
- Published
- 2008
49. Two New Xanthone Glycosides from Ventilago Leiocarpa Benth
- Author
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Lei Ma, Lihong Hu, Jian-Ping Zuo, Xiachang Wang, and Li-Li Wang
- Subjects
Pharmacology ,chemistry.chemical_classification ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,Ventilago leiocarpa ,Traditional medicine ,Drug Discovery ,Xanthone ,Glycoside ,Plant Science ,General Medicine ,Anthraquinone - Abstract
Two new xanthone glycosides, 8-hydroxy-3-methyl-6-methoxyxanthone-1- O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranose (1) and 8-hydroxy-3-methyl-6-methoxyxanthone-1- O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranose (2), together with two known anthraquinones, 1,8-dihydroxy-3-methylanthraquinone (3) and 1,3,8-trihydroxy-6-methylanthraquinone (4), were isolated from the bark of Ventilago leiocarpa Benth. The structures were determined by various NMR spectroscopic and MS analyses. Compounds 1–4 were tested for their inhibitory activities against T and B cell proliferation, and 2 exhibited moderate inhibitory activities against LPS-induced B cell proliferation and ConA-induced T cell proliferation, with IC50 values of 8.8 and 17.9 μM, respectively.
- Published
- 2008
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