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Caixia Chen,
Jian Wang,
Hui Guo,
Weiyuan Hou,
Na Yang,
Biao Ren, Mei Liu,
Huanqin Dai,
Xueting Liu,
Fuhang Song,
Lixin Zhang
[show abstract]
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ABSTRACT: In the course of a screening program for bioactive compounds from a marine natural product library, a newly isolated Actinomycetes strain, designated as MS100061, exhibited strong anti-Mycobacterium bovis Bacillus Calmette-Guérin (BCG) activity. The strain belongs to the genus Streptomyces according to its morphological and 16S rDNA phylogenetic analysis. Bioassay-guided isolation resulted in a new spirotetronate, lobophorin G (1), together with two known compounds, lobophorins A (2) and B (3). The structures were elucidated by extensive spectroscopic methods and comparison with literatures. Compounds 1-3 were subjected to anti-BCG, antituberculosis, and antibacterial screening and exhibited potent anti-BCG activity with minimum inhibitory concentration (MIC) values of 1.56, 1.56, and 0.78 μg/ml, respectively, and moderate anti-Mycobacterium tuberculosis H37Rv activity with MIC values of 32, 32, and 16 μg/ml, respectively. The MIC values of compounds 1-3 against Bacillus subtilis were 3.125, 12.5, and 1.56 μg/ml, respectively, indicating great potential for antibacterial drugs. In addition, this is the first report of the anti-BCG and antituberculosis activities of lobophorins.
Applied Microbiology and Biotechnology 01/2013; · 3.42 Impact Factor
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Feng Xie,
Wenni He,
Mei Liu,
Andrew M Piggott,
Qian Wang,
Huanqin Dai,
Fuhang Song,
Xueting Liu,
Wael M Abdel-Mageed,
Miaomiao Liu,
Jian Wang,
Caixia Chen,
Xue Xiao,
Pei Huang,
Robert J Capon, Hao Xu,
Li Li,
Aaron Monte,
Lixin Zhang,
Hui Guo
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Feng Xie,
Wenni He,
Mei Liu,
Andrew M Piggott,
Qian Wang,
Huanqin Dai,
Fuhang Song,
Xueting Liu,
Wael M Abdel-Mageed,
Miaomiao Liu,
Jian Wang,
Caixia Chen,
Xue Xiao,
Pei Huang,
Robert J Capon, Hao Xu,
Li Li,
Aaron Monte,
Lixin Zhang,
Hui Guo
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Qian Wang,
Fuhang Song,
Xue Xiao,
Pei Huang,
Li Li,
Aaron Monte,
Wael M Abdel-Mageed,
Jian Wang,
Hui Guo,
Wenni He,
Feng Xie,
Huanqin Dai,
Miaomiao Liu,
Caixia Chen,
Hao Xu, Mei Liu,
Andrew M Piggott,
Xueting Liu,
Robert J Capon,
Lixin Zhang
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ABSTRACT: From the deep: The title actinomycete yielded three new abyssomicins J-L. The dimeric thioether J represents a unique example of a masked Michael acceptor with anti-TB properties. Mechanistic insights into the biosynthesis, biomimetic synthesis, stability, and biological mechanism of action of abyssomicins inform our understanding of, and prospects for the development of Michael-acceptor-based drugs.
Angewandte Chemie International Edition 12/2012; · 13.45 Impact Factor
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Fuhang Song,
Xinru Liu,
Hui Guo,
Biao Ren,
Caixia Chen,
Andrew M Piggott,
Ke Yu,
Hong Gao,
Qian Wang, Mei Liu,
Xueting Liu,
Huanqin Dai,
Lixin Zhang,
Robert J Capon
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ABSTRACT: An Aspergillus versicolor isolated from sediment collected from the Bohai Sea, China, yielded the new dimeric diketopiperazine brevianamide S (1), together with three new monomeric cometabolites, brevianamides T (2), U (3), and V (4). Structures were determined by detailed spectroscopic analysis. Brevianamide S exhibited selective antibacterial activity against Bacille Calmette-Guérin (BCG), suggestive of a new mechanism of action that could inform the development of next-generation antitubercular drugs.
Organic Letters 09/2012; 14(18):4770-3. · 5.86 Impact Factor
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ABSTRACT: There is growing interest in discovery of novel bioactive natural products from Burkholderia thailandensis. Here we report a significantly improved genome sequence and reannotation of Burkholderia thailandensis MSMB43, which will facilitate the discovery of new natural products through genome mining and studies of the metabolic versatility of this bacterium.
Journal of bacteriology 09/2012; 194(17):4749-50. · 3.94 Impact Factor
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ABSTRACT: The ketoisovalerate reductase (EC 1.2.7.7 ) is required for the formation of beauvericin via the nonribosomal peptide synthetase biosynthetic pathway. It catalyzes the NADPH-specific reduction of ketoisovaleric acid to hydroxyisovalerate. However, little is known about the bioinformatics' data about the 2-Kiv reductase in Fusarium. To date, heterologous production of the gene KivRFp from Fusarium has not been achieved.
The KivRFp gene was subcloned and expressed in Escherichia coli BL21 using the pET expression system. The gene KivRFp contained a 1,359 bp open reading frame (ORF) encoding a polypeptide of 452 amino acids with a molecular mass of 52 kDa. Sequence analysis indicated that it showed 61% and 52% amino acid identities to ketoisovalerate reductase from Beauveria bassiana ATCC 7159 (ACI30654) and Metarhizium acridum CQMa 102 (EFY89891), respectively; and several conserved regions were identified, including the putative nucleotide-binding signature site, GXGXXG, a catalytic triad (Glu405, Asn184, and Lys285). The KivRFp exhibited the highest activity at 35°C and pH 7.5 respectively, by reduction of ketoisovalerate. It also exhibited the high level of stability over wide temperature and pH spectra and in the presence of metal ions or detergents.
A new ketoisovalerate reductase KivRFp was identified and characterized from the depsipeptide-producing fungus F. proliferatum. KivRFp has been shown to have useful properties, such as moderate thermal stability and broad pH optima, and may serve as the starting points for future protein engineering and directed evolution, towards the goal of developing efficient enzyme for downstream biotechnological applications.
BMC Biotechnology 08/2012; 12:55. · 2.35 Impact Factor
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Xueting Liu,
Caixia Chen,
Wenni He,
Pei Huang,
Miaomiao Liu,
Qian Wang,
Hui Guo,
Krishna Bolla,
Yan Lu,
Fuhang Song,
Huanqin Dai, Mei Liu,
Lixin Zhang
[show abstract]
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ABSTRACT: Multidrug-resistant tuberculosis (MDR-TB) and TB-HIV co-infection have become a great threat to global health. However, the last truly novel drug that was approved for the treatment of TB was discovered 40 years ago. The search for new effective drugs against TB has never been more intensive. Natural products derived from microbes and medicinal plants have been an important source of TB therapeutics. Recent advances have been made to accelerate the discovery rate of novel TB drugs including diversifying strategies for environmental strains, high-throughput screening (HTS) assays, and chemical diversity. This review will discuss the challenges of finding novel natural products with anti-TB activity from marine microbes and plant medicines, including biodiversity- and taxonomy-guided microbial natural products library construction, target- and cell-based HTS, and bioassay-directed isolation of anti-TB substances from traditional medicines.
Antonie van Leeuwenhoek 07/2012; 102(3):447-61. · 2.09 Impact Factor
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Li Ma,
Xiangyang Liu,
Haihua Liang,
Yizhou Che,
Caixia Chen,
Huanqin Dai,
Ke Yu, Mei Liu,
Luyan Ma,
Ching-Hong Yang,
Fuhang Song,
Yuqiang Wang,
Lixin Zhang
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ABSTRACT: In Pseudomonas aeruginosa (P. aeruginosa), quorum sensing (QS) system is closely related to the biofilm formation. We previously demonstrated that 14-Alpha-lipoyl andrographolide (AL-1) has synergistic effects on antibiofilm and antivirulence factors (pyocyanin and exopolysaccharide) of P. aeruginosa when combined with conventional antibiotics, while has little inhibitory effect on its growth. However, its molecular mechanism remains elusive. Here we investigated the effect of AL-1 on QS, especially the Las and Rhl system. It showed that AL-1 can inhibit LasR-3-oxo-C(12)-HSL interactions and repress the transcriptional level of QS-regulated genes. RT-PCR data showed that AL-1 significantly reduced the expression of lasR, lasI, rhlR, and rhlI, in a dose-dependent manner. AL-1 not only decreased the expression of Psl which is positively regulated by Las system, but also increased the secretion of ExoS which is negatively regulated by Rhl system, indicating that AL-1 has multiple effects on both Las and Rhl system. It is no wonder that AL-1 showed synergistic effects with other antimicrobial agents in the treatment of P. aeruginosa infections.
Antimicrobial Agents and Chemotherapy 07/2012; · 4.84 Impact Factor
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Fuhang Song,
Biao Ren,
Ke Yu,
Caixia Chen,
Hui Guo,
Na Yang,
Hong Gao,
Xueting Liu, Mei Liu,
Yaojun Tong,
Huanqin Dai,
Hua Bai,
Jidong Wang,
Lixin Zhang
[show abstract]
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ABSTRACT: Three new alkaloids, including auranomides A and B (1 and 2), a new scaffold containing quinazolin-4-one substituted with a pyrrolidin-2-iminium moiety, and auranomide C (3), as well as two known metabolites auranthine (4) and aurantiomides C (5) were isolated from the marine-derived fungus Penicillium aurantiogriseum. The chemical structures of compounds 1-3 were elucidated by extensive spectroscopic methods, including IR, HRESIMS and 2D NMR spectroscopic analysis. The absolute configurations of compounds 1-3 were suggested from the perspective of a plausible biosynthesis pathway. Compounds 1-3 were subjected to antitumor and antimicrobial screening models. Auranomides A-C exhibited moderate cytotoxic activity against human tumor cells. Auranomides B was the most potent among them with an IC(50) value of 0.097 μmol/mL against HEPG2 cells.
Marine Drugs 06/2012; 10(6):1297-306. · 3.85 Impact Factor
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Michele L Coté, Mei Liu,
Stefano Bonassi,
Monica Neri,
Ann G Schwartz,
David C Christiani,
Margaret R Spitz,
Joshua E Muscat,
Gad Rennert,
Katja K Aben, [......],
Donatella Ugolini,
Henricus F M van der Heijden,
Erich Wichmann,
John K Wiencke,
Penella J Woll,
Ping Yang,
David Zaridze,
Zuo-Feng Zhang,
Carol J Etzel,
Rayjean J Hung
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ABSTRACT: Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals.
Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in the risk of lung cancer, after adjustment for smoking and other potential confounders (95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (odds ratios (OR) = 1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR = 1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR = 1.44, 95% CI: 1.07, 1.93), after adjustment.
The occurrence of lung cancer among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those risks associated with cigarette smoking. While the role of genetic variation in the aetiology of lung cancer remains to be fully characterised, family history assessment is immediately available and those with a positive history represent a higher risk group.
European journal of cancer (Oxford, England: 1990) 03/2012; 48(13):1957-68. · 4.12 Impact Factor
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02/2012; , ISBN: 978-953-307-938-7
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Xiangyang Liu,
Biao Ren,
Hong Gao, Mei Liu,
Huanqin Dai,
Fuhang Song,
Zhenyan Yu,
Shujin Wang,
Jiangchun Hu,
Chandrakant R Kokare,
Lixin Zhang
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ABSTRACT: Two of our long term efforts are to discover compounds with synergistic antifungal activity from metabolites of marine derived microbes and to optimize the production of the interesting compounds produced by microorganisms. In this respect, new applications or mechanisms of already known compounds with a high production yield could be continually identified. Surfactin is a well-known lipopeptide biosurfactant with a broad spectrum of antimicrobial and antiviral activity; however, there is less knowledge on surfactin's antifungal activity. In this study, we investigated the synergistic antifungal activity of C(15)-surfactin and the optimization of its production by the response surface method.
Using a synergistic antifungal screening model, we found that the combination of C(15)-surfactin and ketoconazole (KTC) showed synergistic antifungal effect on Candida albicans SC5314 when the concentrations of C(15)-surfactin and KTC were 6.25 µg/mL and 0.004 µg/mL, respectively. These concentrations were lower than their own efficient antifungal concentrations, which are >100 µg/mL and 0.016 µg/mL, respectively. The production of C(15)-surfactin from Bacillus amyloliquefaciens was optimized by the response surface methodology in shaker flask cultivation. The Plackett-Burman design found sucrose, ammonium nitrate and NaH(2)PO(4) x 2H(2)O to have significant effects on C(15)-surfactin production. The optimum values of the tested variables were 21.17 g/L sucrose, 2.50 g/L ammonium nitrate and 11.56 g/L NaH(2)PO(4)·2H(2)O. A production of 134.2 mg/L, which were in agreement with the prediction, was observed in a verification experiment. In comparison to the production of original level (88.6 mg/L), a 1.52-fold increase had been obtained.
This work first found that C(15)-surfactin was an efficient synergistic antifungal agent, and demonstrated that response surface methodology was an effective method to improve the production of C(15)-surfactin.
PLoS ONE 01/2012; 7(5):e34430. · 4.09 Impact Factor
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Qian Wang,
Fuhang Song,
Xue Xiao,
Pei Huang,
Li Li,
Aaron Monte,
Wael M. Abdel-Mageed,
Jian Wang,
Hui Guo,
Wenni He,
Feng Xie,
Huanqin Dai,
Miaomiao Liu,
Caixia Chen,
Hao Xu, Mei Liu,
Andrew M. Piggott,
Xueting Liu,
Robert J. Capon,
and Lixin Zhang
Angewandte Chemie 01/2012; 124.
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ABSTRACT: Diamagnetic levitation is a technique that uses a strong, spatially varying magnetic field to simulate an altered gravity environment, as in space. In this study, using Streptomyces avermitilis as the test organism, we investigate whether changes in magnetic field and altered gravity induce changes in morphology and secondary metabolism. We find that a strong magnetic field (12T) inhibit the morphological development of S. avermitilis in solid culture, and increase the production of secondary metabolites.
S. avermitilis on solid medium was levitated at 0 g*, 1 g* and 2 g* in an altered gravity environment simulated by diamagnetic levitation and under a strong magnetic field, denoted by the asterix. The morphology was obtained by electromicroscopy. The production of the secondary metabolite, avermectin, was determined by OD(245 nm). The results showed that diamagnetic levitation could induce a physiological response in S. avermitilis. The difference between 1 g* and the control group grown without the strong magnetic field (1 g), showed that the magnetic field was a more dominant factor influencing changes in morphology and secondary metabolite production, than altered gravity.
We have discovered that magnetic field, rather than altered gravity, is the dominant factor in altered gravity simulated by diamagnetic levitation, therefore care should to be taken in the interpretation of results when using diamagnetic levitation as a technique to simulate altered gravity. Hence, these results are significant, and timely to researchers considering the use of diamagnetic levitation to explore effects of weightlessness on living organisms and on physical phenomena.
PLoS ONE 01/2011; 6(10):e24697. · 4.09 Impact Factor
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ABSTRACT: Marine microorganisms are fascinating resources due to their production of novel natural products with antimicrobial activities. Increases in both the number of new chemical entities found and the substantiation of indigenous marine actinobacteria present a fundamental difficulty in the future discovery of novel antimicrobials, namely dereplication of those compounds already discovered. This review will share our experience on the taxonomic-based construction of a highly diversified and low redundant marine microbial natural product library for high-throughput antibiotic screening. We anticipate that libraries such as these can drive the drug discovery process now and in the future.
The Journal of Antibiotics 08/2010; 63(8):415-22. · 1.65 Impact Factor
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Xiangyang Liu,
Biao Ren,
Ming Chen,
Haibin Wang,
Chandrakant R Kokare,
Xianlong Zhou,
Jidong Wang,
Huanqin Dai,
Fuhang Song, Mei Liu,
Jian Wang,
Shujin Wang,
Lixin Zhang
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ABSTRACT: Marine microbes are a rich source of bioactive compounds, such as drugs, enzymes, and biosurfactants. To explore the bioactive compounds from our marine natural product library, an oil emulsification assay was applied to discover biosurfactants and bioemulsifiers. A spore-forming bacterial strain from sea mud was found to produce bioemulsifiers with good biosurfactant activity and a broad spectrum of antimicrobial properties. It was identified as Bacillus velezensis H3 using genomic and phenotypic data analysis. This strain was able to produce biosurfactants with an optimum emulsification activity at pH 6.0 and 2% NaCl by using starch as the carbon source and ammonium sulfate as the nitrogen source. The emulsification-guided isolation and purification procedure led to the discovery of the biosurfactant components, which were mainly composed of nC(14)-surfactin and anteisoC(15)-surfactin as determined by NMR and MS spectra. These compounds can reduce the surface tension of phosphate-buffered saline (PBS) from 71.8 to 24.8 mN/m. The critical micelle concentrations (CMCs) of C(14)-surfactin and C(15)-surfactin in 0.1 M PBS (pH 8.0) were determined to be 3.06 x 10(-5) and 2.03 x 10(-5) mol/L, respectively. The surface tension values at CMCs for C(14)-surfactin and C(15)-surfactin were 25.7 and 27.0 mM/m, respectively. In addition, the H3 biosurfactant exhibited antimicrobial activities against Staphyloccocus aureus, Mycobacterium, Klebsiella peneumoniae, Pseudomonas aeruginosa, and Candida albicans. Thus B. velezensis H3 is an alternative surfactin producer with potential application as an industrial strain for the lipopeptide production.
Applied Microbiology and Biotechnology 08/2010; 87(5):1881-93. · 3.42 Impact Factor
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ABSTRACT: Microbes represent a valuable source of commercially significant natural products that have improved our quality of life. Precision engineering can be used to precisely identify and specifically modify genes responsible for production of natural products and improve this production or modify the genes creating products that would not otherwise be produced. There have been several success stories concerning the manipulation of regulatory genes, pathways, and genomes to increase the productivity of industrial microbes. This review will focus on the strategies and integrated approaches for precisely deciphering regulatory genes by various modern techniques. The applications of precision engineering in rational strain improvement also shed light on the biology of natural microbial systems.
Antonie van Leeuwenhoek 08/2010; 98(2):151-63. · 2.09 Impact Factor
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ABSTRACT: Mutant libraries of avermectin-producing Streptomyces avermitilis strains were constructed by different mutagenesis strategies. A metric was applied to assess the mutation spectrum by calculating the distribution of average phenotypic distance of each population. The results showed for the first time that a microgravity environment could introduce larger phenotype distribution and diversity than UV and N-methyl-N-nitro-N-nitrosoguanidine (NTG) could.
Applied and environmental microbiology 07/2010; 76(13):4583-6. · 3.69 Impact Factor
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Ying Zhuo,
Wenquan Zhang,
Difei Chen,
Hong Gao,
Jun Tao, Mei Liu,
Zhongxuan Gou,
Xianlong Zhou,
Bang-Ce Ye,
Qing Zhang,
Siliang Zhang,
Li-Xin Zhang
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ABSTRACT: Avermectin and its analogues are produced by the actinomycete Streptomyces avermitilis and are widely used in the field of animal health, agriculture, and human health. Here we have adopted a practical approach to successfully improve avermectin production in an industrial overproducer. Transcriptional levels of the wild-type strain and industrial overproducer in production cultures were monitored using microarray analysis. The avermectin biosynthetic genes, especially the pathway-specific regulatory gene, aveR, were up-regulated in the high-producing strain. The upstream promoter region of aveR was predicted and proved to be directly recognized by sigma(hrdB) in vitro. A mutant library of hrdB gene was constructed by error-prone PCR and selected by high-throughput screening. As a result of evolved hrdB expressed in the modified avermectin high-producing strain, 6.38 g/L of avermectin B1a was produced with over 50% yield improvement, in which the transcription level of aveR was significantly increased. The relevant residues were identified to center in the conserved regions. Engineering of the hrdB gene can not only elicit the overexpression of aveR but also allows for simultaneous transcription of many other genes. The results indicate that manipulating the key genes revealed by reverse engineering can effectively improve the yield of the target metabolites, providing a route to optimize production in these complex regulatory systems.
Proceedings of the National Academy of Sciences 06/2010; 107(25):11250-4. · 9.68 Impact Factor
