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Tzeming Chan - One of the best experts on this subject based on the ideXlab platform.
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sch 213766 a novel chemokine receptor ccr 5 inhibitor from chaetomium globosum
The Journal of Antibiotics, 2007Co-Authors: Shuwei Yang, Joseph Terracciano, Vincent P Gullo, Bahige M Baroudy, Ronald Mierzwa, Mohindar S. Puar, Mahesh Patel, Nicole Wagner, Tzeming ChanAbstract:A novel Fungal secondary metabolite, Sch 213766 was isolated from the Fungal Fermentation broth of Chaetomium globosum as the chemokine receptor CCR-5 inhibitor and shown to be the methyl ester of the previously described tetramic acid Sch 210972 on the basis of UV, MS and NMR spectral data analyses. Sch213766 exhibited an IC 50 value of 8.6 mM in the CCR-5 receptor in vitro binding assay. individuals called highly active antiretroviral therapy or HAART consists of three approved antiretroviral drugs, typically two reverse transcriptase inhibitors and one protease inhibitor to suppress HIV infection and reduce morbidity and mortality. Although HAART has proven effective to reduce viral load in patients with continuous dosing for over three years, this drug combination approach has not yet illustrated the capability of complete viral elimination from an infected individual. In addition, long- term toxicity and adverse drug-drug interactions of commercially available anti-HIV drugs are major concerns in medical treatments (2). Furthermore, the emergence of viral resistance to protease and reverse transcriptase inhibitors has been reported due to the increasing use of antiretroviral agents (3). Therefore, searching for effective anti HIV-1 infection agents with new mechanisms of action has become an urgent need. Recent studies indicated that binding to specific, cell surface co-receptors is an essential process before HIV-1 enters the targeted cells of the immune system. The chemokine receptor CCR-5 on macrophages, monocytes and T-cells, which belongs to the super family of seven-trans-membrane G-protein coupled receptors (GPCRs), has been identified as the surface co-receptor with the CD 4 molecule for viral entry (4). The endogenous ligands of the CCR-5 receptor are the
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chemokine receptor ccr 5 inhibitors produced by chaetomium globosum
Journal of Natural Products, 2006Co-Authors: Shuwei Yang, Joseph Terracciano, Vincent P Gullo, Bahige M Baroudy, Tzeming Chan, Ronald Mierzwa, Mohindar S. Puar, Mahesh Patel, Nicole Wagner, And Andrew T. McphailAbstract:Two novel chemokine receptor CCR-5 inhibitors, Sch 210971 (1) and Sch 210972 (2), were isolated from the Fungal Fermentation broth of Chaetomium globosum by normal- and reversed-phase HPLC purifications. The structure determination of 1 and 2 was accomplished on the basis of UV, MS, and NMR spectral data analyses including COSY, NOESY, HMQC, and HMBC experiments. The structure and relative configuration of 2 were determined unequivocally by X-ray crystallographic analysis. The major component 2 demonstrated a potent inhibitory activity of IC50 = 79 nM in the CCR-5 receptor in vitro binding assay.
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two novel diketopiperazines isolated from the fungus tolypocladium sp
Tetrahedron Letters, 1993Co-Authors: Min Chu, Vincent P Gullo, Tzeming Chan, Ronald Mierzwa, Mahesh Patel, Imbi Truumees, Frank Gentile, Mohindar S. PuarAbstract:Abstract Diketopiperazines, Sch 54794 and Sch 54796, have been isolated from a Fungal Fermentation. The structures of these compounds have been established based on spectroscopic data analysis. Sch 54794 exhibited inhibitory activity in the platelet activating factor (PAF) assay.
Colin Webb - One of the best experts on this subject based on the ideXlab platform.
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improving wheat flour hydrolysis by an enzyme mixture from solid state Fungal Fermentation
Enzyme and Microbial Technology, 2009Co-Authors: Ruohang Wang, Apostolis A Koutinas, Shalyda Md Shaarani, Leticia Casas Godoy, Mehmet Melikoglu, Colin WebbAbstract:In traditional cereal-based industrial processes, component separation is often incomplete resulting in a residue of mixed macromolecules including largely starch, protein, phytic acid and many others. The development of a viable cereal-based biorefinery would involve effective bioconversion of cereal components for the production of a nutrient-complete Fermentation feedstock. Simultaneous starch and protein hydrolysis represents an effective approach to the production of platform chemicals from wheat. Solid state Fermentations of wheat pieces and waste bread by Aspergillus oryzae and Aspergillus awamori have been combined in this study to enhance starch and protein hydrolysis. Kinetic studies confirmed that the proteolytic enzymes from A. oryzae introduced no negative effect on the stability of the amylolytic enzymes from A. awamori under the optimal conditions for starch hydrolysis. When applied to hydrolyse wheat flour, the enzyme solution from A. awamori converted nearly all of the starch into glucose and 23% of the total nitrogen (TN) into free amino nitrogen (FAN). Under the same reaction conditions the enzyme solution from A. oryzae hydrolysed 38% of the protein but only 18.5% of the starch. A mixture of the two enzyme solutions hydrolysed 34.1% of the protein, a 1.5-fold increase from that achieved by the enzyme solution from A. awamori, while maintaining a near completion of starch hydrolysis.
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succinic acid production from wheat using a biorefining strategy
Applied Microbiology and Biotechnology, 2007Co-Authors: Sze Ki Carol Lin, Apostolis A Koutinas, Ruohang Wang, Colin WebbAbstract:The biosynthesis of succinic acid from wheat flour was investigated in a two-stage bio-process. In the first stage, wheat flour was converted into a generic microbial feedstock either by Fungal Fermentation alone or by combining Fungal Fermentation for enzyme and Fungal bio-mass production with subsequent flour hydrolysis and Fungal autolysis. In the second stage, the generic feedstock was converted into succinic acid by bacterial Fermentation by Actinobacillus succinogenes. Direct Fermentation of the generic feedstock produced by Fungal Fermentation alone resulted in a lower succinic acid production, probably due to the low glucose and nitrogen concentrations in the Fungal broth filtrate. In the second feedstock production strategy, flour hydrolysis conducted by mixing Fungal broth filtrate with wheat flour generated a glucose-rich stream, while the Fungal bio-mass was subjected to autolysis for the production of a nutrient-rich stream. The possibility of replacing a commercial semi-defined medium by these two streams was investigated sequentially. A. succinogenes Fermentation using only the wheat-derived feedstock resulted in a succinic acid concentration of almost 16 g l–1 with an overall yield of 0.19 g succinic acid per g wheat flour. These results show that a wheat-based bio-refinery employing coupled Fungal Fermentation and subsequent flour hydrolysis and Fungal autolysis can lead to a bacterial feedstock for the efficient production of succinic acid.
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development of an oat based biorefinery for the production of l lactic acid by rhizopus oryzae and various value added coproducts
Journal of Agricultural and Food Chemistry, 2007Co-Authors: Apostolis A Koutinas, Ruohang Wang, Fabien Malbranque, Grant M Campbell, Colin WebbAbstract:A novel oat-based biorefinery producing l(+)-lactic acid and various value-added coproducts (e.g., β-glucan, anti-irritant solution) is proposed. Pearling is employed for sequential separation of bran-rich fractions for the extraction of value-added coproducts. Lactic acid production is achieved via Fungal Fermentation of Rhizopus oryzae on pearled oat flour. Maximum lactic acid concentration (51.7 g/L) and starch conversion yield (0.68 g/g) were achieved when an oat flour concentration of 116.5 g/L was used. Oxygen transfer played a significant role with respect to lactic acid production and starch conversion yield. Rhizopus oryzae produced a range of enzymes (glucoamylase, protease, phosphatase) for the hydrolysis of cereal flour macromolecules. Enzyme production during Fungal Fermentation has been reported. The proposed biorefining strategy could lead to significant operating cost reduction as compared to current industrial practices for lactic acid production from pure glucose achieved by bacterial Fermentations.
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Platform chemical production from wheat-based biorefining strategy
Journal of Biotechnology, 2007Co-Authors: Sze Ki Carol Lin, James H. Clark, Colin WebbAbstract:Development of biorefineries has attracted increasing attention around the world in the past decade. It focuses on alleviating pressure on fossil resources and the environmental burden of current fossil based processes, as well as facilitating sustainable development of the chemical industry. Many chemicals that used to be produced via chemical processes can now potentially be generated biologically from renewable raw materials. At the Satake Centre for Grain Process Engineering, a novel cost-competitive wheat-based biorefining strategy leading to the production of generic microbial feedstocks has been successfully developed (Webb and Wang, 1997 and Webb et al., 2004). These feedstocks are now being evaluated for the production of platform chemicals, biodegradable polymers and biofuels by bacterial Fermentation. In the study reported here, succinic acid has been used as a model product for this biorefining strategy to convert wheat flour into fine chemicals. Another advantage of bio-synthesis of succinic acid is the fixation of CO2, which can help towards tackling the global warming challenge. Wheat is one of the predominant renewable resources in Europe. We aim to exploit all components of the wheat grain, producing both value-added end-products and precursors for chemical synthesis. In our process, whole wheat flour firstly undergoes Fungal Fermentation by Aspergillus awamori. The broth filtrate that is rich in glucoamylase is then used to hydrolyse flour components to generate a glucose-rich stream (flour hydrolysate) while the solid residue is used for Fungal autolysis to produce a nutrient-rich stream (Fungal autolysate). The possibility of replacing a commercial semi-defined medium by a combination of flour hydrolysate and Fungal autolysate was investigated sequentially. Batch Fermentations were performed using a complex medium containing wheat flour hydrolysate instead of commercial glucose. This resulted in a similar yield (0.64 g succinic acid per g glucose) and final succinic acid concentration (27 g/L) compared to Fermentations with a semi-defined medium. The use of Fungal autolysate instead of yeast extract as nitrogen source led to a succinic acid production of 23.2 g/L with a yield of 0.54 g/g. Even Fermentations using the wheat-derived flour hydrolysate and Fungal autolysate alone resulted in a succinic acid concentration of almost 16 g/L and an overall yield of 0.19 g succinic acid per g wheat flour. When Fermentations were carried out with wheat-derived feedstock and an addition of 50 g/L MgCO3, 36.9 g/L succinic acid was produced from 50 g/L initial glucose with a productivity of 1.54 g/L h. The results of these studies demonstrate that a wheat-based biorefinery employing coupled Fungal Fermentation with subsequent flour hydrolysis and Fungal autolysis can produce a suitable feedstock for efficient production of succinic acid.
Mohindar S. Puar - One of the best experts on this subject based on the ideXlab platform.
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sch 213766 a novel chemokine receptor ccr 5 inhibitor from chaetomium globosum
The Journal of Antibiotics, 2007Co-Authors: Shuwei Yang, Joseph Terracciano, Vincent P Gullo, Bahige M Baroudy, Ronald Mierzwa, Mohindar S. Puar, Mahesh Patel, Nicole Wagner, Tzeming ChanAbstract:A novel Fungal secondary metabolite, Sch 213766 was isolated from the Fungal Fermentation broth of Chaetomium globosum as the chemokine receptor CCR-5 inhibitor and shown to be the methyl ester of the previously described tetramic acid Sch 210972 on the basis of UV, MS and NMR spectral data analyses. Sch213766 exhibited an IC 50 value of 8.6 mM in the CCR-5 receptor in vitro binding assay. individuals called highly active antiretroviral therapy or HAART consists of three approved antiretroviral drugs, typically two reverse transcriptase inhibitors and one protease inhibitor to suppress HIV infection and reduce morbidity and mortality. Although HAART has proven effective to reduce viral load in patients with continuous dosing for over three years, this drug combination approach has not yet illustrated the capability of complete viral elimination from an infected individual. In addition, long- term toxicity and adverse drug-drug interactions of commercially available anti-HIV drugs are major concerns in medical treatments (2). Furthermore, the emergence of viral resistance to protease and reverse transcriptase inhibitors has been reported due to the increasing use of antiretroviral agents (3). Therefore, searching for effective anti HIV-1 infection agents with new mechanisms of action has become an urgent need. Recent studies indicated that binding to specific, cell surface co-receptors is an essential process before HIV-1 enters the targeted cells of the immune system. The chemokine receptor CCR-5 on macrophages, monocytes and T-cells, which belongs to the super family of seven-trans-membrane G-protein coupled receptors (GPCRs), has been identified as the surface co-receptor with the CD 4 molecule for viral entry (4). The endogenous ligands of the CCR-5 receptor are the
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chemokine receptor ccr 5 inhibitors produced by chaetomium globosum
Journal of Natural Products, 2006Co-Authors: Shuwei Yang, Joseph Terracciano, Vincent P Gullo, Bahige M Baroudy, Tzeming Chan, Ronald Mierzwa, Mohindar S. Puar, Mahesh Patel, Nicole Wagner, And Andrew T. McphailAbstract:Two novel chemokine receptor CCR-5 inhibitors, Sch 210971 (1) and Sch 210972 (2), were isolated from the Fungal Fermentation broth of Chaetomium globosum by normal- and reversed-phase HPLC purifications. The structure determination of 1 and 2 was accomplished on the basis of UV, MS, and NMR spectral data analyses including COSY, NOESY, HMQC, and HMBC experiments. The structure and relative configuration of 2 were determined unequivocally by X-ray crystallographic analysis. The major component 2 demonstrated a potent inhibitory activity of IC50 = 79 nM in the CCR-5 receptor in vitro binding assay.
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two novel diketopiperazines isolated from the fungus tolypocladium sp
Tetrahedron Letters, 1993Co-Authors: Min Chu, Vincent P Gullo, Tzeming Chan, Ronald Mierzwa, Mahesh Patel, Imbi Truumees, Frank Gentile, Mohindar S. PuarAbstract:Abstract Diketopiperazines, Sch 54794 and Sch 54796, have been isolated from a Fungal Fermentation. The structures of these compounds have been established based on spectroscopic data analysis. Sch 54794 exhibited inhibitory activity in the platelet activating factor (PAF) assay.
Beizhong Han - One of the best experts on this subject based on the ideXlab platform.
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behaviour of staphylococcus aureus during sufu production at laboratory scale
Food Control, 2005Co-Authors: Beizhong Han, Barbara Sesenna, R R Beumer, M Robert J NoutAbstract:Abstract Sufu is a Chinese soybean cheese, obtained by Fungal Fermentation of soybean curd (tofu) with Actinomucor elegans to yield pehtze, followed by enzymatic maturation in brine solution containing 12–16% (w/w) of NaCl for 2–6 months. After equilibration, the final product, sufu, usually contains half of the NaCl concentration of the brine used. We studied the behaviour (survival, growth, formation of enterotoxins) of several strains of Staphylococcus aureus in a laboratory-scale simulation of the production of sufu. Of 15 S. aureus strains tested, strains No. 1, 3, 4, 5, 8, 9, and 10 showed good growth in sterile Brain Heart Infusion broth with high (6–12% w/w) NaCl concentration, demonstrating their halotolerance. S. aureus growth was not negatively influenced by A. elegans, and no interaction between the mould and the bacterial strains was observed during pehtze preparation. S. aureus strains No. 3 and 5 were selected for maturation experiments because they grew up to 8.9–9.5 log cfu/g and they produced their typical enterotoxin in all substrates tested. With the objective of creating a worst-case scenario, halotolerant enterotoxin producing S. aureus strains were inoculated at several stages of the sufu model system. Levels of 6% and 12% of NaCl in the brine solution were still too low to inhibit their growth and enterotoxin production. Even 18% of NaCl in the brine solution could not inhibit their growth, but enterotoxin production was prevented. Brine solution with 24% of NaCl inhibited growth as well as enterotoxin production. In conclusion, a salt concentration of 9% in the final product will be a minimum safeguard against S. aureus enterotoxin formation.
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microbial changes during the production of sufu a chinese fermented soybean food
Food Control, 2004Co-Authors: Beizhong Han, F M Rombouts, Cuifeng Cao, M Robert J NoutAbstract:Abstract Sufu is a Chinese soybean cheese obtained by solid-state Fungal Fermentation of tofu followed by ripening in dressing mixture. The aim of this study was to quantify microflora changes during the sufu process, which is carried out under non-sterile conditions. From tofu to pehtze (tofu overgrown with fungus) stages, total counts of mesophilic aerobic bacteria (TMAB), bacterial endospores (spores), Bacillus cereus, lactic acid bacteria (LAB), Enterobacteriaceae and fungi increased. All of them decreased after the salting of pehtze. TMAB and spores in sufu with 8% and 11% salt content decreased to around 106 cfu/g during the ripening. B. cereus remained at around 103 cfu/g. LAB in sufu with 8% and 11% salt content decreased gradually to
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effect of nacl on textural changes and protein and lipid degradation during the ripening stage of sufu a chinese fermented soybean food
Journal of the Science of Food and Agriculture, 2003Co-Authors: Beizhong Han, Jiahuai Wang, F M Rombouts, M Robert J NoutAbstract:Sufu is made by solid state Fungal Fermentation (using Actinomucor elegans) of tofu, followed by salting and maturation in dressing mixtures containing salt, alcohol and various other ingredients. NaCl in dressing mixtures strongly affected the changes in textural properties and the hydrolysis of protein and lipid of sufu. Higher salt contents (14% w/w) resulted in increased hardness (+100%) and elasticity (+18%) and reduced adhesiveness (-30%). Hardness and elasticity could be used to judge the extent of sufu ripening. SDS-PAGE showed the disappearance of all protein subunits at 80 and 110 g kg(-1) salt content; however, some protein subunits were still detectable at 140 g kg(-1) salt content after 60 days of ripening. Higher ratios of free amino nitrogen to total nitrogen (FAN/TN = 0.4-0.45) and free amino acids to crude protein (FAA/CP = 0.24-0.26) were observed in sufu with lower (80 g kg(-1)) salt content. FAN/TN and FAA/CP in white sufu (obtained with dressing mixtures containing only salt and alcohol) were higher than those in red sufu (obtained with dressing mixtures containing angkak or kojic red rice) owing to different dressing mixture compositions. Increases in free fatty acids (FFA) were also observed during ripening. FFA levels in sufu with lower salt content increased rapidly during the first 30-40 days and then increased slowly, probably resulting from the formation of fatty acid esters. Lowering the salt content (80 g kg(-1)) can shorten the ripening time to 40 days, which is of benefit to manufacturers. However, sufu will spoil, ie undergo souring, during the ripening stage at salt contents of SO g kg(-1) or lower. (C) 2003 Society of Chemical Industry.
And Andrew T. Mcphail - One of the best experts on this subject based on the ideXlab platform.
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chemokine receptor ccr 5 inhibitors produced by chaetomium globosum
Journal of Natural Products, 2006Co-Authors: Shuwei Yang, Joseph Terracciano, Vincent P Gullo, Bahige M Baroudy, Tzeming Chan, Ronald Mierzwa, Mohindar S. Puar, Mahesh Patel, Nicole Wagner, And Andrew T. McphailAbstract:Two novel chemokine receptor CCR-5 inhibitors, Sch 210971 (1) and Sch 210972 (2), were isolated from the Fungal Fermentation broth of Chaetomium globosum by normal- and reversed-phase HPLC purifications. The structure determination of 1 and 2 was accomplished on the basis of UV, MS, and NMR spectral data analyses including COSY, NOESY, HMQC, and HMBC experiments. The structure and relative configuration of 2 were determined unequivocally by X-ray crystallographic analysis. The major component 2 demonstrated a potent inhibitory activity of IC50 = 79 nM in the CCR-5 receptor in vitro binding assay.
