Institute of Food Chemistry

Hamburg, Germany

Institute of Food Chemistry

Hamburg, Germany
Time filter
Source Type

Masini T.,University of Groningen | Lacy B.,Southern Illinois University at Edwardsville | Monjas L.,University of Groningen | Hawksley D.,University of Cambridge | And 7 more authors.
Organic and Biomolecular Chemistry | Year: 2015

The enzyme DXS catalyzes the first, rate-limiting step of the 2-C-methyl-d-erythritol-4-phosphate (MEP, 1) pathway using thiamine diphosphate (ThDP) as cofactor; the DXS-catalyzed reaction constitutes also the first step in vitamin B1 and B6 metabolism in bacteria. DXS is the least studied among the enzymes of this pathway in terms of crystallographic information, with only one complete crystal structure deposited in the Protein Data Bank (Deinococcus radiodurans DXS, PDB: 2O1X). We synthesized a series of thiamine and ThDP derivatives and tested them for their biochemical activity against two DXS orthologues, namely D. radiodurans DXS and Mycobacterium tuberculosis DXS. These experimental results, combined with advanced docking studies, led to the development and validation of a homology model of M. tuberculosis DXS, which, in turn, will guide medicinal chemists in rationally designing potential inhibitors for M. tuberculosis DXS. © The Royal Society of Chemistry.

Rosler S.M.,Westfalische Wilhelms University MunsterCorrensstrasse 45Munster48149 Germany | Kramer K.,Max Planck Institute for Plant Breeding Research | Finkemeier I.,Max Planck Institute for Plant Breeding Research | Humpf H.-U.,Institute of Food Chemistry | Tudzynski B.,Institute of Plant Biology and Biotechnology
Molecular Microbiology | Year: 2016

Post-translational modification of histones is a crucial mode of transcriptional regulation in eukaryotes. A well-described acetylation modifier of certain lysine residues is the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex assembled around the histone acetyltransferase Gcn5 in Saccharomyces cerevisiae. We identified and characterized the SAGA complex in the rice pathogen Fusarium fujikuroi, well-known for producing a large variety of secondary metabolites (SMs). By using a co-immunoprecipitation approach, almost all of the S. cerevisiae SAGA complex components have been identified, except for the ubiquitinating DUBm module and the chromodomain containing Chd1. Deletion of GCN5 led to impaired growth, loss of conidiation and alteration of SM biosynthesis. Furthermore, we show that Gcn5 is essential for the acetylation of several histone 3 lysines in F. fujikuroi, that is, H3K4, H3K9, H3K18 and H3K27. A genome-wide microarray analysis revealed differential expression of about 30% of the genome with an enrichment of genes involved in primary and secondary metabolism, transport and histone modification. HPLC-based analysis of known SMs revealed significant alterations in the Δgcn5 mutant. While most SM genes were activated by Gcn5 activity, the biosynthesis of the pigment bikaverin was strongly increased upon GCN5 deletion underlining the diverse roles of the SAGA complex in F. fujikuroi. © 2016 John Wiley & Sons Ltd.

Unterberg M.,University of Potsdam | Hubner F.,Institute of Food Chemistry | Humpf H.-U.,Institute of Food Chemistry | Lepikhov K.,Saarland University | And 3 more authors.
Toxicology Research | Year: 2014

This study aims to further mechanistically understand toxic modes of action after chronic inorganic arsenic exposure. Therefore long-term incubation studies in cultured cells were carried out, to display chronically attained changes, which cannot be observed in the generally applied in vitro short-term incubation studies. Particularly, the cytotoxic, genotoxic and epigenetic effects of an up to 21 days incubation of human urothelial (UROtsa) cells with pico- to nanomolar concentrations of iAsIII and its metabolite thio-DMAV were compared. After 21 days of incubation, cytotoxic effects were strongly enhanced in the case of iAsIII and might partly be due to glutathione depletion and genotoxic effects on the chromosomal level. These results are in strong contrast to cells exposed to thio-DMAV. Thus, cells seemed to be able to adapt to this arsenical, as indicated among others by an increase in the cellular glutathione level. Most interestingly, picomolar concentrations of both iAsIII and thio-DMAV caused global DNA hypomethylation in UROtsa cells, which was quantified in parallel by 5-medC immunostaining and a newly established, reliable, high resolution mass spectrometry (HRMS)-based test system. This is the first time that epigenetic effects are reported for thio-DMAV; iAsIII induced epigenetic effects occur in at least 8000 fold lower concentrations as reported in vitro before. The fact that both arsenicals cause DNA hypomethylation at really low, exposure-relevant concentrations in human urothelial cells suggests that this epigenetic effect might contribute to inorganic arsenic induced carcinogenicity, which for sure has to be further investigated in future studies. © The Royal Society of Chemistry 2014.

Masini T.,University of Groningen | Pilger J.,Max Planck Institute for Biophysical Chemistry | Kroezen B.S.,University of Groningen | Illarionov B.,Institute of Food Chemistry | And 4 more authors.
Chemical Science | Year: 2014

We applied for the first time an innovative ligand-based NMR methodology (STI) to a medicinal-chemistry project aimed at the development of inhibitors for the enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXS). DXS is the first enzyme of the 2C-methyl-d-erythritol-4-phosphate (MEP) pathway, present in most bacteria (and not in humans) and responsible for the synthesis of the essential isoprenoid precursors. We designed de novo a first generation of fragments, using Deinococcus radiodurans DXS as a model enzyme, targeting the thiamine diphosphate (TDP) pocket of DXS whilst also exploring the putative substrate-binding pocket, where selectivity over other human TDP-dependent enzymes could be gained. The STI methodology-suitable for weak binders-was essential to determine the binding mode in solution of one of the fragments, circumventing the requirement for an X-ray co-crystal structure, which is known to be particularly challenging for this specific enzyme and in general for weak binders. Based on this finding, we carried out fragment growing and optimisation, which led to a three-fold more potent fragment, about as potent as the well-established thiamine analogue deazathiamine. The STI methodology proved therefore its strong potential as a tool to support medicinal-chemistry projects in their early stages, especially when dealing with weak binders. © 2014 the Partner Organisations.

Ivana S.,University of Bucharest | Ivana S.,Asclepius 2008 Research and Development Center | Tuluca E.,Institute of Food Chemistry | Dinu C.P.,Carol Davila University of Medicine and Pharmacy | Dinu C.P.,Scientific Research Center for Defense and Ecology
Cellulose Chemistry and Technology | Year: 2013

The paper presents the results concerning the modifications in the sugar composition resulted from lignocellulosic substrates subjected to the action of lignolytic fungi: Pleurotus ostreatus and Phanerochaete chrysosporium. The substrates used were formed by various mixtures of corn cobs and oak tree leaves, oak tree sawdust and oak tree leaves, and oak tree bark - oak tree leaves, all in ratios of 2:1 (marked as mixtures I, II and III). The evaluation of the sugar composition of the substrates biodegraded by the above-mentioned fungi, for 30 days, was performed after hydrolysis, using IN sulfuric acid at 120 °C, for one hour, followed by sodium carbonate treatment until a pH of 5.8 was reached. The quantitative determinations were performed through gas chromatography. The gathered data showed that the highest degree of the heteropolysaccharide degradation corresponded to Pleurotus ostreatus, while the fungus Phanerochaete chrysosporium cultivated under the same conditions degraded carbohydrates at a lower level. Also, a large consumption of pentoses was recorded, evaluated through the variation of the xylose amounts, which rapidly decreased in case of the Pleurotus ostreatus microorganism, in comparison with the substrate inoculated by Phanerochaete chrysosporium. Similarly, the hexoses consumption levels (mainly of glucose) were quite modest in the case of Pleurotus ostreatus and quite significant for Phanerochaete chrysosporium.

Weiss A.,Institute of Food Chemistry | Kortemeier D.,Institute of Food Chemistry | Brockmeyer J.,Institute of Food Chemistry
Toxins | Year: 2014

The activity of serine proteases is influenced by their substrate specificity as well as by the physicochemical conditions. Here, we present the characterization of key biochemical features of the two SPATE members EspPα and EspI from Shiga-toxin producing Escherichia coli (STEC) and enterohemorrhagic E. coli (EHEC). Both proteases show high activity at conditions mimicking the human blood stream. Optimal activities were observed at slightly alkaline pH and low millimolar concentrations of the divalent cations Ca2+ and Mg2+ at physiological temperatures indicating a function in the human host. Furthermore, we provide the first cleavage profile for EspI demonstrating pronounced specificity of this protease.

Weiss A.,Institute of Food Chemistry | Brockmeyer J.,Institute of Food Chemistry
Toxins | Year: 2013

Enterohemorrhagic E. coli (EHEC) causes severe diseases in humans worldwide. One of its virulence factors is EspP, which belongs to the serine protease autotransporters of Enterobacteriaceae (SPATE) family. In this review we recapitulate the current data on prevalence, biogenesis, structural properties and functionality. EspP has been used to investigate mechanistic details of autotransport, and recent studies indicate that this transport mechanism is not autonomous but rather dependent on additional factors. Currently, five subtypes have been identified (EspPα-EspPε), with EspPα being associated with highly virulent EHEC serotypes and isolates from patients with severe disease. EspPα has been shown to degrade major proteins of the complement cascade, namely C3 and C5 and probably interferes with hemostasis by cleavage of coagulation factor V. Furthermore, EspPα is believed to contribute to biofilm formation perhaps by polymerization to rope-like structures. Together with the proteolytic activity, EspPα might ameliorate host colonization and interfere with host response. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Grawert T.,Institute of Food Chemistry | Hohmann H.-P.,DSM Nutritional Products Inc. | Kindermann M.,DSM Nutritional Products Inc. | Duval S.,DSM Nutritional Products Inc. | And 2 more authors.
Journal of Agricultural and Food Chemistry | Year: 2014

Cattle husbandry is a major contributor to atmospheric methane, which is considered as an important greenhouse gas. Moreover, the generation of methane in the intestine of domestic ruminants by methanogenic bacteria is a drag on feed efficacy. Studies on methanogenesis have typically implied model organisms that are, however, not relevant in the ruminant gut. This paper shows that methyl-CoM reductase catalyzing the final step of methanogenesis in Methanobrevibacter ruminantium, a major participant in methane production by cattle, is inhibited by 2-bromoethanesulfonate, a compound often used as a model in animal agriculture, with an apparent IC50 of 0.4 ± 0.04 μM. © 2014 American Chemical Society.

Trox J.,Institute for Biological Chemistry and Nutrition | Vadivel V.,Institute for Biological Chemistry and Nutrition | Vetter W.,Institute of Food Chemistry | Stuetz W.,Institute for Biological Chemistry and Nutrition | And 4 more authors.
Journal of Agricultural and Food Chemistry | Year: 2010

In the present study, the effects of various conventional shelling methods (oil-bath roasting, direct steam roasting, drying, and open pan roasting) as well as a novel "Flores" hand-cracking method on the levels of bioactive compounds of cashew nut kernels were investigated. The raw cashew nut kernels were found to possess appreciable levels of certain bioactive compounds such as β-carotene (9.57 μg/100 g of DM), lutein (30.29 μg/100 g of DM), zeaxanthin (0.56 μg/100 g of DM), α-tocopherol (0.29 mg/100 g of DM), γ-tocopherol (1.10 mg/100 g of DM), thiamin (1.08 mg/100 g of DM), stearic acid (4.96 g/100 g of DM), oleic acid (21.87 g/100 g of DM), and linoleic acid (5.55 g/100 g of DM). All of the conventional shelling methods including oil-bath roasting, steam roasting, drying, and open pan roasting revealed a significant reduction, whereas the Flores hand-cracking method exhibited similar levels of carotenoids, thiamin, and unsaturated fatty acids in cashew nuts when compared to raw unprocessed samples. © 2010 American Chemical Society.

Loading Institute of Food Chemistry collaborators
Loading Institute of Food Chemistry collaborators