Schweiger P.,Institute For Mikrobiologie Und Biotechnologie |
Gross H.,Institute For Pharmazeutische Biologie |
Deppenmeier U.,Institute For Mikrobiologie Und Biotechnologie
Applied Microbiology and Biotechnology | Year: 2010
Two cytosolic NADPH-dependent carbonyl reductases from Gluconobacter oxydans 621H, Gox0644 and Gox1615, were heterologously produced in Escherichia coli. The recombinant proteins were purified to homogeneity and characterized. Gox0644 and Gox1615 were dimers with native molecular masses of 66.1 and 74.5 kDa, respectively. The enzymes displayed broad substrate specificities and reduced α-ketocarbonyls at the keto moiety most proximal to the terminus of the alkyl chain to produce alpha-hydroxy carbonyls, as demonstrated by NMR. With respect to stereoselectivity, protein Gox0644 specifically reduced 2,3-pentanedione to 2R-hydroxy-pentane-3-one, whereas Gox1615 produced 2S-hydroxy-pentane-3-one. Both enzymes also reduced 1-phenyl-1,2-propanedione to 2-hydroxy-1-phenylpropane-1-one, which is a key intermediate in the production of numerous pharmaceuticals, such as antifungal azoles and antidepressants. Gox0644 displayed highest activities with 2,3-diones, α-ketoaldehydes, α-keto esters, and 2,5-diketogluconate. Gox1615 was less active with these substrates, but displayed a broader substrate spectrum reducing a variety of α-diketones and aldehydes. © 2010 Springer-Verlag.
Dingermann T.,Institute For Pharmazeutische Biologie |
Zundorf I.,Institute For Pharmazeutische Biologie
Aktuelle Neurologie | Year: 2011
What would medicine be without drugs? But are drugs being used optimally? Not at all, as we now know thanks to the findings from molecular medicine. Two aspects should be considered when selecting a drug for a patient: the patients disease on the one hand and the patient him/herself on the other hand. Up to now essentially the disease was treated. The sick patient played a very minor role. That will soon change thanks to the enormously successful genome research. Health professionals are well advised to implement genomic information from the individual patient into novel therapies in a timely manner. We are already able to predict to a large extent whether a particular drug will be efficacious in a patient and whether that patient will tolerate this drug, as suggested from clinical trials. © Georg Thieme Verlag KG Stuttgart - New York.
Hartmann D.,Goethe University Frankfurt |
Lucks J.,Goethe University Frankfurt |
Fuchs S.,Goethe University Frankfurt |
Schiffmann S.,Goethe University Frankfurt |
And 6 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2012
Ceramides are known to be key players in intracellular signaling and are involved in apoptosis, cell senescence, proliferation, cell growth and differentiation. They are synthesized by ceramide synthases (CerS). So far, six different mammalian CerS (CerS1-6) have been described. Recently, we demonstrated that human breast cancer tissue displays increased activity of CerS2, 4, and 6, together with enhanced generation of their products, ceramides C 16:0, C 24:0, and C 24:1. Moreover, these increases were significantly associated with tumor dignity. To clarify the impact of this observation, we manipulated cellular ceramide levels by overexpressing ceramide synthases 2, 4 or 6 in MCF-7 (breast cancer) and HCT-116 (colon cancer) cells, respectively. Overexpression of ceramide synthases 4 and 6 elevated generation of short chain ceramides C 16:0, C 18:0 and C 20:0, while overexpression of ceramide synthase 2 had no effect on ceramide production in vivo, presumably due to limited substrate availability, because external addition of very long chain acyl-CoAs resulted in a significant upregulation of very long chain ceramides. We also demonstrated that upregulation of CerS4 and 6 led to the inhibition of cell proliferation and induction of apoptosis, whereas upregulation of CerS2 increased cell proliferation. On the basis of our data, we propose that a disequilibrium between ceramides of various chain length is crucial for cancer progression, while normal cells require an equilibrium between very long and long chain ceramides for normal physiology. © 2012 Elsevier Ltd. All rights reserved.
Koch K.,Nees Institute For Biodiversitat Der Pflanzen |
Blecher I.C.,Nees Institute For Biodiversitat Der Pflanzen |
Konig G.,Institute For Pharmazeutische Biologie |
Kehraus S.,Institute For Pharmazeutische Biologie |
Barthlott W.,Nees Institute For Biodiversitat Der Pflanzen
Functional Plant Biology | Year: 2014
Most leaves of plants are hydrophobic or even superhydrophobic. Surprisingly the leaves of the tropical herb of Ruellia devosianaMakoyex E. Morr. Hort. (Acanthaceae) are superamphiphilic. Water droplets (10 μL) spread to a film with a contact angle of zero degree within less than 0.3 s. Such surfaces with a high affinity to water are termed superhydrophilic. Droplets of oil applied on R. devosiana leaves and replicas showed a similar spreading behaviour as water. These surfaces are superoleophilic, and in combination with their superhydrophilicity they are called superamphiphilic. Independent of the growing conditions, a reversibility of the superhydrophilicity in R. devosiana leaves was found. Additionally, on 90° tilted leaves a pressure free capillary transport of water occurs against the force of gravity. By using a low pressure environmental scanning electron microscope (ESEM), the water condensation and evaporation process on the leaves has been observed. The leaf surfaces are composed of five different cell types: conical cells, glands, multicellular hairs, hair-papilla cells and longitudinal expanded, flat epidermis cells, which, in combination with the surrounding papilla cells, form channel like structures. Replication of the leaf surface structure and coating of the replicas with hydrophilic Tween 20 and a water soluble extract gained from the leaf surfaces resulted in artificial surfaces with the same fast water spreading properties as described for the leaves. © 2009 CSIRO.
Liu B.,Institute For Pharmazeutische Biologie |
Liu B.,CAS Institute of Botany |
Raeth T.,Institute For Pharmazeutische Biologie |
Beuerle T.,Institute For Pharmazeutische Biologie |
Beerhues L.,Institute For Pharmazeutische Biologie
Plant Molecular Biology | Year: 2010
Coumarin forms in melilotoside (trans-ortho-coumaric acid glucoside)-containing plant species upon cell damage. In moldy melilotoside-containing plant material, trans-ortho-coumaric acid is converted by fungi to 4-hydroxycoumarin, two molecules of which spontaneously combine with formaldehyde to give dicoumarol. Dicoumarol causes internal bleeding in livestock and is the forerunner of the warfarin group of medicinal anticoagulants. Here, we report 4-hydroxycoumarin formation by biphenyl synthase (BIS). Two new BIS cDNAs were isolated from elicitor-treated Sorbus aucuparia cell cultures. The encoded isoenzymes preferred ortho-hydroxybenzoyl (salicoyl)-CoA as a starter substrate and catalyzed a single decarboxylative condensation with malonyl-CoA to give 4-hydroxycoumarin. When elicitor-treated S. aucuparia cell cultures were fed with the N-acetylcysteamine thioester of salicylic acid, 4-hydroxycoumarin accumulated in the culture medium. Incubation of the BIS isoenzymes with benzoyl-CoA and malonyl-CoA resulted in the formation of 3,5-dihydroxybiphenyl which is the precursor of the phytoalexins of the Maloideae. © 2009 Springer Science+Business Media B.V.