Глобализация как фактор радикализации трансформации приоритетов социально-экономического развития в посттранзитивних экономиках

Expression of the for khead transcription factor FOXP1 is essential for early B-cell development, whereas down regulation ofFOXP1at the germinal center (GC) stage is required for GC B-cell function. Aberrantly high FOXP1 expression is frequently observed in diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma, being associated with poor prognosis. Here, by gene expression analysis upon ectopic over expression of FOXP1 in primary

Modulare Enzym-Kaskaden zur Synthese von Glykanepitopen

The aim of this work was the in vitro synthesis of the non-sulfated HNK-1 epitope (GlcA(β1-3)Gal(β1-4)GlcNAc(β1-R) and the glycan epitope 2´ fucosyllactose (2´ FL, Fuc(α1-2)Gal(β1-4)Glc) and furthermore the provision of UDP-glucuronic acid (UDP GlcA) as donor substrate for the non-sulfated HNK-1 epitope with modular enzyme-cascades.For the synthesis of UDP-GlcA two UDP-glucose-dehydrogenases, the human His6UGDH and His6KfiD of E. coli K5 revealed as suitable enzymatic tools. However, because of its higher catalytic efficiency recombinant His6UGDH was preferred. Three different synthesis strategies were tested. The one-step process with the UGDH-module was compared with two combinatorial strategies. In a one-pot system the combination of the SuSy-module with the UGDH-module and furthermore the combination of the SuSy- and UGDH-module with the UMPK-module were carried out. For the UMPK-module a human UMP-kinase was successfully produced and characterized. The functionality of all selected enzyme-module systems was proven by ESI-MS analysis of the target product UDP-GlcA.However, due to the shorter synthesis period and the chemical instability of the nucleotide sugar the one-step process was favoured. With the regeneration of the cofactor NAD+, realized by applying His6NOX-, this strategy reveals as a cost- and time-efficient method with a yield of 92% for UDP-GlcA.Establishing the GlcAT-module required the production of a glucuronyltransferase, which catalyses the regio-specific transfer of GlcA from UDP-GlcA onto the acceptor substrate LacNAc linker-t-Boc. The biochemical characterization confirmed recombinant His6catGlcAT P from Mus musculus as a potential enzymatic tool for the synthesis of the non-sulfated HNK 1 epitope in combinatorial biocatalysis. For the first time step by step optimization of the enzyme cascades led to the combination of the SuSy-module with the UGDH- and GlcAT module in a one-pot system with a yield of 79% on preparative scale. Based on this result the integrated in situ regeneration of UDP GlcA was accomplished with cycle numbers of 18. Thus, this strategy rationalizes synthesis cost for the expensive nucleotide sugar UDP GlcA. The demonstrated EMS has the potential to be used for the synthesis of the non-sulfated HNK-1 epitope modified by various linkers as well as glucuronides by exchange of the acceptor substrates or glucuronyltransferases, respectively.For the production of the glycan-epitope 2´-FL WbgL of E. coli O126 could be identified as novel α1,2 fucosyltransferase with low sequence homology to FutC. In comparison to FutC WbgL shows a three-fold higher activity for the non-natural acceptor substrate lactose. In line with these results WbgL is a favourable enzyme for the enzymatic synthesis of 2´ FL and other natural as well as modified α1,2-fucosylated galakto-oligosaccharides. Furthermore the production of bifunctional L fucokinase/L-Fuc-1-P guanylyltransferase (FKP) of Bacterioides fragilis 9343 allowed the preparative synthesis of the donor substrate GDP Fucose (GDP-Fuc) with a yield of 100% in the FKP-module. The combination of the FKP-module with the FucT-module offered the possibility for preparative synthesis of 2´ FL in classical sequential mode. An international patent was granted for the identification of a novel bacterial α1,2´-fucosyltransferase in the synthesis of 2´ FL (reference number: PCT. Int. Appl. (2012), WO 2012097950 A1 20120726). To date the identified novel enzyme is introduced into industrial production of 2´ FL by the company “Jennewein Biotechnologie GmbH” (Bonn, Germany)

Enzyme Module Systems for the Synthesis of Uridine 5 '-Diphospho-alpha-D-glucuronic Acid and Non-Sulfated Human Natural Killer Cell-1 (HNK-1) Epitope

Engels L, Henze M, Hummel W, Elling L. Enzyme Module Systems for the Synthesis of Uridine 5 '-Diphospho-alpha-D-glucuronic Acid and Non-Sulfated Human Natural Killer Cell-1 (HNK-1) Epitope. Advanced Synthesis & Catalysis. 2015;357(8):1751-1762.Tailor-made strategies for the stereo- and regioselective multi-step enzymatic synthesis of glycoconjugates require well characterized glycosyltransferases and carbohydrate modifying enzymes. We here report on a novel enzyme cascade for the synthesis of uridine 5'-diphospho-alpha-D-glucuronic acid (UDP-GlcA) and the non-sulfated human natural killer cell-1 (HNK-1) epitope including in situ regeneration of UDP-GlcA and the cofactor nicotinamide adenine dinucleotide NAD(+) by the combination of four enzymes in one-pot. In the first enzyme module sucrose synthase 1 (SuSy1) is used to produce uridine 5'-diphospho-alpha-D-glucose (UDP-Glc) from sucrose and uridine 5'-diphosphate (UDP). The combination with UDP-Glc dehydrogenase in the second enzyme module leads to the synthesis of UDP-GlcA with concomitant in situ regeneration of the cofactor NAD(+) by nicotinamide adenine dinucleotide hydride (NADH)-oxidase. In the third enzyme module the mammalian glucuronyltransferase GlcAT-P catalyzes the synthesis of the non-sulfated HNK-1 epitope by regioselective transfer of GlcA onto N-acetyllactosamine type 2 (LacNAc type 2). We present a comprehensive study on substrate kinetics, substrate specificities, variation and relation of enzyme activities as well as cross inhibition of intermediate products. With optimized reaction conditions we obtain superior product yields with streamlined synthesis costs for the expensive nucleotide sugar UDP-GlcA and cofactor NAD(+)

Kombinationsausrüstung auf der Basis von Lichtaktiven Photokatalysatoren

Die Anforderungen an Textilien unterscheiden sich je nach Anwendungsbereich stark, wobei es häufig nicht bei nur einer benötigten Funktionalität bleibt. Im Bereich der Funktions- oder Schutzkleidung bzw. PSA ist es z.B. nötig, die Träger der Kleidung vor UV-Strahlung zu schützen. Gleichzeitig bieten hier selbstreinigende Effekte gewisse Vorteile. Zudem kann eine antimikrobielle Wirkung im Bereich der Funktionskleidung die Bildung unangenehmer Gerüche vermindern, sowie im Bereich der PSA – besonders im Gesundheitswesen – zur Unterbrechung von Infektionsketten beitragen. Eine Möglichkeit, diese 3 gewünschten Funktionen in nur einem Ausrüstungsschritt zu erzielen, ist die Immobilisierung von Titandioxid (TiO2). Dieses wird aber aufgrund einer REACH-Listung kritisch für die Anwendung im textilen Sektor gesehen. Nachteilig ist zudem, dass es seine Wirkung nur unter UV-Einstrahlung entfaltet und damit nicht für den Innenbereich geeignet ist. Alternativ können Photokatalysatoren wie dotierte Zinkoxide (ZnO) verwendet werden, die auch durch Einstrahlung im Bereich des sichtbaren Lichts eine katalytische Aktivität aufweisen, die zur Abtötung von Mikroorganismen und zum Abbau organischer Verschmutzungen führen kann

Säureschutzmantel – Textilausrüstung zum Schutz gegen mikrobiellen Befall

Der pH-Wert der menschlichen Haut liegt nicht im neutralen Bereich, sondern ist mit Werten von 3,5-6 – je nach Körperstelle – leicht Sauer. Das bietet der Kommensalen Hautflora einen geeigneten Lebensraum, wirkt jedoch abtötend auf einige pathogene Mikroorganismen und inaktivierend auf einige Viren. Dieser Säureschutzmantel der Haut stellt somit eine erste äußere Schutzschicht vor dem Befall von Krankheitserregern dar. Ein entsprechender Oberflächen-pH-Wert auf Textilien kann dazu beitragen, die Übertragung von Krankheitserregern durch die Kleidung von Mitarbeitern im Gesundheitswesen zu minimieren und gleichzeitig keinen negativen Einfluss auf die hauteigene Flora auszuüben. Zudem kann die Besiedlung von z.B. Bettwäsche durch pathogene Mikroorganismen vermindert werden. Einen positiven Einfluss kann dies zudem auf die bakterienassoziierte Geruchsbildung auf Funktionskleidung haben