scholarly journals Human Deoxycytidine Kinase Is a Valuable Biocatalyst for the Synthesis of Nucleotide Analogues

Catalysts ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 997 ◽  
Author(s):  
Katja F. Hellendahl ◽  
Sarah Kamel ◽  
Albane Wetterwald ◽  
Peter Neubauer ◽  
Anke Wagner
Keyword(s):  
Substrate Concentration ◽  
Food Additives ◽  
Product Yield ◽  
Building Blocks ◽  
Product Formation ◽  
Industrial Applications ◽  
Modified Nucleosides ◽  
Deoxycytidine Kinase ◽  
Wide Range ◽  
Substrate Concentrations

Natural ribonucleoside-5’-monophosphates are building blocks for nucleic acids which are used for a number of purposes, including food additives. Their analogues, additionally, are used in pharmaceutical applications. Fludarabine-5´-monophosphate, for example, is effective in treating hematological malignancies. To date, ribonucleoside-5’-monophosphates are mainly produced by chemical synthesis, but the inherent drawbacks of this approach have led to the development of enzymatic synthesis routes. In this study, we evaluated the potential of human deoxycytidine kinase (HsdCK) as suitable biocatalyst for the synthesis of natural and modified ribonucleoside-5’-monophosphates from their corresponding nucleosides. Human dCK was heterologously expressed in E. coli and immobilized onto Nickel-nitrilotriacetic acid (Ni-NTA) superflow. A screening of the substrate spectrum of soluble and immobilized biocatalyst revealed that HsdCK accepts a wide range of natural and modified nucleosides, except for thymidine and uridine derivatives. Upon optimization of the reaction conditions, HsdCK was used for the synthesis of fludarabine-5´-monophosphate using increasing substrate concentrations. While the soluble biocatalyst revealed highest product formation with the lowest substrate concentration of 0.3 mM, the product yield increased with increasing substrate concentrations in the presence of the immobilized HsdCK. Hence, the application of immobilized HsdCK is advantageous upon using high substrate concentration which is relevant in industrial applications.

scholarly journals Acid Phosphatases from the Bread Fruit Artocarpus communis Seeds as Novel Plant Phosphorylating Biocatalysts

2019 ◽  
pp. 1-8
Author(s):  
Hubert Kouassi Konan ◽  
Michel Djary Koffi ◽  
Desire Yapi Assoi Yapi ◽  
Lucien Patrice Kouame
Keyword(s):  
High Performance ◽  
Time Course ◽  
Food Additives ◽  
Product Yield ◽  
Industrial Applications ◽  
Synthesis Product ◽  
Acid Phosphatases ◽  
Short Period ◽  
Donor And Acceptor ◽  
Wide Range

Aims: Investigation on the phosphotransferase activity of two non-specific acid phosphatases (EC 3.1.3.2) designated as AP1 and AP2, previously isolated from breadfruit (Artocarpus communis) seeds for further biotechnological and industrial applications. Methodology: Transphosphorylation reactions were tested with sodium pyrophosphate as the phosphoryl donor and phenol as its acceptor. Transfer products were quantified by using high performance liquid chromatography. Results: The two acid phosphatases were able to catalyse phosphoconjugates synthesis using pyrophosphate as the phosphoryl donor and phenol as acceptor. The optimal conditions of transphosphorylation reactions indicated that this synthesis was highly dependent on pH, temperature, time course, donor and acceptor concentrations and enzyme amount. A very short period (1.25 h) was observed for these synthesis reactions catalysed by acid phosphatases isolated from breadfruit (Artocarpus communis) seeds. This suggested energy saving during biotransformation processes. The high average yields of 84.20 and 66.78% obtained for AP1 and AP2, respectively, made them useful to phosphorylate a wide range of nucleophile compounds such as nucleotides often used as food additives and pharmaceutical intermediates. Conclusion: The acid phosphatase AP1 would be the most promising on the basis the better synthesis product yield (84.20%). The two biocatalysts could be considered as new valuable tools for bioprocesses.

Acid phosphatases from the breadfruit Artocarpus communis seeds as novel plant phosphorylating biocatalysts

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Hubert Kouassi Konan ◽  
Michel Djary Koffi ◽  
Desire Yapi Assoi Yapi ◽  
Lucien Patrice Kouame
Keyword(s):  
High Performance ◽  
Time Course ◽  
Food Additives ◽  
Product Yield ◽  
Industrial Applications ◽  
Synthesis Product ◽  
Acid Phosphatases ◽  
Short Period ◽  
Donor And Acceptor ◽  
Wide Range

Abstract Objective Investigation on the phosphotransferase activity of two non-specific acid phosphatases (EC 3.1.3.2) designated as AP1 and AP2, previously isolated from breadfruit (Artocarpus communis) seeds for further biotechnological and industrial applications. Methods Transphosphorylation reactions were tested with sodium pyrophosphate as the phosphoryl donor and phenol as its acceptor. Transfer products were quantified by using high performance liquid chromatography. Results The two acid phosphatases were able to catalyze phosphoconjugates synthesis using pyrophosphate as the phosphoryl donor and phenol as acceptor. The optimal conditions of transphosphorylation reactions indicated that this synthesis was highly dependent on pH, temperature, time course, donor and acceptor concentrations and enzyme amount. A very short period (1.25 h) was observed for these synthesis reactions catalyzed by acid phosphatases isolated from breadfruit (Artocarpus communis) seeds. This suggested energy saving during biotransformation processes. The high average yields of 84.20 and 66.78% obtained for AP1 and AP2, respectively, made them useful to phosphorylate a wide range of nucleophile compounds such as nucleotides often used as food additives and pharmaceutical intermediates. Conclusion The acid phosphatase AP1 would be the most promising on the basis the better synthesis product yield (84.20%). The two biocatalysts could be considered as new valuable tools for bioprocesses.

Deciphering the route to cyclic monoterpenes in Chrysomelina leaf beetles: source of new biocatalysts for industrial application?

2017 ◽  
Vol 72 (9-10) ◽  
pp. 417-427 ◽  
Author(s):  
Antje Burse ◽  
Wilhelm Boland
Keyword(s):  
De Novo ◽  
Sustainable Use ◽  
Building Blocks ◽  
Leaf Beetle ◽  
Industrial Applications ◽  
Metabolic Diversity ◽  
Leaf Beetles ◽  
Wide Range ◽  
Extreme Habitats ◽  
Plant Sources

AbstractThe drastic growth of the population on our planet requires the efficient and sustainable use of our natural resources. Enzymes are indispensable tools for a wide range of industries producing food, pharmaceuticals, pesticides, or biofuels. Because insects constitute one of the most species-rich classes of organisms colonizing almost every ecological niche on earth, they have developed extraordinary metabolic abilities to survive in various and sometimes extreme habitats. Despite this metabolic diversity, insect enzymes have only recently generated interest in industrial applications because only a few metabolic pathways have been sufficiently characterized. Here, we address the biosynthetic route to iridoids (cyclic monoterpenes), a group of secondary metabolites used by some members of the leaf beetle subtribe Chrysomelina as defensive compounds against their enemies. The ability to produce iridoids de novo has also convergently evolved in plants. From plant sources, numerous pharmacologically relevant structures have already been described. In addition, in plants, iridoids serve as building blocks for monoterpenoid indole alkaloids with broad therapeutic applications. As the commercial synthesis of iridoid-based drugs often relies on a semisynthetic approach involving biocatalysts, the discovery of enzymes from the insect iridoid route can account for a valuable resource and economic alternative to the previously used enzymes from the metabolism of plants. Hence, this review illustrates the recent discoveries made on the steps of the iridoid pathway in Chrysomelina leaf beetles. The findings are also placed in the context of the studied counterparts in plants and are further discussed regarding their use in technological approaches.

scholarly journals Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

2017 ◽  
Vol 13 ◽  
pp. 845-854 ◽  
Author(s):  
Katarina Kemper ◽  
Max Hirte ◽  
Markus Reinbold ◽  
Monika Fuchs ◽  
Thomas Brück
Keyword(s):  
Escherichia Coli ◽  
Defense Mechanisms ◽  
Food Additives ◽  
Building Blocks ◽  
Industrial Applications ◽  
Site Directed Mutagenesis ◽  
Terpene Biosynthesis ◽  
Dimethylallyl Diphosphate ◽  
Microbial Systems ◽  
Wall Components

With over 50.000 identified compounds terpenes are the largest and most structurally diverse group of natural products. They are ubiquitous in bacteria, plants, animals and fungi, conducting several biological functions such as cell wall components or defense mechanisms. Industrial applications entail among others pharmaceuticals, food additives, vitamins, fragrances, fuels and fuel additives. Central building blocks of all terpenes are the isoprenoid compounds isopentenyl diphosphate and dimethylallyl diphosphate. Bacteria like Escherichia coli harbor a native metabolic pathway for these isoprenoids that is quite amenable for genetic engineering. Together with recombinant terpene biosynthesis modules, they are very suitable hosts for heterologous production of high value terpenes. Yet, in contrast to the number of extracted and characterized terpenes, little is known about the specific biosynthetic enzymes that are involved especially in the formation of highly functionalized compounds. Novel approaches discussed in this review include metabolic engineering as well as site-directed mutagenesis to expand the natural terpene landscape. Focusing mainly on the validation of successful integration of engineered biosynthetic pathways into optimized terpene producing Escherichia coli, this review shall give an insight in recent progresses regarding manipulation of mostly diterpene synthases.

THE INFLUENCE OF ETHANOL ON THE CONVERSION OF PREGNENOLONE TO PROGESTERONE BY HUMAN PLACENTAL MICROSOMES

1974 ◽  
Vol 76 (1) ◽  
pp. 178-188 ◽  
Author(s):  
H. Lübbert ◽  
K. Pollow ◽  
R. Wagner ◽  
J. Hammerstein
Keyword(s):  
Kinetic Parameters ◽  
Enzyme Preparation ◽  
Ethanol Concentration ◽  
Hydroxysteroid Dehydrogenase ◽  
Product Formation ◽  
Linear Increase ◽  
Maximal Velocity ◽  
Microsomal Enzyme ◽  
Temperature Optima ◽  
Substrate Concentrations

ABSTRACT The effects of ethanol on kinetic parameters of placental Δ5-3β-hydroxysteroid dehydrogenase were studied. In the presence of high pregnenolone concentrations (50 μm, [S] > Km) the microsomal enzyme preparation exhibited an almost linear increase in activity as the ethanol concentration in the medium was raised from 2.5 to 15 % (v/v). At lower substrate concentrations ([S] << Km) ethanol caused inhibition. Other effects of ethanol were: linearity of product formation with time was prolonged; the maximal velocity was markedly increased; the Km for pregnenolone slightly decreased with increasing ethanol concentrations (2.5 to 10 %, v/v) whereas the Km for NAD remained the same. The pH and temperature optima of the reaction were unaffected by ethanol. Other organic solvents caused similar effects.

Factors Affecting Molecular Self-Assembly and Its Mechanism

2012 ◽  
Vol 9 (1) ◽  
pp. 43 ◽  
Author(s):  
Hueyling Tan
Keyword(s):  
Self Assembly ◽  
Building Blocks ◽  
Molecular Engineering ◽  
Molecular Structures ◽  
Polymer Science ◽  
New Approach ◽  
Factors Affecting ◽  
Dna Structures ◽  
Self Assembling ◽  
Wide Range

Molecular self-assembly is ubiquitous in nature and has emerged as a new approach to produce new materials in chemistry, engineering, nanotechnology, polymer science and materials. Molecular self-assembly has been attracting increasing interest from the scientific community in recent years due to its importance in understanding biology and a variety of diseases at the molecular level. In the last few years, considerable advances have been made in the use ofpeptides as building blocks to produce biological materials for wide range of applications, including fabricating novel supra-molecular structures and scaffolding for tissue repair. The study ofbiological self-assembly systems represents a significant advancement in molecular engineering and is a rapidly growing scientific and engineering field that crosses the boundaries ofexisting disciplines. Many self-assembling systems are rangefrom bi- andtri-block copolymers to DNA structures as well as simple and complex proteins andpeptides. The ultimate goal is to harness molecular self-assembly such that design andcontrol ofbottom-up processes is achieved thereby enabling exploitation of structures developed at the meso- and macro-scopic scale for the purposes oflife and non-life science applications. Such aspirations can be achievedthrough understanding thefundamental principles behind the selforganisation and self-synthesis processes exhibited by biological systems.

Substituent Effects on the Thermal Decomposition of Phosphate Esters on Ferrous Surfaces

2019 ◽  
Author(s):  
James Ewen ◽  
Carlos Ayestaran Latorre ◽  
Arash Khajeh ◽  
Joshua Moore ◽  
Joseph Remias ◽  
...  
Keyword(s):  
Thermal Decomposition ◽  
Film Formation ◽  
Substituent Effects ◽  
Vapour Phase ◽  
Industrial Applications ◽  
Phosphate Esters ◽  
Antiwear Additives ◽  
Formation Mechanisms ◽  
Phosphate Ester ◽  
Wide Range

<p>Phosphate esters have a wide range of industrial applications, for example in tribology where they are used as vapour phase lubricants and antiwear additives. To rationally design phosphate esters with improved tribological performance, an atomic-level understanding of their film formation mechanisms is required. One important aspect is the thermal decomposition of phosphate esters on steel surfaces, since this initiates film formation. In this study, ReaxFF molecular dynamics simulations are used to study the thermal decomposition of phosphate esters with different substituents on several ferrous surfaces. On Fe<sub>3</sub>O<sub>4</sub>(001) and α-Fe(110), chemisorption interactions between the phosphate esters and the surfaces occur even at room temperature, and the number of molecule-surface bonds increases as the temperature is increased from 300 to 1000 K. Conversely, on hydroxylated, amorphous Fe<sub>3</sub>O<sub>4</sub>, most of the molecules are physisorbed, even at high temperature. Thermal decomposition rates were much higher on Fe<sub>3</sub>O<sub>4</sub>(001) and particularly α-Fe(110) compared to hydroxylated, amorphous Fe<sub>3</sub>O<sub>4</sub>. This suggests that water passivates ferrous surfaces and inhibits phosphate ester chemisorption, decomposition, and ultimately film formation. On Fe<sub>3</sub>O<sub>4</sub>(001), thermal decomposition proceeds mainly through C-O cleavage (to form surface alkyl and aryl groups) and C-H cleavage (to form surface hydroxyls). The onset temperature for C-O cleavage on Fe<sub>3</sub>O<sub>4</sub>(001) increases in the order: tertiary alkyl < secondary alkyl < primary linear alkyl ≈ primary branched alkyl < aryl. This order is in agreement with experimental observations for the thermal stability of antiwear additives with similar substituents. The results highlight surface and substituent effects on the thermal decomposition of phosphate esters which should be helpful for the design of new molecules with improved performance.</p>

Stereospecific, Palladium-catalyzed C(sp3)–H Alkenylation and Alkynylation of a Proline Derivative Enabled by 8-Aminoquinoline as a Directing Group

2020 ◽  
Author(s):  
Aleksandra Balliu ◽  
Aaltje Roelofje Femmigje Strijker ◽  
Michael Oschmann ◽  
Monireh Pourghasemi Lati ◽  
Oscar Verho
Keyword(s):  
Carboxylic Acid ◽  
Building Blocks ◽  
Wide Range ◽  
Palladium Catalyzed ◽  
Directing Group ◽  
High Yields ◽  
Vinyl Iodides ◽  
Initial Results

<p>In this preprint, we present our initial results concerning a stereospecific Pd-catalyzed protocol for the C3 alkenylation and alkynylation of a proline derivative carrying the well utilized 8‑aminoquinoline directing group. Efficient C–H alkenylation was achieved with a wide range of vinyl iodides bearing different aliphatic, aromatic and heteroaromatic substituents, to furnish the corresponding C3 alkenylated products in good to high yields. In addition, we were able show that this protocol can also be used to install an alkynyl group into the pyrrolidine scaffold, when a TIPS-protected alkynyl bromide was used as the reaction partner. Furthermore, two different methods for the removal of the 8-aminoquinoline auxiliary are reported, which can enable access to both <i>cis</i>- and <i>trans</i>-configured carboxylic acid building blocks from the C–H alkenylation products.</p>

Efficient Prediction of Structural and Electronic Properties of Hybrid 2D Materials Using DFT and Machine Learning

2018 ◽  
Author(s):  
Sherif Tawfik ◽  
Olexandr Isayev ◽  
Catherine Stampfl ◽  
Joseph Shapter ◽  
David Winkler ◽  
...  
Keyword(s):  
Machine Learning ◽  
Band Gap ◽  
Density Functional ◽  
2D Materials ◽  
Van Der Waals ◽  
Building Blocks ◽  
Machine Learning Techniques ◽  
Interlayer Distance ◽  
Computational Screening ◽  
Wide Range

Materials constructed from different van der Waals two-dimensional (2D) heterostructures offer a wide range of benefits, but these systems have been little studied because of their experimental and computational complextiy, and because of the very large number of possible combinations of 2D building blocks. The simulation of the interface between two different 2D materials is computationally challenging due to the lattice mismatch problem, which sometimes necessitates the creation of very large simulation cells for performing density-functional theory (DFT) calculations. Here we use a combination of DFT, linear regression and machine learning techniques in order to rapidly determine the interlayer distance between two different 2D heterostructures that are stacked in a bilayer heterostructure, as well as the band gap of the bilayer. Our work provides an excellent proof of concept by quickly and accurately predicting a structural property (the interlayer distance) and an electronic property (the band gap) for a large number of hybrid 2D materials. This work paves the way for rapid computational screening of the vast parameter space of van der Waals heterostructures to identify new hybrid materials with useful and interesting properties.

PLATINUM

Alloy Digest ◽  
1970 ◽  
Vol 19 (11) ◽  
Keyword(s):  
Corrosion Resistance ◽  
High Temperature ◽  
Heat Treating ◽  
Industrial Applications ◽  
High Melting ◽  
High Melting Point ◽  
White Metal ◽  
Temperature Performance ◽  
Wide Range ◽  
Corrosion And Oxidation

Abstract PLATINUM is a soft, ductile, white metal which can be readily worked either hot or cold. It has a wide range of industrial applications because of its excellent corrosion and oxidation resistance and its high melting point. This datasheet provides information on composition, physical properties, hardness, elasticity, and tensile properties. It also includes information on high temperature performance and corrosion resistance as well as forming, heat treating, machining, and joining. Filing Code: Pt-1. Producer or source: Matthey Bishop Inc..

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