Rewiring cellular metabolism for heterologous biosynthesis of Taxol

Abstract

Taxol is one of the anticancer drugs synthesized naturally in the evergreen Taxus brevifolia forest tree belonging to the yew family (Taxaceae) growing on the Pacific. There are reportedly evidence for treating ovarian, breast and lung cancers through this drug given its unique structural and functional features. Extraction of this drug from yew trees bark is one of the most common ways of producing this drug, but 3000 trees are needed to obtain a kilogram of Taxol. Hence, further attention has recently been attracted to the metabolic engineering strategies, including, engineering cellular metabolism of microorganisms and their optimization. Accordingly, the present paper article was aimed to review recent advances in elevating the production and commercialization of Taxol through metabolic engineering techniques.     

Development of a new synthesis approach for S-pregabalin by optimizing the preparation stages

Journal of the Iranian Chemical Society - In the present study, we aimed to optimize the synthesis stages of S-pregabalin ((S)-3-(aminomethyl)-5-methylhexanoic acid), a well-known anticonvulsant...     

Computational fluid-dynamics-based analysis of a ball valve performance in the presence of cavitation

In this paper, the ball valve performance is numerically simulated using an unstructured CFD (Computational Fluid Dynamics) code based on the finite volume method. Navier-Stokes equations in addition to a transport equation for the vapor volume fraction were coupled in the RANS solver. Separation is modeled very well with a modification of turbulent viscosity. The results of CFD calculations of flow through a ball valve, based on the concept of experimental data, are described and analyzed. Comparison of the flow pattern at several opening angles is investigated. Pressure drop behind the ball valve and formation of the vortex flow downstream the valve section are also discussed. As the opening of the valve decreases, the vortices grow and cause higher pressure drop. In other words, more energy is lost due to these growing vortices. In general, the valve opening plays very important roles in the performance of a ball valve.     

The electrochemical behaviors of methylene blue on the surface of nanostructured NiWO4 prepared by coprecipitation method

A simple coprecipitation method was used for preparation of monoclinic nanostructured NiWO₄ from an aqueous solution at a fixed pH and temperature of 7.0 and 80 °C, respectively. The prepared material was characterized by X-ray diffraction, scanning electron microscopy, photoluminescence spectroscopy, and electrochemical measurements. Nano-NiWO₄ was incorporated into a carbon paste electrode and by means of cyclic voltammetry; the electrochemical behavior of methylene blue on the surface of nano-NiWO₄ was investigated. A mechanism on terms of obtained cyclic voltammograms showing one reduction peak and two sequential oxidation peaks was suggested by emphasizing on the stabilizing role of nano-NiWO₄ for semi-methylene blue. A diffusion coefficient of 5.30?×?10^?6 cm²/s was gained for methylene blue.     

Thermodynamic Consistency Test of Vapor–liquid Equilibrium Data of Binary Systems Including Carbon Dioxide (CO 2 ) and Ionic Liquids Using the Generic Redlich–Kwong Equation of State

The thermodynamic consistency test of solubility P–T–x data for binary mixtures including carbon dioxide (CO2) + a room temperature ionic liquid has been investigated. Experimental solubility data taken from the open literature for 32 binary mixtures of CO2/RTILs contains 80 isotherms. The applied consistency test is based on the fundamental Gibbs–Duhem equation with use of the generic Redlich–Kwong (GRK) equation of state (EoS) coupled with the van der Waals–Berthelot (GRK/vdWB) mixing rule. The optimum parameters were obtained by minimizing the summation of per cent relative deviations between modeled and experimental data, based on the bubble pressure algorithm. Modeling was found acceptable for all isotherms, which demonstrated the usability of the GRK equation of state. Results of the thermodynamic consistency test showed that 36 of the isothermal data sets were thermodynamically consistent, 37 were not fully consistent, 6 were thermodynamically inconsistent and only one data set was found to need another model.     

Copper-catalyzed domino reaction between terminal alkynes,isocyanates, and oxiranes: An atom-economic route to morpholine derivatives

In situ generated copper acetylides react with isocyanates and oxiranes to form a decent range of morpholine derivatives. The reactions proceeded with acceptable yields and excellent regioselectivity. The presence of oxygen and moisture completely inhibited the reaction. The scope of the reaction is wide and the reactions involve consecutive C–C, C–N, and C–O bond formations.     

Static Headspace GC/MS Method for Determination of Methanol and Ethanol Contents,as the Degradation Markers of Solid Insulation Systems of Power Transformers

Methanol in insulating oil has been proposed as a new marker for condition assessment of the solid insulation system of power transformers. In the current work, as a first step of using the new marker, an analytical static headspace gas chromatography/mass spectrometry method has been developed, optimized, and validated to measure methanol and ethanol contents in the insulating mineral oil. The analyzing setup consists of a 6890 N gas chromatograph equipped with a 5973 network mass spectrometer (MS) in the absence of a costly headspace autosampler, and the chromatography separation was performed on a 60 m × 320 µm × 0.5 µm VF-WAXms GC column. Calibration curves have been provided using several concentrations of the alcohols, and also limit of detection (LOD), limit of quantification (LOQ), and relative standard deviation percentage (RSD%) have been determined.     

Preparation and biodistribution study of technetium-99m-labeled quercetin as a potential radical scavenging agent

Free radicals and oxidative stress are the primary causes of several chronic diseases such as cancer and heart disease. Quercetin is a natural compound with potent antioxidant activity. We have prepared and evaluated technetium-99m (^99mTc)-labeled quercetin as a potential radical scavenging radiotracer. A ^99mTc-quercetin complex was prepared using quercetin, SnCl₂ and Na^99mTcO₄ in a buffered solution over 30 min. The participation coefficient was measured in octanol and queues solutions. The stability was determined in phosphate buffered saline and serum. The biodistribution in normal mice was evaluated at 0.5, 2, 6 and 24 h post-injection. The radiochemical purity (>99%) was determined by thin layer chromatography (TLC) in normal saline solution as the mobile phase. It has a log P of 0.204. It was mainly cleared by the kidneys and showed negligible brain uptake at four time points measured post-injection. The pharmacological properties of quercetin, mainly its free radical scavenging, may potentially cat as a radiopharmaceutical agent for radical-targeted imaging of tissue with high levels of reactive oxygen species.     

Bifurcation analysis on a generalized recurrent neural network with two interconnected three-neuron components

A class of recurrent neural networks is constructed by generalizing a specific class of n-neuron networks. It is shown that the newly constructed network experiences generic pitchfork and Hopf codimension one bifurcations. It is also proved that the emergence of generic Bogdanov–Takens, pitchfork–Hopf and Hopf–Hopf codimension two, and the degenerate Bogdanov–Takens bifurcation points in the parameter space is possible due to the intersections of codimension one bifurcation curves. The occurrence of bifurcations of higher codimensions significantly increases the capability of the newly constructed recurrent neural network to learn broader families of periodic signals.     

CD47 in the Brain and Neurodegeneration: An Update on the Role in Neuroinflammatory Pathways

CD47 is a receptor belonging to the immunoglobulin (Ig) superfamily and broadly expressed on cell membranes. Through interactions with ligands such as SIRPα, TSP-1, integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), CD47 regulates numerous functions like cell adhesion, proliferation, apoptosis, migration, homeostasis, and the immune system. In this aspect, previous research has shown that CD47 modulates phagocytosis via macrophages, the transmigration of neutrophils, and the activation of T-cells, dendritic cells, and B-cells. Moreover, several studies have reported the increased expression of the CD47 receptor in a variety of diseases, including acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), bladder cancer, acute myeloid leukemia (AML), Gaucher disease, Multiple Sclerosis and stroke among others. The ubiquitous expression of the CD47 cell receptor on most resident cells of the CNS has previously been established through different methodologies. However, there is little information concerning its precise functions in the development of different neurodegenerative pathologies in the CNS. Consequently, further research pertaining to the specific functions and roles of CD47 and SIRP is required prior to its exploitation as a druggable approach for the targeting of various neurodegenerative diseases that affect the human population. The present review attempts to summarize the role of both CD47 and SIRP and their therapeutic potential in neurodegenerative disorders.