Structural Insights into the Interaction of Heme with Protein Tyrosine Kinase JAK2**

Janus kinase 2 (JAK2) is the most important signal-transducing tyrosine kinase in erythropoietic precursor cells. Its malfunction drives several myeloproliferative disorders. Heme is a small metal-ion-carrying molecule that is incorporated into hemoglobin in erythroid precursor cells to transport oxygen. In addition, heme is a signaling molecule and regulator of various biochemical processes. Here, we show that heme exposure leads to hyperphosphorylation of JAK2 in a myeloid cancer cell line. Two peptides identified in JAK2 are heme-regulatory motifs and show low-micromolar affinities for heme. These peptides map to the kinase domain of JAK2, which is essential for downstream signaling. We suggest these motifs to be the interaction sites of heme with JAK2, which drive the heme-induced hyperphosphorylation. The results presented herein could facilitate the development of heme-related pharmacological tools to combat myeloproliferative disorders.     

A review of air separation technologies and their integration with energy conversion processes

Cryogenic air separation technology has been successfully employed for many years to supply oxygen for the gasification of a wide range of hydrocarbon feedstocks to generate synthesis gas for the production of fuels, chemicals and other valuable products. Examples include the conversion of liquid and solid refinery waste streams into hydrogen for use within the refinery along with the coproduction of electricity, and the growing interest in gas-to-liquids (GTL) processes which convert natural gas into synthetic crude oil, waxes and fuels. Recently, increased attention has been focused on methods of integrating the oxygen production process with the downstream hydrocarbon processing units to reduce facility cost or increase efficiency. A review of traditional and developing processes to generate oxygen is presented, along with integration schemes to improve the economics of these facilities.     

Advanced development in upstream of petroleum industry using nanotechnology

Nowadays, energy supply is one of the most important issues due to limitation of oil, gas and coal sources. Because of rapid population, civilization and energy consumption growth, the improved technologies to make optimal use of the sources, solving related problems and finding new energy sources are important. More than 10 years ago, nanotechnology as one of the most important technologies has also been applied to progress in the oil and gas industry (upstream, midstream and downstream). The experience of these years has shown that application of nanotechnology in the oil industry improves the exploration of crude oil and natural gas (underground or deep water), drilling and bringing the crude oil or raw natural gas to the surface, as well as transportation, storage, processing and purifying methods. Nanoparticles with high specific surface area, pore volume and small size show unique physical and chemical properties, which could be applied in several applications. In this regard, many researchers have been focused on various nanoparticles for upstream industries and studied their potential in oil exploration, drilling, production and enhanced oil recovery (EOR). Also, in downstream and midstream which involve refining of crude oil, processing and purifying of raw natural gas, transportation and storage of crude or refined petroleum products, the nanomaterials have been used to improve the quality of oil and make it appropriate for the environment. Lowering sulfur gasoline, enhancing the octane number and coating the transportation system are among the goals that have been achieved successfully using nanotechnology. In this work, various types of nanoparticles such as metallic, metal oxide, hybrid nanoparticles, carbon nanomaterials, nano-composites and their applications in oil upstream industry are reviewed. Also, their usage in different types of oil upstream processes is discussed.     

Complex polymer architectures via RAFT polymerization: From fundamental process to extending the scope using click chemistry and nature's building blocks

Reversible addition fragmentation chain transfer (RAFT) polymerization has made a huge impact in macromolecular design. The first block copolymers were described early on, followed by star polymers and then graft polymers. In the last five years, the types of architectures available have become more and more complex. Star and graft polymers now have block structures within their branches, or a range of different branches can be found growing from one core or backbone. Even the synthesis of hyperbranched polymers can be positively influenced by RAFT polymerization, allowing end group control or control over the branching density. The creative combination of RAFT polymerization with other polymerization techniques, such as ATRP or ring-opening polymerization, has extended the array of available architectures. In addition, dendrimers were incorporated either as star core or endfunctionalities. A range of synthetic chemistry pathways have been utilized and combined with polymer chemistry, pathways such as ‘click chemistry’. These combinations have allowed the creation of novel structures. RAFT processes have been combined with natural polymers and other naturally occurring building blocks, including carbohydrates, polysaccharides, cyclodextrins, proteins and peptides. The result from the intertwining of natural and synthetic materials has resulted in the formation of hybrid biopolymers. Following these developments over the last few years, it is remarkable to see that RAFT polymerization has grown from a lab curiosity to a polymerization tool that is now been used with confidence in material design. Most of the described synthetic procedures in the literature in recent years, which incorporate RAFT polymerization, have been undertaken in order to design advanced materials.     

Conformational Ensembles Explored Dynamically from Disordered Peptides Targeting Chemokine Receptor CXCR4

This work reports on the design and the synthesis of two short linear peptides both containing a few amino acids with disorder propensity and an allylic ester group at the C-terminal end. Their structural properties were firstly analyzed by means of experimental techniques in solution such as CD and NMR methods that highlighted peptide flexibility. These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles. They revealed a network of transient and dynamic H-bonds and interactions with water molecules. Binding assays with a well-known drug-target, i.e., the CXCR4 receptor, were also carried out in an attempt to verify their biological function and the possibility to use the assays to develop new specific targets for CXCR4. Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target.     

Production of protein and metabolites by yeast grown in solid state fermentation: present status and perspectives

Culture conditions for the generation of products using yeast have been optimized for fermentative processes in industry involving predominantly submerged medium (SmF). However, solid‐state fermentation (SSF) is now a realistic alternative system for the production of recombinant proteins and metabolites of interest in the market, with great potential in biofuels production, food, chemical and pharmaceutical industries. One of the main advantages of SSF over SmF is the reduction of downstream expenses. Also, the use of artificial and very cheap solid supports for yeast SSF such as polyurethane foam or amberlite helps with study of the physiology of such systems. This mini‐review makes an overview of previous research and emphasizes the major physiological advantages of yeast SSF that can be used for new processes and product development and stresses the need for integrated approaches between adaptive evolution and high‐throughput genetic analysis. © 2015 Society of Chemical Industry     

Production and purification of glutamic acid: A critical review towards process intensification

Amidst growing environmental awareness and stringent discharge regulations, chemical and allied process industries are now desperately seeking replacement of the conventional, polluting processes by clean and green processes. In this context, production and purification of amino acids like l-glutamic acid assumes significance. Concerned conventional process involves several steps like fermentation, centrifugation, carbon adsorption, evaporation, crystallization, ion-exchange and so on to get glutamic acid in desired concentration and purification. Despite its tremendous potential for large scale use in a wide variety of applications, cost-effective production of high purity glutamic acid has remained a challenge for decades, mainly due to several downstream processing steps and the associated cost factors. With emergence of tailor-made membranes and modules, possibility of using membranes in downstream purification of glutamic acid appears imminent with expectation of a turnaround in amino acid manufacturing industry. The present study through a brief yet comprehensive review of the very critical aspects of glutamic acid production and purification, attempts to direct research efforts towards process intensification encompassing the concepts of green processing, compact and flexible design with promise of more economically attractive production with better quality.     

Applications of in situ magnetic resonance techniques in chemical reaction engineering

NMR spectroscopy is now a well‐established technique for the in situ study of surface chemistry and the chemical processes occurring during catalytic reactions. Developments in probe design are making the sample environments ever closer to the operating conditions of the catalyst in industrial use. In parallel with these advances there is an increasing interest in the application of field gradient magnetic resonance techniques, namely pulsed gradient spin echo (PGSE) NMR and magnetic resonance imaging (MRI), to in situ studies of mass transport processes in catalysts and reactors. An overview of the recent developments in in situ NMR spectroscopy, PGSE NMR and MRI studies in application to catalysis and reaction engineering is presented and the potential of these techniques in the numerical modelling of catalytic processes and reactor design is highlighted. This revised version was published online in August 2006 with corrections to the Cover Date.     

Structure optimization of tailored ionic liquids and process simulation for shale gas separation

Shale gas, as a potential substitute for energy source, requires important processing steps before utilization. The most common separation technology applied is distillation, which is energy-intensive. With good stability, non-volatility, and tailored properties, ionic liquids (ILs) are regarded as novel potential solvents and alternative media for gas absorption. Therefore, a new strategy for hybrid shale gas separation processing, where IL-based absorption together with distillation is employed for energy-efficient and cost-economic gas processing, is developed. In this work, a three-stage methodology for shale gas separation process is proposed: IL screening, where a systematic screening method with two options (database screening and computer-aided design based on universal quasichemical functional-group activity coefficient model) is established; suitable ILs are selected as promising candidates; process design and simulation, where separation schemes and important design issues in the IL-based processes are determined; and, process evaluation, where the performance of the final separation process is evaluated and verified.     

Molecular machines for protein degradation

One of the most precisely regulated processes in living cells is intracellular protein degradation. The main component of the degradation machinery is the 20S proteasome present in both eukaryotes and prokaryotes. In addition, there exist other proteasome-related protein-degradation machineries, like HslVU in eubacteria. Peptides generated by proteasomes and related systems can be used by the cell, for example, for antigen presentation. However, most of the peptides must be degraded to single amino acids, which are further used in cell metabolism and for the synthesis of new proteins. Tricorn protease and its interacting factors are working downstream of the proteasome and process the peptides into amino acids. Here, we summarise the current state of knowledge about protein-degradation systems, focusing in particular on the proteasome, HslVU, Tricorn protease and its interacting factors and DegP. The structural information about these protein complexes opens new possibilities for identifying, characterising and elucidating the mode of action of natural and synthetic inhibitors, which affects their function. Some of these compounds may find therapeutic applications in contemporary medicine.     

Purification of Aspergillus carbonarius polygalacturonase using polymeric membranes

BACKGROUND: Microfiltration (MF: 70–450 nm) and ultrafiltration (UF: 10–500 kDa) membranes were used to eliminate carbohydrates and other non‐protein impurities from Aspergillus carbonarius culture broth containing polygalacturonase enzyme (EC 3.2.1.15) that would otherwise interfere with the purification processes and lead to enzyme loss. Further, diafiltration was attempted to improve the elimination of impurities as well as recovery of enzymes. RESULTS: MF resulted in removal of 2–25% carbohydrates with an enzyme recovery of 69–82% from the crude culture broth owing to the secondary layer formation. UF with 10 kDa membrane eliminated most of the carbohydrates (96%), phosphate salts and total acids with a recovery of 96% polygalacturonase and resulted in greater productivity. Using the above procedure, the enzyme was concentrated nearly 10‐fold while the purity improved from 4.6 to 49.4 U mg^?1 of dry matter. CONCLUSIONS: The results of this study focused on the elimination of carbohydrates and other non‐protein impurities showed that UF could be used efficiently as a primary purification step during downstream processing of microbial culture broths containing enzymes. The present approach will ensure complete elimination of non‐protein impurities thereby reducing the losses and difficulties in the subsequent purification steps. Copyright © 2008 Society of Chemical Industry     

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

At present, much attention is paid to the use of antimicrobial peptides (AMPs) of natural and artificial origin to combat pathogens. AMPs have several points that determine their biological activity. We analyzed the structural properties of AMPs, as well as described their mechanism of action and impact on pathogenic bacteria and viruses. Recently published data on the development of new AMP drugs based on a combination of molecular design and genetic engineering approaches are presented. In this article, we have focused on information on the amyloidogenic properties of AMP. This review examines AMP development strategies from the perspective of the current high prevalence of antibiotic-resistant bacteria, and the potential prospects and challenges of using AMPs against infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).     

Applications of process synthesis: Moving from conventional chemical processes towards biorefinery processes

Concerns about diminishing petroleum reserves, enhanced worldwide demand for fuels and fluctuations in the global oil market, together with climate change and national security have promoted many initiatives for exploring alternative, non-petroleum based processes. Among these initiatives, biorefinery processes for converting biomass derived carbohydrates into transportation fuels and chemicals are now gaining more and more attention from both academia and industry. Process synthesis, which has played a vital role for the development, design and operation of (petro) chemical processes, can be predicted to play a significant role in the design and commercialization of sustainable and cost-effective biorefinery processes. The main objective of this perspective paper is to elucidate the potential opportunities that biorenewables processing offers to optimal synthesis; challenges and future directions in this field are also concisely discussed. An attempt is made with this perspective to stimulate more and more efforts to optimally synthesize and design biorenewable conversion process to accelerate the commercialization of the biorefinery technology and further reduce the heavily reliance on petroleum-derive fuels.     

Successful Removal of Algae through the Control of Zeta Potential

Abstract

Algae can interfere with treatment processes at a water treatment works. Coagulation control is critical to reduce the impact of algae on downstream processes. This paper investigates the coagulation and flotation of four species of algae – Asterionella formosa, Melosira sp., Microcystis aeruginosa, and Chlorella vulgaris. The zeta potential at optimum removal was measured and it was observed that when the zeta potential was reduced to between ?8 mV and +2 mV, removal of algae and associated organic material was optimized, irrespective of the coagulant dose or pH. Process control using zeta potential is therefore a viable tool for algae removal.     

Design and application of stimulus-responsive peptide systems

The ability of peptides and proteins to change conformations in response to external stimuli such as temperature, pH and the presence of specific small molecules is ubiquitous in nature. Exploiting this phenomenon, numerous natural and designed peptides have been used to engineer stimulus-responsive systems with potential applications in important research areas such as biomaterials, nanodevices, biosensors, bioseparations, tissue engineering and drug delivery. This review describes prominent examples of both natural and designed synthetic stimulus-responsive peptide systems. While the future looks bright for stimulus-responsive systems based on natural and rationally engineered peptides, it is expected that the range of stimulants used to manipulate such systems will be significantly broadened through the use of combinatorial protein engineering approaches such as directed evolution. These new proteins and peptides will continue to be employed in exciting and high-impact research areas including bionanotechnology and synthetic biology.     

A REVIEW OF MIXED REVERSE MICELLE SYSTEM FOR ANTIBIOTIC RECOVERY

This article discusses the application of mixed reverse micelles in downstream processing of antibiotics. Purification and recovery processes for antibiotics in downstream processing are major expenses, about 70% of the total cost of production, giving them a significant impact on manufacturing cost. Moreover, there are a number of challenges and difficulties in the separation process requirements for antibiotics, since the mixture is quite complex, with broth, hazardous solvents, by-products, intermediate material, and impurities; in addition, antibiotics are easy to denature. Therefore, the development of effective separation techniques is required to produce high-purity of biomaterials. The use of reverse micelles is thought to be among the most promising due to the process's high selectivity and efficiency. Most studies on reverse micelle extraction technology have been performed by using anionic surfactant sodium bis (2-ethyl-1-hexyl) sulfosuccinate (AOT). However, the activities of antibiotics hosted in this type of surfactant have a significant effect due to the strong electrostatic and hydrophobic interaction between antibiotic and surfactant molecules. Due to these problems many alternatives have been developed recently, and reverse micelles have high potential in the purification of biomolecules. Therefore, this review discusses the ability of mixed ionic-nonionic reverse micelles to provide a safe microenvironment for antibiotics by maintaining the strength of attraction between the reverse micelle molecule and the antibiotic while avoiding the denaturation of the antibiotic. The article highlights the potential of mixed ionic-nonionic reverse micelle technology as a tool of antibiotic recovery from various mediums.     

Toward reducing the formation temperature of diopside via wet-chemical synthesis routes using chloride precursors

Reducing the formation temperature of single-phase multioxides is one of the classic challenges in ceramic processing, including wet-chemical synthesis routes. Toward pursuing this aim for diopside (MgCaSi₂O₆), the merit of different sol-gel and coprecipitation processes using the related chloride precursors followed by calcination was compared from the viewpoints of crystallinity and homogeneity. In accordance to the results, the use of the sol-gel techniques, directed with/without an alkaline catalyst, gave rise to the unfavorable creation of multiphase and low-crystallinity structures. Regarding the coprecipitation methods, the one-step addition of a precipitant agent is accompanied by an indirect low-temperature formation of nano-diopside, while a direct crystallization into this phase was explored in the dropwise condition, albeit with a lower crystallinity. Thus, by employing a suitable synthesis processing, it is feasible to take control of a wide range of nanoparticulate diopside-based structures achieved after a low-temperature calcination.     

Experimental study on the failure mechanism of recycled concrete

In this study, Young's modulus, strength, and peak strain of recycled concrete under both compressive and tensile loading were experimentally studied to understand its failure mechanism. Due to the different colors of natural aggregates, old hardened mortar, new hardened mortar, and interfacial transition zone (ITZ), the quantity and the distribution of each phase were analyzed by images processing and analysis of cut sections. With the tests, the failure processes and crack situation of the recycled concrete under tensile and compressive loadings were illustrated. It was found that some mechanical properties of recycled concrete are similar to those of mortar, for instance, lower Young's modulus, higher peak strain and more brittleness, due to a larger volume content of both new and old hardened mortar. When compared with old hardened mortar, new hardened mortar has more significant influence on both the strength and the Young's modulus of recycled concrete.     

Glycosyltransferases and their Assays

Glycosyltransferases (GTs) are a large family of enzymes that are essential in all domains of life for the biosynthesis of complex carbohydrates and glycoconjugates. GTs catalyse the transfer of a sugar from a glycosyl donor to a variety of acceptor molecules, for example, oligosaccharides, peptides, lipids or small molecules. Such glycosylation reactions are central to many fundamental biological processes, including cellular adhesion, cell signalling and bacterial‐ and plant‐cell‐wall biosynthesis. GTs are therefore of significant interest as molecular targets in chemical biology and drug discovery. In addition, GTs have found wide application as synthetic tools for the preparation of complex carbohydrates and glycoconjugates. In order to exploit the potential of GTs both as molecular targets and synthetic tools, robust and operationally simple bioassays are essential, especially as more and more protein sequences with putative GT activity but unknown biochemical function are being identified. In this minireview, we give a brief introduction to GT biochemistry and biology. We outline the relevance of GTs for medicinal chemistry and chemical biology, and describe selected examples for recently developed GT bioassays, with a particular emphasis on fluorescence‐based formats.     

Whey-Derived Peptides at the Heart of the COVID-19 Pandemic

The renin–angiotensin system (RAS) is a key regulator of blood pressure and hypertension. Angiotensin-converting enzyme 2 (ACE2) and angiotensin-converting enzyme I (ACE) are two main components of the RAS that play a major role in blood pressure homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 as a receptor to enter cells. Despite some controversies, numerous studies have reported a significant association between the use of ACE inhibitors and reduced risk of COVID-19. In our previous studies, we produced and identified peptide sequences present in whey hydrolysates exhibiting high ACE inhibitory activity. Therefore, the aim of this work is to obtain an improved understanding of the function of these natural peptides as RAS inhibitors and investigate their potential therapeutic role in the COVID-19 pandemic. The molecular interactions between peptides IPP, LIVTQ, IIAE, LVYPFP, and human ACE2 were assessed by employing a molecular docking approach. The results show that natural whey-derived peptides have a dual inhibitory action against both ACE and ACE2. This dual activity distinguishes these ACE inhibitory peptides from synthetic drugs, such as Captopril and Lisinopril which were not shown to inhibit ACE2 activity, and may represent a potential strategy in the treatment of COVID-19.