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  • World’s first discovery of defect-related Raman scattering signal by using tip-enhanced Raman spectroscopy

    Energy Science Prof. JEONG, MUNSEOK ·Researcher LEE, CHANWOO

    World’s first discovery of defect-related Raman scattering signal by using tip-enhanced Raman spectroscopy

    Prof. Mun Seok JEONG’s research team (Department of Energy Science) reported that the defect-related Raman scattering signal was successfully obtained from a monolayer tungsten disulfide by using tip-enhanced Raman spectroscopy. Two-dimensional transition metal dichalcogenides (TMD) materials have been widely investigated due to their optical properties such as the bandgap engineering that depends on the number of layers. In particular, monolayer tungsten disulfide (WS2) shows intense photoluminescence with a relatively high quantum yield among TMDs. Thus, monolayer WS2 has attracted much interest as an outstanding material for 2D optoelectronic devices. To achieve the high performance of optoelectronic devices, the defect-free WS2 is highly required. Accordingly, it is necessary to establish a quality evaluation method by investigating the defects of monolayer WS2. The research team was able to detect new signals in areas with many defects by using tip-enhanced Raman spectroscopy, which can simultaneously perform surface nanostructure analysis and optical measurement. In addition, density functional theory (DFT) calculations confirmed that this signal is attributable to the sulfur atom (S) vacancies. The researchers called it a "D mode" from the defect and reported that it provides a criterion for evaluating the quality of monolayer WS2 compared to the intensity of the signal in the defect-free area. Prof. JEONG said, “It is notable that this study was the first to detect signals related to defects in two-dimensional semiconductor materials. In the future, it can be applied to various two-dimensional semiconductor materials to determine quality evaluation standards, and it can accelerate the commercialization of two-dimensional semiconductors. These findings have been published in the journal “ACS Nano (IF = 13.709)” (October 23rd 2018). This work was supported by IBS-R011-D1 and the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2016R1A2B2015581). Mr. Chanwoo LEE (Ph.D. candidate, Departmentof Energy Science) participated as the lead author and Dr. Seung Mi LEE (Korea Research Institute of Standards and Science) participated as a co-corresponding author. (Diagram) Measurement of defects

  • Development of Catalytic Asymmetric Synthetic Method of Cyclobutanones

    Chemistry Prof. RYU, DOHYUN ·Researcher SHIM, SUYONG

    Development of Catalytic Asymmetric Synthetic Method of Cyclobutanones

    A research team led by Prof. Do Hyun RYU (Dept. of Chemistry) has developed Lewis acid catalyzed asymmetric synthetic method of cyclobutanones. Chiral four-membered carbocyclic compounds are key structures of bioactive natural products. Therefore, they have attracted a lot of attention in the academic and industrial world. Although four-membered carbocyclic ketone compounds can be obtained from cyclopropane compounds through ring-opening reactions, there has been no example of asymmetric synthesis of cyclobutanones from cyclopropyl aldehydes through rearrangement reactions. The research team developed asymmetric synthetic method of cyclobutanones with chiral Lewis acid catalyst through tandem cyclopropanation/semipinacol rearrangement reaction to give good yields and high enantioselectivities. The newly developed methodology exhibits excellent atom economy because it utilizes simple starting materials and only produces nitrogen gas (N2) as a by-product. Prof. RYU said, “the synthesis of chiral cyclobutanone compounds through rearrangement of cyclopropyl aldehydes has been an unresolved challenge for the last 50 years. This work is highly valuable because this is the first research result with a catalyst and provides experimental results to elucidate the reaction mechanism.” Cyclobutanones are highly useful compounds because they can be utilized in ring expansion or ring opening reactions due to their innate ring strain. In this regard, this synthetic method is expected to be valuable synthetic tool for further organic synthesis. This research was published in the ‘Journal of the American Chemical Society (JACS; IF : 14.357)’ as of August 8th, 2018, with the title of “Asymmetric Synthesis of Cyclobutanone via Lewis Acid Catalyzed Tandem Cyclopropanation/Semipinacol Rearrangement”. This work was selected as the cover page.

  • Conversion of CO2 to value-added petrochemicals using highly ordered mesoporous metal oxides and zeolites

    Chemical Engineering Prof. BAE, JONG WOOK ·Researcher HAM, HYUNGWON

    Conversion of CO2 to value-added petrochemicals using highly ordered mesoporous metal oxides and zeolites

    The energy and chemical consumptions in the world have been steadily increasing, and it has led to the rapid depletion of energy and petrochemical resources. When fossil fuels are burnt they predominantly produce CO2, which has been identified as a major factor contributing to climate changes. The present use of natural resources does not secure the ability of future generations to meet their own energy and petrochemical needs. The utilization of these fossil and unconventional resources also impair the problems associated with the greenhouse gas emissions (especially, CO2) and thus it is vital for mankind to find renewable, sustainable and environmentally friendly alternative chemicals. Figure 1. (a) World’s primary energy resources and (b) their uses [Green Chem. 16 (2014) 2015] Conversions of syngas including CO2 into a broad spectrum of hydrocarbon fuels (gasoline, diesel and jet fuels), oxygenates (dimethyl ether and alcohols) and building-block chemicals (light olefins and aromatics) are the core technology of C1 chemistry (Figure 1). This method has a significant potential to replace the existing petroleum-derived products in the petrochemical industry. It uses biomass for syngas generation, which can produce CO2-neutral fuels and chemicals as well. Syngas (primarily a mixture of CO and H2 with various amount of CO2), a key feedstock in chemical, oil and energy industries, can be obtained from non-petroleum carbon resources namely coal, natural gas, biomass and solid waste. Therefore, most of the research efforts have been currently devoted to the developments of efficient and stable transition metal-based catalysts with suitable reaction parameters. Syngas conversions are largely motivated in C1 chemistry (Figure 2). Figure 2. Transformations of syngas into various carbon containing fuels, oxygenates and building-block chemicals via different catalytic processes In our Laboratory, the synthesis of dimethyl ether (DME) from syngas containing CO2, which is widely used as one of the crucial chemical intermediates for producing of value-added petrochemicals, and its transformations to value-added chemicals such as benzene, toluene and xylenes (BTX) have been intensively studied by using the highly stable ordered mesoporous metal oxides as well as highly crystalline zeolites. Those heterogeneous catalytic systems can be one of the efficient routes to utilize the CO2 greenhouse gas to the value-added chemical intermediates through CO or CO2 hydrogenation reaction. Those recent results were published in the journals of Applied Catalysis B (2017, IF: 11.698), ACS Catalysis (2018, IF: 11.384) and Advanced Materials (2019, IF: 21.95) as well. Figure 3. Utilization of alternative feedstock to value-added petrochemicals by using highly ordered mesoporous metal oxides combined with crystalline zeolites

  • Did Life Begin Within A Water Cage?

    Chemistry Prof. SONG, CHOONGEUI

    Did Life Begin Within A Water Cage?

    Prof. Choong Eui Song (Department of Chemistry) and his students have recently published a significant article, titled “Hydrophobic chirality amplification in confined water cages” in the world-renowned international journal, Nature Communications. In this study, they provided a plausible scenario for the chiral amplification process, which might help unlock secrets of homochirality on our planet. Homochirality is a fundamental component of molecular recognition in biological systems. Enantiomers (optical isomers) are chiral molecules that are mirror images of one another. They are also non-superimposable to one another. For all intents and purposes, pairs of enantiomers have the same Gibbs free energy. Thus, both enantiomers of a compound will form in equal amounts (a racemic mixture) when we synthesize them in the laboratory under non-chiral environment. However, all living forms on Earth consist of single enantiomer of molecules like D-sugars and L-amino acids, which are basic components for DNA, RNA and proteins (i.e., homochiral). Although homochirality in life forms is found in all living things from wild grasses to human beings, its origin still remains as an unsolved mystery. Most theories for biological homochirality require a chiral amplification mechanism that acts to enhance a small initial asymmetry. Prof. Song’s research team discovered that water can act as a chirality amplifier and thus the enantioselectivity of an asymmetric catalytic reaction can be greatly amplified in the aqueous microdroplets. Flow and batch reactors were evaluated to confirm this general water-induced hydrophobic effects on enantioselectivity. They presumed that this water-enabled chirality amplification stems from the hydrophobic hydration effect, which enforces proximity of the hydrophobic catalyst and substrates in confined water cages and consequently leads to a more compact transition state. Prof. Song says, “This remarkable observation could provide some inspiration for developing new strategies to enhance the enantioselectivity of some catalytic reactions and thus has the potential to open a new chapter in the field of asymmetric catalysis. In addition, considering that the aqueous environment of early Earth resembled aerosol droplets (mist, clouds, and spray, etc.) at the surface of oceans, our results would also offer one of the reasonable scenarios for the chirality amplification process which led to the present homochirality life on our planet. Furthermore, it is likely that the limited diffusion of enantio-enriched products in such droplets might provide a chance to participate in a self-replicating, evolvable system in the prebiotic era.” *Article title: Hydrophobic chirality amplification in confined water cages” Nature Communications, 10, 851 (2019) (DOI: 10.1038/s41467-019-08792-z). Figure 1. Photos of asymmetric catalytic reaction under on-water conditions. a. before reaction; b. during reaction; c. after reaction. Figure 2. Flow microchip reactor Figure 3. (a) Flow microreactor system (b) Plug volume can be controlled by varying the relative flow rates of the two phases (c) Effect of biphasic microfluidic conditions

  • GABA-modulating bacteria of the human gut microbiota

    Pharmacy Prof. KIM, KI HYUN

    GABA-modulating bacteria of the human gut microbiota

    □ Prof. Ki Hyun KIM (School of Pharmacy) and his co-researchers in Northeastern University and Harvard Medical School have recently published a significant article, titled “GABA-modulating bacteria of the human gut microbiota” in the world-renowned international journal, Nature Microbiology (Impact Factor 14.174). □ The gut microbiota affects many important host functions, including the immune response and the nerve system. However, while substantial progress has been made in growing diverse microorganisms of the microbiota, 23–65% of species residing in the human gut remain uncultured, which is an obstacle for understanding their biological roles. A likely reason for this unculturation is the absence in artificial medium of key growth factors that are provided by neighbouring bacteria in situ. □ In the present study, we used co-culture to isolate KLE1738, which required the presence of Bacteroides fragilis to grow. Bioassay-driven purification of B. fragilis supernatant led to the isolation of the growth factor, which, surprisingly, is the major inhibitory neurotransmitter GABA (γ-aminobutyric acid). Surprisingly, GABA was the only tested nutrient that supported the growth of KLE1738, and a genome analysis supported a GABA-dependent metabolism mechanism. □ Using growth of KLE1738 as an indicator, we isolated a variety of GABA-producing bacteria, and found that Bacteroides ssp. produced large quantities of GABA. Genome-based metabolic modelling of the human gut microbiota revealed multiple genera with the predicted capability to produce or consume GABA. A transcriptome analysis of human stool samples from healthy individuals showed that GABA-producing pathways are actively expressed by Bacteroides, Parabacteroides and Escherichia species. □ By coupling 16S ribosmal RNA sequencing with functional magentic resonance imaging in patients with major depressive disorder, a disease associated with an altered GABA-mediated response, we found that the relative abundance levels of faecal Bacteroides are negatively correlated with brain diseases associated with depression. □ The research is evaluated to be the first case of integrated research between human gut microorganism cultivation and natural product chemistry. It is expected to propose potential in the development of new therapeutic and preventive agents to treat depression using GABA-modulating bacteria. *Thesis title: GABA-modulating bacteria of the human gut microbiota, Nature Microbiology, 4, 396–403 (2019) (doi.org/10.1038/s41564-018-0307-3). Fig. 1 Co-culture assay to isolate KLE1738. Fig. 2 In vitro and in silico identification of GABA-modulating bacteria. Fig. 3 Relative abundance of faecal Bacteroides inversely correlates with functional connectivity between left DLPFC and DMN structures in patients with MDD.

  • Skeletal muscle-specific Prmt1 deletion causes muscle atrophy via deregulation of the PRMT6-FOXO3 axis

    Medicine Prof. KANG, JONG SUN ·Dr. JUNG, Hyun Joo

    Skeletal muscle-specific Prmt1 deletion causes muscle atrophy via deregulation of the PRMT6-FOXO3 axis

    Skeletal muscle wasting is caused by physical disuse, aging and chronic diseases and it is detrimental for the metabolic health and aggravates other chronic diseases, leading to increased morbidity and mortality. In atrophying muscles, FOXO transcription factors are activated which in turn regulate multiple components of the ubiquitin-proteasome pathway, such as the muscle-specific ubiquitin ligases muscle RING-finger (MuRF1) and Atrogin1/MAFbx, leading to accelerated proteolysis and atrophy. Thus, the mechanism by which FOXO transcription factors are regulated in skeletal muscle needs to be investigated to better understand muscle homeostasis and dysfunction. Protein arginine methyltransferases (PRMTs) have emerged as important regulators of skeletal muscle metabolism and regeneration. However, their function in skeletal muscle remodeling and homeostasis remains unclear. In this study, we investigated the role of PRMT1 in skeletal muscle by utilizing skeletal muscle-specific PRMT1 knockout mice. We found that muscle-specific PRMT1 deficiency leads to muscle atrophy. PRMT1 level is decreased in the fasted state of skeletal muscle while increased in the refed condition. Consistently, PRMT1-deficient muscles exhibit enhanced levels of FoxO3a and muscle-specific ubiquitin ligases, MuRF1 and Atrogin1 that are associated with protein degradation. The mechanistic study reveals that PRMT1 regulates FOXO3 through PRMT6 modulation. In the absence of PRMT1, increased PRMT6 specifically methylates FOXO3 at arginine 188 and 249, leading to its activation. Finally, we demonstrate that PRMT1 deficiency triggers FOXO3 hyperactivation, which is abrogated by PRMT6 depletion. Taken together, PRMT1 is a key regulator for PRMT6/ FOXO3 axis in the control of skeletal muscle maintenance. Thus, PRMT1 may be a target to prevent muscle wasting under specific pathological conditions and related metabolic diseases. This research was conducted as a joint research of researchers from SKKU and Korea University. It was posted on the online version of the Autophagy journal on January 2019. Diagram 1. Cross sectional areas of the muscle that manifests Myh type IIb (MYH4) is reduced in Skeletal muscle specific PRMT1 deficient mice’s anterior (TA) and muscle extensor digitorum longus (EDL) Diagram 2. The manifestation of PRMT1 inskeletal muscle reduced from the fasted state while increased in the state of refed Diagram 3. In a PRMT1 deficient muscle the excessive increase of PRMT6 causes muscle wasting due to the continual activation of FOXO3

  • Development of an energy-efficient and robust zirconium carboxylate metal-organic framework

    Chemistry Prof. CHANG, JONGSAN

    Development of an energy-efficient and robust zirconium carboxylate metal-organic framework

    Prof. Jong-San CHANG (Professor, Dept. of Chemistry, Sungkyunkwan University and KRICT) and his co-researchers in the French CNRS have recently published an important article, titled with “A robust large-pore zirconium carboxylate metal-organic framework for energy-efficient water-sorption-driven refrigeration’’ in Nature Energy (doi: 10.103 /s41560-018-0261-6). The use of electric air conditioners is rapidly increasing due to recent weather changes and global warming. There are more than 1.6 billion electric air conditioners operating in the world. Amount of greenhouse gas emissions due to the use of air conditioner was 1.25 billion tons in 2016. The IEA recently estimated that outdoor units of electric air-conditioners raise the temperature by 1oC overnight in the cities. The new generation of air conditioners will get rid of noisy compressors and greenhouse gas coolants and instead rely on the cooling power of water, thanks to a super adsorbent metal-organic framework (MOF). The porous material could drive adsorption chillers that, instead of consuming huge amounts of electricity, run on industrial waste heat or solar energy. The water sorption (i.e., molecules capable of fixing water at the surface) is used for heat recovery from industrial processes and solar energy. The typical temperature of in-house warm water systems involving a cogeneration producer does not exceed 63°C, and it can be used for cooling systems and heat pumps. Currently it is based on inorganic porous commercial adsorbents (zeolites or related solids) that suffer from high regeneration temperatures and/or limited pore volumes leading to energy-inefficient systems. To overcome these drawbacks, the researchers designed a new hydrophilic nanoporous hybrid solid with large pores, made of zirconium oxoclusters. Made from zirconium oxo clusters linked by tetracarboxylate units, the MOF can store almost twice as many water in its hydrophilic channels than the silica gel, a common desiccant. The researchers also showed that their material outperforms a commercial zeolite absorbent in terms of cooling performance which is the ratio of cooling to energy input required to release the coolant. For cooling, the overall performance relies not only on evaporation and condensation temperatures of water, but also on adsorption (exothermic) and desorption (endothermic) temperatures, the storage capacity, stability and kinetics of heat exchange. The new Zr-MOF exhibits a microporous structure very stable in presence of hot water. It shows a highly pronounced hydrophilic behavior with significant heat exchanges and a pore size sufficient enough to adsorb large amount of water and also a lower regeneration temperature during desorption step (<65°C). They have performed energetic performance calculations (ratio of the energy taken from the evaporator and the energy needed to regenerate the adsorbent). This analysis revealed that the solid is more efficient than any other evaluated porous materials so far for this type of application. It will lead to the development of a new generation of cooling to recover solar energy or even energy from heat sources related to human activities. *Thesis title: A robust large-pore zirconium carboxylate metal–organic framework for energy-efficient water-sorption-driven refrigeration, Nature Energy, 3, 985-993 (2018). (DOI:10.1038/s41560-018-0261-6)

  • Solution to the heterologous synthesis of “Two-Dimensional Matter”

    Physics Prof. LEE, YOUNGHEE

    Solution to the heterologous synthesis of “Two-Dimensional Matter”

    Prof. Younghee LEE (Dept. of Energy Science) has developed a technology to synthesize Hexagonal boron nitride, a Two-Dimensional matter composed of two elements (nitrogen and boron) into a single crystal through a joint research. *Hexagonal boron nitride; hBN: a flat layered material composed of boron and nitrogen with an atomic structure of a hexagon (like graphene) The result of the research has been published in the world-renowned international journal Science (issue date: November 16th). *Title of the thesis: Wafer-scale single-crystal hexagonal boron nitride film via self-collimated grain formation *Lead author: Researcher Joosong LEE(KIST, 1st author), Dr. Soomin KIM (KIST, Corresponding author), Head Younghee LEE (IBS, Corresponding author), Prof. Kigang KIM (Univ. of Dongguk, Corresponding author) Two-dimensional matters are excellent in the electrical feature, flexibility and transparency and is recognized as the core element of future electronic devices. It blocks the penetration of gas, which makes it suitable to be used for the protection of the elements. Boron nitride is receiving attention for its use as an insulation shield of transparent flexible electronic devices because it is the only two-dimensional matter that has the feature of insulation. However, the problem remains as they need to solve the issue of synthesizing it into a single crystal in order to keep the feature of boron nitride. The large-scaled boron nitride from the previous synthesis method was synthesized into a form of polycrystal, which showed deficiency in insulation and atomic linkage. Single Crystal: the state of crystals gathered in a specific order Polycrystal: many crystals are gathered in an irregular form. The linkage between crystals are imperfect The research team was able to synthesize a thin-film of single crystal boron nitride by using the phenomenon of self-collimation on the surface of liquid gold. This method enables the synthesis of single crystal regardless of the size of thin-film. *Self-Collimation: when the crystal grain of boron nitride is formed on the surface of the liquid gold, nitrogen and boron atoms cause an electrical gravitational pull to push and pull one another to keep an optimal distance. Also the team was able to synthesize other two-dimensional matters such as graphene, WS2, MoS2 into a single crystal by using the thin-film. They were also successful in synthesizing graphene and boron nitride into a form of layered structure. *Graphene: one of allotropes of carbon. The carbon atoms are formed in a shape of hexagon with a thin layer and shows high physical and chemical stability. The research is evaluated to have opened a new paradigm by developing an original technology to synthesize two-dimensional matter into a large-scaled single crystal. It is expected to bring innovation in the development of future transparent flexible electronic devices, gas barrier, sensors and filters. This research was conducted with the support of the Ministry of Science and ICT, Institute for Basic Science and the KIST (Korea Institute of Science and Technology). [Figure 1] A mimetic diagram of large-scaled single crystal synthesis due to self-collimation and two-dimensional boron nitride crystal grain [Figure 2] The synthesis of two-dimensional matters with the use of large-scaled single crystal boron nitride. Observed that it is arrange in a single direction. [Figure 3] Effective in improving the penetration of moisture in air and oxidation of metal despite the 0.3nm of thin-film.

  • Finding a hope to overcome antibiotics resistance from the herbal plant

    Medicine Prof. KIM, KYEONG KYU ·Dr. REKHA ARYA

    Finding a hope to overcome antibiotics resistance from the herbal plant

    According to the Sweden Global Challenges Foundation, antibiotic resistance is one of top 10 global catastrophic risks, and a solution needs to be found emergently. UK Parliamentary Papers in 2016 warned that over 10 million people will die in 2050 from superbacteria, if a solution to the antibiotic resistance problem cannot be found. It is certain that the antibiotics resistance is a problem of urgency and grave seriousness. Antibiotic resistance is a natural phenomenon that occurs inevitably as the bacteria adapts to the antibiotics through the process of mutation. Hence, developing new antibiotics with a new mechanism is necessary. Prof. Kim’s team identified that xanthoangelol B, which was extracted from ashitaba, inhibited the synthesis of virulence factors in Staphylococcus aureus, one of the most serious antibioticresistant bacteria, and induced clearance through a host immune response without pathogenesis. The group additionally established chemical synthesis methods for xanthoangelol, and prepared its derivatives. Among such derivatives, PM-56 showed anti-virulence activity more effective than that of the original xanthoangelol. Ashitaba is also called the “Hermit grass” and the name came from the traditional belief that those who eat ashitaba can become Taoist hermits. Also, its binomial name, Angelica utilis, is translated as “angel’s gift”. As the names suggest, ashitaba was believed to have special drug effects, and has been widely used as a healthy ingredient. This research has proven its effect by discovering its antivirul role. Professor Kyeoing Kyu Kim said, “In this study, we successfully validated a potency of the virulence-inhibitory antibiotics as a new concept of antibiotic mechanism. We expect further development of new therapeutic approaches for bacterial infection, which are free from drug resistance.” This study was conducted in “Institute for antimicrobial resistance and therapeutics” (https://shb.skku.edu/iamrt/), and published in Medicinal Chemistry (Nov, 2018). In addition, it was introduced in YTN science and Donga Newspaper. YTN Science: https://youtu.be/Ax_Rd8-85IM Donga Science: http://news.donga.com/3/all/20181202/93122384/1 Figure 1. Mechanism of PM-56, antivirulence inhibitor, to S. aureus. PM-56 blocks relay of phosphate group from a histidine kinase SeaS to a response regulator SaeR in SaeRS system. By blocking transfer of phosphate group, synthesis of virulence factors in downstream of SaeRS system is also blocked. Figure 2. Model experiment to validate antibiotic effect The viability of antibiotics resistant bacteria-infected Galleria mellonella larvae is 20% after 72 h. However, the viability of PM-56-treated larvae is increased dose-dependently, and finally 4.262 mg/kg body weigh-treated larvae shows 100% viability. It means S. aureus infection can be cured by the PM-56 treatment.

  • Development of biocatalysts for anti-inflammatory drug synthesis

    Medicine Prof. KIM, KYEONG KYU ·Dr. OH, CHANG SUK

    Development of biocatalysts for anti-inflammatory drug synthesis

    So far, the method of chemical synthesis had been used to produce fine chemicals such as medicine. However, the synthesis carries problems such as low economic efficiency and use of hazardous substances. The use of environment-friendly biocatalysts is one of the solutions to overcome these problems. The key advantages of the biocatalysts are the specificity of enzymes to substrates, reactions and stereoisomers, which can reduce the complexity involved in the process of chemical synthesis. Another great advantage is that it reacts in conditions at mild temperature, on atmospheric pressure, or in aqueous solution. For these reasons, the biocatalyst is under the spotlight as the core part of green chemistry, with less by-products and hazardous waste produced during the synthesis process. Protein engineering tools are applied in developing biocatalysts, by improving enzyme activities. There are two main streams in protein engineering: 1) directed evolution (the topic of Nobel Prize on Chemistry, 2018) and 2) structure-based rational design. Rational design is only applicable when structure and mechanism of the protein are available, but it is more efficient than the directed evolutionary approach. Ketoprofen, a non-steroidal anti-inflammatory drug, is an analgesic or a fever reducer, releasing inflammation and pain mediated by rheumatoid arthritis or osteoarthritis. It is used in external painkillers in forms of gel or patches. Ketoprofen has two stereoisomers, S- and R-form, with the S-form showing higher drug effect. The US Food and Drug Administrator guides that stereo isomeric drug should be an enantiomer, not a racemate. The ketoprofen from racemate is required to be highly purified. For high purity of ketoprofen in synthesis, Professor Kyeong Kyu Kim’s group identified 3D structure of esterase Est-Y29 complex, which is extracted from metagenomic library originated from soil in Korea, with (S)-ketoprofen in high resolution using X-ray crystallography. It showed that aromatic residues in substrate-binding pocket of the enzyme positively affects enantioselectivity of Est-Y29 to S-form by the interaction with ketoprofen ethyl ester (a precursor of ketoprofen). Based on 3D structural information of the complex, Kim’s group designed a mutant that has increased aromaticity in the substrate binding pocket and consequently succeeded in developing a new enzyme, whose enantioselectivity toward (S)-ketoprofen was about 5 times higher compared to wild-type. This research is noteworthy in its successful increase of protein function using rational design and the research has been published in ACS Catalysis Online on 2018 Dec 24. Professor Kyeong Kyu Kim explained the significance of the research as follows: “In the research, we developed a new biocatalyst which may displace chemical catalysts, using a 3D structure-based, protein engineering approach. It also proposes a potency of production of effective medicines such as ketoprofen, through environment-friendly methods.” Figure 1. The principal of enantioselectivity of Est-Y29 (S)-ketoprofen ethyl ester (SKE, magenta) forms π-alkyl interaction (pink dashed line) with aromatic residues (Y123, F125, Y170) in substrate-binding pocket of Est-Y29. However, most of the interaction was not shown to (R)-ketoprofen ethyl ester (RKE, blue), so S-form can bind to Est-Y29 more specifically. Figure 2. Increased production of (S)-ketoprofen in Est-Y29 F125W Replacement of phenylalanine at 125 in Wild-type Est-Y29 (top left) to tryptophan (Est-Y29 F125W, top right) increases aromaticity (orange) in substrate-binding pocket (cloud-like shape). The mutation increases affinity to S-form, and finally enhances (S)-ketoprofen production (bottom).

  • Research on the role of Protein arginine methyltransferase 1 in preventing heart failure

    Medicine Prof. KANG, JONG SUN

    Research on the role of Protein arginine methyltransferase 1 in preventing heart failure

    Cardiac disease is one of the most common adult diseases and a leading cause of death worldwide. The increasing rate of cardiac disorder is due to westernized lifestyle and aging population. It is an urgent matter to develop a method of treatment by researching the pathogenesis of cardiac disorders. The cause of most cardiac disorders roots from the regenerating process of the cardiomyocyte. When the cardiomyocyte cannot self-regenerate, it chooses to extend or increase in size, resulting ‘Cardiac hypertrophy’. Cardiac hypertrophy is kind of an adaptive response to physiological and pathological stimuli. However, pathological cardiac hypertrophy leads to heart failure. This study exhibited that mice with deficiency of cardiac PRMT1 showed a rapid progression to dilated cardiomyopathy and heart failure within 2 months of birth. Heart failure was accompanied with cardiomyocyte hypertrophy and fibrosis. From this, the research team discovered that PRMT1 is essential for the maintenance and survival of the cardiac function. CaMKII δ(Calcium/calmodulin-dependent protein kinase II δ), which was identified as the main target of this study has been linked with maintenance of Ca2+ homeostasis by phosphorylating various proteins important for excitation–contraction coupling and cell survival including ion channels. Thus, they proved that dysregulation of CaMKII δ is closely linked with myocardial hypertrophy and heart failure. However, the mechanism that regulates CaMKII activity is still in need for further research. The most important finding of this study was the fact that the protein arginine methyltransferase 1 (PRMT1) is essential for preventing cardiac CaMKII hyperactivation. The level of active CaMKII is significantly elevated in PRMT1-deficient hearts or cardiomyocytes. PRMT1 interacts with methylates CaMKII, leading to the inhibition. Accordingly, pharmacological inhibition of CaMKII restores contractile function in PRMT1-deficient mice. Thus, our study suggests that PRMT1 is a critical regulator of CaMKII to maintain cardiac function and potential therapeutic target of cardiac disease. Figure 1. Discovered that PRMT1 is the main factor that controls the level of stress that causes hypertrophy Figure 2. Identified that PRMT1 controls the activation of CaMKII δ

  • Development of muscle-mimetic cell-laden Nanofiber using 3D Cell-Electrospinning

    Bio-Mechatronic Engineering Prof. KIM, GEUNHYUNG

    Development of muscle-mimetic cell-laden Nanofiber using 3D Cell-Electrospinning

    Prof. Geun Hyung KIM and his research team reported that they have successfully aligned the nanofibrous structure by producing live myoblast cells and bioink suitable for electrospinning. Nano-muscular fibers implanted with live myoblast cells acted as if it were a real muscle tissue and accelerated the regeneration of muscle tissue by guiding the muscle cell to grow in a uniaxial direction. Tissue Regeneration Engineering is a field of study developed to improve the regeneration process of damaged tissues/organs by inserting a biological substitute, which is called scaffold. 3D cell-printing and electrospinning has been widely used for this process. However, the cells cultured by 3D cell-printing and electrospinning grew randomly, which was a serious problem for muscles that required its cells to be aligned for proper regeneration. To control cell morphology, they have developed electrospinning to a cell-electrospinning process. The research team used a biocompatible hydrogel to generate cell-laden nanofibers. Also, the hydrogel was added with a material with high processability to produce a bioink, which was applied with high-voltage direct current (Figure 1). After this, myoblast-laden nanofiber can be generated with an aligned pattern. -the myoblast-laden nanofibers showed over 90% of initial cell viability, which was a sign that it overcame the problem of low cell viability from the previous conventional cell-electrospinning process. Moreover, the cell alignment and differentiation improved threefold incomparison to the 3D cell-printing process (Figure 2). -the myoblast-laden nanofibers induced cells to grow in a uniaxial direction, which assists the regeneration of skeletal and cardiac muscle. Prof. KIM said, “This was the first case to successfully produce cell-laden nanofibers in uniaxial arrangement. It suggested a possibility to become a new method of regenerating aligned tissue structure.” This research was supported by a grant from the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology. It was selected as the cover page for a world-renowned journal, ‘Small’(Figure 3). * Read article at YTN Science Figure 1. Mimetic diagram of Electrospinning and electric radiation depending on the solution Figure 2. Comparison of newly developed electrospinnng and the previous 3D cell-printing process Figure 3. The cover page of 'Small'

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