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Scientist of October, Professor Haeshin Lee
(Professor Haeshin Lee from the Department of Chemistry)
Professor Haeshin Lee from the Department of Chemistry received the ‘Science and Technology Award of October’ from the Ministry of Science and ICT and the National Research Foundation of Korea for his contribution to developing an antibleeding injection needle. This novel outcome will fundamentally prevent the problem of secondary infections of AIDS, Ebola and Hepatitis viruses transmitting from patients to medical teams.
This needle’s surface is coated with hemostatic materials. Its concept is simple and the key to this technology is to make materials that are firmly coated on the needle so that they can endure frictional force when being injected into skin and blood vessels. Moreover, the materials should be adhesive to skin and the interior of blood vessels, but harmless to humans.
Professor Lee found a solution from natural polymer ingredients. Catecholamine can be found in mussels. Professor Lee conjugated catechol groups on the chitosan backbone. He applied this mussel-inspired adhesive polymer Chitosan-catechol, which immediately forms an adhesive layer with blood, as a bioadhesion for the antibleeding injection needle.
Professor Lee said, “Chitosan-catechol, which copies the adhesive mechanism of mussels, shows high solubility in physiological saline as well as great mucoadhesion. Hence, it is perfectly suitable for coating the injection needle. Combining it with proteins allows for efficient drug delivery to the heart, which is a challenging injection location, so it will be also useful for treating incurable heart disease.”
2018.10.05 View 10410 -
Flexible Piezoelectric Acoustic Sensors for Speaker Recognition
A KAIST research team led by Professor Keon Jae Lee from the Department of Material Science and Engineering has developed a machine learning-based acoustic sensor for speaker recognition.
Acoustic sensors were spotlighted as one of the most intuitive bilateral communication devices between humans and machines. However, conventional acoustic sensors use a condenser-type device for measuring capacitance between two conducting layers, resulting in low sensitivity, short recognition distance, and low speaker recognition rates.
The team fabricated a flexible piezoelectric membrane by mimicking the basilar membrane in the human cochlear. Resonant frequencies vibrate corresponding regions of the trapezoidal piezoelectric membrane, which converts voice to electrical signal with a highly sensitive self-powered acoustic sensor.
This multi-channel piezoelectric acoustic sensor exhibits sensitivity more than two times higher and allows for more abundant voice information compared to conventional acoustic sensors, which can detect minute sounds from farther distances. In addition, the acoustic sensor can achieve a 97.5% speaker recognition rate using a machine learning algorithm, reducing by 75% error rate than the reference microphone.
AI speaker recognition is the next big thing for future individual customized services. However, conventional technology attempts to improve recognition rates by using software upgrades, resulting in limited speaker recognition rates. The team enhanced the speaker recognition system by replacing the existing hardware with an innovative flexible piezoelectric acoustic sensor. Further software improvement of the piezoelectric acoustic sensor will significantly increase the speaker and voice recognition rate in diverse environments.
Professor Lee said, “Highly sensitive self-powered acoustic sensors for speaker recognition can be used for personalized voice services such as smart home appliances, AI secretaries, always-on IoT, biometric authentication, and FinTech.”
These research “Basilar Membrane-Inspired Self-Powered Acoustic Sensor” and “Machine Learning-based Acoustic Sensor for Speaker Recognition” were published in the September 2018 issue of Nano Energy.
Firgure 1: A flexible piezoelectric acoustic sensor mimicking the human cochlear.
Figure 2: Speaker recognition with a machine learning algorithm.
2018.10.04 View 7571 -
KAIST Develops VRFB with Longer Durability
(from left: PhD candidate Soohyun Kim, Professor Hee-Tak Kim and PhD candidate Junghoon Choi)
There has been growing demand for large-scale storage for energy produced from renewable energy sources in an efficient and stable way. To meet this demand, a KAIST research team developed a new vanadium redox-flow battery (VRFB) with 15 times greater capacity retention and five times longer durability. This VRFB battery can be an excellent candidate for a large-scale rechargeable battery with no risk of explosion.
The VRFB has received much attention for its high efficiency and reliability with the absence of cross-contamination. However, it has the limitation of having insufficient charge and discharge efficiency and a low capacity retention rate because its perfluorinated membrane is very permeable to any active materials. To minimize energy loss, it needs a membrane that has low vanadium ion permeability and high ion conductivity. Hence, there was an attempt to incorporate a hydrocarbon membrane that has low cost and high ion selectivity but it turned out that the VO₂+ caused chemical degradation, which led to shortening the battery life drastically.
To develop a membrane with pore sizes smaller than the hydrated size of vanadium ions yet larger than that of the protons, a research team co-led by Professor Hee-Tae Jung and Professor Hee-Tak Kim from the Department of Chemical and Biomolecular Engineering implemented a graphene-oxide framework (GOF) membrane by cross-linking graphene oxide nanosheets. They believed that GOF, having strong ion selectivity, would be a good candidate for the membrane component for the VRFB. The interlayer spacing between the GO sheets limited moisture expansion and provided selective ion permeation.
The GOF membrane increased the capacity retention of the VRFB, which showed a 15 times higher rate than that of perfluorinated membranes. Its cycling stability was also enhanced up to five times, compared to conventional hydrocarbon membranes.
These pore-sized-tuned graphene oxide frameworks will allow pore-sized tuning of membranes and will be applicable to electrochemical systems that utilize ions of various sizes, such as rechargeable batteries and sensors.
Professor Kim said, “Developing a membrane that prevents the mixing of positive and negative active materials has been a chronic issue in the field of redox-flow batteries. Through this research, we showed that nanotechnology can prevent this crossover issue and membrane degradation. I believe that this technology can be applied to various rechargeable batteries requiring large-scale storage.”
This research was published in Nano Letters on May 3.
Figure 1. Electrochemical performances of the VRFBs with Nafion 115, SPAES (sulfonated poly), and GOF/SPAES: discharge capacity
Figure 2. Schematic of the selective ion transfer of hydrated vanadium ions and protons in the GOF membrane and the molecular structure of the GOF membrane, showing that the GO nanosheets are cross-linked with EDA (ethylenediamine)
2018.09.20 View 7468 -
Using Donut-shaped Lithium Sulfide for Higher Performing Batteries
(from left: Research Professor Fangmin Ye and Professor Hee-Tak Kim)
A KAIST research team developed a lithium-sulfur battery with a doughnut-shaped active material structure showing a record lifecycle of over 600 cycles. Having higher energy density and lower production cost than a lithium-ion battery (LIB), it can be used in electric vehicles that require a longer battery life.
There has been an intense research conducted for developing lithium-sulfur batteries with high energy density because LIBs only allow for a very short travel distance per charge. However, Li-S batteries are still unable to provide a longer lifecycle due to the poor reversibility of the lithium metal cathode.
To tackle this issue, Professor Hee-Tak Kim from the Department of Chemical and Biomolecular Engineering and his team used lithium sulfide (Li₂S) cathodes and combine them with graphite anodes to enhance energy density and lifecycles for the batteries.
Yet, lithium sulfide is costly and, so far, there has not been an electrode architecture and electrolyte design that enables a longer lifecycle between the graphite anodes and lithium sulfide cathodes.
Hence, the team produced a doughnut-shaped lithium sulfide cathode active material from low-cost lithium sulfide developed from raw materials. They have also developed a lithium sulfide ion battery with a graphite anode and lithium sulfide cathode using a high concentration salt electrolyte.
This doughnut-shaped lithium sulfide showed outstanding charge and discharge reversibility through improving the transfer of lithium ions. Its highly concentrated salt electrolyte formed a stable film on the surface of the graphite electrode, which showed strong durability.
Through this technology, the team achieved 30% higher energy density than that of conventional LIBs and secured a lifecycle of more than 600 cycles. This doughnut-shaped lithium sulfide-based electrode can be manufactured using low-cost raw materials and a single heat treatment process. The electrode can also be applied to existing LIBs.
Professor Kim said, “We have demonstrated that applying low-cost sulfur compounds to LIBs can improve both energy density and the lifecycle simultaneously.”
This research, led by Research Professor Fangmin Ye, was published in Advanced Science on May 7.
Figure 1. Structural characterization of Li₂SO₄/CNT and Li₂S/CNT electrodes and suggested mechanism for the formation of the holey-Li₂S nanoarchitecture
2018.09.19 View 5756 -
Effective Drug Delivery to Heart with Tannic Acid
(Professor Haeshin Lee from the Department of Chemistry) Typical methods of drug delivery to the heart require surgical procedures involving incisions in the chest wall and bones. To efficiently treat cardiovascular and related vascular diseases without surgery, a KAIST research team developed a heart-targeting drug delivery technology using tannin acid via intravenous systemic injection. This method can be applied to the development of a variety of new protein-based drugs.
Cardiovascular-circulatory disease is currently the second leading cause of death in Korea. A typical example of this disease is myocardial infarction caused by poor oxygen and nutrient supply due to narrowed coronary arteries and poor blood flow to the heart.
Although there have been numerous research projects to develop chemotherapeutic drugs and therapeutic proteins, clinics still rely on surgical procedures. Drug delivery can be an alternative, but it is quite challenging because ceaseless dynamic cycles of the heart and massive exchanges of blood mean administered therapeutics do not stay inside the heart very long.
Professor Haeshin Lee from the Department of Chemistry and his team employed tannic acid (TA), which is known for giving bitter taste to wines. It is one of the most abundant polyphenols and can be easily found in plants, such as fruits, vegetables, cacao, and others. TA has also been used as a multifunctional coating molecule.
Using these properties of TA, the team complexed protein and peptide therapeutics with tannic acid and succeeded in targeting protein and peptide therapeutics to the heart. TA, coated on the surface of a granulated protein complex, helps maintain cardiac function because it adheres to extracellular matrices, elastin, and collagens in heart tissues allowing the protein to stay attached to the heart tissue for a longer period.
The team confirmed that these Tannic-acid-modified proteins stay in blood vessels five days longer than with protein-only injections. Additionally they found that TA-protein complexes do not show any cardiac toxicity and do not cause noticeable pathology.
The team has been continuously developing biomaterials for medical applications by testing various polyphenolic materials that feature adhesive and coating properties, including tannic acid. They have injected a mixture of TA and fibroblast growth factors (FGF) into animal models with myocardial infarctions. After four weeks, they confirmed that the infarction was reduced and the left ventricular pressure and cardiac output were almost normalized.
Professor Lee said, “Although there have been numerous drugs related to heart disease, so far there has not been efficient drug delivery to the heart so this technology will be able to reformulate existing drugs into new and more efficient drugs.”
This research, jointly led by Dr. Ki-Suk Kim from the Predictive Model Research Center, was published in Nature Biomedical Engineering on April 30 ( http://www.nature.com/articles/s41551-018-0227-9 ).
Figure 1. Schematic for the heart-targeting mechanism of TANNylated protein nanocomplexes: (1) size-dependent permeation, (2) phenolic (that is, TA), and (3) internalization by internalization by myoblasts
Figure 2. Effect of TA based protein complexes on cardiac cell transport efficiency and viral gene expression efficiency and therapeutic function in animal models with myocardial infarction
2018.09.18 View 5493 -
Engineered E. coli Using Formic Acid and CO2 As a C1-Refinery Platform Strain
(Figure: Formic acid and CO2 assimilation pathways consisting of the reconstructed THF cycle and reverse glycine cleavage reaction. This schematic diagram shows the formic acid and CO2 assimilation procedure through the pathway. Plasmids used in this study and the genetic engineering performed in this study are illustrated.)
A research group at KAIST has developed an engineered E. coli strain that converts formic acid and CO2 to pyruvate and produces cellular energy from formic acid through reconstructed one-carbon pathways. The strategy described in this study provides a new platform for producing value-added chemicals from one-carbon sources.
Formic acid is a carboxylic acid composed of one carbon. Formic acid was produced from CO2 by the chemical method. Recently, the C1 Gas Refinery R&D Center has successfully developed a biological process that produces formic acid from carbon monoxide for the first time. Formic acid is in a liquid state when at room temperature and atmospheric pressure. In addition, it is chemically stable and less toxic, thus, easy to store and transport. Therefore, it can be used as an alternative carbon source in the microbial fermentation process. In order to produce value-added chemicals using formic acid, a metabolic pathway that converts formic acid into cellular molecules composed of multiple carbons is required. However, a metabolic pathway that can efficiently convert formic acid into cellular molecules has not been developed. This acted as an obstacle for the production of value-added chemicals using formic acid
A research group of Ph.D. student Junho Bang and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering addressed this issue. This study, entitled “Assimilation of Formic Acid and CO2 by Engineered Escherichia coli Equipped with Reconstructed One-Carbon Assimilation Pathways”, has been published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on September 18.
There has been increasing interest in utilizing formic acid as an alternative carbon source for the production of value-added chemicals. This research reports the development of an engineered E. coli strain that can convert formic acid and CO2 to pyruvate and produce cellular energy from formic acid through the reconstructed one-carbon pathways.
The metabolic pathway that efficiently converts formic acid and CO2 into pyruvate was constructed by the combined use of the tetrahydrofolate cycle and reverse glycine cleavage reaction. The tetrahydrofolate cycle was reconstructed by utilizing Methylobacterium extorquens formate-THF ligase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase. The glycine cleavage reaction was reversed by knocking out the repressor gene (gcvR) and overexpressing the gcvTHP genes that encode enzymes related with the glycine cleavage reaction. Formic acid and CO2 conversion to pyruvate was increased via metabolic engineering of the E. coli strain equipped with the one-carbon assimilation pathway.
In addition, in order to reduce glucose consumption and increase formic acid consumption, Candida boidnii formate dehydrogenase was additionally introduced to construct a cellular energy producing pathway from formic acid. This reduces glucose consumption and increases formic acid consumption.
The reconstructed one-carbon pathways can supply cellular molecules and cellular energies from the formic acid and CO2. Thus, the engineered E. coli strain equipped with the formic acid and CO2 assimilation pathway and cellular energy producing pathway from formic acid showed cell growth from formic acid and CO2 without glucose. Cell growth was monitored and 13C isotope analysis was performed to confirm E. coli growth from the formic acid and CO2. It was found that the engineered E. coli strain sustained cell growth from the formic acid and CO2 without glucose.
Professor Lee said, “To construct the C1-refinery system, a platform strain that can convert one-carbon materials to higher carbon materials needs to be developed. In this report, a one-carbon pathway that can efficiently convert formic acid and CO2 to pyruvate was developed and a cellular energy producing pathway from formic acid was introduced. This resulted in an engineered E. coli strain that can efficiently utilize formic acid as a carbon source while glucose consumption was reduced. The reconstructed one-carbon pathways in this research will be useful for the construction of the C1-refinery system.”
This work was supported by the C1 Gas Refinery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2016M3D3A1A01913250). For further information: Sang Yup Lee, Distinguished Professor of Chemical and Biomolecular Engineering, KAIST (leesy@kaist.ac.kr, Tel: +82-42-350-3930)
2018.09.18 View 6887 -
Mathematical Principle behind AI's 'Black Box'
(from left: Professor Jong Chul Ye, PhD candidates Yoseob Han and Eunju Cha)
A KAIST research team identified the geometrical structure of artificial intelligence (AI) and discovered the mathematical principles of highly performing artificial neural networks, which can be applicable in fields such as medical imaging.
Deep neural networks are an exemplary method of implementing deep learning, which is at the core of the AI technology, and have shown explosive growth in recent years. This technique has been used in various fields, such as image and speech recognition as well as image processing.
Despite its excellent performance and usefulness, the exact working principles of deep neural networks has not been well understood, and they often suffer from unexpected results or errors. Hence, there is an increasing social and technical demand for interpretable deep neural network models.
To address these issues, Professor Jong Chul Ye from the Department of Bio & Brain Engineering and his team attempted to find the geometric structure in a higher dimensional space where the structure of the deep neural network can be easily understood. They proposed a general deep learning framework, called deep convolutional framelets, to understand the mathematical principle of a deep neural network in terms of the mathematical tools in Harmonic analysis.
As a result, it was found that deep neural networks’ structure appears during the process of decomposition of high dimensionally lifted signal via Hankel matrix, which is a high-dimensional structure formerly studied intensively in the field of signal processing.
In the process of decomposing the lifted signal, two bases categorized as local and non-local basis emerge. The researchers found that non-local and local basis functions play a role in pooling and filtering operation in convolutional neural network, respectively.
Previously, when implementing AI, deep neural networks were usually constructed through empirical trial and errors. The significance of the research lies in the fact that it provides a mathematical understanding on the neural network structure in high dimensional space, which guides users to design an optimized neural network.
They demonstrated improved performance of the deep convolutional framelets’ neural networks in the applications of image denoising, image pixel in painting, and medical image restoration.
Professor Ye said, “Unlike conventional neural networks designed through trial-and-error, our theory shows that neural network structure can be optimized to each desired application and are easily predictable in their effects by exploiting the high dimensional geometry. This technology can be applied to a variety of fields requiring interpretation of the architecture, such as medical imaging.”
This research, led by PhD candidates Yoseob Han and Eunju Cha, was published in the April 26th issue of the SIAM Journal on Imaging Sciences.
Figure 1. The design of deep neural network using mathematical principles
Figure 2. The results of image noise cancelling
Figure 3. The artificial neural network restoration results in the case where 80% of the pixels are lost
2018.09.12 View 6425 -
Distinguished Professor Sang Yup Lee Announced as the Eni Award Recipient
(Distinguished Professor Sang Yup Lee)
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering will be awarded the 2018 Eni Advanced Environmental Solutions Prize in recognition of his innovations in the fields of energy and environment. The award ceremony will take place at the Quirinal Palace, the official residence of Italian President Sergio Mattarella, who will also be attending on October 22.
Eni, an Italian multinational energy corporation established the Eni Award in 2008 to promote technological and research innovation of efficient and sustainable energy resources. The Advanced Environmental Solutions Prize is one of the three categories of the Eni Award. The other two categories are Energy Transition and Energy Frontiers. The Award for Advanced Environmental Solutions recognizes a researcher or group of scientists that has achieved internationally significant R&D results in the field of environmental protection and recovery. The Eni Award is referred to as the Nobel Award in the fields of energy and environment.
Professor Lee, a pioneering leader in systems metabolic engineering was honored with the award for his developing engineered bacteria to produce chemical products, fuels, and non-food biomass materials sustainably and with a low environmental impact. He has leveraged the technology to develop microbial bioprocesses for the sustainable and environmentally friendly production of chemicals, fuels, and materials from non-food renewable biomass.
The award committee said that they considered the following elements in assessing Professor Lee’s achievement: the scientific relevance and the research innovation level; the impact on the energy system in terms of sustainability as well as fairer and broader access to energy; and the adequacy between technological and economic aspects.
Professor Lee, who already won two other distinguished prizes such as the George Washington Carver Award and the PV Danckwerts Memorial Lecture Award this year, said, “I am so glad that the international academic community as well as global industry leaders came to recognize our work that our students and research team has made for decades.”
Dr. Lee’s lab has been producing a lot of chemicals in environmentally friendly ways. Among them, many were biologically produced for the first time and some of these processes have been already commercialized. “We will continue to strive for research outcomes with two objectives: First, to develop bio-based processes suitable for sustainable chemical industry. The other is to contribute to the human healthcare system through development of platform technologies integrating medicine and nutrition,” he added.
2018.09.12 View 7809 -
KAIST Core Technology Fair Accelerates Commercialization
(President Shin makes opening remarks at the KAIST Core Tech Transfer Day in Seoul.)
Technology commercialization is the one of the innovation initiatives KAIST is strongly driving. KAIST showcased six core technologies developed by KAIST research teams during the 2018 KAIST Core Tech Transfer Day on September 10 at Coex in Seoul. More than 300 investors, buyers, and venture capitalists showed up for the fair. This is the second fair organized as one of the strategic innovation initiatives that KAIST is promoting.
Developers of key technologies selected in the fields of bio, nano, AI, and semiconductors presented their distinct technological prowess to the attendees. The technologies are highly relevant for the new industrial environment trends in the Fourth Industrial Revolution.
The 15-member committee comprised of patent attorneys, venture capitalists, and commercialization specialists selected the six core technologies based on their innovativeness, applicability, and marketability. The Office of University-Industry Cooperation (OUIC) plans to offer buyers various services for developing business models, business strategy analysis, and marketing at home and abroad. The six core technologies featured at the fair include:
- Novel technology of a nano patterning platform by Professor Hee Tae Chung from the Department of Chemical and Biomolecular Engineering
- Anticancer therapeutic candidate materials strengthening immune function by Professor Byung Sok Choi from the Department of Chemistry
- Biofuel mass production using micro-organisms by Distinguished Professor Sang-Yup Lee from the Department of Chemical and Biomolecular Engineering
- Compact single-shot hyperspectral camera technology by Min Hyuk Kim from the School of Computing
- AI-powered high speed ultra-high definition upscaling technology by Professor Munchurl Kim from the School of Electrical Engineering - A radiation strong MOSFET device by Hee Chul Lee from the School of Electrical Engineering
President Sung-Chul Shin stressed in his opening remarks that universities should make contributions to economic development through innovation. “Global leading universities are taking an instrumental role in creating new jobs and economic growth with their own technologies. KAIST, as the leading university in Korea, is accelerating the commercialization of technology produced internally to create a meaningful impact for the economy as well as the job market beyond Korea,” he said.
“We are aiming for the global market, not just in Korea. I want KAIST to be a global value creator that can contribute to the betterment of the world through our innovations,” he added.
2018.09.10 View 6556 -
Rh Ensemble Catalyst for Effective Automobile Exhaust Treatment
(from left: Professor Hyunjoo Lee and PhD candidate Hojin Jeong)
A KAIST research team has developed a fully dispersed Rh ensemble catalyst (ENS) that shows better performance than commercial diesel oxidation catalyst (DOC). This newly developed ENSs could improve low-temperature automobile exhaust treatment.
Precious metals have been used for various heterogeneous reactions, but it is crucial to maximize efficiency of catalysts due to their high cost. Single-atom catalysts (SACs) have received much attention because it is possible for all of the metal atoms to be used for reactions, yet they do not show catalytic activity for reactions that require ensemble sites.
Meanwhile, hydrocarbons, such as propylene (C3H6) and propane (C3H8) are typical automobile exhaust gas pollutants and must be converted to carbon dioxide (CO2) and water (H2O) before they are released as exhaust. Since the hydrocarbon oxidation reaction proceeds only during carbon-carbon (C-C) or carbon-hydrogen (C-H) bond cleavage, it is essential to secure the metal ensemble site for the catalytic reaction. Therefore, precious metal catalysts with high dispersion and ensemble sites are greatly needed.
To solve this issue, Professor Hyunjoo Lee from the Department of Chemical and Biomolecular Engineering and Professor Jeong Woo Han from POSTECH developed an Rh ensemble catalyst with 100% dispersion, and applied it to automobile after-treatment. Having a 100% dispersion means that every metal atom is used for the reaction since it is exposed on the surface.
SACs also have 100% dispersion, but the difference is that ENSs have the unique advantage of having an ensemble site with two or more atoms.
As a result of the experiment, the ENSs showed excellent catalytic performance in CO, NO, propylene, and propane oxidation at low temperatures. This complements the disadvantage of nanoparticle catalyst (NPs) that perform catalysis poorly at low temperatures due to low metal dispersion, or SACs without hydrocarbon oxidation.
In particular, the ENSs have superior low-temperature activity even better than commercial DOC, hence they are expected to be applied to automobile exhaust treatment.
Professor Lee said, “I believe that the ENSs have given academic contribution for proposing a new concept of metal catalysts, differentiating from conventional SACs and NPs. At the same time, they are of great value in the industry of exhaust treatment catalysts.”
This research, led by PhD candidate Hojin Jeong, was published in the Journal of the American Chemical Society on July 5.
Figure 1. Concept of Rh ensemble catalyst for automobile exhaust treatment
Figure 2. Structure and performance comparison of single-atom catalyst and ensemble catalyst
Figure 3. Energy-dispersive X-ray spectroscopy (EDS) mapping images for SAC, ENS, and NP, respectively (green, Eh; red, Ce)
2018.08.29 View 7313 -
Metabolic Engineering of E. coli for the Secretory Production of Free Haem
Researchers of KAIST have defined a novel strategy for the secretory production of free haem using engineered Escherichia coli (E. coli) strains. They utilized the C5 pathway, the optimized downstream pathways, and the haem exporter to construct a recombinant micro-organism producing extracellular haem using fed-batch fermentation. This is the first report to extracellularly produce haem using engineered E. coli.
This strategy will expedite the efficient production of free haem to serve as a bioavailable iron-supplying agent and an important prosthetic group of multiple hemoproteins for medical uses. This study, led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, was published in Nature Catalysis on Aug. 28.
Haem, an organometallic compound complexed with a ferrous ion, is an essential molecule delivering oxygen in the blood of many animals. It is also a key component of electron transport chains responsible for the respiration of aerobic organisms including diverse bacteria. It is now being widely applied as a bioavailable iron-supplying agent in the healthcare and dietary supplement industries. The demand for haem and the need for the efficient production of this compound continue to grow.
Many previous researchers have attempted to produce free haem using engineered E. coli. However, none of the studies was successful in producing free haem extracellularly, requiring an additional step to extract the accumulated haem from cells for subsequent uses. The secretion of haem in the form of haem peptides or proteins also requires an extraction step to isolate the free haem from the secreted products. Thus, the secretory production of free haem is an important task for the economical production of haem that is suitable for human consumption.
Although some researchers could produce intracellular haem using recombinant E. coli strains, its final titer was extremely low, resulting from the use of sub-optimal metabolic pathways. Furthermore, the addition of the precursors L-glycine and succinate was deemed undesirable for massive industrial production. Thus, it is necessary to construct an optimized haem biosynthetic pathway to enable the efficient production of haem and examine the consequent secretion of free haem.
To address this issue, the KAIST team used multiple strategies to produce extracellular free haem by enhancing its biosynthesis in E. coli. First, the capacities of the C4 and C5 pathways to produce aminolevulinate (ALA) without feeding precursors were examined. After confirming the superior performance of the C5 pathway over the C4 pathway, the metabolic genes of the C5 pathway and downstream pathways for haem biosynthesis were overexpressed. Then, the metabolic pathways were optimized by adjusting the expression levels of the relevant genes and disrupting the putative haem degradation enzyme encoded by the yfeX gene.
Consequently, the resulting engineered strain secreted a significant amount of haem to the medium. Subsequent optimization of the cultivation conditions and the supplementation of nitrogen sources further increased both the titer of the total free haem and the amount of free haem secreted to the medium. Finally, the overexpression of the ccmABC genes encoding the haem exporter further enhanced the production and secretion of haem, producing the highest titer of haem both intracellularly and extracellularly from glucose.
Professor Lee said, “The eco-friendly and sustainable chemical industry is a key global agenda every nation faces. We are conducting research to bio-synthesize high concentrations, high yields, and high productivity in natural products. This novel technology will serve as an opportunity to advance the biochemical industry moving forward.”
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea. Further Contact: Dr. Sang Yup Lee, Distinguished Professor, KAIST, Daejeon, Korea ( leesy@kaist.ac.kr+82-42-350-3930).
2018.08.28 View 5980 -
Flexible Drug Delivery Microdevice to Advance Precision Medicine
(Schematic view of flexible microdevice: The flexible drug delivery device for controlled release fabricated via inorganic laser lift off.)
A KAIST research team has developed a flexible drug delivery device with controlled release for personalized medicine, blazing the path toward theragnosis.
Theragnosis, an emerging medical technology, is gaining attention as key factor to advance precision medicine for its featuring simultaneous diagnosis and therapeutics. Theragnosis devices including smart contact lenses and microneedle patches integrate physiological data sensors and drug delivery devices. The controlled drug delivery boasts fewer side-effects, uniform therapeutic results, and minimal dosages compared to oral ingestion. Recently, some research groups conducted in-human applications of controlled-release bulky microchips for osteoporosis treatment. However they failed to demonstrate successful human-friendly flexible drug delivery systems for controlled release.
For this microdevice, the team under Professor Daesoo Kim from the Department of Biological Science and Professor Keon Jae Lee from the Department of Materials Science and Engineering, fabricated a device on a rigid substrate and transferred a 50 µm-thick active drug delivery layer to the flexible substrate via inorganic laser lift off. The fabricated device shows mechanical flexibility while maintaining the capability of precise administration of exact dosages at desired times. The core technology is to produce a freestanding gold capping layer directly on top of the microreservoir with the drugs inside, which had been regarded as impossible in conventional microfabrication.
The developed flexible drug delivery system can be applied to smart contact lenses or the brain disease treatments by implanting them into cramped and corrugated organs. In addition, when powered wirelessly, it will represent a novel platform for personalized medicine. The team already proved through animal experimentation that treatment for brain epilepsy made progress by releasing anti-epileptic medication through the device.
Professor Lee believes the flexible microdevice will further expand the applications of smart contact lenses, therapeutic treatments for brain disease, and subcutaneous implantations for daily healthcare system. This study “Flexible Wireless Powered Drug Delivery System for Targeted Administration on Cerebral Cortex” was described in the June online issue of Nano Energy.
(Photo: The flexible drug delivery device for contolled relase attached on a glass rod.)
2018.08.13 View 9175