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Professor Lee Co-chairs the Global Future Councils on Biotechnology of the WEF
The World Economic Forum (WEF) established a new global network of the world’s leading experts, “The Annual Meeting of the Global Future Councils,” to explore innovative solutions for the most pressing global challenges. The Councils’ first meeting took place on November 13-14, 2016, in Dubai, the United Arab Emirates (UAE). Some 25 nations joined as member states. The Councils have 35 committees. Over 700 global leaders in business, government, civil society and academia gathered at the inaugural meeting to “develop ideas and strategies to prepare the world for the Fourth Industrial Revolution, with topics including smart cities, robotics, and the future of mobility,” according to a statement issued by the WEF. Distinguished Professor Sang Yup Lee of Chemical and Biomolecular Engineering at KAIST was appointed to co-chair one of the Councils' committees, The Annual Meeting of the Global Future Councils on Biotechnology, for two years. The other chairperson is Dr. Feng Zhang, a professor of Biomedical Engineering at the Massachusetts Institute of Technology (MIT), who played a critical role in the development of optogenetics and CRISPR technologies. The Biotechnology Committee consists of 24 globally recognized professionals in life sciences, law, ethics and policy including Thomas Connelly, the executive director of the American Chemical Society, Tina Fano, the executive vice president of Novozymes, and Mostafa Ronaghi, the chief technology officer of Illumina. Professor Lee also serves as a committee member of The Annual Meeting of the Global Future Councils on the Fourth Industrial Revolution. “Life sciences and engineering will receive more attention as a key element of the Fourth Industrial Revolution that the global society as a whole has been experiencing now. Together with thought leaders gathered worldwide, I will join the international community’s concerted efforts to address issues of importance that impact greatly on the future of humanity,” Professor Lee said. In addition, Professor Lee received the James E. Bailey Award 2016 from The Society for Biological Engineering on November 15, 2016. He is the first Asian researcher to be recognized for his contributions to the field of biotechnology.
'The 2016 Top 100 Research Projects in Korea'
The Ministry of Science, ICT and Future Planning (MSIP) of Korea recently released a list of the 2016 Top 100 Research Projects in Korea. The list included the work of KAIST Professors Dong-Ho Cho of the School of Electrical Engineering, Jeung Ku Kang of the Graduate School of Energy, Environment, Water and Sustainability (EEWS), and Sang Yup Lee of the Chemical and Biomolecular Engineering Department. Experts from academia, universities, and industries selected the 100 research projects, among 620 projects recommended by various government offices, in consideration of their contribution to the growth of science and technology in the nation. Professor Cho conducts research on the development of 5G mobile communication systems based on the pattern polarization beam-division multiple access method. Professor Kang works on the production of highly efficient energy materials and equipment by controlling them at the electron and atomic level. Professor Lee focuses on the creation of strategies to produce important chemicals through a biological approach, i.e., microorganisms, which will help develop the means to mitigate climate change. The MISP will publish a book that describes in detail each research project and will distribute copies of it to the National Assembly of Korea, libraries, and other public organizations. For more information on the list, please go to www.ntis.go.kr. Pictured from left to right are Professors Dong-Ho Cho, Jeung Ku Kang, and Sang Yup Lee.
Top 10 Emerging Technologies by World Economic Forum
The World Economic Forum’s Meta-Council on Emerging Technologies announced its annual list of breakthrough technologies, the “Top 10 Emerging Technologies of 2016,” on June 23, 2016. The Meta-Council chose the top ten technologies based on the technologies’ potential to improve lives, transform industries, and safeguard the planet. The research field of systems metabolic engineering, founded by Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department at KAIST, was also citied. Systems metabolic engineering, which combines elements of synthetic biology, systems biology, and evolutionary engineering, offers a sustainable process for the production of useful chemicals in an environmentally friendly way from plants such as inedible biomass, reducing the need of using fossil fuels. Details about the list follow below: https://www.weforum.org/press/2016/06/battery-powered-villages-sociable-robots-rank-among-top-10-emerging-technologies-of-2016 The picture below shows the “systems metabolic engineering of E. coli for the production of PLGA." PLGA is poly(lactate-co-glycolate), which is widely used for biomedical applications, and has been made by chemical synthesis. Now it is possible to produce PLGA eco-friendly by one-step fermentation of a gut bacterium which is developed through systems metabolic engineering.
KAIST to Participate in Summer Davos Forum 2016 in China
A group of KAIST researchers will share their insights on the future and challenges of the current technological innovations impacting all aspects of society, while showcasing their research excellence in artificial intelligence and robotics. Scientific and technological breakthroughs are more important than ever as key agents to drive social, economic, and political changes and advancements in today’s world. The World Economic Forum (WEF), an international organization that provides one of the broadest engagement platforms to address issues of major concern to the global community, will discuss the effects of these breakthroughs at its 10th Annual Meeting of the New Champions, a.k.a., the Summer Davos Forum, in Tianjin, China, June 26-28, 2016. Three professors from the Korea Advanced Institute of Science and Technology (KAIST) will join the Annual Meeting and offer their expertise in the fields of biotechnology, artificial intelligence, and robotics to explore the conference theme, “The Fourth Industrial Revolution and Its Transformational Impact.” The Fourth Industrial Revolution, a term coined by WEF founder, Klaus Schwab, is characterized by a range of new technologies that fuse the physical, digital, and biological worlds, such as the Internet of Things, cloud computing, and automation. Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department will speak at the Experts Reception to be held on June 25, 2016 on the topic of “The Summer Davos Forum and Science and Technology in Asia.” On June 27, 2016, he will participate in two separate discussion sessions. In the first session entitled “What If Drugs Are Printed from the Internet?,” Professor Lee will discuss the impacts of advancements in biotechnology and 3D printing technology on the future of medicine with Nita A. Farahany, a Duke University professor. Clare Matterson, the Director of Strategy at Wellcome Trust in the United Kingdom, will serve as the moderator. The discussants will note recent developments made in the way patients receive their medicine, for example, downloading drugs directly from the internet and the production of yeast strains to make opioids for pain treatment through systems metabolic engineering. They will also suggest how these emerging technologies will transform the landscape of the pharmaceutical industry in the years to come. In the second session, “Lessons for Life,” Professor Lee will talk about how to nurture life-long learning and creativity to support personal and professional growth necessary in an era of the new industrial revolution. During the Annual Meeting, Professors Jong-Hwan Kim of the Electrical Engineering School and David Hyunchul Shim of the Aerospace Department will host, together with researchers from Carnegie Mellon University and AnthroTronix, an engineering research and development company, a technological exhibition on robotics. Professor Kim, the founder of the internally renowned Robot World Cup, will showcase his humanoid soccer-playing micro-robots and display their various cutting-edge technologies such as imaging processing, artificial intelligence, walking, and balancing. Professor Shim will present a human-like robotic piloting system, PIBOT, which autonomously operates a simulated flight program by employing control sticks and guiding an airplane from takeoff to landing. In addition, the two professors will join Professor Lee, who is also a moderator, to host a KAIST-led session on June 26, 2016, entitled “Science in Depth: From Deep Learning to Autonomous Machines.” Professors Kim and Shim will explore new opportunities and challenges in their fields from machine learning to autonomous robotics, including unmanned vehicles and drones. Since 2011, KAIST has participated in the World Economic Forum’s two flagship conferences, the January and June Davos Forums, to introduce outstanding talents, share their latest research achievements, and interact with global leaders. KAIST President Steve Kang said, “It is important for KAIST to be involved in global forums that identify issues critical to humanity and seek answers to solve them, and where our skills and knowledge in science and technology can play a meaningful role. The Annual Meeting in China will become another venue to accomplish this.”
Unveiling the Distinctive Features of Industrial Microorganism
KAIST researchers have sequenced the whole genome of Clostridium tyrobutyricum, which has a higher tolerance to toxic chemicals, such as 1-butanol, compared to other clostridial bacterial strains. Clostridium tyrobutyricum, a Gram-positive, anaerobic spore-forming bacterium, is considered a promising industrial host strain for the production of various chemicals including butyric acid which has many applications in different industries such as a precursor to biofuels. Despite such potential, C. tyrobutyricum has received little attention, mainly due to a limited understanding of its genotypic and metabolic characteristics at the genome level. A Korean research team headed by Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department at the Korea Advanced Institute of Science and Technology (KAIST) deciphered the genome sequence of C. tyrobutyricum and its proteome profiles during the course of batch fermentation. As a result, the research team learned that the bacterium is not only capable of producing a large amount of butyric acid but also can tolerate toxic compounds such as 1-butanol. The research results were published in mBio on June 14, 2016. The team adopted a genoproteomic approach, combining genomics and proteomics, to investigate the metabolic features of C. tyrobutyricum. Unlike Clostridium acetobutylicum, the most widely used organism for 1-butanol production, C. tyrobutyricum has a novel butyrate-producing pathway and various mechanisms for energy conservation under anaerobic conditions. The expression of various metabolic genes, including those involved in butyrate formation, was analyzed using the “shotgun” proteome approach. To date, the bio-based production of 1-butanol, a next-generation biofuel, has relied on several clostridial hosts including C. acetobutylicum and C. beijerinckii. However, these organisms have a low tolerance against 1-butanol even though they are naturally capable of producing it. C. tyrobutyricum cannot produce 1-butanol itself, but has a higher 1-butanol-tolerance and rapid uptake of monosaccharides, compared to those two species. The team identified most of the genes involved in the central metabolism of C. tyrobutyricum from the whole-genome and shotgun proteome data, and this study will accelerate the bacterium’s engineering to produce useful chemicals including butyric acid and 1-butanol, replacing traditional bacterial hosts. Professor Lee said, “The unique metabolic features and energy conservation mechanisms of C. tyrobutyricum can be employed in the various microbial hosts we have previously developed to further improve their productivity and yield. Moreover, findings on C. tyrobutyricum revealed by this study will be the first step to directly engineer this bacterium.” Director Jin-Woo Kim at the Platform Technology Division of the Ministry of Science, ICT and Future Planning of Korea, who oversees the Technology Development Program to Solve Climate Change, said, “Over the years, Professor Lee’s team has researched the development of a bio-refinery system to produce natural and non-natural chemicals with the systems metabolic engineering of microorganisms. They were able to design strategies for the development of diverse industrial microbial strains to produce useful chemicals from inedible biomass-based carbon dioxide fixation. We believe the efficient production of butyric acid using a metabolic engineering approach will play an important role in the establishment of a bioprocess for chemical production.” The title of the research paper is “Deciphering Clostridium tyrobutyricum Metabolism Based on the Who-Genome Sequence and Proteome Analyses.” (DOI: 10.1128/mBio.00743-16) The lead authors are Joungmin Lee, a post-doctoral fellow in the BioProcess Research Center at KAIST, currently working in CJ CheilJedang Research Institute; Yu-Sin Jang, a research fellow in the BioProcess Research Center at KAIST, currently working at Gyeongsang National University as an assistant professor; and Mee-Jung Han, an assistant professor in the Environmental Engineering and Energy Department at Dongyang University. Jin Young Kim, a senior researcher at the Korea Basic Science Institute, also participated in the research. This research was supported by the Technology Development Program to Solve Climate Change’s research project entitled “Systems Metabolic Engineering for Biorefineries” from the Ministry of Science, ICT and Future Planning through the National Research Foundation of Korea (NRF-2012M1A2A2026556). Schematic Diagram of C. tyrobutyricum’s Genome Sequence and Its Proteome Profiles The picture below shows the complete genome sequence, global protein expression profiles, and the genome-based metabolic characteristics during batch fermentation of C. tyrobutyricum.
Non-Natural Biomedical Polymers Produced from Microorganisms
KAIST researchers have developed metabolically engineered Escherichia coli strains to synthesize non-natural, biomedically important polymers including poly(lactate-co-glycolate) (PLGA), previously considered impossible to obtain from biobased materials. Renewable non-food biomass could potentially replace petrochemical raw materials to produce energy sources, useful chemicals, or a vast array of petroleum-based end products such as plastics, lubricants, paints, fertilizers, and vitamin capsules. In recent years, biorefineries which transform non-edible biomass into fuel, heat, power, chemicals, and materials have received a great deal of attention as a sustainable alternative to decreasing the reliance on fossil fuels. A research team headed by Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department at KAIST has established a biorefinery system to create non-natural polymers from natural sources, allowing various plastics to be made in an environmentally-friendly and sustainable manner. The research results were published online in Nature Biotechnology on March 7, 2016. The print version will be issued in April 2016. The research team adopted a systems metabolic engineering approach to develop a microorganism that can produce diverse non-natural, biomedically important polymers and succeeded in synthesizing poly(lactate-co-glycolate) (PLGA), a copolymer of two different polymer monomers, lactic and glycolic acid. PLGA is biodegradable, biocompatible, and non-toxic, and has been widely used in biomedical and therapeutic applications such as surgical sutures, prosthetic devices, drug delivery, and tissue engineering. Inspired by the biosynthesis process for polyhydroxyalkanoates (PHAs), biologically-derived polyesters produced in nature by the bacterial fermentation of sugar or lipids, the research team designed a metabolic pathway for the biosynthesis of PLGA through microbial fermentation directly from carbohydrates in Escherichia coli (E. coli) strains. The team had previously reported a recombinant E. coli producing PLGA by using the glyoxylate shunt pathway for the generation of glycolate from glucose, which was disclosed in their patents KR10-1575585-0000 (filing date of March 11, 2011), US08883463 and JP5820363. However, they discovered that the polymer content and glycolate fraction of PLGA could not be significantly enhanced via further engineering techniques. Thus, in this research, the team introduced a heterologous pathway to produce glycolate from xylose and succeeded in developing the recombinant E. coli producing PLGA and various novel copolymers much more efficiently. In order to produce PLGA by microbial fermentation directly from carbohydrates, the team incorporated external and engineered enzymes as catalysts to co-polymerize PLGA while establishing a few additional metabolic pathways for the biosynthesis to produce a range of different non-natural polymers, some for the first time. This bio-based synthetic process for PLGA and other polymers could substitute for the existing complicated chemical production that involves the preparation and purification of precursors, chemical polymerization processes, and the elimination of metal catalysts. Professor Lee and his team performed in silico genome-scale metabolic simulations of the E. coli cell to predict and analyze changes in the metabolic fluxes of cells which were caused by the introduction of external metabolic pathways. Based on these results, genes are manipulated to optimize metabolic fluxes by eliminating the genes responsible for byproducts formation and enhancing the expression levels of certain genes, thereby achieving the effective production of target polymers as well as stimulating cell growth. The team utilized the structural basis of broad substrate specificity of the key synthesizing enzyme, PHA synthase, to incorporate various co-monomers with main and side chains of different lengths. These monomers were produced inside the cell by metabolic engineering, and then copolymerized to improve the material properties of PLGA. As a result, a variety of PLGA copolymers with different monomer compositions such as the US Food and Drug Administration (FDA)-approved monomers, 3-hydroxyburate, 4-hydroxyburate, and 6-hydroxyhexanoate, were produced. Newly applied bioplastics such as 5-hydroxyvalerate and 2-hydroxyisovalerate were also made. The team employed a systems metabolic engineering application which, according to the researchers, is the first successful example of biological production of PGLA and several novel copolymers from renewable biomass by one-step direct fermentation of metabolically engineered E.coli. Professor Lee said, “We presented important findings that non-natural polymers, such as PLGA which is commonly used for drug delivery or biomedical devices, were produced by a metabolically engineered gut bacterium. Our research is meaningful in that it proposes a platform strategy in metabolic engineering, which can be further utilized in the development of numerous non-natural, useful polymers.” Director Ilsub Baek at the Platform Technology Division of the Ministry of Science, ICT and Future Planning of Korea, who oversees the Technology Development Program to Solve Climate Change, said, “Professor Lee has led one of our research projects, the Systems Metabolic Engineering for Biorefineries, which began as part of the Ministry’s Technology Development Program to Solve Climate Change. He and his team have continuously achieved promising results and been attracting greater interest from the global scientific community. As climate change technology grows more important, this research on the biological production of non-natural, high value polymers will have a great impact on science and industry.” The title of the research paper is “One-step Fermentative Production of Poly(lactate-co-glycolate) from Carbohydrates in Escherichia coli (DOI: 10.1038/nbt.3485).” The lead authors are So Young Choi, a Ph.D. candidate in the Department of Chemical and Biomolecular Engineering at KAIST, and Si Jae Park, Assistant Professor of the Environmental Engineering and Energy Department at Myongji University. Won Jun Kim and Jung Eun Yang, both doctoral students in the Department of Chemical and Biomolecular Engineering at KAIST, also participated in the research. This research was supported by the Technology Development Program to Solve Climate Change’s research project titled “Systems Metabolic Engineering for Biorefineries” from the Ministry of Science, ICT and Future Planning through the National Research Foundation of Korea (NRF-2012M1A2A2026556). Figure: Production of PLGA and Other Non-Natural Copolymers This schematic diagram shows the overall conceptualization of how metabolically engineered E. coli produced a variety of PLGAs with different monomer compositions, proposing the chemosynthetic process of non-natural polymers from biomass. The non-natural polymer PLGA and its other copolymers, which were produced by engineered bacteria developed by taking a systems metabolic engineering approach, accumulate in granule forms within a cell.
Asia Pacific Biotech News' Special Coverage of Korean Biotechnology
The Asia Pacific Biotech News covered five major biotechnology research projects sponsored by the Korean government in the areas of biofuels, biomedicine, bio-nano healthcare, and biorefinery. The Asia Pacific Biotech News (APBN), a monthly magazine based in Singapore, which offers comprehensive reports on the fields of pharmaceuticals, healthcare, and biotechnology, recently published a special feature on Korea’s biotechnology research and development (R&D) programs. The magazine feature selected five research programs sponsored by the Korean government, which are either part of the Global Frontier or the Climate Change Technology Development Projects. The programs are: Systems Metabolic Engineering Research: Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department at the Korea Advanced Institute of Science and Technology (KAIST) has been leading a research group to develop biorefining technology using renewable non-food biomass to produce chemicals, fuels, and materials that were largely drawn from fossil resources through petrochemical refinery processes. Applying a systems metabolic engineering approach, the group succeeded in modifying the metabolic pathways of microorganisms. As a result, they produced, for the first time in the world, engineered plastic raw materials and gasoline. The team also developed a technique to produce butanol and succinic acid with a higher titer and yield using metabolically engineered microorganisms. Next-generation Biomass Research: Under the leadership of Professor Yong- Keun Chang of the Chemical and Biomolecular Engineering Department at KAIST, the research project, which belongs to the Global Frontier Project, develops biofuels and bioproducts utilizing microalgae typically found in water and other marine systems. Convergence Research for Biomedicine: Professor Sung-Hoon Kim of Seoul National University leads this project that develops targeted new drugs based on convergence research strategies. Bionano Healthcare Chip Research: Director Bong-Hyun Chung of the Korea Research Institute of Bioscience and Biotechnology has integrated information and communications technology, nanotechnology, and biotechnology to develop a diagnostic kit that can screen toxic germs, virus, and toxic materials in a prompt and accurate manner. Biosynergy Research: Led by Professor Do-Hun Lee of the Bio and Brain Engineering Department at KAIST, this research project develops new treatments with a multi-target, multi-component approach in the context of systems biology through an analysis of synergistic reactions between multi-compounds in traditional East Asian medicine and human metabolites. In East Asian medicine, treatment and caring of the human body are considered analogous to the politics of governing a nation. Based on such system, the research focuses on designing a foundation for the integration of traditional medicine with modern drug discovery and development. Director Ilsub Baek at the Platform Technology Division of the Ministry of Science, ICT and Future Planning, Republic of Korea, who is responsible for the Global Frontier Program and the Technology to Solve Climate Change, said, “It is great to see that Asia Pacific Biotech News published an extensive coverage of Korea’s several key research programs on biotechnology as its first issue of this year. I am sure that these programs will lead to great outcomes to solve many worldwide pending issues including climate change and healthcare in the aging society.” Professor Sang Yup Lee, who served as an editor of the feature, said, “At the request of the magazine, we have already published lead articles on our biotechnology research three times in the past in 2002, 2006, and 2011. I am pleased to see continued coverage of Korean biotechnology by the magazine because it recognizes the excellence of our research. Biotechnology has emerged as one of the strong fields that addresses important global issues such as climate change and sustainability.”
IdeasLab Presents Biotechnology Solutions for Aging Populations at 2016 Davos Forum
KAIST researchers will discuss how biological sciences and health technologies can address challenges and opportunities posed by aging populations in an era of increasing longevity. Many countries around the world today are experiencing the rapid growth of aging populations, with a decline in fertility rate and longer life expectancy. At this year's Annual Meeting of the World Economic Forum (a.k.a. Davos Forum) on January 20-23, 2016 in Davos-Klosters, Switzerland, four researchers in the field of biological sciences and biotechnology at the Korea Advanced Institute of Science and Technology (KAIST) will discuss the implications of an aging population and explore possible solutions to provide better health care services to the elderly. KAIST will host an IdeasLab twice on the theme "Biotechnology Solutions for Ageing Populations" on January 21st and 23rd, respectively. Professor Byung-Kwan Cho of the Biological Sciences Department will give a presentation on "Rejuvenation via the Microbiome," explaining how microorganisms in the human gut play an important role in preventing aging, or even rejuvenating it. Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department will talk about "Traditional Medicine Reimagined through Modern Systems Biology." Professor Lee will introduce his research results published in Nature Biotechnology (March 6, 2015) and some more new results. He discovered the mechanisms of traditional oriental medicine's (TOM) efficacy by applying systems biology to study structural similarities between natural and nontoxic multi-compounds in the medicine and human metabolites. He will discuss TOM's multi-target approach, which is based on the synergistic combinations of multi-compounds to treat symptoms of a disease, can contribute to the development of new drugs, cosmetics, and nutrients. Professor Youn-Kyung Lim of the Industrial Design Department will speak about a mobile and the Internet of Things-based health care service called "Dr. M" in her presentation on "Advanced Mobile Healthcare Systems." Professor Daesoo Kim of the Biological Sciences Department will share his research on human's happiness and greed in the context of nueroscience and behavioral and biological sciences in a talk entitled "A Neural Switch for Being Happy with Less on a Crowded Planet." KAIST has hosted IdeasLabs several times at the Summer Davos Forum in China, but this is the first time it will participate in the Davos Forum in January. Professor Lee said, "Just like climate change, the issue of how to address aging populations has become a major global issue. We will share some exciting research results and hope to have in depth discussion on this issue with the leaders attending the Davos Forum. KAIST will engage actively in finding solutions that benefit not only Korea but also the international community."
HUBO to Present at the 2016 World Economic Forum
KAIST researchers will lead an IdeasLab on biotechnology for an aging society while HUBO, the winner of the 2015 DARPA Robotics Challenge, will interact with the forum participants, offering an experience of state-of-the-art robotics technology. Representatives from KAIST will attend the 2016 Annual Meeting of the World Economic Forum to run an IdeasLab and showcase its humanoid robot. With over 2,500 leaders from business, government, international organizations, civil society, academia, media, and the arts expected to participate, the 2016 Annual Meeting will take place on January 20-23, 2016 in Davos-Klosters, Switzerland. Under the theme of “Mastering the Fourth Industrial Revolution,” global leaders will discuss the period of digital transformation that will have profound effects on economies, societies, and human behavior. President Sung-Mo Kang will join the Global University Leaders Forum (GULF), a high-level academic meeting to foster collaboration among experts on issues of global concern for the future of higher education and the role of science in society. He will discuss how the emerging revolution in technology will affect the way universities operate and serve society. KAIST is the only Korean university participating in GULF, which is composed of prestigious universities invited from around the world. Four KAIST professors, including Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department, will lead an IdeasLab on “Biotechnology for an Aging Society.” Professor Lee said, “In recent decades, much attention has been paid to the potential effect of the growth of an aging population and problems posed by it. At our IdeasLab, we will introduce some of our research breakthroughs in biotechnology to address the challenges of an aging society.” In particular, he will present his latest research in systems biotechnology and metabolic engineering. His research has explained the mechanisms of how traditional Oriental medicine works in our bodies by identifying structural similarities between effective compounds in traditional medicine and human metabolites, and has proposed more effective treatments by employing such compounds. KAIST will also display its networked mobile medical service system, “Dr. M.” Built upon a ubiquitous and mobile Internet, such as the Internet of Things, wearable electronics, and smart homes and vehicles, Dr. M will provide patients with a more affordable and accessible healthcare service. In addition, Professor Jun-Ho Oh of the Mechanical Engineering Department will showcase his humanoid robot, “HUBO,” during the Annual Meeting. His research team won the International Humanoid Robotics Challenge hosted by the United States Defense Advanced Research Projects Agency (DARPA), which was held in Pomona, California, on June 5-6, 2015. With 24 international teams participating in the finals, HUBO completed all eight tasks in 44 minutes and 28 seconds, 6 minutes earlier than the runner-up, and almost 11 minutes earlier than the third-place team. Team KAIST walked away with the grand prize of USD 2 million. Professor Oh said, “Robotics technology will grow exponentially in this century, becoming a real driving force to expedite the Fourth Industrial Revolution. I hope HUBO will offer an opportunity to learn about the current advances in robotics technology.” President Kang pointed out, “KAIST has participated in the Annual Meeting of the World Economic Forum since 2011 and has engaged with a broad spectrum of global leaders through numerous presentations and demonstrations of our excellence in education and research. Next year, we will choreograph our first robotics exhibition on HUBO and present high-tech research results in biotechnology, which, I believe, epitomizes how science and technology breakthroughs in the Fourth Industrial Revolution will shape our future in an unprecedented way.”
KAIST and Hanwha Chemical Agree on Research Collaboration
KAIST signed a memorandum of understanding (MOU) with Hanwha Chemical Co., Ltd., a Korean chemical and auto manufacturer, on November 2, 2015 to establish a research center on campus. The research center, which will be named “KAIST-Hanwha Chemical Future Technology Research Center,” will implement joint research projects for five years beginning from 2016 to develop innovative, green technologies that will help the Korean chemical industry boost its global competitiveness and to nurture top researchers and engineers in chemical engineering. The research center will lead the development of next-generation petrochemical materials and manufacturing technology and the establishment of pure high-refining processes which are more energy-efficient and environmentally friendly. KAIST and Hanwha will strive to secure new technologies that have the greatest commercialization potential in the global market. They will also establish a scholarship fund for 15 KAIST doctoral students in the Department of Chemical and Biomolecular Engineering. Many professors from the Chemical and Biomolecular Engineering Department including Distinguished Professor Sang Yup Lee, who was listed in the Top 20 Translational Researchers of 2014 by Nature Biotechnology this year, and Professor Hyunjoo Lee who received the Woman Scholar award at the 2015 World Chemistry Conference, will work at the research center. Professor Lee, the head of the research center, said, “Collaborating with Hanwha will give us a strong basis for our efforts to carry out original research and train the best researchers in the field.” Chang-Bum Kim, the Chief Executive Officer (CEO) of Hanwha Chemical, said, “We hope our collaborations with KAIST will go beyond the typical industry and university cooperation. The two organizations will indeed jointly operate the research center, and this will become a new model for industry and university cooperation. We expect that the research center will play a crucial role in the development of new products and technologies to grow the Korean chemical industry.” In the photo, President Steve Kang of KAIST (fourth from left) and CEO Chang-Bum Kim of Hanwha Chemical (fifth from left) hold the MOU together.
Establishment of System Metabolic Engineering Strategies
Although conventional petrochemical processes have generated chemicals and materials which have been useful to mankind, they have also triggered a variety of environmental problems including climate change and relied too much on nonrenewable natural resources. To ameliorate this, researchers have actively pursued the development of industrial microbial strains around the globe in order to overproduce industrially useful chemicals and materials from microbes using renewable biomass. This discipline is called metabolic engineering. Thanks to advances in genetic engineering and our knowledge of cellular metabolism, conventional metabolic engineering efforts have succeeded to a certain extent in developing microbial strains that overproduce bioproducts at an industrial level. However, many metabolic engineering projects launched in academic labs do not reach commercial markets due to a failure to fully integrate industrial bioprocesses. In response to this, Distinguished Professor Sang Yup Lee and Dr. Hyun Uk Kim, both from the Department of Chemical and Biomolecular Engineering at KAIST, have recently suggested ten general strategies of systems metabolic engineering to successfully develop industrial microbial strains. Systems metabolic engineering differs from conventional metabolic engineering by incorporating traditional metabolic engineering approaches along with tools of other fields, such as systems biology, synthetic biology, and molecular evolution. The ten strategies of systems metabolic engineering have been featured in Nature Biotechnology released online in October 2015, which is entitled "Systems strategies for developing industrial microbial strains." The strategies cover economic, state-of-the-art biological techniques and traditional bioprocess aspects. Specifically, they consist of: 1) project design including economic evaluation of a target bioproduct; 2) selection of host strains to be used for overproduction of a bioproduct; 3) metabolic pathway reconstruction for bioproducts that are not naturally produced in the selected host strains; 4) increasing tolerance of a host strain against the bioproduct; 5) removing negative regulatory circuits in the microbial host limiting overproduction of a bioproduct; 6) rerouting intracellular fluxes to optimize cofactor and precursor availability necessary for the bioproduct formation; 7) diagnosing and optimizing metabolic fluxes towards product formation; 8) diagnosis and optimization of microbial culture conditions including carbon sources; 9) system-wide gene manipulation to further increase the host strain's production performance using high-throughput genome-scale engineering and computational tools; and 10) scale-up fermentation of the developed strain and diagnosis for the reproducibility of the strain's production performance. These ten strategies were articulated with successful examples of the production of L-arginine using Corynebacterium glutamicum, 1,4-butanediol using Escherichia coli, and L-lysine and bio-nylon using C. glutamicum. Professor Sang Yup Lee said, "At the moment, the chance of commercializing microbial strains developed in academic labs is very low. The strategies of systems metabolic engineering outlined in this analysis can serve as guidelines when developing industrial microbial strains. We hope that these strategies contribute to improving opportunities to commercialize microbial strains developed in academic labs with drastically reduced costs and efforts, and that a large fraction of petroleum-based processes will be replaced with sustainable bioprocesses." Lee S. Y. & Kim, H. U. Systems Strategies for Developing Industrial Microbial Strains. Nature Biotechnology (2015). This work was supported by the Technology Development Program to Solve Climate Change on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556) and by the Intelligent Synthetic Biology Center through the Global Frontier Project (2011-0031963) from the Ministry of Science, ICT and Future Planning (MSIP), Korea, and through the National Research Foundation (NRF) of Korea. This work was also supported by the Novo Nordisk Foundation. Picture: Concept of the Systems Metabolic Engineering Framework (a) Three major bioprocess stages (b) Considerations in systems metabolic engineering to optimize the whole bioprocess. List of considerations for the strain development and fermentation contribute to improving microbial strain's production performance (red), whereas those for the separation and purification help in reducing overall operation costs by facilitating the downstream process (blue). Some of the considerations can be repeated in the course of systems metabolic engineering.
Discovery of Redox-Switch of KEenzyme Involved in N-Butanol Biosynthesis
Research teams at KAIST and Kyungpook National University (KNU) have succeeded in uncovering the redox-switch of thiolase, a key enzyme for n-butanol production in Clostridium acetobutylicum, one of the best known butanol-producing bacteria. Biological n-butanol production was first reported by Louis Pasteur in 1861, and the bioprocess was industrialized usingClostridium acetobutylicum. The fermentation process by Clostridium strains has been known to be the most efficient one for n-butanol production. Due to growing world-wide issues such as energy security and climate change, the biological production of n-butanol has been receiving much renewed interest. This is because n-butanol possesses much better fuel characteristics compared to ethanol, such as higher energy content (29.2 MJ/L vs 19.6 MJ/L), less corrosiveness, less hygroscopy, and the ease with which it can be blended with gasoline and diesel. In the paper published in Nature Communications, a broad-scope, online-only, and open access journal issued by the Nature Publishing Group (NPG), on September 22, 2015, Professor Kyung-Jin Kim at the School of Life Sciences, KNU, and Distinguished Professor Sang Yup Lee at the Department of Chemical and Biomolecular Engineering, KAIST, have proved that the redox-switch of thiolase plays a role in a regulation of metabolic flux in C. acetobutylicum by using in silico modeling and simulation tools. The research team has redesigned thiolase with enhanced activity on the basis of the 3D structure of the wild-type enzyme. To reinforce a metabolic flux toward butanol production, the metabolic network of C. acetobutylicum strain was engineered with the redesigned enzyme. The combination of the discovery of 3D enzyme structure and systems metabolic engineering approaches resulted in increased n-butanol production in C. acetobutylicum, which allows the production of this important industrial chemical to be cost competitive. Professors Kim and Lee said, "We have reported the 3D structure of C. acetobutylicum thiolase-a key enzyme involved in n-butanol biosynthesis, for the first time. Further study will be done to produce butanol more economically on the basis of the 3D structure of C. acetobutylicum thiolase." This work was published online in Nature Communications on September 22, 2015. Reference: Kim et al. "Redox-switch regulatory mechanism of thiolase from Clostridium acetobutylicum," Nature Communications This research was supported by the Technology Development Program to Solve Climate Changes from the Ministry of Education, Science and Technology (MEST), Korea, the National Research Foundation of Korea, and the Advanced Biomass Center through the Global Frontier Research Program of the MEST, Korea. For further information, contact Dr. Sang Yup Lee, Distinguished Professor, KAIST, Daejeon, Korea (firstname.lastname@example.org, +82-42-350-3930); and Dr. Kyung-Jin Kim, Professor, KNU, Daegu, Korea (email@example.com, +82-53-950-6088). Figure 1: A redox-switch of thiolase involves in butanol biosynthesis in Clostridium acetobutylicum. Thiolase condenses two acetyl-CoA molecules for initiating four carbon flux towards butanol. Figure 2: Thiolase catalyzes the condensation reaction of acetyl-CoA to acetoacetyl-CoA. Two catalytic cysteine residues at 88th and 378th are oxidized and formed an intermolecular disulfide bond in an oxidized status, which results in inactivation of the enzyme for n-butanol biosynthesis. The intermolecular disulfide bond is broken enabling the n-butanol biosynthesis, when the environment status is reduced.
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