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Special Lecture by Professor Sung-Hou Kim of UC Berkeley
As part of its special lecture series, the Department of Biological Sciences at KAIST has invited Professor Sung-Hou Kim of the Department of Chemistry at the University of California, Berkeley, to lecture on his research in structural biology. He will speak twice on May 23 and 30, respectively, on the topics “Origin of Universe and Earth—A Narrative” and “Origin of Life and Human Species—A Narrative.” Professor Kim's research addresses the structural basis of molecules to reveal how they communicate with each other to activate or inhibit particular processes in cell growth, cell differentiation, and cancer. Using the single-crystal X-ray diffraction technology, he discovered, for the first time in the world, the three-dimensional (3-D) structure of a transfer RNA (t-RNA) and received much praise for this work from the scientific community. Since then, he has been cited as a candidate for a Nobel Prize in Chemistry for many years. He also examined the 3-D structures of a RAS protein in normal and cancer cells and identified the mutations of the RAS protein as a cause for cancer. His work has assisted in the development of target drugs for cancer treatment. In recent years, he has adopted a computational biology approach to study the structure and function of biological genomics, with which he has tried to predict disease-sensitive genes. Professor Kim graduated from Seoul National University in 1962 and received his Ph.D. degree in chemistry from the University of Pittsburgh in the United States in 1966. He worked at the Massachusetts Institute of Technology (MIT) as a senior research scientist, and has taught at UC Berkeley since 1978.
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.
Meditox Donates 600 Million KRW Scholarship
On February 17, a Korean biopharmaceutical company Meditox, headed by Chief Executive Officer (CEO) Hyun-Ho Jeong, signed a memorandum of understanding (MOU) with KAIST to establish the “Meditox Fellowship” and donated a total of 600 million Korean won (KRW) to the university to assist in promoting more scientists in the field of biology. Meditox CEO Hyun-Ho Jeong, KAIST President Steve Kang, Dean of Life Science and Bioengineering College Jung-Hoe Kim, and Dean of the Department of Biological Sciences Byung-Ha Oh participated in the agreement ceremony. According to the MOU, Meditox will donate 60,000,000 KRW over a ten year period, from which KAIST can draw on to grant scholarships for master’s and doctoral students. The “Meditox Fellowship” will support promising and enthusiastic students whose finances limit their studies. The first scholarship students for 2016 were: Kwang-Uk Min, In-suk Yeo, Sung-ryung- Lee, Si-on Lee, and Jung-hyun Kim. Meditox CEO Jeong, who graduated from KAIST’s Department of Biological Sciences, said, "I felt it was important to start the Meditox Fellowship at my alma mater to contribute to the cultivation of outstanding scientists in the field of biological sciences." He also said that he would plan to launch projects that aim to support not only those who receive the scholarship but also the development of Korea’s biological sciences in general. President Steve Kang (right) and Chief Executive Officer Hyun-Ho Jeong (left) of Meditox hold the signed memorandum of understanding together.
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."
Professor Joonho Choe Appointed as the President of the KSMCB
Professor Joonho Choe of the Biological Sciences Department at KAIST has been elected the 25th president of Korean Society for Molecular and Cellular Biology (KSMCB). His presidency will last one year, beginning on January 1, 2016. Established in 1989, the Society has served as the largest academic gathering in the field of life sciences, holding an international conference every fall. It has more than 12,400 fellows. Professor Choe served as the vice president of KSMC as well as the editor of its journal, Molecules and Cells. He said, “The 2016 International Conference of the KSMCB will take place on October 12-14, 2016 at the COEX Convention and Exhibition Hall in Seoul. This year, we are preparing 20 symposiums and will invite four international renowned keynote speakers in the field including a Nobel Laureate. We hope many people, students and young researchers in particular, from academia and industry will join the conference.” Professor Choe received his doctoral degree from the University of California, Los Angeles (UCLA) after graduating from Seoul National University with his bachelor and master’s degrees.
KAIST and the University of Minnesota-Twin Cities Partner for Research and Education Collaboration
President Steve Kang of KAIST and President Eric W. Kaler of the University of Minnesota-Twin Cities (United States) signed a memorandum of understanding to create exchange programs for students and faculty and to conduct joint research in the field of health and food. The following is an excerpt from President Kaler’s blog (https://storify.com/UMNstory/globalumn-hksk#edaadf) on his visit of KAIST on November 18, 2015: A visit to the Korea Advanced Institute of Science and Technology About 90 miles from Seoul—and more than that two-and-a-half-hours of a bus ride through the rugged early-morning traffic of South Korea’s capital city—sits Daejeon, Korea’s sixth largest city and home to KAIST, the Korea Advanced Institute of Science and Technology. Today, President Kaler and the small University of Minnesota delegation accompanying him visited what’s considered Korea’s MIT, a place focused on research and known to push the limits toward the future. Fingernail heart monitors? Wireless anesthetic-monitoring devices? KAIST is working on them. The overlap of interests—from biomedical engineering to nanotechnology to robotics—between KAIST (pronounced “Kyst”) and the U are remarkable. Smartphone apps to monitor human health and GPS-driven robots to serve military interests or deliver packages were among the developing inventions that KAIST scientists showed to Kaler. And even the personal relationships seem to illustrate the cliché of a small world and the natural affinity of Minnesota and KAIST. KAIST’s President Sang Mo Kang was once the head of the University of Illinois’ department of electrical and computer engineering, and he and Kaler—a renowned chemical engineer before becoming the U’s president—hit it off … despite disagreeing about the potential outcome of Saturday’s Illinois-Gophers football game. Accompanying Kaler on the day’s journey, meetings, and signing of a Memorandum of Understanding between the two schools to advance collaborations was U Associate Professor Sang Hyun Oh. Oh happens to be a physics graduate of this very KAIST and is now a rising star in Minnesota’s Department of Electrical and Computer Engineering. The two sides agreed to focus on matching scholars on their respective campuses to discuss the sorts of research the two institutions can partner on. The idea of “Grand Challenges,” at the core of the U’s Twin Cities campus Strategic Plan, has fascinated Korean higher education leaders during Kaler’s weeklong visit, and KAIST’s leadership was interested in the health and food research, two U strengths. ###
Dr. Ryu of KAIST Receives the S-Oil Outstanding Paper Award
Dr. Je-Kyung Ryu of KAIST’s Department of Physics has been awarded the S-Oil Outstanding Paper Award for his doctoral dissertation’s originality and applicability. Professor Tae-Young Yoon of Physics is his doctoral advisor. The award ceremony took place on November 25, 2015 at the Press Center in Seoul. This S-Oil Outstanding Paper Award, jointly sponsored by the Korean Academy of Science and Technology (KAST) and the Scholastic University Presidential Association, was established to foster young talented scientists in basic science and to advance the field. The award is given every other year for each of the fields of physics, chemistry, mathematics, biology, and earth sciences. With the award, Dr. Ryu received a research grant of USD 8,600. He discovered, for the first time in the world, how NSF (N-ethylmaleimide-sensitive factor), a protein involved in a vesicular transport in cellular activities, disassembles a SNARE (soluble NSF attachment protein receptor) complex, using a unimolecular biophysics method. Unlike the existing studies, he proposed a model in which NSF disassembles SNARE complexes at one step, and as a result, provided evidence of how the SNARE complex influenced the fusion of biological membranes. His research was published in the scientific journal Science issued on March 27, 2015. The title of the paper is “Spring-loaded Unraveling of a Single SNARE Complex by NSF in One Round of ATP Turnover.”
More Donations Arrive to Establish the New Medicine Research and Development Center on Campus
A raft of businesses continues to make donations to establish a new medicine research and development center on campus. The Department of Biological Sciences at KAIST is leading the fundraising campaign. On November 9, 2015, Nikon Instruments Korea Co., Ltd. contributed USD 8,500 to the fundraising, followed by Carl Zeiss AG and Three-Shine Inc., which donated USD 12,800 and 8,500, respectively. Bruno Lin, an Executive Director at Carl Zeiss AG in Korea, said, “I’m very glad to participate in this fundraising initiative for the Biological Sciences Department at KAIST, one rapidly reaching out to the world.” From the left in the picture are Vice President Tae-Hoon Kim, Director Gyu-Hyeok Lee, and Executive Director Bruno Lin of Carl Zeiss AG, Byung-Ha Oh, Dean of the Biological Sciences Department, and Professor Eunjoon Kim. From the left in the picture are Byung-Ha Oh, Dean of the Biological Sciences Department, President Chun-Gui Park of Three-Shine Inc., and Professor Daesoo Kim. President Chun of Three-Shine Inc., said, “We hope that the Department of Biological Sciences at KAIST, aided by the construction of new research center, will produce practical research achievements and stand on the frontier of new medicine development research in Korea.” The New Medicine Research and Development Center will be equipped with state-of-the-art, purpose-built research facilities to support convergent, interdisciplinary research in biomedicine.
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.
Professor Ki-Jun Jeong Wins the 2015 Dam Yeun Academic Award
The 11th Dam Yeun Academic Award presented by the Korean Society for Biotechnology and Bioengineering (KSBB) to a biologist under 45 years old went to Professor Ki-Jun Jeong of the Chemical and Biomolecular Engineering Department at KAIST. The award ceremony took place on October 13, 2015, at the annual conference of KSBB held at Songdo Convensia in Incheon City. Each year KSBB announces the recipient of the award based on the publications by researchers in the last five years at peer-reviewed international journals or KSBB Journal as well as the record of patent registration and technology transfers. Professor Jeong is recognized for his pioneering research in protein, antibody, cellular engineering, and protein displays and chips.
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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