research
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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.
2015.10.19 View 10804 -
Nikon Instruments Korea Donates a Fund to KAIST's Department of Biological Sciences
Representatives from Nikon Instruments Korea Co., Ltd., a producer of microscopes and measuring instruments, visited the KAIST campus on September 25, 2015, and donated USD 9,000 to the Department of Biological Sciences at KAIST.
A small ceremony to mark the donation took place at the department’s conference room.
In the picture from left to right were Professor Won-Do Heo, Department Head Byung-Ha Oh, Professor Sangyong Jon, President Sam-Sup Jang of Korea Instech, and Director Ik-Soo Yoo of Nikon Instruments Korea.
The department announced that the fund would be used to build its new research center to house the state-of-the-art research equipment and tools for the development of new medicine.
2015.10.03 View 5254 -
KAIST and Oberthur Technologies Agree for Research and Development in Mobile Security
Professor Kwangjo Kim of the School of Computing at KAIST has signed a research and development (R&D) agreement with Marc Bertin, the Chief Technology Officer of Oberthur Technologies (OT), a French security solutions firm, on September 18, 2015 in Paris.
Under the agreement, KAIST and OT will conduct joint research on mobile security as well as implement an internship program for KAIST graduate students to work either at OT’s R&D center in Korea or in France.
OT has established a research center in Korea in July 2014, which was the fourth of its research centers in Asia.
Professor Kim said, “Our goal at KAIST is to cultivate top-level security experts in security technologies. By partnering with such a leader in security technologies as OT, we know that we will both help shape tomorrow’s security solution for the IoT (Internet of Things) space.”
In the picture, Professor Kwangjo Kim (left) shakes hands with Marc Bertin, the Chief Technology Officer of Oberthur Technologies (right), after the signing of a memorandum of understanding.
2015.09.24 View 7621 -
KAIST and Chongqing University of Technology in China Open an International Program
With the help of KAIST, Chongqing University of Technology (CQUT) in China established an electrical engineering and computer science program and admitted their first 66 freshmen this fall semester.
The joint program was created to foster skilled engineers in the fields of electrical engineering and computer science, which are necessary for the development of the Korean and Chinese Industrial Complex located in Chongqing City.
KAIST has provided CQUT with a majority of the program’s curricula currently offered to its students in Daejeon, Korea.
Under the jointly administered program, KAIST takes on education and research while CQUT is responsible for student selection and administration.
KAIST has dispatched eight professors to teach the related fields in English, and 17 CQUT professors will teach the rest of the curricula.
In August 2014, KAIST and CQUT singed a cooperation agreement for education and research exchange and created the CQUT-KAIST Education Cooperation Center, which is headed by Professor Young-Nam Han of the Electrical Engineering Department at KAIST.
The two universities will expand their collaboration to include graduate programs by 2016.
In the picture below, President Steve Kang of KAIST (right) shakes hands with President Shi Xiaohui of Chongqing University of Technology (left).
2015.09.17 View 10387 -
Professor Woontack Woo Demonstrates an Optical Platform Technology for Augmented Reality at Smart Cloud Show
Professor Woontack Woo of the Graduate School of Culture Technology at KAIST participated in the Smart Cloud Show, a technology exhibition, hosted by the university’s Augmented Human Research Center and presented the latest development of his research, an optical platform system for augmented reality.
This event took place on September 16-17, 2015 at Grand Seoul Nine Tree Convention Center in Seoul.
At the event, Professor Woo introduced a smart glass with an embedded augmented reality system, which permits remote collaboration between an avatar and the user’s hand.
The previous remote collaboration was difficult for ordinary users to employ because of its two-dimensional screen and complicated virtual reality system.
However, with the new technology, the camera attached to artificial reality (AR) glasses recognizes the user’s hand and tracks it down to collaborate. The avatar in the virtual space and the user’s hand interact in real space and time.
The key to this technology is the stable, real-time hand-tracking technique that allows the detection of the hand’s locations and the recognition of finger movements even in situations of self-occlusion.
Through this method, a user can touch and manipulate augmented contents as if they were real-life objects, thereby collaborating remotely with another user who is physically distant by linking his or her movements with an avatar.
If this technology is adopted widely, it may bring some economic benefits such as increased productivity due to lower costs for mobility and reduction in social overhead costs from the decrease in the need of traveling long distance.
Professor Woo said, “This technology will provide us with a greater opportunity for collaboration, not necessarily restricted to physical travelling, which can be widely used in the fields of medicine, education, entertainment, and tourism.”
Professor Woo plans to present his research results on hand-movement tracking and detection at the 12th International Conference on Ubiquitous Robots and Ambient Intelligence (URAI 2015), to be held on October 28-30, 2015, at Kintex in Goyang, Korea.
He will also present a research paper on remote collaboration at the ICAT-EGVE 2015 conference, the merger of the 25th International Conference on Artificial Reality and Telexistence (ICAT 2015) and the 20th Eurographics Symposium on Virtual Environments (EGVE 2015), which will take place on October 28-30, 2015 at the Kyoto International Community House, Kyoto, Japan.
2015.09.16 View 8881 -
KAIST Participates in the World Economic Forum's Annual Meeting of the New Champions 2015 in China
KAIST’s president and its professors actively engage in discussions of major issues on higher education, technology innovation, and industry-university collaboration with global leaders from across all sectors.
President Steve Kang of KAIST participated in the Annual Meeting of the New Champions 2015 (a.k.a., Summer Davos Forum) hosted by the World Economic Forum (WEF). With the theme of “Charting a New Course for Growth,” the Summer Davos Forum took place on September 9-11, 2015 in, Dalian, China.
Currently, KAIST is a member of the Global University Leaders Forum (GULF) of WEF, a gathering of the presidents of the top 25 universities in the world, including Harvard University, Massachusetts Institute of Technology, University of Tokyo, University of Oxford, Peking University, and National University of Singapore. GULF allows university leaders an opportunity to have high-level dialogues on higher education and research and explore prospects for cooperative ventures.
President Kang led the discussion of the GULF session at the Summer Davos Forum, which was held on September 10, 2015, with 25 university leaders as well as two business leaders from Chinese companies: Huawei Technologies Co. Ltd., and Sanofi China. The participants shared candid perspectives on industry-university collaboration, particularly the need for such partnerships in Asia.
In addition, KAIST hosted the fourth IdeasLab session, entitled “Bio versus Nano Materials, on September 9, 2015. At the session, four KAIST professors held an in-depth debate and discussion with the audience on whether the next industrial revolution would be driven by advances in biomaterials or nanomaterials.
The topics under discussion were:
- New materials that mimic biology by Professor Hea Shin Lee
- Bio-based materials that replace petroleum-based materials by Professor Sang Yup Lee
- New materials designed at sub-nano scale by Professor Hee Tae Jung
- A hydrogen economy with nanomaterials by Professor Eun Ae Cho
Since its establishment in 2007, the Summer Davos Forum has become the biggest business and political gathering in Asia, held annually either in Dalian or Tianjin, China. The Forum has attracted more than 1,500 participants primarily from emerging nations such as China, India, Russia, Mexico, and Brazil, and has offered an open platform to address issues important to the region and the global community.
2015.09.14 View 8545 -
Professor Jeong Ho Lee Receives the 2015 Pediatric Epilepsies Research Award
The award identifies leading scientists worldwide and funds their cutting-edge research in epilepsy.
The Citizen United for Research in Epilepsy (CURE) announced on September 7, 2015, that Jeong Ho Lee, a professor of the Graduate School of Medical Science and Engineering at KAIST, will be awarded the 2015 Pediatric Epilepsies Research Award.
The Pediatric Epilepsies Research Award is given annually to a researcher who has conducted novel, innovative research projects that address severe, intractable pediatric epilepsies as well as collaborative, interdisciplinary projects that explore new approaches to find a treatment for pediatric epilepsies.
Lee was recognized for his leading study in the field of intractable epilepsy. He is the first Korean who has ever received this award, securing a research grant of USD 250,000 for two years.
Lee has conducted research on brain somatic mutations as the novel cause of childhood intractable epilepsy. Pediatric epilepsies account for approximately 70% of all cases of epilepsy.
Established in 1998, CURE is a non-profit American organization based in Chicago, Illinois, which is committed to funding research and various initiatives that will lead to breakthroughs to cure epilepsy.
Since its inception, CURE has been at the forefront of epilepsy research, raising more than USD 32 million to support researchers and scientists worldwide. It has also awarded more than 180 cutting-edge projects in 13 countries.
2015.09.09 View 11141 -
Nature Biotechnology Nominates Sang Yup Lee of KAIST for Top 20 Translational Researchers of 2014
Nature Biotechnology, recognized as the most prestigious journal in the field of biotechnology, has released today its list of the Top 20 Translational Researchers of 2014. Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST (Korea Advanced Institute of Science and Technology) ranked seventh in the list. He is the only Asian researcher listed.
The journal, in partnership with IP Checkups, a patent analytics firm, presents an annual ranking of researchers based on their paper and patent output. The list includes, among others, each researcher’s most-cited patent in the past five years and their H index, a measurement to evaluate the impact of a researcher’s published work utilizing citation analysis. (More details can be found at http://www.nature.com/bioent/2015/150801/full/bioe.2015.9.html.)
American institutions made up the majority of the list, with 18 universities and research institutes, and the remainder was filled by KAIST in Korea and the Commonwealth Scientific and Industrial Research Organization (CSIRO) in Australia.
Globally known as a leading researcher in systems metabolic engineering, Professor Lee has published more than 500 journal papers and 580 patents. He has received many awards, including the Citation Classic Award, Elmer Gaden Award, Merck Metabolic Engineering Award, ACS Marvin Johnson Award, SIMB Charles Thom Award, POSCO TJ Park Prize, Amgen Biochemical Engineering Award, and the Ho Am Prize in Engineering.
2015.08.27 View 10350 -
'Engineered Bacterium Produces 1,3-Diaminopropane'
A research team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST reported, for the first time, the production of 1,3-diaminopropane via fermentation of an engineered bacterium.
1,3-Diaminopropane is a three carbon diamine, which has a wide range of industrial applications including epoxy resin and cross-linking agents, as well as precursors for pharmaceuticals, agrochemicals, and organic chemicals. It can also be polymerized with dicarboxylic acids to make polyamides (nylons) for use as engineering plastics, medical materials, and adhesives.
Traditionally, 1,3-diaminopropane is derived from petroleum-based processes. In effort to address critical problems such as the depletion of petroleum and environmental issues inherent to the petroleum-based processes, the research team has developed an Escherichia coli (E. coli) strain capable of producing 1,3-diaminopropane. Using this technology, 1,3-diaminopropane can now be produced from renewable biomass instead of petroleum.
E. coli as found in nature is unable to produce 1,3-diaminopropane. Metabolic engineering, a technology to transform microorganisms into highly efficient microbial cell factories capable of producing chemical compounds of interest, was utilized to engineer the E. coli strain. First, naturally existing metabolic pathways for the biosynthesis of 1,3-diaminopropane were introduced into a virtual cell in silico to determine the most efficient metabolic pathway for the 1,3-diaminopropane production. The metabolic pathway selected was then introduced into an E. coli strain and successfully produced 1,3-diaminopropane for the first time in the world.
The research team applied metabolic engineering additionally, and the production titer of 1,3-diaminopropane increased about 21 fold. The Fed-batch fermentation of the engineered E. coli strain produced 13 grams per liter of 1,3-diaminoproapne. With this technology, 1,3-diaminopropane can be produced using renewable biomass, and it will be the starting point for replacing the current petroleum-based processes with bio-based processes.
Professor Lee said, “Our study suggested a possibility to produce 1,3-diaminopropane based on biorefinery. Further study will be done to increase the titer and productivity of 1,3-diaminopropane.”
This work was published online in Scientific Reports on August 11, 2015.
Reference: Chae, T.U. et al. "Metabolic engineering of Escherichia coli for the production of 1,3-diaminopropane, a three carbon diamine," Scientific Reports:
http://www.nature.com/articles/srep13040
This research was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from Ministry of Science, ICT and Future Planning (MSIP) through the National Research Foundation (NRF) of Korea.
Figure 1: Metabolic engineering strategies for 1,3-diaminopropane production using C4 pathway
Figure 2: Fed-batch fermentation profiles of two final engineered E. coli strains
2015.08.12 View 11024 -
3D Plasmon Antenna Capable of Focusing Light into Few Nanometers
Professors Myung-Ki Kim and Yong-Hee Lee, both of the Physics Department at KAIST, and their research teams have developed a three dimensional (3D) gap-plasmon antenna which can focus light into a space a few nanometers wide. Their research findings were published in the June 10th issue of Nano Letters.
Focusing light into a point-like space is an active research field with many applications. However, concentrating light into a smaller space than its wavelength is often hindered by diffraction. To tackle this problem, many researchers have utilized the plasmonic phenomenon of a metal where light can be confined to a greater extent by overcoming the diffraction limit.
Many researchers have focused on developing a two dimensional (2D) plasmon antenna and were able to focus a light under 5 nanometers wide. However, this 2D antenna revealed a challenge: the light disperses to the opposite end regardless of how small its beam was focused. To solve this difficulty, a 3D structure had to be employed to maximize the light's intensity.
Adopting the proximal focused-ion-beam milling technology, the KAIST research team developed a 3D four nanometer wide gap-plasmon antenna. By squeezing the photons into a 3D nano space of 4 x 10 x 10 nm3 size, the researchers were able to increase the intensity of light by 400,000 times stronger than that of the incident light. Capitalizing on the enhanced intensity of light within the antenna, they intensified the second-harmonic signal and verified that the light was focused in the nano gap by scanning cathodoluminescent images.
The researchers anticipate that this technology will improve the speed of data transfer and processing up to the level of a terahertz (one trillion times per second) and to enlarge the storage volume per unit area on hard disks by 100 times. In addition, high definition images of submolecule size can be taken with actual light, instead of with an electron microscope, while improving the semiconductor process to a smaller size of few nanometers.
Professor Kim said, “A simple yet ingenious idea has shifted the research paradigm from 2D gap-plasmon antennas to 3D antennas. This technology will see numerous applications including in the field of information technology, data storage, imaging medical science, and semiconductor processes.”
The research was sponsored by the National Research Foundation of Korea.
Figure 1: 3D Gap-Plasmon Antenna Structure and Simulation Results
Figure 2 – Constructed 3D Gap-Plasmon Antenna Structure
Figure 3 – Amplified Second Harmonic Signal Generation and Light Focused in the Nano Gap
2015.06.24 View 10306 -
Professor Jinwoo Shin of the Electrical Engineering Department Receives the 2015 ACM SIGMETRICS Rising Star Research Award
Professor Jinwoo Shin of the Electrical Engineering Department at KAIST was selected as the recipient of the 2015 ACM SIGMETRICS Rising Star Research Award.
As a computer systems performance evaluation community, SIGMETRICS annually awards a junior researcher. He was selected as the 8th annual recipient, being the first from an Asian university.
Professor Shin was recognized for his work in theoretical analysis of stochastic queueing networks and machine learning. He said, “I would like to contribute to the expansion of computing and network theory in Korea wherein those fields are unrecognized.”
He has received numerous awards including Kennneth C. Sevcik (Best Student Paper) Award at SIGMETRICS 2009, George M. Sprowls (Best MIT CS PhD Thesis) Award 2010, Best Paper Award at MOBIHOC 2013, Best Publication Award from INFORMS Applied Probability Society 2013, and Bloomberg Scientific Research Award 2015.
2015.06.21 View 9464 -
Science and Technology Policy Professor Chihyung Jeon Awarded Rachel Carson Fellowship
KAIST Graduate School of Science and Technology Policy Professor Chihyung Jeon has been awarded the Rachel Carson Fellowship 2015-2016.
Rachel Carson Center for Environment and Society is a research center for environmental humanities and social sciences, supported by the German Federal Ministry of Education and Research. It was founded by Ludwig-Maximilians-Universität, Munich, Germany and the Deutsches Museum as a joint initiative in 2009.
Rachel Carson Center supports researches in humanities and social sciences on the interactions between the environment and the society, following the footsteps of Rachel Cason, who raised awareness on the chemical environmental damage and started global environmental movement through her published book “Silent Spring” in 1962.
The center is awarding Rachel Carson Fellowships to established researchers to fund their writing and promote exchange of research. This year, 31 fellowships were awarded.
Professor Jeon will conduct research on "A Dredged Nation: The Four Rivers Restoration Project and the Envirotechnical Transformation of South Korea" and will also hold an additional post of International Curatorial Fellow at the Deutsches Museum.
2015.06.11 View 9813