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'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
Professor Sang-Yup Lee Receives the Order of Service Merit Red Stripes from the Korean Government
The government of the Republic of Korea named Professor Sang-Yup Lee of the Department of Chemical and Bio-molecular Engineering at KAIST as the fiftieth recipient of the Order of Service Merit Red Stripes on May 19, 2015. This medal is awarded to government employees, officials, and teachers in recognition of their contributions to public services including education. Professor Lee is regarded as a leading scientist in the field of metabolic engineering, genomics, proteomics, metabolomics, and bioinformatics on microorganism producing various primary and secondary metabolites. He contributed significantly to the advancement of bio-based engineering research in Korea. In addition, his research in microorganism metabolic engineering propelled him to the front of his field, making him the world’s founder of systems metabolic engineering, inventing numerous technologies in strain development. Professor Lee has received many patent rights in bioprocess engineering. While at KAIST, he applied for 585 patents and registered 227 patents. In particular, he has applied for 135 patents and registered 99 patents in the past five years, successfully turning research results into commercial applications. Professor Lee said, “I’m glad to contribute to the development of Korean science and technology as a researcher and teacher. I would like to share this honor with my students, master’s and doctoral students in particular, because without their support, it wouldn’t have been possible to pull off the highest level of research results recognized by this medal.”
Professor Sangyong Jon Appointed Fellow of AIMBE
Professor Sangyong Jon of the Department of Biological Sciences at KAIST has been appointed a member of the American Institute for Medical and Biological Engineering (AIMBE) fellowship. Established in 1991, AIMBE is a non-profit organization based in Washington, D.C., representing 50,000 individuals and the top 2% of medical and biological engineers. AIMBE provides policy advice and advocacy for medical and biological engineering for the benefit of humanity. It has had about 1,500 fellows over the past 25 years. Among the members, only 110 are non-American nationalities. Following the appointment of Dr. Hae-Bang Lee, the former senior researcher at the Korean Research Institute of Chemical Technology, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST, Professor Jon is the third Korean to become an AIMBE fellow. He had an induction ceremony for the appointment of his fellowship at the AIMBE’s Annual Event held on March 15-17, 2015 in Washington, D.C. An authority on nanomedicine, Professor Jon has developed many original technologies including multi-functional Theranostics nano particles for the diagnosis and treatment of diseases. He received the Most Cited Paper Award from Theranostics, an academic journal specialized in nanomedicine, last February. Additionally, Professor Jon is a leading researcher in the field of translational medicine, using a multi-disciplinary, highly collaborative, “Bench to Bedside” approach for disease treatment and prevention. He created a biotechnology venture company and transferred research developments to the industry in Korea.
System Approach Using Metabolite Structural Similarity Toward TOM Suggested
A Korean research team at KAIST suggests that a system approach using metabolite structural similarity helps to elucidate the mechanisms of action of traditional oriental medicine. Traditional oriental medicine (TOM) has been practiced in Asian countries for centuries, and is gaining increasing popularity around the world. Despite its efficacy in various symptoms, TOM has been practiced without precise knowledge of its mechanisms of action. Use of TOM largely comes from empirical knowledge practiced over a long period of time. The fact that some of the compounds found in TOM have led to successful modern drugs such as artemisinin for malaria and taxol (Paclitaxel) for cancer has spurred modernization of TOM. A research team led by Sang-Yup Lee at KAIST has focused on structural similarities between compounds in TOM and human metabolites to help explain TOM’s mechanisms of action. This systems approach using structural similarities assumes that compounds which are structurally similar to metabolites could affect relevant metabolic pathways and reactions by biosynthesizing structurally similar metabolites. Structural similarity analysis has helped to identify mechanisms of action of TOM. This is described in a recent study entitled “A systems approach to traditional oriental medicine,” published online in Nature Biotechnology on March 6, 2015. In this study, the research team conducted structural comparisons of all the structurally known compounds in TOM and human metabolites on a large-scale. As a control, structures of all available approved drugs were also compared against human metabolites. This structural analysis provides two important results. First, the identification of metabolites structurally similar to TOM compounds helped to narrow down the candidate target pathways and reactions for the effects from TOM compounds. Second, it suggested that a greater fraction of all the structurally known TOM compounds appeared to be more similar to human metabolites than the approved drugs. This second finding indicates that TOM has a great potential to interact with diverse metabolic pathways with strong efficacy. This finding, in fact, shows that TOM compounds might be advantageous for the multitargeting required to cure complex diseases. “Once we have narrowed down candidate target pathways and reactions using this structural similarity approach, additional in silico tools will be necessary to characterize the mechanisms of action of many TOM compounds at a molecular level,” said Hyun Uk Kim, a research professor at KAIST. TOM’s multicomponent, multitarget approach wherein multiple components show synergistic effects to treat symptoms is highly distinctive. The researchers investigated previously observed effects recorded since 2000 of a set of TOM compounds with known mechanisms of action. TOM compounds’ synergistic combinations largely consist of a major compound providing the intended efficacy to the target site and supporting compounds which maximize the efficacy of the major compound. In fact, such combination designs appear to mirror the Kun-Shin-Choa-Sa design principle of TOM. That principle, Kun-Shin-Choa-Sa (君臣佐使 or Jun-Chen-Zuo-Shi in Chinese) literally means “king-minister-assistant-ambassador.” In ancient East Asian medicine, treating human diseases and taking good care of the human body are analogous to the politics of governing a nation. Just as good governance requires that a king be supported by ministers, assistants and/or ambassadors, treating diseases or good care of the body required the combined use of herbal medicines designed based on the concept of Kun-Shin-Choa-Sa. Here, the Kun (king or the major component) indicates the major medicine (or herb) conveying the major drug efficacy, and is supported by three different types of medicines: the Shin (minister or the complementary component) for enhancing and/or complementing the efficacy of the Kun, Choa (assistant or the neutralizing component) for reducing any side effects caused by the Kun and reducing the minor symptoms accompanying major symptom, and Sa (ambassador or the delivery/retaining component) which facilitated the delivery of the Kun to the target site, and retaining the Kun for prolonged availability in the cells. The synergistic combinations of TOM compounds reported in the literature showed four different types of synergisms: complementary action (similar to Kun-Shin), neutralizing action (similar to Kun-Choa), facilitating action or pharmacokinetic potentiation (both similar to Kun-Choa or Kun-Sa). Additional structural analyses for these compounds with synergism show that they appeared to affect metabolism of amino acids, co-factors and vitamins as major targets. Professor Sang Yup Lee remarks, “This study lays a foundation for the integration of traditional oriental medicine with modern drug discovery and development. The systems approach taken in this analysis will be used to elucidate mechanisms of action of unknown TOM compounds which will then be subjected to rigorous validation through clinical and in silico experiments.” Sources: Kim, H.U. et al. “A systems approach to traditional oriental medicine.” Nature Biotechnology. 33: 264-268 (2015). This work was supported by the Bio-Synergy Research Project (2012M3A9C4048759) of the Ministry of Science, ICT and Future Planning through the National Research Foundation. This work was also supported by the Novo Nordisk Foundation. The picture below presents the structural similarity analysis of comparing compounds in traditional oriental medicine and those in all available approved drugs against the structures of human metabolites.
Professor Sang Yup Lee Appointed Founding Board Member of Cell Systems
Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST has been appointed a member of the founding editorial board of the newly established journal Cell Systems. Cell Systems will be a sister journal of Cell, one of the three most prestigious scientific journals along with Nature and Science, that publishes a wide range of papers on biological engineering. The first issue of Cell Systems will be published this July. Cell Systems plans to publish innovative discoveries, reviews of various research instruments, and research findings on integrated and quantified systems in the field of biology. Professor Lee is a pioneer in metabolic engineering of microorganism with a focus on biopolymers and metabolites production. He is the editor-in-chief of Biotechnology Journal and serves on the editorial board of numerous international journals. He is also a member of the Global Agenda Council of the World Economic Forum and the Presidential Advisory Committee on Science and Technology in Korea. Professor Lee said, “Cell Systems will present research findings that discuss whole biological systems methodically.” He continued, “I hope many research findings of Korean scholars will be published in Cell Systems, which will become a representative journal of systems biology and systems biological engineering.”
Distinguished Professor Sang Yup Lee Accepts an Honorary Professorship at Beijing University of Chemical Technology
Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST has been appointed an honorary professor at Beijing University of Chemical Technology (BUCT). Founded in 1958, BUCT is one of the outstanding universities in mainland China, especially in chemistry studies. In addition to the Chinese Academy of Sciences (2012), Shanghai Jiao Tong University (2013), Wuhan University (2014), and Hebei University of Technology (2014), this is the fifth honorary professorship Professor Lee has received from higher education institutions in China. Professor Lee was recognized for his pioneering research in systems metabolic engineering of microorganisms necessary for the development of green chemical industries. He succeeded in producing succinic acid through bacterial fermentation and engineering plastic raw materials in the most effective and economical method for the first time in the world. Professor Lee also developed polylactic acid, a bio-based polymer that allows plastics to be produced through natural and renewable resources, as well as the microbial production of alkanes, an alternative to gasoline that can be produced from fatty acids. Professor Lee has been actively working as a member of a group of global leaders supported by the World Economic Forum (WEF), serving as the Chairman of the Future of Chemicals, Advanced Materials & Biotechnology, Global Agenda Councils, WEF.
Wuhan University, China, Appoints Distinguished Professor Sang Yup Lee as Honorary Professor
Sang Yup Lee, Distinguished Professor of the Department of Chemical and Biomolecular Engineering at KAIST, has been appointed an honorary professor at Wuhan University in Hubei Province, China. This is the third time that Professor Lee has received an honorary professorship from Chinese academic institutions. The Chinese Academy of Sciences appointed him an honorary professor in 2012, and Shanghai Jia Tong University asked him to serve as an advisory professor in 2013, respectively. Professor Lee was recognized for his pioneering research in systems metabolic engineering of microorganisms necessary for the development of green chemical industries. He succeeded in producing succinic acid through bacterial fermentation and engineering plastic raw materials in the most effective and economical method for the first time in the world. Professor Lee also developed polylactic acid, a bio-based polymer that allows plastics to be produced through natural and renewable resources, as well as the microbial production of alkanes, an alternative to gasoline that can be produced from fatty acids. Professor Lee has been actively working as a member of a group of global leaders supported by the World Economic Forum (WEF), serving the Chairman of the Future of Chemicals, Advanced Materials & Biotechnology, Global Agenda Councils, WEF. Wuhan University is a comprehensive and key national university selected by the Chinese government as a major recipient of state funding for research. It is also known as one of the most beautiful campuses in China.
Distinguished Professor Sang Yup Lee Gives Special Lecture at Tianjin University, China
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering at KAIST gave a special lecture at Tianjin University, China, on September 12, 2014. The university has invited prestigious scholars and scientists including Nobel Prize laureates from all around the world to their program called the "BeiYang Lecture Series." Professor Lee said: "The lecture series has invited many eminent global leaders such as Dr. Steven Chu, who received the Nobel Prize in Physics in 1997 and also served the 12th United States Secretary of Energy. It is a great honor to participate in the program as a speaker. The university told me that in recognition of my research in the development of sustainable biochemical industry through systems metabolic engineering, I was invited to speak.” Professor Lee presented his speech entitled “Production of Chemical Materials through Microorganism Metabolic Systems Engineering” and took questions from the audience. Professor Lee developed the world’s most efficient microorganism and bioprocess such as succinate, butanol, and engineering plastic raw materials. In recent years, he has succeeded in producing a small quantity of gasoline through converting in-vivo generated fatty acids.
Distinguished Professor Sang Yup Lee Participates in the 2014 Summer Davos Forum
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering, KAIST, was invited to lead four sessions at the Annual Meeting 2014, the World Economic Forum, also known as the Summer Davos Forum, which was held in Tianjin, China, from September 10th to 12th. Two of the four sessions Professor Lee participated in were held on September 10th. At the first session entitled “Biotechnology Ecosystem,” he examined with other panelists the future of bioengineering in depth and discussed major policies and industry trends that will be necessary for the development of future biotechnologies. Professor Lee later attended the “Strategic Shifts in Healthcare” session as a moderator. Issues related to transforming the health industry such as the next-generation genomics, mobile health and telemedicine, and wearable devices and predictive analytics were addressed. On September 12, Professor Lee joined the “IdeasLab with KAIST” and gave a presentation on nanotechnology. There was a total of ten IdeasLab sessions held at the Summer Davos Forum, and KAIST was the only Korean university ever invited to host this session. In addition to Professor Lee’s presentation, three more presentations were made by KAIST professors on such topics as “Sustainable Energy and Materials” and “Next-generation Semiconductors.” Lastly, Professor Lee participated in the “Global Promising Technology” session with the World Economic Forum’s Global Agenda Council members. At this session, he explained the selection of the “World’s Top 10 Most Promising Technologies” and “Bio Sector’s Top 10 Technologies” and led discussions about the “2015 Top 10 Technologies” with the council members. The Davos Forum has been announcing the “World’s Top 10 Most Promising Technologies” since 2012, and Professor Lee has played a key role in the selection while working as the Chairman of Global Agenda Council. The selection results are presented at the Davos Forum every year and have attracted a lot of attention from around the world.
President Steve Kang of KAIST Attends the 2014 Summer Davos Forum in Tianjin, China
President Steve Kang of KAIST will attend the 2014 Annual Meeting of the New Champions, the World Economic Forum (WEF), to be held on September 10-12, 2014 in Tianjin, China. KAIST holds its own IdeasLab session on nanotechnology on September 12, 2014. On September 10, 2014, President Steve Kang will participate in a private session hosted by the Global University Leaders Forum (GULF) community at WEF as a panelist. In addition to President Kang, eight presidents from top global universities such as the National University of Singapore, Peking University, ETH Zurich (Swiss Federal Institute of Technology), University of Tokyo, and Carnegie Mellon University will join the panel discussion under the topic, “Increasing the Translational Impact of University Research.” Specifically, the presidents will address issues related to the importance of university-led technology transfer in Asia, key strategies and goals for technology transfer, and implementation approaches taken by each university to promote technology transfer from university to industry. President Kang was invited to this GULF session, the only attendant from Korean universities, in recognition of his long time experience and expertise in education and research. In 2006, WEF created the GULF, a small community of the presidents of top universities in the world, aiming to offer an open platform for high-level dialogues on issues of higher education and research with other sectors, as well as to foster collaboration between universities in areas of significance for global policy. As of 2014, a total of 25 globally leading universities, including Harvard University, University of Cambridge, and Massachusetts Institute of Technology, are GULF members. KAIST, which joined the club this year, is the only Korean university. The 2014 Annual Meeting of the New Champions, also known as the Summer Davos Forum, hosts numerous sessions under the theme of “Creating Value through Innovation.” At the Forum, a total of ten IdeasLab sessions will be hosted. KAIST was invited to run its own IdeasLab on nanotechnology on September 12, 2014. Together with President Kang, Professors Sang Ouk Kim and Keon Jae Lee from the Department of Materials Science Engineering, KAIST, and Professors Sang Yup Lee and Hyunjoo Lee from the Department of Chemical and Biomolecular Engineering, KAIST, will present their own speeches on the topic entitled “From diagnostics to materials, how is nanotechnology changing lives?” President Kang will give the opening speech at the KAIST IdeasLab. He said that an invitation from WEF to join the IdeasLab spoke well for KAIST: “KAIST is the first and the only Korean university ever invited to run its own IdeasLab at the World Economic Forum. The IdeasLab is an expert group meeting, conducted only by the world’s most prestigious universities and research institutes. At the IdeasLab sessions, global leaders from different sectors identify major issues facing higher education and humanity and explore solutions through science and technology innovation. Holding our own IdeasLab on one of our strongest fields, nanotechnology, is indeed an excellent opportunity for KAIST to show its strength in academic and research excellence on the global stage.”
Distinguished Professor Sang Yup Lee Attends World Economic Forum's Workshop
Sang Yup Lee, Distinguished Professor of Chemical and Biomolecular Engineering at KAIST was invited to attend the Technology Pioneer and Global Growth Company CEO Workshop hosted by the World Economic Forum (WEF) on June 19-20, 2014 in San Francisco. During the workshop, Professor Lee joined a discussion on “disruptive technologies” as a panelist. Currently serving for the evaluation committee that selects technology pioneers for the workshop, during the discussion, Professor Lee identified important issues facing humanity, analyzed the issues through forecasting, and presented converging disruptive technologies that provide solutions to the problems. He also shared the “ten emerging technologies” announced by the Global Agenda Council on Emerging Technologies, WEF and the Korean government’s technology innovation strategies adopted to achieve its economic development policy called creative economy.
KAIST Participates in the 2014 Davos Forum on January 22-25 in Switzerland
Through the sessions of the Global University Leaders Forum, IdeasLab, and Global Agenda Councils on Biotechnology, KAIST participants will actively engage with global leaders in the discussion of issues on education innovation and technological breakthroughs. The 2014 Annual Meeting of the World Economic Forum (WEF), known as the Davos Forum, will kick off on January 22-25 in Davos-Klosters, Switzerland, under the theme of "The Reshaping of the World: Consequences for Society, Politics, and Business." Each year, the Forum attracts about 2,500 distinguished leaders from all around the world and provides an open platform to identify the current and emerging challenges facing the global community and to develop ideas and actions necessary to respond to such challenges. President Sung-Mo Steve Kang and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering, KAIST, will attend the Forum and engage in a series of dialogues on such issues as Massive Open Online Courses, new paradigms for universities and researchers, the transformation of higher education, the role and value of scientific discoveries, and the impact of biotechnology on the future of society and business. At the session entitled "New Paradigms for Universities of the Future" hosted by the Global University Leaders Forum (GULF), President Kang will introduce KAIST"s ongoing online education program, Education 3.0. GULF was created in 2006 by WEF, which is a small community of the presidents and senior representatives of the top universities in the world. Implemented in 2012, Education 3.0 incorporates advanced information and communications technology (ICT) to offer students and teachers a learner-based, team-oriented learning and teaching environment. Under Education 3.0, students study online and meet in groups with a professor for in-depth discussions, collaboration, and problem-solving. KAIST plans to expand the program to embrace the global community in earnest by establishing Education 3.0 Global in order to have interactive real-time classes for students and researchers across regions and cultures. President Kang will also present a paper entitled "Toward Socially Responsible Technology: KAIST"s Approach to Integrating Social and Behavioral Perspectives into Technology Development" at another session of GULF called "Seeking New Approaches to Critical Global Challenges." In the paper, President Kang points out that notwithstanding the many benefits we enjoy from the increasingly interconnected world, digital media may pose a threat to become a new outlet for social problems, for example, Internet or digital addiction. Experts say that early exposure to digital devices harms the healthy development of cognitive functions, emotions, and social behavior. President Kang will introduce KAIST"s recent endeavor to develop a non-intrusive technology to help prevent digital addiction, which will ultimately be embedded in the form of a virtual coach or mentor that helps and guides people under risk to make constructive use of digital devices. President Kang stresses the fundamental shift in the science and technology development paradigm from research and development (R&D) to a research and solution development (R&SD), taking serious consideration of societal needs, quality of life, and social impacts when conducting research. Professor Sang Yup Lee will moderate the IdeasLab session at the Davos Forum entitled "From Lab to Life with the California Institute of Technology (Caltech)." Together with scientists from Caltech, he will discuss scientific breakthroughs that transform institutions, industries, and individuals in the near future, such as the development of damage-tolerant lightweight materials with nanotechnology, the ability to read and write genomes, and wireless lab-in-the-body monitors. In addition, he will meet global business leaders at the session of "Sustainability, Innovation, and Growth" and speak about how emerging technologies, biotechnology in particular, will transform future societies, business, and industries. As a current special adviser of the World Economic Forum"s (WEF) Chemicals Industry Community, Professor Lee will meet global chairs and chief executive officers of chemical companies and discuss ways to advance the industry to become more bio-based and environmentally friendly. He served as a founding chairman of WEF"s Global Agenda Councils on Biotechnology in 2013. President Sung-Mo Steve Kang Distinguished Professor Sang Yup Lee
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