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One-Step Production of Aromatic Polyesters by E. coli Strains
KAIST systems metabolic engineers defined a novel strategy for microbial aromatic polyesters production fused with synthetic biology from renewable biomass. The team of Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering produced aromatic polyesters from Escherichia coli (E. coli) strains by applying microbial fermentation, employing direct microbial fermentation from renewable feedstock carbohydrates. This is the first report to determine a platform strain of engineered E. coli capable of producing environmentally friendly aromatic polyesters. This engineered E. coli strain, if desired, has the potential to be used as a platform strain capable of producing various high-valued aromatic polyesters from renewable biomass. This research was published in Nature Communications on January 8. Conventionally, aromatic polyesters boast solid strength and heat stability so that there has been a great deal of interest in fermentative production of aromatic polyesters from renewable non-food biomass, but without success. However, aromatic polyesters are only made by feeding the cells with corresponding aromatic monomers as substrates, and have not been produced by direct fermentation from renewable feedstock carbohydrates such as glucose. To address this issue, the team prescribed the detailed procedure for aromatic polyester production through identifying CoA-transferase that activates phenylalkanoates into their corresponding CoA derivatives. In this process, researchers employed metabolic engineering of E. coli to produce phenylalkanoates from glucose based on genome-scale metabolic flux analysis. In particular, the KAIST team made a modulation of gene expression to produce various aromatic polyesters having different monomer fractions. The research team successfully produced aromatic polyesters, a non-natural polymer using the strategy that combines systems metabolic engineering and synthetic biology. They succeeded in biosynthesis of various kinds of aromatic polyesters through the system, thus proving the technical excellence of the environmentally friendly biosynthetic system of this research. Furthermore, his team also proved the potential of expanding the range of aromatic polyesters from renewable resources, which is expected to play an important role in the bio-plastic industry. Professor Lee said, “An eco-friendly and sustainable chemical industry is the key global agenda every nation faces. We are making a research focus to a biochemical industry free from petroleum dependence, and conducting diverse research activities to address the issue. This novel technology we are presenting will serve as an opportunity to advance the biochemical industry moving forward.” This work was supported by the Intelligent Synthetic Biology Center through the Global Frontier Project (2011-0031963) and also by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation of Korea. Figure: Biosynthesis of aromatic polyesters by metabolically engineered E. coli.This schematic diagram shows the overall conceptualization of how metabolically engineered E. coli produced aromatic polyesters from glucose.
2018.01.09
View 6116
Meet the KAISTian of 2017, Professor YongKeun Park
Professor YongKeun Park from the Department of Physics is one of the star professors in KAIST. Rising to the academic stardom, Professor Park’s daily schedule is filled with series of business meetings in addition to lab meetings and lectures. The year 2017 must have been special for him. During the year, he published numerous papers in international journals, such as Nature Photonics, Nature Communications and Science Advances. These high performances drew international attention from renowned media, including Newsweek and Forbes. Moreover, recognizing his research performance, he was elected as a fellow member of the Optical Society (OSA) in his mid-30s. Noting that the members’ age ranges from late 50s to early 60s, Professor Park’s case considered to be quite exceptional. Adding to his academic achievement, he has launched two startups powered of his own technologies. One is called Tomocube, a company specialized in 3-D imaging microscope using holotomography technology. His company is currently exporting the products to multiple countries, including the United States and Japan. The other one is The.Wave.Talk which has technologies for examining pre-existing bacteria anywhere and anytime. His research career and entrepreneurship are well deserved recipient of many honors. At the 2018 kick-off ceremony, Professor Park was awarded the KAISTian of 2017 in recognition of his developing holographic measure and control technology as well as founding a new field for technology application. KAISTian of the Year, first presented in 2001, is an award to recognize the achievements and exemplary contribution of KAIST member who has put significant effort nationally and internationally, enhancing the value of KAIST. While receiving the award, he thanked his colleagues and his students who have achieved this far together. He said, “I would like to thank KAIST for providing environment for young professors like me so that we can engage themselves in research. Also, I would like to mention that I am an idea seeder and my students do the most of the research. So, I appreciate my students for their hard works, and it is very pleasure to have them. Lastly, I thank the professors for teaching these outstanding students. I feel great responsibility over this title. I will dedicate myself to make further progress in commercializing technology in KAIST.” Expecting his successful startup cases as a model and great inspiration to students as well as professors, KAIST interviewed Professor Park. Q What made you decide to found your startups? A I believed that my research areas could be further used. As a professor, I believe that it is a university’s role to create added value through commercializing technology and creating startups. Q You have co-founded two startups. What is your role in each company? A So, basically I have two full-time jobs, professor in KAIST and CTO in Tomocube. After transferring the technology, I hold the position of advisor in The.Wave.Talk. (Holographic images captured by the product Professor Park developed) Q Do your students also participate in your companies or can they? A No, the school and companies are separate spaces; in other words, they are not participating in my companies. They have trained my employees when transferring the technologies, but they are not directly working for the companies. However, they can participate if they want to. If there’s a need to develop a certain technology, an industry-academia contract can be made. According to the agreement, students can work for the companies. Q Were there any hardships when preparing the startups? A At the initial stage, I did not have a financial problem, thanks to support from Startup KAIST. Yet, inviting capital is the beginning, and I think every step I made to operate, generate revenue, and so on is not easy. Q Do you believe KAIST is startup-friendly? A Yes, there’s no school like KAIST in Korea and any other country. Besides various programs to support startup activities, Startup KAIST has many professors equipped with a great deal of experience. Therefore, I believe that KAIST provides an excellent environment for both students and professors to create startups. Q Do you have any suggestion to KAIST institutionally? A Well, I would like to make a comment to students and professors in KAIST. I strongly recommend them to challenge themselves by launching startups if they have good ideas. Many students wish to begin their jobs in government-funded research institutes or major corporates, but I believe that engaging in a startup company will also give them valuable and very productive experience. Unlike before, startup institutions are well established, so attracting good capital is not so hard. There are various activities offered by Startup KAIST, so it’s worthwhile giving it a try. Q What is your goal for 2018 as a professor and entrepreneur? A I don’t have a grand plan, but I will work harder to produce good students with new topics in KAIST while adding power to my companies to grow bigger. By Se Yi Kim from the PR Office
2018.01.03
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President Shin Reaffirms Innovation Initiatives in New Year Speech
(President Shin and representatives of faculty, students, staff celebrate the New Year in a reception held on January 2 at the auditorium.) The KAIST community gathered to celebrate a fresh start for the year 2018. At the ceremony, held in the auditorium on January 2, members of KAIST community reaffirmed their commitment to be the trailblazers of Korea and beyond through unwavering innovations. President Sung-Chul Shin presented his new vision and plan in his New Year speech, which focused on innovation for enhancing institutional competitiveness and global visibility. He said that as you are the future of KAIST, KAIST is the future of Korea. KAIST’s vision for a better future will have a significant impact on national progress and beyond. He stressed that innovation in the five pillars of education, research, technology commercialization, globalization, and future strategy will further advance the excellence of KAIST. At the ceremony, President Shin also presented the award for ‘the KAISTian of the Year’ to Professor YongKeun Park of the Department of Physics. The annual award recognizes a distinguished professor whose academic accomplishments made the most significant impact. In his New Year speech, President Shin said that the year 2018 will provide an opportunity to take a leap forward for becoming a ‘Global Value Creative, World-Leading University. The Vision 2031 Committee endorsed the five innovation initiatives to fulfill KAIST’s long-term vision and will open its recommendations to the public on March 20. Educational innovation tops the initiatives. President Shin explained that the future of Korea is in the hands of talented individuals in science and technology, emphasizing the need to nurture creative, transdisciplinary talents with the capacity to enhance the social value of science and technology. To this end, KAIST will establish a new undergraduate non-departmental program for transdisciplinary education. This plan will eventually provide students with more options in choosing their major, as well as help students build a strong foundation in basic science and engineering and encourage multidisciplinary approaches. For creating an innovative institutional research infrastructure, KAIST plans to build a Network of Excellence for the Fourth Industrial Revolution (NExFire) for convergence research. The plan of ‘Cross-Generational Collaborative Labs,’ will bring out a new collaboration platform by pairing up senior and junior faculty. President Shin said it will be a stepping stone to extend the spectrum of knowledge without any cessation. For technology commercialization, KAIST will maximize its intellectual property and economic value by stimulating technology-invested companies and startups. Close cooperation with venture capitalists at home and abroad will further accelerate the commercialization drive at KAIST. Saying that the globalization is no long an option but a necessity, he stressed KAIST will strengthen its efforts to established a bilingual campus. “KAIST will make every effort to create a more welcoming and comfortable atmosphere for the international community and their families. We will expand benefits to our international community, such as access to the KAIST Child Care Center and collaboration with the Taejon Christian International School (TCIS),” he said. President Shin added he will further expand global networks and partnerships this year, participating in a diverse range of international events at home and abroad for increasing global visibility. He also said that well-designed future strategies will complete innovation initiatives. The Future Strategy Research Center will serve as a think tank for identifying future agendas, establishing strategies and advocating for them. In addition to the five innovation initiatives, President Shin emphasized a new organizational culture that embraces inclusiveness and mutual respect among all of the members of KAIST. “So far, the ideal qualifications expected of KAISTians have included creativity and a challenging spirit. From now on, we will nurture talents with a focus on the 3Cs: Creativity, Challenge, and Caring. I would like to make a campus in which all members care for each other to help attain mutual growth with warmth and respect," he said. For the full text, Click
2018.01.02
View 6613
CLKIP Bearing Fruit in China
The Chongqing Liangjiang KAIST International Program (CLKIP) is rapidly gaining steam in China. CLKIP, an educational program operated in Chongqing internationally by KAIST since 2015, offers two majors, Electronic Information Engineering and Computer Science and Technology, applying the same curriculum as at KAIST. To operate the program, KAIST assigns professors from the School of Electrical Engineering and the School of Computing to the program every year. They are in charge of one-third of the major courses, and transfer KAIST’s educational curriculum and know-how. A total of 13 professors from Chongqing University of Technology (CQUT) have received or are receiving training on advanced education methodologies and technical know-how, including an on and offline integrated learning program, called Education 4.0 and large-scale internet open learning.As CLKIP is gaining in popularity, the number of students for its undergraduate courses keeps increasing, from 66 in 2015 to 172 in 2016 and 200 students in 2017, achieving the student volume for enrollment annually. CLKIP selected seven exchange undergraduate students and five dual-degree students this fall, and they are currently studying in KAIST for either one semester or one full year. CLKIP is located in Chongqing, one of the major direct-controlled municipalities and a focal point for notable government projects. The Korea-China industrial zone is also located in this area. Considering its location, CLKIP is more than just an international programs for educational cooperation. The program will provide opportunities to cooperate with Korean enterprises including Hyundai, SK Hynix, LG Chem and Hankook Tire. While cooperating in research and development as well as technical assistance, KAIST hopes that these enterprises will play a bridging role for KAIST alumni entering the Chinese market. President Sung-Chul Shin said, “The success of CLKIP shows that KAIST programs for fostering future manpower and developing cutting-edge technologies do work in other countries. Based on this case, KAST will put more effort into transferring our innovative education systems abroad. We are also pushing ahead to establish a joint institute between KAIST and CQUT by 2018, which will become a foundation for facilitating the entry of KAIST’s cutting-edge technologies into the Chinese market.” “KAIST aims to become an entrepreneurial university that creates value through technology commercialization. In this sense, KAIST plans to transfer advanced technologies to domestic and international companies located in the Liangjiang district,” he added.
2017.12.12
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MoU by KAIST-Seoul-Seocho-gu for the 4th Industrial Revolution
The opening ceremony of the Yangjae R&CD Innovation Hub was held in Seoul on December 5. More than 400 guests came to the ceremony from major institutes and companies that are based in the hub. KAIST President Sung-Chul Shin, the Mayor of Seoul, Won-soon Park, and the Mayor of Seocho-gu, Eun Hee Cho, signed an MoU for Seoul to be the leading city for successfully realizing the Fourth Industrial Revolution. The three organizations aim to cooperate with one another in various areas, including an economic boost for local job creation, technology development, and the promotion of projects through an industry-academia-institute network and fostering manpower. Yangjae R&CD is the first facility specializing in and dedicated for Artificial Intelligence, which is the major topic of the Fourth Industrial Revolution. The hub is comprised of enterprises specializing in AI, open co-work spaces, conference rooms, an open networking lounge, and spaces for fostering professional manpower. The hub will recruit additional enterprises and individuals who wish to move in. KAIST, an institute containing professors and researchers in the field of AI, and Modulabs, an organization becoming distinguished in AI research, will be in charge of operating the facility together. The Yangjae R&CD Innovation Hub will operate a professional training program with participation from KAIST professors, which aims to produce 500 professionals in AI research and development by 2020. It will also provide inexpensive space as well as consultations and venture capital to startup and venture companies. It plans to find and foster 50 innovation companies by 2020. In particular, the hub will operate a course for new AI business models 24 times over three years. The hub also offers job consultations, academic conferences, public space for companies residing in the hub, a free GPU cluster server, technical training, seminars, forums, investment attraction, overseas expansion, and one-to-one technical consultations. The Yangjae R&CD Zone is the place established for the Fourth Industrial Revolution by Seoul. R&CD is a concept combining Research and Development, Connection, Companies, Community, and Culture. Seoul aims to create the Yangjae Zone as an urban innovation hub for facilitating industry-academia linkage as well as establishing a startup-settlement-growth technical ecosystem.
2017.12.11
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Professor Dong Ho Cho Awarded at the Haedong Conference 2017
Professor Dong Ho Cho of the School of Electrical Engineering at KAIST received an award at the 13th Haedong Conference 2017 in Seoul on the first of December. The Korean Institute of Communications and Information Sciences recognized Professor Cho for his significant contributions in the field of mobile communication networks. He has carried out groundbreaking research on mobile systems, including architecture, protocols, algorithms, optimization, and efficiency analysis. As a result, he has produced 73 papers in renowned international journals, 138 papers at international conferences, and filed 52 international patents and 121 domestic patents. In addition, he transferred 14 of the patents he filed to Korean and international companies.
2017.12.07
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WEF-KAIST to Host a Forum Next April in Korea
(President Shin poses with Chairman Schwab at the meeting in Dubai) President Sung-Chul Shin and Executive Chairman Klaus Schwab of the World Economic Forum agreed to co-host the Fourth Industrial Revolution Forum next April in Seoul during a meeting at the WEF Global Future Councils 2017 held in Dubai November 11-12. Next April’s forum will be a follow-up event of the roundtable discussion KAIST and the WEF Center for the Fourth Industrial Revolution co-hosted in October in Seoul. The two hosted the roundtable discussion titled “Mastering the Fourth Industrial Revolution: The Future of Jobs and Inclusive Growth in Korea.” During the annual meeting in Dubai, Chairman Schwab expressed his deep appreciation to President Shin for hosting the roundtable discussion and proposed a full-fledged forum in partnership with KAIST once again, which Chairman Schwab will be scheduled to attend. Chairman Schwab emphasized once again that Korea, who has the world’s top high-end technologies such as 5G telecommunications and semiconductor memory, will be the best fit to realize the Fourth Industrial Revolution most rapidly. He also expressed his great interest in the city of Daejeon in which is being considered to become the Special City for the Fourth Industrial Revolution. The Global Future Council of the WEF is the interdisciplinary knowledge network dedicated to promoting innovative thinking on the future. The annual council convenes in Dubai the most relevant and knowledgeable thought leaders from academia, government, business, and civil society to challenge conventional thinking and develop new insights and perspectives on key global systems, as well as the impact and governance of key emerging technologies. This year, more than 850 world-leading experts from 74 countries participated. Under the theme of ‘Vision 2030,’ participants explored systematic changes in key areas such as energy, mobility, and infrastructure while reflecting on the impact of technological breakthroughs in artificial intelligence, biotechnology, and other areas related to the Fourth Industrial Revolution.
2017.11.13
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LG's Woo Jong Lee Named the Alumnus of College of Engineering
The College of Engineering at KAIST selected Woo Jong Lee, President and Head of the VC Business Division at LG Electronics Inc., as the 2017 Alumnus of the Year for the College of Engineering. ‘Alumnus of the Year’ is an award given to a distinguished alumnus who has contributed to the development of industrial technology or made outstanding academic achievements. Lee graduated from KAIST with the master’s degrees in Industrial Engineering. He also worked at Daewoo Motors as an executive member in the development division. He has been a crucial human resource for LG since he joined the company in 2000. While leading the VC business Division, which was established in 2013, Lee is recognized as a creative engineer as well as a leader in the automotive industry. Focusing on autonomous driving and eco-friendliness, he has been engaged in the production of major projects from the beginning to the end. Since 2014, outstanding alumni whose achievements have represented KAIST at the highest level have received the award. The first recipient was Tae-Kyung Yoo, an executive at Lumens Co., Ltd., and the second recipient was Jung-Ju Kim, the founder of NXC. In 2016, the award was not given because an appropriate candidate could not be identified. The award was held in the Industrial Engineering & Management Building (E2) on November 8. Faculty members including the dean of the College of Engineering Jong-Hwan Kim, the vice dean Hyochoong Bang, the head of Industrial & Systems Engineering Taesik Lee, and the dean of the KAIST Academy Tae-Eog Lee attended the ceremony. After the ceremony, Lee delivered a lecture on ‘Auto-components Business of LG Electronics’ to KAIST students.
2017.11.09
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Professor Lee's Research Selected as Top 100 National R&D Projects
A research project, led by Research Professor Ju Yong Lee from the KAIST Institute for IT Convergence, was selected as one of the Top 100 National Research and Development Projects 2017. This research project, titled LTE-A-based Single RF Small Base Station supporting Multiple Streams, developed 300Mbps low power, low complexity and broadband small base station technology that supports 4x4 MIMO (Multiple Input and Multiple Output) by proposing a new antenna structure and a new RF (Radio Frequency) structure based on LTE-A. Professors from the School of Electrical Engineering at KAIST, Dong Ho Cho, Songcheol Hong, and Yong Hoon Lee also collaborated on the project. The existing heterodyne method of communication systems generates the problems of increasing unit price and system complexity. In this project, however, Professor Lee directly modulated the baseband signal from the RF stage through an impedance loading-based RF chip. This method was designed to facilitate low power as well as low complexity while supporting broadband service. Based on this, his team developed source technology for RF that can be applied to fourth and even fifth generation networks. Furthermore, this base station is smallest among the small-cell stations so far, providing an eco-friendly installation environment. It contributes to the market for fifth generation mobile communications by reducing power consumption significantly yet providing high-capacity services. Professor Lee said, “This technology will contribute to creating a new market and additional jobs because business based on the fifth mobile generation can provide multi-functional services, including multiband. Requiring low power and providing high-capacity services anywhere at any time will enhance national competence and reduce costs for establishing a next generation mobile communication system. It is expected that this technology will help with disseminating mobile communication infrastructure through expanding information and communication system as well as the infrastructure of island areas.”
2017.11.08
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In Jin Cho Earned the Best Poster Prize at ME Summit 2017
In Jin Cho, a Ph.D. student in the Department of Chemical and Biomolecular Engineering at KAIST received the best poster prize at the International Metabolic Engineering Summit 2017 held on October 24 in Beijing, China. The International Metabolic Engineering Summit is a global conference where scientists and corporate researchers in the field of metabolic engineering present their latest research outcomes and build networks. At this year’s summit, about 500 researchers from around the world participated in active academic exchanges, including giving keynote speeches and presenting posters. During the poster session, the summit selects one person for the KeAi-synthetic and Systems Biotechnology Poster Award, two for Microbial Cell Factories Poster Awards, and three for Biotechnology Journal Poster Awards among the posters presented by graduate students, post-doctoral fellows and researchers. Cho received the KeAi-synthetic and Systems Biotechnology Poster Award. Her winning poster is on the biotransformation of p-xylene to terephthalic acid using engineered Escherichia coli. Terephthalic acid is generally produced by p-xylene oxidation; however, this process requires a high temperature and pressure as well as a toxic catalyst during the reaction process. Cho and Ziwei Luo, a Ph.D. student at KAIST, co-conducted the research and developed a successful biological conversion process. Compared to the existing chemical process, it does not require a high temperature and pressure; and it is environmentally friendly with a relatively high conversion rate of approximately 97%. Cho’s advisor, Distinguished Professor Sang Yup Lee said, “Further research on glucose-derived terephthalic acid will enable us to produce biomass-based eco-friendly terephthalic acid through engineered Escherichia coli.”
2017.10.31
View 6724
KAIST and KOICA Invited Dominican Republic Officials for Workshop
KAIST will host a two-week workshop for Dominican Republic officials and scholars in collaboration with KOICA (Korea International Cooperation Agency) beginning October 23 at KAIST. The workshop aims to encourage academia-industry cooperation as one of the Projects for Human Resource Development for Science and Technology at KOICA. Dominican participants including the assistant minister of the Ministry of Higher Education, Science and Technology (MESCYT) and deans of engineering colleges at major universities will enjoy lectures from experts and visit enterprises known for excellent academia-industry collaboration. According to the Center for Overseas Development, at which Professor WonJoon Kim in the School of Business and Technology Management at KAIST holds the position of director, the workshop is designed to develop human resources in the science and technology (S&T) area, share knowledge on research and development in the field of academia-industry cooperation, and help the participants acquire know-how for managing partnerships between related organizations and industries. During the workshop, KAIST plans to transfer know-how and share knowledge on its academia-industry cooperation R&D system, in hopes that the workshop will help the Dominican Republic foster its manpower in higher education. The workshop organizers hope that the officers and scholars will be able to apply what they will learn for establishing and carrying out detailed action plans for academia-industry cooperation policies in an effective manner. “This workshop provides an opportunity to learn about the development of S&T in Korea, academia-industry cooperation R&D, and fostering manpower in advanced S&T. Through the knowledge sharing, we can have a better understanding of academia-industry cooperation as well as education on advanced manpower,” said Pedro Antonio Eduardo, the assistant minister of MESCYT. He added, “I hope that this workshop will further detailed cooperation between the two countries for Korean high-tech enterprises’ overseas expansion and advanced manpower education. The development model in Korea has many essential elements, so learning its engine for growth and polytechnic manpower education will help develop my country’s industry sector.” The Project for Human Resource Development for Science and Technology is one of the official development assistance projects running from last year until 2019. It promotes R&D activities for S&T in the Dominican Republic, encouraging academia-industry cooperation by improving trainers in charge of advanced manpower education.
2017.10.30
View 5708
Development of a Highly-Accurate Computational Model of Human Metabolism
A research team from KAIST developed a computational framework that enables the reconstruction of a comprehensive computational model of human metabolism, which allows for an accurate prediction of personal metabolic features (or phenotypes). Understanding personal metabolic phenotypes allows us to design effective therapeutic strategies for various chronic and infectious diseases. A human computational model called the genome-scale metabolic model (GEM) contains information on thousands of metabolic genes and their corresponding reactions and metabolites, and has played an important role in predicting metabolic phenotypes. Although several versions of human GEMs have been released, they had room for further development, especially as to incorporating biological information coming from a human genetics mechanism called “alternative splicing.” Alternative splicing is a genetic mechanism that allows a gene to give rise to multiple reactions, and is strongly associated with pathology. To tackle this problem, Jae Yong Ryu (a Ph.D. student), Dr. Hyun Uk Kim (Research Fellow), and Distinguished Professor Sang Yup Lee, all from the Department of Chemical and Biomolecular Engineering at KAIST, developed a computational framework that systematically generates metabolic reactions, and adds them to the human GEM. The resulting human GEM was demonstrated to accurately predict metabolic phenotypes under varied environmental conditions. The research results were published online in Proceedings of the National Academy of Sciences (PNAS) on October 24, 2017, under the title “Framework and resource for more than 11,000 gene-transcript-protein-reaction associations in human metabolism.” The research team first updated the biological contents of a previous version of the human GEM. The updated biological contents include metabolic genes and their corresponding metabolites and reactions. In particular, metabolic reactions catalyzed by already-known protein isoforms were additionally incorporated into the human GEM; protein isoforms are multiple variants of proteins generated from individual genes through the alternative splicing process. Each protein isoform is often responsible for the operation of a metabolic reaction. Although multiple protein isoforms generated from one gene can play different functions by having different sets of protein domains and/or subcellular localizations, such information was not properly considered in previous versions of human GEMs. Upon the initial update of the human GEM, named Recon 2M.1, the research team subsequently implemented a computational framework that systematically generates information on Gene-Transcript-Protein-Reaction Associations (GeTPRA) in order to identify protein isoforms that were previously not identified. This framework was developed in this study. As a result of the implementation of the framework for GeTPRA, more than 11,000 GeTPRA were automatically predicted, and thoroughly validated. Additional metabolic reactions were then added to Recon 2M.1 based on the predicted GeTPRA for the previously uncharacterized protein isoforms; Recon 2M.1 was renamed Recon 2M.2 from this upgrade. Finally, Recon 2M.2 was integrated with 446 sets of personal biological data (RNA-Seq data) in order to build patient-specific cancer models. These patient-specific cancer models were used to predict cancer metabolism activities and anticancer targets. The development of a new version of human GEMs along with the computational framework for GeTPRA is expected to boost studies in fundamental human genetics and medicine. Model files of the human GEMs Recon 2M.1 and 2M.2, a full list of the GeTPRA and the source code for the computational framework to predict the GeTPRA are all available as part of the publication of this study. Distinguished Professor Lee said, “The predicted GeTPRA from the computational framework is expected to serve as a guideline for future experiments on human genetics and biochemistry, whereas the resulting Recon 2M.2 can be used to predict drug targets for various human diseases.” This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea. (Figure 1:A scheme of Recon 2M.1 development and its use in reconstructing personal genome-scale metabolic models (GEMs). (A) A concept of alternative splicing of human genes and its use in Gene-Transcript-Protein-Reaction Associations (GeTPRA) of Recon 2M.1. (B) A procedure of systematic refinement of the Recon 2Q. Recon 2Q is one of the previously released human GEMs. Biochemically inconsistent reactions include unbalanced, artificial, blocked, and/or redundant reactions. Iterative manual curation was conducted while validating the Recon 2M.1. (C) Reconstruction of cancer patient-specific GEMs using Recon 2M.1 for further simulation studies. In this study, personal biological data (RNA-Seq data) were obtained from The Cancer Genome Atlas (TCGA; https://cancergenome.nih.gov/ ) across the ten cancer types. (Figure 2: Computational framework for the systematic generation of Gene-Transcript-Protein-Reaction Associations (GeTPRA; red box in the flowchart). Peptide sequences of metabolic genes defined in Recon 2M.1 were retrieved from a database called Ensembl. EC numbers and subcellular localizations of all the protein isoforms of metabolic genes in Recon 2M.1 were predicted using software programs EFICAz2.5 and Wolf PSort, respectively. Information on the newly predicted GeTPRA was systematically incorporated into the Recon 2M.1, thereby resulting in Recon 2M.2.)
2017.10.25
View 7839
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