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New drug targeting method for microbial pathogens developed using in silico cell
A ripple effect is expected on the new antibacterial discovery using “in silico” cells
Featured as a journal cover paper of Molecular BioSystems
A research team of Distinguished Professor Sang Yup Lee at KAIST recently constructed an in silico cell of a microbial pathogen that is resistant to antibiotics and developed a new drug targeting method that could effectively disrupt the pathogen"s growth using the in silico cell.
Hyun Uk Kim, a graduate research assistant at the Department of Chemical and Biomolecular Engineering, KAIST, conducted this study as a part of his thesis research, and the study was featured as a journal cover paper in the February issue of Molecular BioSystems this year, published by The Royal Society of Chemistry based in Europe.
It was relatively easy to treat infectious microbes using antibiotics in the past. However, the overdose of antibiotics has caused pathogens to increase their resistance to various antibiotics, and it has become more difficult to cure infectious diseases these days.
A representative microbial pathogen is Acinetobacter baumannaii. Originally isolated from soils and water, this microorganism did not have resistance to antibiotics, and hence it was easy to eradicate them if infected. However, within a decade, this miroorganism has transformed into a dreadful super-bacterium resistant to antibiotics and caused many casualties among the U.S. and French soldiers who were injured from the recent Iraqi war and infected with Acinetobacter baumannaii.
Professor Lee’s group constructed an in silico cell of this A. baumannii by computationally collecting, integrating, and analyzing the biological information of the bacterium, scattered over various databases and literatures, in order to study this organism"s genomic features and system-wide metabolic characteristics. Furthermore, they employed this in silico cell for integrative approaches, including several network analysis and analysis of essential reactions and metabolites, to predict drug targets that effectively disrupt the pathogen"s growth. Final drug targets are the ones that selectively kill pathogens without harming human body.
Here, essential reactions refer to enzymatic reactions required for normal metabolic functioning in organisms, while essential metabolites indicate chemical compounds required in the metabolism for proper functioning, and their removal brings about the effect of simultaneously disrupting their associated enzymes that interact with them.
This study attempted to predict highly reliable drug targets by systematically scanning biological components, including metabolic genes, enzymatic reactions, that constitute an in silico cell in a short period of time.
This research achievement is highly regarded as it, for the first time, systematically scanned essential metabolites for the effective drug targets using the concept of systems biology, and paved the way for a new antibacterial discovery. This study is also expected to contribute to elucidating the infectious mechanism caused by pathogens.
"Although tons of genomic information is poured in at this moment, application research that efficiently converts this preliminary information into actually useful information is still lagged behind. In this regard, this study is meaningful in that medically useful information is generated from the genomic information of Acinetobacter baumannii," says Professor Lee. "In particular, development of this organism"s in silico cell allows generation of new knowledge regarding essential genes and enzymatic reactions under specific conditions," he added.
This study was supported by the Korean Systems Biology Project of the Ministry of Education, Science and Technology, and the patent for the development of in silico cells of microbial pathogens and drug targeting methods has been filed.
[Picture 1 Cells in silico]
[Picture 2 A process of generating drug targets without harming human body while effectively disrupting the growth of a pathogen, after predicting metabolites from in silico cells]
2010.04.05 View 20590 -
Prof. Lee"s Team Succeeds in Producing Plastics Without Use of Fossil Fuels
A team of scientists led by Prof. Sang-Yup Lee of the Department of Biological Sciences at KAIST have succeeded in producing the polymers used for everyday plastics through bioengineering, rather than through the use of fossil fuel based chemicals, the university authorities said on Tuesday (Nov. 24).
This groundbreaking research, which may now allow for the production of environmentally conscious plastics, has been published in two papers in the journal Biotechnology and Bioengineering.
Polymers are molecules found in everyday life in the form of plastics and rubbers. The team consisted of scientists from KAIST and Korean chemical company LG Chem focused their research on polylactic acid (PLA), a bio-based polymer which holds the key to producing plastics through natural and renewable resources.
"The polyesters and other polymers we use everyday are mostly derived from fossil oils made through the refinery or chemical process," said Lee. "The idea of producing polymers from renewable biomass has attracted much attention due to the increasing concerns of environmental problems and the limited nature of fossil resources. PLA is considered a good alternative to petroleum based plastics as it is both biodegradable and has a low toxicity to humans."
Until now PLA has been produced in a two-step fermentation and chemical process of polymerization, which is both complex and expensive. Now, through the use of a metabolically engineered strain of E.coli, the team has developed a one-stage process which produces polylactic acid and its copolymers through direct fermentation. This makes the renewable production of PLA and lactate-containing copolymers cheaper and more commercially viable.
"By developing a strategy which combines metabolic engineering and enzyme engineering, we"ve developed an efficient bio-based one-step production process for PLA and its copolymers," said Lee. "This means that a developed E. coli strain is now capable of efficiently producing unnatural polymers, through a one-step fermentation process,"
This combined approach of systems-level metabolic engineering and enzyme engineering now allows for the production of polymer and polyester based products through direct microbial fermentation of renewable resources.
"Global warming and other environmental problems are urging us to develop sustainable processes based on renewable resources," concluded Lee. "This new strategy should be generally useful for developing other engineered organisms capable of producing various unnatural polymers by direct fermentation from renewable resources".
2009.11.30 View 17413 -
KAIST, CJ Sign MOU for Joint Research in Fundamental Technologies
KAIST and CJ Corporation, Korea"s leading foodstuff maker, have reached an agreement for an enhanced industry-academy cooperation in the biotechnology area, the university authorities said on Tuesday (Nov. 10).
KAIST President Nam-Pyo Suh signed a memorandum of understanding with Kim Jin-soo, CEO of CJ, at the KAIST campus on Tuesday (Nov. 10).
Under the agreement, KAIST and CJ will cooperate in nurturing elite research manpower and conducting joint researches in fundamental technologies. Specifically, CJ researchers will suggest research subjects linked with doctorate programs to KAIST, and once these subjects are accepted by KAIST, CJ researchers will conduct research under the guidance of KAIST professors to get doctorate degrees. All the costs including research expenses incurred during the program will be provided by CJ.
The agreement also calls for CJ to provide funding for the research subjects it selected among the ones suggested by KAIST"s biotechnology professors.
CJ CEO Jin-Soo Kim said: "Through the joint researches with KAIST which has the highest research capabilities, CJ can strengthen basic research capabilities and secure elite research manpower. We hope that the KAIST-CJ partnership will become a successful model for cooperation between industry and academia."
2009.11.11 View 15080 -
Prof. Lee"s Team Pioneers Biotechnological Production of Chemical Using Renewable Materials
A research team led by Prof. Sang-Yup Lee of the Bio and Brain Engineering Department at KAIST has succeeded in engineering the bacterium E. coli to produce the industrial chemical putrescine, university authorities said on Monday (Aug. 31).
Putrescine, a four carbon chain diamine, is an important platform chemical with a wide range of applications for the pharmaceutical, agrochemical and chemical industries. It is currently used to synthesize nylon-4,6, a widely used engineering plastic.
The research result, published in the Biotechnology and Bioengineering journal, proviDrdes a renewable alternative to the traditional process using fossil fuels.
Currently the production of putrescine on an industrial scale relies on chemical synthesis, which requires non-renewable petrochemicals and expensive catalyst systems. This process is highly toxic and flammable with potentially severe repercussions for both the environment and human health.
"For the first time we have developed a metabolically engineered E. coli strain that efficiently produces putrescine," said Professor Lee. "The development of a bio-refinery for chemicals and materials is very important in a world where dependency on fossil fuels is an increasing concern."
The team developed a strain of E.coli capable of producing putrescine through metabolic engineering. This is where a cell"s metabolic and regulatory networks are enhanced in order to increase production of a needed material.
First the team weakened or deleted competing metabolic pathways within the E. coli strain before deleting pathways which cause putrescine degradation. They also amplified the crucial enzyme Spec C, which converts the chemical ornithine into putrescine. Finally the putrescine exporter, which allows excretion of intracellularly made putrescine, was engineered while a global regulator was engineered to further increase the concentration of putrescine. The final result of this process was an engineered E.coli strain which produced 24.2 g of putrescine per litre.
However, as it was believed that putrescine is toxic to microorganisms the team had to study putrescine tolerance in E.coli before it could be engineered to overproduce the chemical to the levels needed for industrial production.
The results revealed that E. coli can tolerate at least 0.5 M of putrescine, which is tenfold higher than the usual concentration in the cell. This level of tolerance was an important surprise as it means that E. coli can be engineered to overproduce putrescine to industrially competitive levels.
"The previously expected toxicity of putrescine may explain why its microbial production has been overlooked," said Lee. "Now a metabolically engineered E. coli strain has been developed which is capable of efficiently producing putrescine using renewable methods to an industrial level. This metabolic engineering framework should be useful for developing metabolically engineered microorganisms for the efficient production of other chemicals from renewable resources," he added.
2009.09.01 View 17483 -
KAIST Professor Sang-Yup Lee Chair of International Metabolic Engineering Conference Due Next Year
KAIST distinguished professor Sang-Yup Lee was named to chair the 17th Metabolic Engineering Conference which will convene on Jeju Island, Korea, next year, under the theme of "Metabolic Engineering for Green Growth." It was decided at the 16th Biochemical Engineering Conference held in Burlington, Vermont, on July 5-9.
Metabolic Engineering Conference in 2010 will not only involve presentations and discussions about metabolic engineering, but will inaugurate the “World Council on Industrial Biotechnology,” which will bring together global corporations and the world’s experts in industrial biochemical engineering, according to sources at KAIST.
A KAIST official commented, “The fact that the Metabolic Engineering Conference is to be held here [in Korea] proves that Korea is being acknowledged as a key player in this field.”
As the world faces the depletion of fossil fuels and environmental pollution, nations are showing increasing interest in industrial biochemical alternatives, such as microscopic organisms or new chemicals, to solve their problems. In addition, efficient production of biochemical materials and bio-fuels using microbes is deemed vital for the future.
“The Korean government has become a model to other countries thanks to its leadership in carrying out the ‘Green Growth’ policy,” Professor Sang-Yup Lee said. He stated that KAIST is recognized for its research in advanced biochemical material and fuel production methods.
“Green Growth,” a concept first developed by ESCAP, the UN agency working for social and economic cooperation in Asia and the Pacific, aims to achieve sustainable economic growth without destroying the environment.
Ref. Department of Biochemical Engineering, Metabolic and BioMolecular Engineering Lab, KAIST
2009.07.17 View 15958 -
Six Organizations Join Forces to Induce Projected National Brain Institute to Daejeon
Six major organizations including KAIST have joined forces to help Daejeon City to win the government approval to build the envisioned Korean Brain Institute in Daedeok Research Complex.
The six organizations signed a memorandum of understanding on cooperating in establishing the government-funded institute built within the Daedeok Research Complex in the city of Daejeon, at KAIST on Jan. 14. The six organizations are KAIST, the Daejeon City Government, Korea Research Institute of Bioscience and Biotechnology, Korea Research Institute of Standard and Science, Asan Medical Center, and SK Corp., a pioneer in effective therapeutic invention for serious brain disorders.
The partnership of the six organizations is expected to bring a broad-based cooperation opportunities and create a massive synergy effect in the brain science researches and the development of new therapeutic treatment for brain disorders by combining their resources and infrastructures.
The six organizations have also built an international research network with such globally-renowned brain research institutions as RIKEN, a large natural sciences research institute in Japan, Max Plank Institute in Germany, Federal Institute of Technology, Lausanne, in Switzerland and Brain Research Institute of University of Queensland in Australia. The research network is under the support and guidance of Dennis Choi, a prominent neuroscientist who once served as the President of the Society for Neuroscience and is currently a professor in the Departments of Neurology and biology at Emory University.
The tentatively titled Korea Brain Institute is envisioned to help fight brain disorders and create Korea"s new growth engine, as well as lengthening life span, by conducting convergence researches in nero science, brain science and pharmacology. If the consortium of the six organizations wins the government approval to build the proposed institute within the Daedeok complex, the central government and the Daejeon city government are expected to pour a total of 329.7 billion won into the project by 2020.
2009.01.14 View 21467 -
KAIST, KRIBB Agree to Cooperate in Research of Convergence Technologies
Oct. 15, 2008 -- KAIST and Korea Research Institute of Bioscience and Biotechnology (KRIBB) have agreed to cooperate in the research of convergence fields of biotechnology, information technology and nanotechnology.
To this end, the two institutions concluded a memorandum of understanding to create a new academia-institute cooperative model in the convergence fields on Oct. 15 in Seoul, with KAIST President Nam-Pyo Suh, KRIBB Director Young-Hoon Park and Vice Minister of Education, Science and Technology Jong-Koo Park in attendance.
Under the agreement, the two institutions will set up the tentatively-named KAIST-KRIBB BINT Convergence Institute for the development of technologies and nurturing skilled manpower in the convergence fields.
The partnership of the two institutions is expected to bring broad-based cooperation opportunities and create a massive synergy effect by combining their resources and infrastructure for the development of convergence technologies, KAIST officials said..
The proposed institute is also designed to build a world-class research hub in systems biotechnology by combining strengths of the two institutions with initiatives to achieve the Korean government"s new vision for "low carbon, green growth."
The institute will also serve as a base for domestic brain convergence by concentrating the nation"s research capacities in genetics and brain technology.
KAIST also signed a memorandum of understanding for cooperation in researches in Oriental medicine with three institutions, KRIBB, Daegu Hanny University and Korea Institute of Oriental Medicine.
The agreement calls for the four institutions to conduct joint researches in traditional sciences and Oriental medicine based on systems biology, develop manpower in related fields and share academic and research information.
The agreement is expected to provide impetus to reinforcing competitiveness in compound and convergence technologies and discover new properties in Oriental medicine, according to KAIST authorities.
2008.10.16 View 20028 -
KAIST Professors Article Featured as Cover Thesis of Biotechnology Journal
An article authored by a research team of Prof. Sang-yup Lee at the Department of Chemical and Biomolecular Engineering and Dr. Jin-Hwan Park at the KAIST Institute for the BioCentury has been featured as the cover thesis of the August 2008 issue of Trends in Biotechnology.
The paper, titled "General strategy for strain improvement by means of systems metabolic engineering," focuses on the application of systems biology for the development of strains and illustrates future prospects. Trends in Biotechnology, published by Cell Press, is one of the most prestigious review journals in the field.
Jin-Hwan Park, the primary author of the research thesis, said that the KAIST team"s research work was expected to provide substantial help to researchers involved in biotechnology industry.
The strategy has been established on the basis of the experiences gained in the actual microbial production process using the systems biology methods which his research team has recently worked on, Prof. Park said.
2008.07.24 View 19129
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Int'l Conference for Integration of Science & Technology into Society Opens
The 2008 International Conference for the Integration of Science and Technology into Society (ICISTS-KAIST) opened a four-day meeting on Tuesday (July 15) at Daejeon KAIST campus. The conference is an annual event organized by a group of KAIST undergraduate students.
The fifth-year gathering is designed to provide participants with an opportunity to broaden their scientific perspectives by sharing ideas and experiences in related topics, as well as building an international human network. This year"s event has drawn about 200 students from 40 countries.
The centerpiece of the conference is three workshops on the following themes; Human-Robot Symbiotic Society, Neo-brain Science and Trafficmatics. Myung-Ja Kim, former Korean Environment Minister, will appear as a keynote speaker.
In the workshop sessions, two speakers will discuss specific issues and arrive at a tentative conclusion. Participants will have the opportunity to participate in the debate through Q&A for each session.
The first theme "Human-Robot Symbiotic Society" delves into the current trend that robot is being transformed into a perceivable and touchable concept from an abstract one. Guests for the workship include June-Ho Oh, professor at the Department of Mechanical Engineering, KAIST; James Dater, professor at the Department of Political Science, University of Hawaii at Manoa, and Director of the Hawaii Research Center for Future; Michael Pollitt, CEO of Shadow Robot Company; and Steven Dubowsky, professor at the Department of Mechanical Engineering, MIT.
The second theme "Neo-Brain Science" focuses on attempts to shed light on brain from diverse perspectives including psychology, economics and art. Among invited speakers are Prof. Jai-Seung Jung at the Department of Bio and Brain Engineering, KAIST; Prof. Un-Jung Kang at the University of Chicago Medical Center; and Peter Geyer, a consultant for the Association for Psychological Type.
The third workshop on "Traffimatics" will deal with "intelligent transport systems (ITS)" which will discusst new paradigm in transportation policy and traffic engineering. On the list of speakers are Assaf Biderman, assistant director, SENSEable City Laboratory, MIT; Prof. Richard Tay, at the Department of Civil Engineering, University of Calgary; Prof. Shoshi Mizokami at Kumamoto University; and Ho-Jong Baik, research associate professor of Virginia Tech.
2008.07.16 View 24098 -
International Science Journal Spotlights Korean Biotechnology
Biotechnology Journal published by German-based Wiley-VCH, one of the world"s major scientific and technical publishers, devoted its entire special edition for May to biotechnology in Korea.
The monthly journal"s special issue was planned by KAIST Professor Sang-Yup Lee of the Chemical and Biomolecular Engineering Department who is one of the journal"s two editors-in-chief.
The special issue outlines the current status and future prospect of biotechnology in Korea, and presents five review papers and eight original papers by leading Korean biotech researchers to showcase recent developments in Korean biotechnology. Among these papers, a review by Dr. Byung-Hwan Hyeon and his colleagues describes in detail the Korean biotechnology strategies represented by "Bio-Vision 2016," and another by Dr. Ji-Hyun Kim and his collaborators presents recent progress in microbial genome projects in Korea.
In the editorial of the journal, Prof. Lee said, "Heavy industry and IT industry have been the two drivers of Korean economic growth. Korea is now considering biotechnology as its next generation growth engine."
Underscoring the growing importance of fusion research, he mentioned that integration of biotechnology with information technology and nanotechnology is advancing rapidly in Korea. Another special edition of Biotechnology Journal focusing on these exciting biotech developments in Korea is planned for the future.
2008.05.20 View 17649 -
Prof. Sang-Yup Lee Co-Editor-in-Chief of Biotechnology Journal
Prof. Sang-Yup Lee of KAIST"s Department of Chemical and Biomolecular Engineering has been appointed as co-editor-in-chief of Biotechnology Journal published by Wiley-VCH, a German-based leading technical publisher, university authorities said Tuesday, April 15.
Launched in January 2006, Biotechnology Journal has covered biological process, brain ailments, biological medicine, protein design and other applied bio-sciences.
Starting in May, Lee will be responsible for setting and overseeing editorial direction of the journal along with Prof. Alois Jungbauer of Austria.
Professor Lee has been gaining recognition in and outside the country for his research on metabolic engineering. In 2002, he was chosen as one of Asia"s next generation leaders by the World Economic Forum. In 2007, Lee was elected a fellow of the American Association for the Advancement of Science, the world"s largest general scientific society. He is also serving as an editorial member of more than ten international journals including Biotechnology & Bioengineering.
Awards and honors include the First Young Scientist"s Award from the President of Korea, the Scientist of the Month Award from the Korean Ministry of Science and Technology, the Best Patent Award from Korean Intellectual Property Office, the Citation Classic Award from ISI, USA, and the First Elmer Gaden Award (1999 Best Paper Award) from Biotechnology and Bioengineering (John Wiley & Sons, USA) at the ACS National meeting.
2008.04.16 View 16569 -
Professor Sang-Yup Lee Senior Editor of U.S. Biotechnology Journal
Professor Sang-Yup Lee Named Senior Editor of U.S. Biotechnology Journal
Will supervise paper examination in the fields of system biology, system bioengineering and
metabolic engineering, and set editing direction
Professor Sang-Yup Lee, LG Chemical’s Chair-Professor and the leader of BK project group of KAIST Chemical and Biomolecular Engineering Department, was named senior editor of Biotechnology Journal published by the U.S. Wiley-VCH.
Professor Lee will supervise paper examination in the fields of system biology, system bioengineering and metabolic engineering, and set and manage the editing direction of the journal.
‘Biotechnology Journal’ was first published in January 2006 to exchange rapidly-exchanging knowledge and information in life science and its relevant fields by Wiley, a world-famous science journal publisher with the history of 208 years (founded in 1799). Particularly, ‘Biotechnology Journal’ is a new-typed scientific journal treating various fields such as life science research-relevant ethics and cultures necessary for general people as well as expertise research information of life science.
“Although taking charge of editing of many scientific journals spends much time, it’s very fruitful that I’ll lead the direction of research papers of many world-famous scientific journals and I can make efforts to prevent outstanding papers by Korean scientists from being disadvantaged,” said Professor Lee.
“More Korean scholars are taking charge of editing jobs of world-famous scientific journals. It’s a good indication that the capacities of Korean science and engineering have been enhanced significantly as much,” a staff of KAIST PR team said.
Meanwhile, Professor Lee, distinguished by outstanding research performances in the fields of metabolic engineering and system life engineering, is now ▲associate editor of Biotechnology and Bioengineering, top scientific journal of biotech engineering published by the U.S. Wiley ▲editor of Applied Microbiology and Biotechnology published by German Springer ▲ associate editor of Bioprocess and Biosystems Engineering by German Springer, and editing member of ▲ Journal of Bioinformatics and Computational Biology by Singapore’s World Scientific ▲ Asia Pacific Biotech News ▲ Biochemical Engineering Journal, Metabolic Engineering, and Microbial Cell Factory by Elsevier.
2007.02.02 View 18561