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The Bio-Synergy Research Center, KAIST, Hosts an Annual Meeting
The Ministry of Science, ICT and Future Planning of the Republic of Korea founded the Bio-Synergy Research Center (BSRC) at KAIST in 2013 to develop source technology and generate new knowledge by conducting convergence research projects in natural resources with information technology (IT) and biotechnology.
The BSRC hosted an annual meeting on November 21, 2014, at the KAIST campus and reviewed the progress it made this year with the participation of President Steve Kang of KAIST, Commissioner Young-min Kim of KIPO, and Director Doheon Lee of BSRC.
The Korean Intellectual Property Office (KIPO) provided BSRC with its database in Korean traditional medicine that includes a vast amount of information about disease symptoms, native medicinal herbs and plant extracts, prescriptions, and chemical compounds used for medication. The database, “Compound Combination-Oriented Natural Product Database with Unified Terminology (COCUNUT),” holds approximately one million data sets in four major categories: prescriptions, medicinal resources, medicine components and functions, and diseases.
Based on COCUNUT, BSRC has been working on the standardization of Korean traditional medicine such as the development of data mapping and text mining technology and the analysis of big data in accordance with the said categories. Using IT and biotechnology, the center has also created a virtual human body to explain how traditional medicine works in human body, thereby contributing to the development of new natural materials for medicine.
2014.12.03 View 7442 -
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.
2014.09.15 View 10652 -
Professor Ki Jun Jeong Selected As the Winner of the 'Young Asian Biotechnologist Prize'
Professor Ki Jun Jeong from the Department of Chemical and Biomolecular Engineering, KAIST, has been selected as the winner of this year’s Young Asian Biotechnologist Prize.
Professor Jeong was invited to the 66th Japan Biotechnology and Bioengineering Society Conference scheduled in September 9th-11th, 2014, in Sapporo, Japan, where his award ceremony will be held.
The award is presented to Professor Jeong in recognition of his outstanding research on microbial-based production of antibodies and efficiency improvement.
The Young Asian Biotechnologist Prize is awarded annually by the Japan Biotechnology and Bioengineering Society to the researchers in Asia under the age of 45, who have achieved excellent research results in the field of bioengineering.
2014.06.14 View 8556 -
First International Conference on Science and Technology for Society
KAIST co-organized the 2013 International Conference on Science and Technology for Society which was held on November 28 at the Grace Hall in Seoul EL-Tower. More than 300 people, including members of the Global Social Technology Advisory Board, domestic social technology experts, private companies, government officials, private citizens, and students joined the conference to discuss the roles and responsibilities of science and technology for society.
R&D policies and technologies for solving social issues were introduced, and discussions were held on desirable directions for technological development.
The first speaker, Yasushi Watanabe, Director of RISTEX (Research Institute of Science and Technology for Society) in Japan, introduced the importance of science and technology for society under the title “Change of R&D Paradigm for Society.”
Robert Wimmer, GrAT (Center for Appropriate Technology), Vienna University of Technology in Austria, presented “Need-oriented Design & Solutions for Development.” Kiyoaki Murakami, MRI, Japan, presented “Introduction of Platinum Vision” and Robert Ries, University of Florida, U.S.A., presented “Evaluating the Social Impacts of the Built Environment Using Life Cycle Assessment.”
Case studies on social enterprises and presentations on R&D for solving social problems were introduced by ICISTS (International Conference for the Integration of Science, Technology and Society), which is a student group at KAIST, National Research Foundation of Korea (NRF), Korea Institute of Machinery and Materials (KIMM), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Korea Institute of Industrial Technology (KITECH), Electronics and Telecommunication Research Institute (ETRI), and Korea Research Institute of Chemical Technology (KRICT).The conference was hosted by the Ministry of Science, ICT, and Future Planning and co-organized by NRF, KIMM, KRIBB, KITECH, ETRI and KRICT.
2013.12.11 View 10059 -
Top Ten Ways Biotechnology Could Improve Our Everyday Life
The Global Agenda Council on Biotechnology, one of the global networks under the World Economic Forum, which is composed of the world’s leading experts in the field of biotechnology, announced on February 25, 2013 that the council has indentified “ten most important biotechnologies” that could help meet rapidly growing demand for energy, food, nutrition, and health. These new technologies, the council said, also have the potential to increase productivity and create new jobs.
“The technologies selected by the members of the Global Agenda Council on Biotechnology represent almost all types of biotechnology.Utilization of waste, personalized medicine,and ocean agricultureare examples of the challenges where biotechnology can offer solutions,”said Sang Yup Lee, Chair of the Global Agenda Council on Biotechnology and Distinguished Professor in the Department of Chemical and Biomolecular Engineering at the Korea Advanced Institute of Science and Technology (KAIST). He also added that “the members of the council concluded that regulatory certainty, public perception, and investment are the key enablers for the growth of biotechnology.”
These ideas will be further explored during “Biotechnology Week” at the World Economic Forum’s Blog (http://wef.ch/blog) from Monday, 25 February, 2013. The full list follows below:
Bio-based sustainable production of chemicals, energy, fuels and materials
Through the last century, human activity has depleted approximately half of the world’s reserves of fossil hydrocarbons. These reserves, which took over 600 million years to accumulate, are non-renewable and their extraction, refining and use contribute significantly to human emissions of greenhouse gases and the warming of our planet. In order to sustain human development going forward, a carbon-neutral alternative must be implemented. The key promising technology is biological synthesis; that is, bio-based production of chemicals, fuels and materials from plants that can be re-grown.
Engineering sustainable food production
The continuing increase in our numbers and affluence are posing growing challenges to the ability of humanity to produce adequate food (as well as feed, and now fuel). Although controversial, modern genetic modification of crops has supported growth in agricultural productivity. In 2011, 16.7 million farmers grew biotechnology-developed crops on almost 400 million acres in 29 countries, 19 of which were developing countries. Properly managed, such crops have the potential to lower both pesticide use and tilling which erodes soil.
Sea-water based bio-processes
Over 70% of the earth surface is covered by seawater, and it is the most abundant water source available on the planet. But we are yet to discover the full potential of it. For example with halliophic bacteria capable of growing in the seawater can be engineered to grow faster and produce useful products including chemicals, fuels and polymeric materials. Ocean agriculture is also a promising technology. It is based on the photosynthetic biomass from the oceans, like macroalgae and microalgae.
Non-resource draining zero waste bio-processing
The sustainable goal of zero waste may become a reality with biotechnology. Waste streams can be processed at bio-refineries and turned into valuable chemicals and fuels, thereby closing the loop of production with no net waste. Advances in biotechnology are now allowing lower cost, less draining inputs to be used, including methane, and waste heat. These advances are simplifying waste streams with the potential to reduce toxicity as well as support their use in other processes, moving society progressively closer to the sustainable goal of zero waste.
Using carbon dioxide as a raw material
Biotechnology is poised to contribute solutions to mitigate the growing threat of rising CO2 levels. Recent advances are rapidly increasing our understanding of how living organisms consume and use CO2. By harnessing the power of these natural biological systems, scientists are engineering a new wave of approaches to convert waste CO2 and C1 molecules into energy, fuels, chemicals, and new materials.
Regenerative medicine
Regenerative medicine has become increasingly important due to both increased longevity and treatment of injury. Tissue engineering based on various bio-materials has been developed to speed up the regenerative medicine. Recently, stem cells, especially the induced pluripotent stem cells (iPS), have provided another great opportunity for regenerative medicine. Combination of tissue engineering and stem cell (including iPS) technologies will allow replacements of damaged or old human organs with functional ones in the near future.
Rapid and precise development and manufacturing of medicine and vaccines
A global pandemic remains one of the most real and serious threats to humanity. Biotechnology has the potential to rapidly identify biological threats, develop and manufacture potential cures. Leading edge biotechnology is now offering the potential to rapidly produce therapeutics and vaccines against virtually any target. These technologies, including messenger therapeutics, targeted immunotherapies, conjugated nanoparticles, and structure-based engineering, have already produced candidates with substantial potential to improve human health globally.
Accurate, fast, cheap, and personalized diagnostics and prognostics
Identification of better targets and combining nanotechnology and information technology it will be possible to develop rapid, accurate, personalized and inexpensive diagnostics and prognostics systems.
Bio-tech improvements to soil and water
Arable land and fresh water are two of the most important, yet limited, resources on earth. Abuse and mis-appropriation have threatened these resources, as the demand on them has increased. Advances in biotechnology have already yielded technologies that can restore the vitality and viability of these resources. A new generation of technologies: bio-remediation, bio-regeneration and bio-augmentation are being developed, offering the potential to not only further restore these resources, but also augment their potential.
Advanced healthcare through genome sequencing
It took more than 13 years and $1.5 billion to sequence the first human genome and today we can sequence a complete human genome in a single day for less than $1,000. When we analyze the roughly 3 billion base pairs in such a sequence we find that we differ from each other in several million of these base pairs. In the vast majority of cases these difference do not cause any issues but in rare cases they cause disease, or susceptibility to disease. Medical research and practice will increasingly be driven by our understanding of such genetic variations together with their phenotypic consequences.
2013.03.19 View 10967 -
An efficient strategy for developing microbial cell factories by employing synthetic small regulatory RNAs
A new metabolic engineering tool that allows fine control of gene expression level by employing synthetic small regulatory RNAs was developed to efficiently construct microbial cell factories producing desired chemicals and materials
Biotechnologists have been working hard to address the climate change and limited fossil resource issues through the development of sustainable processes for the production of chemicals, fuels and materials from renewable non-food biomass. One promising sustainable technology is the use of microbial cell factories for the efficient production of desired chemicals and materials. When microorganisms are isolated from nature, the performance in producing our desired product is rather poor. That is why metabolic engineering is performed to improve the metabolic and cellular characteristics to achieve enhanced production of desired product at high yield and productivity. Since the performance of microbial cell factory is very important in lowering the overall production cost of the bioprocess, many different strategies and tools have been developed for the metabolic engineering of microorganisms.
One of the big challenges in metabolic engineering is to find the best platform organism and to find those genes to be engineered so as to maximize the production efficiency of the desired chemical. Even Escherichia coli, the most widely utilized simple microorganism, has thousands of genes, the expression of which is highly regulated and interconnected to finely control cellular and metabolic activities. Thus, the complexity of cellular genetic interactions is beyond our intuition and thus it is very difficult to find effective target genes to engineer. Together with gene amplification strategy, gene knockout strategy has been an essential tool in metabolic engineering to redirect the pathway fluxes toward our desired product formation. However, experiment to engineer many genes can be rather difficult due to the time and effort required; for example, gene deletion experiment can take a few weeks depending on the microorganisms. Furthermore, as certain genes are essential or play important roles for the survival of a microorganism, gene knockout experiments cannot be performed. Even worse, there are many different microbial strains one can employ. There are more than 50 different E. coli strains that metabolic engineer can consider to use. Since gene knockout experiment is hard-coded (that is, one should repeat the gene knockout experiments for each strain), the result cannot be easily transferred from one strain to another.
A paper published in Nature Biotechnology online today addresses this issue and suggests a new strategy for identifying gene targets to be knocked out or knocked down through the use of synthetic small RNA. A Korean research team led by Distinguished Professor Sang Yup Lee at the Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), a prestigeous science and engineering university in Korea reported that synthetic small RNA can be employed for finely controlling the expression levels of multiple genes at the translation level. Already well-known for their systems metabolic engineering strategies, Professor Lee’s team added one more strategy to efficiently develop microbial cell factories for the production of chemicals and materials.
Gene expression works like this: the hard-coded blueprint (DNA) is transcribed into messenger RNA (mRNA), and the coding information in mRNA is read to produce protein by ribosomes. Conventional genetic engineering approaches have often targeted modification of the blueprint itself (DNA) to alter organism’s physiological characteristics. Again, engineering the blueprint itself takes much time and effort, and in addition, the results obtained cannot be transferred to another organism without repeating the whole set of experiments. This is why Professor Lee and his colleagues aimed at controlling the gene expression level at the translation stage through the use of synthetic small RNA. They created novel RNAs that can regulate the translation of multiple messenger RNAs (mRNA), and consequently varying the expression levels of multiple genes at the same time. Briefly, synthetic regulatory RNAs interrupt gene expression process from DNA to protein by destroying the messenger RNAs to different yet controllable extents. The advantages of taking this strategy of employing synthetic small regulatory RNAs include simple, easy and high-throughput identification of gene knockout or knockdown targets, fine control of gene expression levels, transferability to many different host strains, and possibility of identifying those gene targets that are essential.
As proof-of-concept demonstration of the usefulness of this strategy, Professor Lee and his colleagues applied it to develop engineered E. coli strains capable of producing an aromatic amino acid tyrosine, which is used for stress symptom relief, food supplements, and precursor for many drugs. They examined a large number of genes in multiple E. coli strains, and developed a highly efficient tyrosine producer. Also, they were able to show that this strategy can be employed to an already metabolically engineered E. coli strain for further improvement by demonstrating the development of highly efficient producer of cadaverine, an important platform chemical for nylon in the chemical industry.
This new strategy, being simple yet very powerful for systems metabolic engineering, is thus expected to facilitate the efficient development of microbial cell factories capable of producing chemicals, fuels and materials from renewable biomass.
Source: Dokyun Na, Seung Min Yoo, Hannah Chung, Hyegwon Park, Jin Hwan Park, and Sang Yup Lee, “Metabolic engineering of Escherichia coli using synthetic small regulatory RNAs”, Nature Biotechnology, doi:10.1038/nbt.2461 (2013)
2013.03.19 View 9305
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New BioFactory Technique Developed using sRNAs
Professor Sang Yup Lee
- published on the online edition of Nature Biotechnology. “Expected as a new strategy for the bio industry that may replace the chemical industry.”-
KAIST Chemical & Biomolecular engineering department’s Professor Sang Yup Lee and his team has developed a new technology that utilizes the synthetic small regulatory RNAs (sRNAs) to implement the BioFactory in a larger scale with more effectiveness.
* BioFactory: Microbial-based production system which creates the desired compound in mass by manipulating the genes of the cell.
In order to solve the problems of modern society, such as environmental pollution caused by the exhaustion of fossil fuels and usage of petrochemical products, an eco-friendly and sustainable bio industry is on the rise. BioFactory development technology has especially attracted the attention world-wide, with its ability to produce bio-energy, pharmaceuticals, eco-friendly materials and more.
For the development of an excellent BioFactory, selection for the gene that produces the desired compounds must be accompanied by finding the microorganism with high production efficiency; however, the previous research method had a complicated and time-consuming problem of having to manipulate the genes of the microorganism one by one.
Professor Sang Yup Lee’s research team, including Dr. Dokyun Na and Dr. Seung Min Yoo, has produced the synthetic sRNAs and utilized it to overcome the technical limitations mentioned above.
In particular, unlike the existing method, this technology using synthetic sRNAs exhibits no strain specificity which can dramatically shorten the experiment that used to take months to just a few days.
The research team applied the synthetic small regulatory RNA technology to the production of the tyrosine*, which is used as the precursor of the medicinal compound, and cadaverine**, widely utilized in a variety of petrochemical products, and has succeeded developing BioFactory with the world’s highest yield rate (21.9g /L, 12.6g / L each).
*tyrosine: amino acid known to control stress and improve concentration
**cadaverine: base material used in many petrochemical products, such as polyurethane
Professor Sang Yup Lee highlighted the significance of this research: “it is expected the synthetic small regulatory RNA technology will stimulate the BioFactory development and also serve as a catalyst which can make the chemical industry, currently represented by its petroleum energy, transform into bio industry.”
The study was carried out with the support of Global Frontier Project (Intelligent Bio-Systems Design and Synthesis Research Unit (Chief Seon Chang Kim)) and the findings have been published on January 20th in the online edition of the worldwide journal Nature Biotechnology.
2013.02.21 View 9894
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Future of Petrochemical Industry: The Age of Bio-Refineries
The concept of bio-refinery is based on using biomass from seaweeds and non-edible plant sources to produce various materials.
Bio-refineries has been looked into with increasing interest in modern times due to the advent of global warming (and the subsequent changes in the atmosphere) and the exhaustion of natural resources.
However past 20 years of research in metabolic engineering had a crucial limitation; the need to improve the efficiency of the microorganisms that actually go about converting biomass into biochemical materials.
In order to compensate for the inefficiency, Professor Lee Sang Yeop combined systems biology, composite biology, evolutionary engineering to form ‘systems metabolic engineering’.
This allows combining various data to explain the organism’s state in a multi-dimensional scope and respond accordingly by controlling the metabolism.
The result of the experiment is set as the cover dissertation of ‘Trends in Biotechnology’ magazine’s August edition.
2011.07.28 View 10769
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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 14584
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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 13846 -
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 11219 -
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 12872