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Non-Natural Biomedical Polymers Produced from Microorganisms
KAIST researchers have developed metabolically engineered Escherichia coli strains to synthesize non-natural, biomedically important polymers including poly(lactate-co-glycolate) (PLGA), previously considered impossible to obtain from biobased materials.
Renewable non-food biomass could potentially replace petrochemical raw materials to produce energy sources, useful chemicals, or a vast array of petroleum-based end products such as plastics, lubricants, paints, fertilizers, and vitamin capsules. In recent years, biorefineries which transform non-edible biomass into fuel, heat, power, chemicals, and materials have received a great deal of attention as a sustainable alternative to decreasing the reliance on fossil fuels.
A research team headed by Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department at KAIST has established a biorefinery system to create non-natural polymers from natural sources, allowing various plastics to be made in an environmentally-friendly and sustainable manner. The research results were published online in Nature Biotechnology on March 7, 2016. The print version will be issued in April 2016.
The research team adopted a systems metabolic engineering approach to develop a microorganism that can produce diverse non-natural, biomedically important polymers and succeeded in synthesizing poly(lactate-co-glycolate) (PLGA), a copolymer of two different polymer monomers, lactic and glycolic acid. PLGA is biodegradable, biocompatible, and non-toxic, and has been widely used in biomedical and therapeutic applications such as surgical sutures, prosthetic devices, drug delivery, and tissue engineering.
Inspired by the biosynthesis process for polyhydroxyalkanoates (PHAs), biologically-derived polyesters produced in nature by the bacterial fermentation of sugar or lipids, the research team designed a metabolic pathway for the biosynthesis of PLGA through microbial fermentation directly from carbohydrates in Escherichia coli (E. coli) strains.
The team had previously reported a recombinant E. coli producing PLGA by using the glyoxylate shunt pathway for the generation of glycolate from glucose, which was disclosed in their patents KR10-1575585-0000 (filing date of March 11, 2011), US08883463 and JP5820363. However, they discovered that the polymer content and glycolate fraction of PLGA could not be significantly enhanced via further engineering techniques. Thus, in this research, the team introduced a heterologous pathway to produce glycolate from xylose and succeeded in developing the recombinant E. coli producing PLGA and various novel copolymers much more efficiently.
In order to produce PLGA by microbial fermentation directly from carbohydrates, the team incorporated external and engineered enzymes as catalysts to co-polymerize PLGA while establishing a few additional metabolic pathways for the biosynthesis to produce a range of different non-natural polymers, some for the first time. This bio-based synthetic process for PLGA and other polymers could substitute for the existing complicated chemical production that involves the preparation and purification of precursors, chemical polymerization processes, and the elimination of metal catalysts.
Professor Lee and his team performed in silico genome-scale metabolic simulations of the E. coli cell to predict and analyze changes in the metabolic fluxes of cells which were caused by the introduction of external metabolic pathways. Based on these results, genes are manipulated to optimize metabolic fluxes by eliminating the genes responsible for byproducts formation and enhancing the expression levels of certain genes, thereby achieving the effective production of target polymers as well as stimulating cell growth.
The team utilized the structural basis of broad substrate specificity of the key synthesizing enzyme, PHA synthase, to incorporate various co-monomers with main and side chains of different lengths. These monomers were produced inside the cell by metabolic engineering, and then copolymerized to improve the material properties of PLGA. As a result, a variety of PLGA copolymers with different monomer compositions such as the US Food and Drug Administration (FDA)-approved monomers, 3-hydroxyburate, 4-hydroxyburate, and 6-hydroxyhexanoate, were produced. Newly applied bioplastics such as 5-hydroxyvalerate and 2-hydroxyisovalerate were also made.
The team employed a systems metabolic engineering application which, according to the researchers, is the first successful example of biological production of PGLA and several novel copolymers from renewable biomass by one-step direct fermentation of metabolically engineered E.coli.
Professor Lee said, “We presented important findings that non-natural polymers, such as PLGA which is commonly used for drug delivery or biomedical devices, were produced by a metabolically engineered gut bacterium. Our research is meaningful in that it proposes a platform strategy in metabolic engineering, which can be further utilized in the development of numerous non-natural, useful polymers.”
Director Ilsub Baek at the Platform Technology Division of the Ministry of Science, ICT and Future Planning of Korea, who oversees the Technology Development Program to Solve Climate Change, said, “Professor Lee has led one of our research projects, the Systems Metabolic Engineering for Biorefineries, which began as part of the Ministry’s Technology Development Program to Solve Climate Change. He and his team have continuously achieved promising results and been attracting greater interest from the global scientific community. As climate change technology grows more important, this research on the biological production of non-natural, high value polymers will have a great impact on science and industry.”
The title of the research paper is “One-step Fermentative Production of Poly(lactate-co-glycolate) from Carbohydrates in Escherichia coli (DOI: 10.1038/nbt.3485).” The lead authors are So Young Choi, a Ph.D. candidate in the Department of Chemical and Biomolecular Engineering at KAIST, and Si Jae Park, Assistant Professor of the Environmental Engineering and Energy Department at Myongji University. Won Jun Kim and Jung Eun Yang, both doctoral students in the Department of Chemical and Biomolecular Engineering at KAIST, also participated in the research.
This research was supported by the Technology Development Program to Solve Climate Change’s research project titled “Systems Metabolic Engineering for Biorefineries” from the Ministry of Science, ICT and Future Planning through the National Research Foundation of Korea (NRF-2012M1A2A2026556).
Figure: Production of PLGA and Other Non-Natural Copolymers
This schematic diagram shows the overall conceptualization of how metabolically engineered E. coli produced a variety of PLGAs with different monomer compositions, proposing the chemosynthetic process of non-natural polymers from biomass. The non-natural polymer PLGA and its other copolymers, which were produced by engineered bacteria developed by taking a systems metabolic engineering approach, accumulate in granule forms within a cell.
2016.03.08 View 11039 -
KAIST Commencement 2016
KAIST hosted its 2016 commencement ceremony on February 19, 2016 at the Sports Complex on campus.
KAIST celebrated the event with five thousand participants including graduating students, faculty, guests, Vice Minister Nam-Ki Hong of Science, ICT and Future Planning of Korea, Chairman Jang-Moo Lee of KAIST's Board of Trustees, and President Jeong-Sik Ko of the KAIST Alumni Association.
President Patrick Aebischer of the Swiss Federal Institute of Technology in Lausanne (EPFL), Switzerland, and the former Speaker of the National Assembly of Korea Chang-Hee Kang received honorary doctorates in science and technology for their contributions to the advancement of science and engineering in education and research.
KAIST granted 570 doctoral degrees, 1,329 master’s degrees, and 867 bachelor degrees on this day.
Yoon-Bum Lee of the Chemistry Department graduated with honors; Woo-Young Jin of the Mathematical Sciences Department received the Chairman’s Award of the KAIST Board and Eun-Hee Yoo of the Biological Sciences Department for the KAIST Presidential Award. Min-Hyun Cho and Yoon-Seok Chang were recipients of the President’s Award of the KAIST Alumni Association and the President’s Award of the University Supporting Association, respectively.
President Steve Kang addressed the ceremony and congratulated the graduates, saying,
“Now, your task is to make significant contributions to your communities: be leaders in your fields and remain active members of society. Given your academic knowledge and vision for the future, I encourage you to dream big.”
2016.02.23 View 41006 -
Workshop on Techniques in Prediction Analysis for the Industry
There has been growing interest in the value and the application of “big data” in recent years. To meet this interest, a workshop was held to discuss the possibility and the future of prediction analysis, which is the next big step in data mining after big data.
On February 25 in COEX, Seoul, the Department of Knowledge Service Engineering at KAIST held the 4th knowledge service workshop on “Techniques in Prediction Analysis for the Industry.”
Predication analysis is a technique that can predict the future based on the understanding of the past and the present through analyzing “big data.” If “big data” is fuel in figurative sense, the prediction analysis serves as the engine.
The Department seeks to help those companies interested in data mining by introducing fundamentals and some application examples to the executives of companies who are interested in implementation of the technique.
The lecture was delivered by six professors from the Department of Knowledge Service Engineering and the Department of Industrial and Systems Engineering at KAIST.
Thomas Miller, the author of Modeling Techniques in Predictive Analytics, covered the contents of his book at the event. Professor Moon-Yong Yi, Chair of the Department of Knowledge Service Engineering, said, “This conference will be important to companies that are considering the implementation of the prediction analysis as well as to students who are interested in the field.”
2016.02.22 View 4714 -
GSIS Graduates Its First Doctor
The Graduate School of Information Security at KAIST (GSIS) granted its first doctoral degree to Il-Goo Lee at the university’s 2016 commencement on February 19, 2016.
Lee received the degree for his dissertation entitled “Interference-Aware Secure Communications for Wireless LANs.”
He explained the background of his research:
“As we use wireless technology more and more in areas of the Internet of Things (IoT), unmanned vehicles, and drones, information security will become an issue of major concern. I would like to contribute to the advancement of communications technology to help minimize wireless interference between devices while ensuring their optimal performance.”
Based on his research, he developed a communications technique to increase wireless devices’ energy efficiency and the level of their security, and created a prototype to showcase that technique.
He plans to continue his research in the development of the next generation WiFi chip sets to protect the information security of IoT and wireless devices.
Since its establishment in March 2011, KAIST’s GSIS has conferred 50 master’s and one doctoral degrees.
2016.02.18 View 7843 -
KAIST Opens a Campus Laundromat
The young and older generations are cooperating to create work places for the local elderly.
The KAIST Graduate Association and the Korean Labor Force Development Institute for the Aged (KORDI) held an opening ceremony for a campus laundromat on January 26, 2016 at the multi-purpose hall of the International Center.
The newly-opened laundromat has two large washing machines, two front-loading washers, and two large dryers that can handle up to 400 kg of laundry.
The KAIST Graduate Association asked KORDI to operate the laundromat to offer job opportunities to seniors in the local community, while providing KAIST students with more conveniences in campus life. As a result, ten seniors are working at the laundromat, providing a variety of cleaning services.
Chan Park, President of the KAIST Graduate Association, said, “I have been contemplating ways in which universities can cooperate with the local community. I hope this particular business model will make a modest improvement in the creation of jobs for the elderly.”
2016.01.26 View 3705 -
Professors Jeon and Choi Receive the Young Scientist Award
Professors Seokwoo Jeon of the Department of Materials Science and Engineering and Jang Wook Choi of the Graduate School of Energy, Environment, Water and Sustainability (EEWS) at KAIST received the Young Scientist Award.
The award ceremony took place at the Korea Press Center in Seoul. Presented by the Ministry of Science, ICT and Future Planning of Korea and the National Academy of Engineering of Korea, the Young Scientist Award is given to outstanding scientists under the age of 40 who have demonstrated excellence in their research in the field of natural science.
Each year the award is given to three scientists in different areas.
Professor Jeon was recognized for his achievement in creating a new property of materials. He studied synthesis and development of low-dimensional nanomaterials and developed a large area nanostructure.
Professor Choi’s research area was to discover optimal materials for rechargeable batteries. By applying his research, he developed rechargeable batteries with high efficiency, making the wearable system more feasible.
2016.01.11 View 10277 -
Prof. Jae-Kyu Lee Campaigns on "Bright Internet" Worldwide
Professor Jae-Kyu Lee (pictured on the right) from the College of Business at KAIST is one step closer to fulfilling his dream of achieving the “Bright Internet,” a campaign that he first proposed as he became the president of the Association for Information Systems (AIS) in June 2015.
On December 12, 2015, Professor Lee signed a memorandum of understanding (MOU) at a convention center in Fort Worth, Texas, between the AIS and the International Telecommunication Union (ITU)—a specialized agency of the United Nations that is responsible for issues related to information and communication technologies—on a collaborative research and development program to make the Internet safer for everyone.
The MOU pursues building a trusted international information and communication technology (ICT) infrastructure by proposing telecommunication policies, developing international standards, and organizing interdisciplinary conferences.
The Bright Internet is an initiative to protect online users from cyber terrors, privacy breaches, and cyber-crimes. Further, it involves putting accountability to those who initiate or deliver cyber threats, thereby eliminating the possible source of Internet related crimes.
Following the MOU agreement, Prof. Lee delivered a speech on his campaign at the 2015 International Conference on Information Systems and received positive responses from the audience.
The Bright Internet campaign has been selected as visions of various ICT organizations worldwide including the Korea Society of Management Information System and the International Federation of Information Processing. KAIST and Tsinghua University in China adopted it as an academic topic for research and teaching.
Prof. Lee claimed that the Internet should be used in a manner based on the values of trust, ethics, and decorum. He further noted that it is important to build Internet environments that not only protect individuals from cyber threats or attacks, but also hold those who commit online crimes accountable for their actions.
2015.12.28 View 8124 -
KAIST Wins the Korea Donation for Education Awards 2015
KAIST received the grand prize for the university section at the Korea Donation for Education Awards 2015. The award ceremony took place at Seoul Plaza Hotel on December 15, 2015.
The Ministry of Education created the award in 2012 to raise awareness about the need for charitable donations for education and to encourage the public’s participation in such endeavors. Recipients have included private companies, public institutions, non-profit organizations, universities, and individuals who have made notable contributions to education, for example, by offering educational programs or fundraising for such programs throughout a year.
Many organizations within KAIST, including the KAIST Center of Donation for Education, the Midam Scholarship Committee, the Donation for Software Education Group, the Chalk Academy, KAIST Student Volunteers, and K-LET, have been collectively recognized for their efforts to develop educational materials and managing academic camps and programs.
In addition to the grand prize which KAIST won, the Ministry of Education gave Neung-In Jang, a student pursuing a social entrepreneurship MBA at KAIST, an award for his efforts to provide quality education to teenagers by establishing the Midam Scholarship Committee in 2009. The Scholarship aims to revitalize the culture of donation for education by offering free math and science classes to high school students who are less privileged and by inspiring other universities in Korea to follow suit the committee’s volunteering activities.
2015.12.22 View 8494 -
KAIST and Charles University Agree to Cooperate
KAIST and Charles University in Prague, the Czech Republic, agreed to cooperate in research and education.
President Steve Kang of KAIST (pictured on the left) and Rector Tomáš Zima of Charles University signed the agreement on December 2, 2015, at the Hilton Hotel in Prague.
Minster Yang-Hee Choi of Science, ICT and Future Planning of the Republic of Korea and Minister Kateřina Valachová of Education, Youth and Sports of the Czech Republic also joined the signing ceremony.
Under the agreement, the two institutions will exchange students and researchers, as well as implement joint research programs.
President Kang said, “We are pleased to work with one of the most prestigious universities in the Czech Republic and hope to build a good partnership in the years ahead.”
Founded in 1348, Charles University in Prague is the oldest and largest university in the Czech Republic. The university received two Nobel prizes in physiology or medicine and in chemistry in 1947 and 1959, respectively.
2015.12.03 View 6899 -
Dr. Ryu of KAIST Receives the S-Oil Outstanding Paper Award
Dr. Je-Kyung Ryu of KAIST’s Department of Physics has been awarded the S-Oil Outstanding Paper Award for his doctoral dissertation’s originality and applicability.
Professor Tae-Young Yoon of Physics is his doctoral advisor.
The award ceremony took place on November 25, 2015 at the Press Center in Seoul.
This S-Oil Outstanding Paper Award, jointly sponsored by the Korean Academy of Science and Technology (KAST) and the Scholastic University Presidential Association, was established to foster young talented scientists in basic science and to advance the field.
The award is given every other year for each of the fields of physics, chemistry, mathematics, biology, and earth sciences.
With the award, Dr. Ryu received a research grant of USD 8,600.
He discovered, for the first time in the world, how NSF (N-ethylmaleimide-sensitive factor), a protein involved in a vesicular transport in cellular activities, disassembles a SNARE (soluble NSF attachment protein receptor) complex, using a unimolecular biophysics method.
Unlike the existing studies, he proposed a model in which NSF disassembles SNARE complexes at one step, and as a result, provided evidence of how the SNARE complex influenced the fusion of biological membranes.
His research was published in the scientific journal Science issued on March 27, 2015. The title of the paper is “Spring-loaded Unraveling of a Single SNARE Complex by NSF in One Round of ATP Turnover.”
2015.11.27 View 7905 -
KAIST and Four Science and Technology Universities Host a Start-up Competition
KAIST and four other science and technology universities, such as Gwangju Institute of Science and Technology (GIST), Ulsan National Institute of Science and Technology (UNIST), Daegu Gyeongbuk Institute of Science and Technology (DGIST), and Pohang University of Science and Technology (POSTECH), hosted a startup competition on November 27, 2015 at the Dongdaemun Design Plaza in Seoul.
Approximately 150 participants including students from the five universities, "angel" investors, and entrepreneurs attended the competition.
The competition was held to promote startups that are based on research achievements in science and technology and to foster entrepreneurs with great potential.
Two hundred and sixty applicants from 81 teams competed this year. Only ten teams made it to the finals.
KAIST students presented two business plans: an experience-centered education platform and mobile taxi-pooling service. Students from other universities presented a brain-stimulating simulation software (GIST), handy smart health trainer (GIST), real-time reporting system for luggage (DGIST), a flower delivery system (UNIST), surveillance and alarm system for stock-related events via machinery studies (UNIST), augmented emotion toys using augmented reality (POSTECH), and a nasal spray for fine dust prevention (POSTECH).
KAIST also displayed an exhibition of “wearable haptic device for multimedia contents” and “next generation recommendation service platform based on one-on-one matching system with high expandability and improved user experience system.”
The winning team received an award from the Minister of Science, ICT and Future Planning of Korea, as well as an opportunity to participate in overseas startup programs over the course of ten days.
Joongmyeon Bae, Director of the KAIST Industry and University Cooperation, who organized the contest, said, “The alumni of Stanford University (USA) has annually created over 5.4 million jobs through startup activities. Likewise, we hope that our event will contribute to job creation by fostering innovative entrepreneurs.”
2015.11.26 View 9670 -
Professor Keon-Jae Lee Lectures at IEDM and ISSCC Forums
Professor Keon-Jae Lee of KAIST’s Materials Science and Engineering Department delivered a speech at the 2015 Institute of Electrical and Electronics Engineers (IEEE) International Electron Devices Meeting (IEDM) held on December 7-9, 2015 in Washington, D.C.
He will also present a speech at the 2016 International Solid-State Circuits Conference scheduled on January 31-February 4, 2016 in San Francisco, California.
Both professional gatherings are considered the world’s most renowned forums in electronic devices and semiconductor technology. It is rare for a Korean researcher to be invited to speak at these global conferences.
Professor Lee was recognized for his research on flexible NAND chips. The Korea Times, an English language daily newspaper in Korea, reported on his participation in the forums and his recent work. An excerpt of the article follows below:
“KAIST Professor to Lecture at Renowned Tech Forums”
By Lee Min-hyung, The Korea Times, November 26, 2015
Recently he has focused on delivering technologies for producing flexible materials that can be applied to everyday life. The flexible NAND flash memory chips are expected to be widely used for developing flexible handsets. His latest research also includes flexible light-emitting diodes (LED) for implantable biomedical applications.
Lee is currently running a special laboratory focused on developing new flexible nano-materials. The research group is working to develop what it calls “self-powered flexible electronic systems” using nanomaterials and electronic technology.
Lee’s achievement with flexible NAND chips was published in the October edition of Nano Letters, the renowned U.S.-based scientific journal.
He said that flexible memory chips will be used to develop wearable computers that can be installed anywhere.
2015.11.26 View 9581