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Study Identifies the Novel Molecular Signal for Triggering Septic Shock
Professor Seyun Kim’s team at the Department of Biological Sciences reported the mechanism by which cellular signaling transduction networks are precisely controlled in mediating innate immune responses, such as sepsis, by the enzyme IPMK (Inositol polyphosphate multikinase) which is essential for inositol biosynthesis metabolism.
In collaboration with Professor Hyun Seong Roh at Seoul National University, the study’s first author, Eunha Kim, a Ph.D. candidate in Department of Biological Sciences, performed a series of cellular, biochemical, and physiological experiments searching for the new function of IPMK enzymes in macrophages. The research findings were published in Science Advances on April 21.
Professor Kim’s team has been investigating various inositol metabolites and their biosynthesis metabolism for several years and has multilaterally identified the signaling actions of IPMK for controlling cellular growth and energy homeostasis.
This research showed that the specific deletion of IPMK enzymes in macrophages could significantly reduce levels of inflammation and increase survival rates in mice when they were challenged by microbial septic shock and endotoxins. This suggests a role for IPMK enzymes in mediating innate inflammatory responses that are directly related to a host’s defense against pathogenic bacterial infection.
The team further discovered that IPMK enzymes directly bind to TRAF6 proteins, a key player in immune signaling, thus protecting TRAF6 proteins from ubiquitination reactions that are involved in protein degradation. In addition, Kim and his colleagues successfully verified this IPMK-dependent immune control by employing short peptides which can specifically interfere with the binding between IPMK enzymes and TRAF6 proteins in macrophage cells.
This research revealed a novel function of IPMK enzymes in the fine tuning of innate immune signaling networks, suggesting a new direction for developing therapeutics targeting serious medical conditions such as neuroinflammation, type 2 diabetes, as well as polymicrobial sepsis that are developed from uncontrolled host immune responses. This research was funded by the Ministry of Science, ICT and Future Planning.
(Figure: Deletion of IPMK (inositol polyphosphate multikinase) in macrophages reduces the stability of TRAF6 protein which is the key to innate immune signaling, thereby blocking excessive inflammation in response to pathological bacterial infection.)
2017.05.11 View 9226 -
Policy Debate Series for Industry 4.0
(Photo caption: President Shin takes the podium as the first speaker of a year-long monthly policy dabate series on Industry 4.0 on May 11.)
KAIST will kick off a monthly policy debate series on Industry 4.0 every Thursday from May 11 at the Startup KAIST building. The year-long series, featuring professors from key technology fields associated with Industry 4.0, is designed to help policy makers from government, industry, and research institutes respond better to the ramifications that Industry 4.0 brings about in each sector.
The series will help them establish the vision and strategy that will work for the new industrial environment to take the lead in the new industrial era.
Twelve professors, including President Sung-Chul Shin, from departments that are researching emerging technologies will speak on the megatrend of new technology, while facilitating debates and Q& A sessions with participants.
The participants will include officials from the government complexes in Sejong and Daejeon cities, government-funded research institutes in Daejeon, and businessmen, among others. For registration, please go to https://startup.kaist.ac.kr/register.
Schedule
Speaker
Theme
May 11
President Sung-Chul Shin
Challenges and Innovations of KAIST in the Era of Industry 4.0
June 8
Professor Jonghwan Kim
Machine Intelligence and Deep Learning
July 6
Professor Jun Ho Oh
Robot Technology and the Future
Aug. 3
Professor Hyunchul Shim
Unmanned Vehicle Technology and Industry 4.0
Sept. 7
Professor Hawoong Jeong
Complex Systems and Data Science
Oct. 12
Professor Yongdae Kim
Technology, Policy, and the Fostering of Talents: Industry 4.0 and Information Protection
Nov. 9
Professor Sang Yup Lee
The Role of Biotechnology in Industry 4.0
Dec. 7
Professor Meeyoung Cha
AI-Based Research for Fake News Detection
2018 Jan. 4
Professor Joungho Kim
Innovation for the Korean Semiconductor Industry: Kim’s Law
Feb. 8
Professor Jaekyun Moon
Education for Industry 4.0
March 8
Professor Sang Kil Cha
Artificial Intelligence Cyber Warfare: Its Present and Future
April 5
Professor Jaeseung Jeong
The Future of Brain Engineering and Artificial Intelligence
2017.05.08 View 10440 -
Professor Lee Recognized by the KMS as Best Paper Awardee
Professor Ji Oon Lee of the Department of Mathematical Sciences was selected as the 2017 Best Paper Awardee by the Korean Mathematical Society. The award will be presented during the KMS spring meeting on April 29. Dr. Lee is being honored for proving a necessary and sufficient condition for the Tracy-Wisdom law of Wigner matrices. In a paper titled ‘A Necessary and Sufficient Condition for Edge Universality of Wigner Matrices,’ he proposed a solution for one of the many unanswered problems in the field of random matrix theory that have existed for decades. The paper, co-authored with Professor Jun Yin at the University of Wisconsin – Madison, was published in the Duke Mathematical Journal in 2014. Professor Lee joined KAIST in 2010 after finishing his Ph.D. at Harvard University. He was named a ‘POSCI Science Fellow’ and received the ‘Young Scientist Award’ from the KMS in 2014.
2017.04.27 View 9408 -
Professor Otfried Cheong Named as Distinguished Scientist by ACM
Professor Otfried Cheong (Schwarzkopf) of the School of Computing was named as a Distinguished Scientist of 2016 by the Association for Computing Machinery (ACM).
The ACM recognized 45 Distinguished Members in the category of Distinguished Scientist, Educator, and Engineer for their individual contributions to the field of computing. Professor Cheong is the sole recipient from a Korean institution. The recipients were selected among the top 10 percent of ACM members with at least 15 years of professional experience and five years of continuous professional membership.
He is known as one of the authors of the widely used computational geometry textbook Computational Geometry: Algorithms and Applications and as the developer of Ipe, a vector graphics editor. Professor Cheong joined KAIST in 2005, after earning his doctorate from the Free University of Berlin in 1992. He previously taught at Ultrecht University, Pohang University of Science and Technology, Hong Kong University of Science and Technology, and the Eindhoven University of Technology.
2017.04.17 View 8073 -
Expanding the Genetic Code of Mus Musculus
Professor Hee-Sung Park of the Department of Chemistry, who garnered attention for his novel strategy of installing authentic post-translational modifications into recombinant proteins, expanded his research portfolio to another level. Professor Park’s team was the first to report the generation of a mouse strain with an expanded genetic code, allowing site-specific incorporation of unnatural amino acids.
Professor Park published the research on the new chemical biology method for achieving selective chemical modifications in proteins in Science last September. The research team, this time in collaboration with Professor Chan Bae Park of the Department of Physiology at the Ajou University School of Medicine, demonstrated temporal and spatial control of protein acetylation in various organs of the transgenic mouse using a recombinant green fluorescent protein as a model protein. This research was published in the online edition of Nature Communications on February 21.
This approach enables the rapid onset of position-specific acetylation of a target protein at any developmental stage, facilitating temporal and spatial control of protein acetylation in various organs of the transgenic mouse. Such temporal and spatial control of protein acetylation will be of prime importance for investigating many essential biological processes and human diseases at the tissue and organism level.
Almost all human proteins, the products of about 25,000 genes, are known to undergo various post-translational modifications during and after synthesis. Post-translation modifications regulate the function of cellular proteins, playing a key role in many essential processes such as delivering signals and body growth. However, the unusual protein modifications, aroused from genetic and/or environmental factors, trigger severe diseases including cancer, dementia, and diabetes.
The team inserted transgenes into the mouse genome to allocate the site-specific addition of unnatural amino acids. The researchers inserted a modified version of lysine into the house mice, which allowed for the control of the acetylation. They used recombinant green fluorescent proteins from transgenic house mice as models for control of the acetylation.
The team was also able to regulate the acetylation of specific temporal and spatial frames in the mice, restraining the abnormality in proteins to certain organs such as the liver and kidneys. The research team said the strategy will provide a powerful tool for systematic in vivo study of cellular proteins in the most commonly used mammalian model organisms for human physiology and disease. Professor Park said, “This method can be easily extended to generate a wide range of custom-made transgenic mouse strains for further investigating diverse proteins of interest.” He added, “This method can be further extended to generate a wide range of custom-made transgenic mouse strains, opening a new paradigm for investigating anti-cancer and cerebral disease treatments.
This work was supported by grants from KAIST Systems Healthcare and the Medicinal Bioconvergence Research Center and the Intelligent Synthetic Biology Center of the Global Frontier Project funded by the Ministry of Science, ICT & Future Planning and the Ministry of Food and Drug Safety.
(Figure:Temporal and spatial control of in vivo protein acetylation)
(a) Temporal expression of acetylated GFPuv in the AcK-GFPamber mouse. The expression of GFPuv in skeletal muscle, liver, and lung tissues was detected only in the AcK-injected mouse. Scale bar, 200 µm. (b) Western blotting of anti-FLAG-immunoprecipitated proteins from tissues of the AcK-GFPamber mouse. Acetylated GFPuv was produced after AcK injection. (c) Spatial expression of acetylated GFPuv in the AcK-GFPamber mouse. Acetylated GFPuv was observed only in skeletal muscle when AcK was directly delivered to the tissues. Sacle bar, 200 µm.
2017.03.27 View 9723 -
Professor Jae Kyoung Kim Receives the 2017 HSFP Award
The Human Frontier Science Program (HSFP), one of the most competitive research grants in life sciences, has funded researchers worldwide across and beyond the field since 1990. Each year, the program selects a handful of recipients who push the envelope of basic research in biology to bring breakthroughs from novel approaches. Among its 7,000 recipients thus far, 26 scientists have received the Nobel Prize. For that reason, HSFP grants are often referred to as “Nobel Prize Grants.”
Professor Jae Kyoung Kim of the Mathematical Sciences Department at KAIST and his international collaborators, Professor Robert Havekes from the University of Groningen, the Netherlands, Professor Sara Aton from the University of Michigan in Ann Arbor, the United States, and Professor Matias Zurbriggen from the University of Düsseldorf, Germany, won the Young Investigator Grants of the 2017 HSFP.
The 30 winning teams of the 2017 competition (in 9 Young Investigator Grants and 21 Program Grants) went through a rigorous year-long review process from a total of 1,073 applications submitted from more than 60 countries around the world. Each winning team will receive financial support averaging 110,000-125,000 USD per year for three years.
Although Professor Kim was trained as a mathematician, he has extended his research focus into biological sciences and attempted to solve some of the most difficult problems in biology by employing mathematical theories and applications including nonlinear dynamics, stochastic process, singular perturbation, and parameter estimation.
The project that won the Young Investigator Grants was a study on how a molecular circadian clock may affect sleep-regulated neurophysiology in mammals. Physiological and metabolic processes such as sleep, blood pressure, and hormone secretion exhibit circadian rhythms in mammals. Professor Kim used mathematical modeling and analysis to explain that the mammalian circadian clock is a hierarchical system, in which the master clock in the superchiasmatic nucleus, a tiny region in the brain that controls circadian rhythms, functions as a pacemaker and synchronizer of peripheral clocks to generate coherent systematic rhythms throughout the body.
Professor Kim said, “The mechanisms of our neuronal and hormonal activities regulating many of our bodily functions over a 24-hour cycle are not yet fully known. We go to sleep every night, but do not really know how it affects our brain functions. I hope my experience in mathematics, along with insights from biologists, can find meaningful answers to some of today’s puzzling problems in biological sciences, for example, revealing the complexities of our brains and showing how they work.”
“In the meantime, I hope collaborations between the fields of mathematics and biology, as yet a rare phenomenon in the Korean scientific community, will become more popular in the near future.”
Professor Kim received his doctoral degree in Applied and Interdisciplinary Mathematics in 2013 from the University of Michigan and joined KAIST in 2015. He has published numerous articles in reputable science journals such as Science, Molecular Cell, Proceedings of the National Academy of Sciences, and Nature Communications.
Both the Program Grants and Young Investigator Grants support international teams with members from at least two countries for innovative and creative research. This year, the Program Grants were awarded to research topics ranging from the evolution of counting and the role of extracellular vesicles in breast cancer bone metastasis to the examination of obesity from a mechanobiological point of view.
The Young Investigator Grants are limited to teams that established their independent research within the last five years and received their doctoral degrees within the last decade. Besides Professor Kim’s study, such topics as the use of infrasound for navigation by seabirds and protein formation in photochemistry and photophysics were awarded in 2017.
Full lists of the 2017 HFSP winners are available at: http://www.hfsp.org/awardees/newly-awarded.
About the Human Frontier Science Program (HFSP):
The HFSP is a research funding program implemented by the International Human Frontier Science Program (HFSPO) based in Strasbourg, France. It promotes intercontinental collaboration and training in cutting-edge, interdisciplinary research specializing in life sciences. Founded in 1989, the HFSPO consists of the European Union and 14 other countries including the G7 nations and South Korea.
2017.03.21 View 10655 -
Professor Kwangjo Kim Named as Fellow of IACR
Professor Kwangjo Kim of the Graduate School of Information Security has been selected as a fellow of the International Association for Cryptologic Research (IACR).
The IACR has honored outstanding scholars who have achieved academic excellence in cryptologic research since 2004. He is the first Korean scholar to receive an IACR fellowship.
The IACR, established in 1981, is responsible for organizing international cryptologic conferences every year including the three major cryptologic academic conferences Eurocrypt, Crypto, and Asiacript. The IACR also sponsors workshop series such as the Theory of Cryptography Conference (TCC), the Workshop on Fast Software Encryption (FSE), the Public Key Cryptography Workshop (PKC), and Cryptographic Hardware and Embedded Systems (CHES).
Professor Kim, an internationally acclaimed scholar in the fields of cryptology and information security theory and its applications, was recognized for his outstanding academic achievements and leadership. He has made significant contributions to cryptology in Korea by hosting Asiacript in 1996 and 2001 as well as CHES in 2014. During his 34 years of academic activities, he has published more than 80 SCI journal papers and garnered more than 20,000 citations.
Professor Kim served on the board of the directors of the IACR from 2000 to 2004 and was the chairperson of the Asiacript Steering Committee from 2005 to 2008. He is on the editorial board of the online journal Cryptography.
Professor Kim said, “I am so humbled and honored to be named as a fellow of such a prestigious academic association. I will continue to strive to assist highly educated information security personnel with further research in cryptology.”
2017.03.16 View 8476 -
13 KAIST Faculty Named as Inaugural Members of Y-KAST
The Korean Academy of Science and Technology (KAST) launched the Young Korean Academy of Science and Technology (Y-KAST) and selected 73 scientists as its inaugural members on February 24. Among them, 13 KAIST faculty were recognized as the inaugural members of Y-KAST.
Y-KAIST, made up of distinguished mid-career scientists under the age of 45, will take the leading role in international collaboration as well as innovative agenda-making in science and technology.
The inaugural members include Professor Hyotcherl Ihee of the Department of Chemistry and Dr. Sung-Jin Oh of the Center for Mathematical Challenges at the Korea Institute for Advanced Study (KIAS), affiliated with KAIST. Professor Ihee is gaining wide acclaim in the fields of physics and chemistry, and in 2016, Dr. Oh was the youngest ever awardee of the Presidential Award of Young Scientist.
The other Y-KAIST members are as follows: Professors Haeshin Lee of the Department of Chemistry; Mi Young Kim, Byung-Kwan Cho, and Ji-Joon Song of the Department of Biological Sciences; Song-Yong Kim of the Department of Mechanical Engineering; Sang-il Oum of the Department of Mathematical Sciences; Jung Kyoon Choi of the Department of Bio and Brain Engineering; Seokwoo Jeon, Sang Ouk Kim, and Il-Doo Kim of the Department of Materials Science and Engineering; Jang Wook Choi of the Graduate School of EEWS (Energy, Environment, Water and Sustainability); and Jeong Ho Lee of the Graduate School of Medical Science and Engineering.
The leading countries of the Academy of Science, which include Germany, Sweden, Belgium, Canada, and Japan, have established the Young Academy of Science since 2010 in order to encourage the research activities of their young scientists and to establish a global platform for collaborative research projects through their active networking at home and abroad.
President Myung-Chul Lee of KAST said, “We will spare no effort to connect these outstanding mid-career researchers for their future collaboration. Their networking will make significant impacts toward their own research activities as well as the global stature of Korea’s science and technology R&D.
(Photo caption: Members of Y-KAST pose at the inaugural ceremony of Y-KAST on February 24.)
2017.03.02 View 17927 -
Quantum Dot Film Can Withstand High Temperatures and Humidity
The joint KAIST research team of Professor Byeong-Soo Bae of the Department of Materials Science and Engineering and Professor Doh Chang Lee of the Department of Chemical and Biomolecular Engineering was able to fabricate a siloxane-encapsulated quantum dot film, which exhibits stable emission intensity over one month even at high temperatures and humidity.
The results of this study were published in the Journal of the American Chemical Society (JACS) on November 29, 2016. The research article is entitled “Quantum Dot/Siloxane Composite Film Exceptionally Stable against Oxidation under Heat and Moisture.” (DOI: 10.1021/jacs.6b10681)
Quantum dots (QDs), light-emitting diodes (LEDs) for next-generation displays, are tiny particles or nanocrystals of semiconducting materials. Their emission wavelength can easily be adjusted by changing their sizes, which are just a few nanometers. A wide spectrum of their colors can also achieve ultra-high definition displays.
Due to these characteristics, QDs are coated on a film as a polymer resin in dispersed form, or they are spread on an LED light source. They are thus considered to be crucial for next generation displays.
Despite their exceptional optical properties, however, QDs are easily oxidized in a high temperature and high humidity environment, and, as a result, this greatly deteriorates their luminescence quality (quantum efficiency). Therefore, they are encapsulated in an extra thin layer to block oxygen and moisture.
QD displays in the current market have a film inserted to separate them from LEDs, which create heat. The high unit cost of this protective layer, however, increases the overall cost of displays, lowering their price competitiveness in the market.
For a solution, the research team applied the sol-gel condensation reaction of silane precursors with QDs. This technology uses the reactions of chemical substances to synthesize ceramics or glass at a low temperature.
The team applied QDs in a heat resistant siloxane polymer by employing this technology. The siloxane resin acted as a cup holding the QDs and also blocked heat and moisture. Thus, their performance can be maintained without an extra protective film.
QDs are evenly dispersed into the resin from a chemical process to fabricate a QD embedded film and retained the high quality luminescence not only at a high temperature of 85°C and in a high humidity of 85%, but also in a high acid and high base environment. Remarkably though, the luminescence actually increased in the high humidity environment.
If this technology is used, the overall price of displays will decrease by producing a stable QD film without an extra protective barrier. In the future, the QD film can be directly applied to a blue LED light source. As a result, it will be possible to develop a QD display that can reduce the amount of QDs needed and improve its performance.
Professor Bae said, “We have proposed a way to make quantum dots overcome their limitations and have wide applications as they are being developed for next-generation displays. Our technology will make significant contributions to the display industry in the country.”
He also added, “In the future, we plan to cooperate with companies both in and out of the country to improve the performance of quantum dots and concentrate on their commercialization.”
The research team is currently applying for related patents both in and out of the country. The team is also plan ning to transfer the patents to Sol Ip Technology Inc., a company founded at KAIST, to start the commercialization.
Picture 1:
Siloxane-encapsulated quantum dot (QD) films showing performance stability in boiling water
Picture 2 and 3:
So-gel condensation reaction in silane precursors between Methacryloxypropyltrimethoxysilane (MPTS) and diphenylsilanediol (DPSD). The inset shows photographs of a QD-oligosiloxane resin under room light (left) and a UV lamp (λ = 365 nm) (right).
Free radical addition reactions among carbon double bonds of methacryl functional groups and oleic acids. The inset shows photographs of a QD-silox film under room light (left) and a UV lamp (λ = 365 nm) (right).
2017.02.24 View 10437 -
KAIST Alumni of the Year
(From left Chul-Hwan Kim, president and CEO of Orange Power, Hooshik Kim, president & CEO of Vieworks, Chilhee Chung, presient of Samsung Advanced Institute of Technology, KAIST President Sung-Mo Kang, KAIST Alumni Association President Jung-Sik Ko, Won-Pil Baek, senior vice president for R&D program at Korea Atomic Energy Research Insitute, Hyonho Jung, CEO of Medytox, Jaehwa Kim on behalf of Han-Oh Park, president & CEO of Bioneer Corporation)
The KAIST Alumni Association presented the Alumni of the Year award to six of its most accomplished alumni at the New Year dinner held at the Lotte Hotel in Seoul on January 14.
KAIST alumni community, which numbers over 500,000, has made a significant impact around the globe in science and technology, industry, education, and the public sector. Each year, the KAIST Alumni Association honors individuals who have made a significant contribution with outstanding leadership through the Alumni of the Year awards.
KAIST Alumni Association President Jung-Sik Ko awarded the recipients at the dinner. About 200 alumni, faculty, and students, including KAIST President Sung-Mo Kang, joined the celebration.
The 2016 awardees are Dr. Chilhee Chung, president of Samsung Advanced Institute of Technology(SAIT); Dr.Won-Pil Baek, senior vice president for R&D program at Korea Atomic Energy Research Institute(KAERI); Dr.Han-Oh Park, president & CEO of Bioneer Corporation; Dr.Hyonho Jung, CEO of Medytox; Hooshik Kim, president & CEO of Vieworks; and Dr.Chul-Hwan Kim, president & CEO of Orange Power.
Dr. Chung of SAIT (MS in physics ’79) played a leading role in developing top-notch system semiconductors and memory device technology while serving as president of the Samsung Electronic Semiconductor R&D Center. He has focused on the development of cutting-edge future technology, the Quantum Dot, by incorporating eco-friendly materials with the highest efficiency and color purity which is cadmium-free.
Working at KAERI since 2001, Dr. Baek (Ph.D. in nuclear and quantum engineering ’87) has made contributions to help Korea emerge as a nuclear technology powerhouse. He played a critical role in developing and facilitating a global nuclear safety verification facility dubbed ‘ATLAS.’ Such nuclear technological prowess led the Korean government to advance into the foreign markets, such as exporting nuclear power plants to United Arab Emirates.
The CEO of Bioneer, Dr. Park (Ph.D. in chemistry ’87) started a bio-venture in Korea. His company has developed hundreds of reagents, diagnostic kits, and advanced equipment for gene research over two decades. Bioneer has paved the way for establishing a world-class level of infrastructure in genomic technology. By developing the innovative technology "SAMiRNA ™ (Self-Assembled-Micelle-inhibitory-RNA)" that overcomes the problems in drug development, Bioneer presented a new solution for the treatment of incurable diseases. In collaboration with global pharmaceutical companies and research groups, Dr. Park has successfully led joint development in the licensing of new therapeutic medicine candidates for various incurable diseases.
Dr. Jung (Ph.D. in biological sciences ’88) founded the bio-pharmaceutical company Medytox in 2000. Medytox is the first company in Korea that commercialized botulinum toxin formulation. Medytox developed the non-animal liquid botulinum toxin formulation for the first time in the world. It successfully localized botulinum preparation that can treat various neurological diseases. Medytox’s new toxin formulation resulted in improving public health care as well as relieving the heavy dependence on importing bio-pharmaceutical products.
As the CEO of Vieworks, Kim (MS in physics ’95) succeeded in commercializing of digital X-ray. Especially, it is leading the design of optical and image systems that affect the quality of digital X-ray image. Kim’s company established related technology base, contributing to human health promotion and national industrial development.
President Kim of Orange Power (Ph.D. in chemical and biomolecular engineering ’93) is also the founder of the KITE Entrepreneurship Foundation. He launched Biogenix Co., Ltd. and Image and Materials Co. in 2005. In order to nurture an entrepreneurship and start-ups eco-system, he invested 10 billion KRW from the proceeds of the sale of one of his start-ups. In addition, he started Orange Power Co., Ltd. in 2012 to solve the secondary battery heat problem and established a global partnership with Hydro Quebec in Canada, Nexion in UK, Volkswagen of Germany, and Tesla of the US.
2017.01.16 View 12122 -
Professor Kwon to Represent the Asia-Pacific Region of the IEEE RAS
Professor Dong-Soon Kwon of the Mechanical Engineering Department at KAIST has been reappointed to the Administrative Committee of the Institute of Electrical and Electronics Engineers (IEEE) Robotics and Automation Society (IEEE RAS). Beginning January 1, 2017, he will serve his second three-year term, which will end in 2019. In 2014, he was the first Korean appointed to the committee, representing the Asia-Pacific community of the IEEE Society.
Professor Kwon said, “I feel thankful but, at the same time, it is a great responsibility to serve the Asian research community within the Society. I hope I can contribute to the development of robotics engineering in the region and in Korea as well.”
Consisted of 18 elected members, the administrative committee manages the major activities of IEEE RAS including hosting its annual flagship meeting, the International Conference on Robotics and Automation.
The IEEE RAS fosters the advancement in the theory and practice of robotics and automation engineering and facilitates the exchange of scientific and technological knowledge that supports the maintenance of high professional standards among its members.
2016.12.06 View 9993 -
Mystery of Biological Plastic Synthesis Machinery Unveiled
Plastics and other polymers are used every day. These polymers are mostly made from fossil resources by refining petrochemicals. On the other hand, many microorganisms naturally synthesize polyesters known as polyhydroxyalkanoates (PHAs) as distinct granules inside cells.
PHAs are a family of microbial polyesters that have attracted much attention as biodegradable and biocompatible plastics and elastomers that can substitute petrochemical counterparts. There have been numerous papers and patents on gene cloning and metabolic engineering of PHA biosynthetic machineries, biochemical studies, and production of PHAs; simple Google search with “polyhydroxyalkanoates” yielded returns of 223,000 document pages. PHAs have always been considered amazing examples of biological polymer synthesis. It is astounding to see PHAs of 500 kDa to sometimes as high as 10,000 kDa can be synthesized in vivo by PHA synthase, the key polymerizing enzyme in PHA biosynthesis. They have attracted great interest in determining the crystal structure of PHA synthase over the last 30 years, but unfortunately without success. Thus, the characteristics and molecular mechanisms of PHA synthase were under a dark veil.
In two papers published back-to-back in Biotechnology Journal online on November 30, 2016, a Korean research team led by Professor Kyung-Jin Kim at Kyungpook National University and Distinguished Professor Sang Yup Lee at the Korea Advanced Institute of Science and Technology (KAIST) described the crystal structure of PHA synthase from Ralstonia eutropha, the best studied bacterium for PHA production, and reported the structural basis for the detailed molecular mechanisms of PHA biosynthesis. The crystal structure has been deposited to Protein Data Bank in February 2016. After deciphering the crystal structure of the catalytic domain of PHA synthase, in addition to other structural studies on whole enzyme and related proteins, the research team also performed experiments to elucidate the mechanisms of the enzyme reaction, validating detailed structures, enzyme engineering, and also N-terminal domain studies among others.
Through several biochemical studies based on crystal structure, the authors show that PHA synthase exists as a dimer and is divided into two distinct domains, the N-terminal domain (RePhaC1ND) and the C-terminal domain (RePhaC1CD). The RePhaC1CD catalyzes the polymerization reaction via a non-processive ping-pong mechanism using a Cys-His-Asp catalytic triad. The two catalytic sites of the RePhaC1CD dimer are positioned 33.4 Å apart, suggesting that the polymerization reaction occurs independently at each site. This study also presents the structure-based mechanisms for substrate specificities of various PHA synthases from different classes.
Professor Sang Yup Lee, who has worked on this topic for more than 20 years, said,
“The results and information presented in these two papers have long been awaited not only in the PHA community, but also metabolic engineering, bacteriology/microbiology, and in general biological sciences communities. The structural information on PHA synthase together with the recently deciphered reaction mechanisms will be valuable for understanding the detailed mechanisms of biosynthesizing this important energy/redox storage material, and also for the rational engineering of PHA synthases to produce designer bioplastics from various monomers more efficiently.”
Indeed, these two papers published in Biotechnology Journal finally reveal the 30-year mystery of machinery of biological polyester synthesis, and will serve as the essential compass in creating designer and more efficient bioplastic machineries.
References:
Jieun Kim, Yeo-Jin Kim, So Young Choi, Sang Yup Lee and Kyung-Jin Kim. “Crystal structure of Ralstonia eutropha polyhydroxyalkanoate synthase C-terminal domain and reaction mechanisms” Biotechnology Journal DOI: 10.1002/biot.201600648
http://onlinelibrary.wiley.com/doi/10.1002/biot.201600648/abstract
Yeo-Jin Kim, So Young Choi, Jieun Kim, Kyeong Sik Jin, Sang Yup Lee and Kyung-Jin Kim. “Structure and function of the N-terminal domain of Ralstonia eutropha polyhydroxyalkanoate synthase, and the proposed structure and mechanisms of the whole enzyme” Biotechnology Journal DOI: 10.1002/biot.201600649
http://onlinelibrary.wiley.com/doi/10.1002/biot.201600649/abstract
2016.12.02 View 10347