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Efficiently Producing Fatty Acids and Biofuels from Glucose
Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production. The newly developed strain, created by Distinguished Professor Sang Yup Lee and his team, showed the highest efficiency in producing fatty acids and biodiesels ever reported. It will be expected to serve as a new platform to sustainably produce a wide array of fatty acid-based products from glucose and other carbon substrates. Fossil fuels, which have long been energy resources for our daily lives, are now facing serious challenges: depletion of their reserves and their role in global warming. The production of sustainable bio-based renewable energy has emerged as an essential alternative and many studies to replace fossil fuels are underway. One of the representative examples is biodiesel. Currently, it is mainly being produced through the transesterification of vegetable oils or animal fats. The research team engineered oleaginous microorganisms, Rhodococcus opacus, to produce fatty acids and their derivatives that can be used as biodiesel from glucose, one of the most abundant and cheap sugars derived from non-edible biomass. Professor Lee’s team has already engineered Escherichia coli to produce short-chain hydrocarbons, which can be used as gasoline (published in Nature as the cover paper in 2013). However, the production efficiency of the short-chain hydrocarbons using E. coli (0.58 g/L) fell short of the levels required for commercialization. To overcome these issues, the team employed oil-accumulating Rhodococcus opacus as a host strain in this study. First, the team optimized the cultivation conditions of Rhodococcus opacus to maximize the accumulation of oil (triacylglycerol), which serves as a precursor for the biosynthesis of fatty acids and their derivatives. Then, they systematically analyzed the metabolism of the strain and redesigned it to enable higher levels of fatty acids and two kinds of fatty acid-derived biodiesels (fatty acid ethyl esters and long-chain hydrocarbons) to be produced. They found that the resulting strains produced 50.2, 21.3, and 5.2 g/L of fatty acids, fatty acid ethyl esters, and long-chain hydrocarbons, respectively. These are all the highest concentrations ever reported by microbial fermentations. It is expected that these strains can contribute to the future industrialization of microbial-based biodiesel production. “This technology creates fatty acids and biodiesel with high efficiency by utilizing lignocellulose, one of the most abundant resources on the Earth, without depending on fossil fuels and vegetable or animal oils. This will provide new opportunities for oil and petroleum industries, which have long relied on fossil fuels, to turn to sustainable and eco-friendly biotechnologies,” said Professor Lee. This paper titled “Engineering of an oleaginous bacterium for the production of fatty acids and fuels” was published in Nature Chemical Biology on June 17. This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557). (Figure: Metabolic engineering for the production of free fatty acids (FFAs), fatty acid ethyl esters (FAEEs), and long-chain hydrocarbons (LCHCs) in Rhodococcus opacus PD630. Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production.) # # # Source: Hye Mi Kim, Tong Un Chae, So Young Choi, Won Jun Kim and Sang Yup Lee. Engineering of an oleaginous bacterium for the production of fatty acids and fuels. Nature Chemical Biology ( https://www.nature.com/nchembio/ ) DOI: 10.1038/s41589-019-0295-5 Profile Dr. Sang Yup Lee leesy@kaist.ac.kr Distinguished Professor at the Department of Chemical and Biomolecular Engineering KAIST
2019.06.19
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Engineered Microbial Production of Grape Flavoring
(Image 1: Engineered bacteria that produce grape flavoring.) Researchers report a microbial method for producing an artificial grape flavor. Methyl anthranilate (MANT) is a common grape flavoring and odorant compound currently produced through a petroleum-based process that uses large volumes of toxic acid catalysts. Professor Sang-Yup Lee’s team at the Department of Chemical and Biomolecular Engineering demonstrated production of MANT, a naturally occurring compound, via engineered bacteria. The authors engineered strains of Escherichia coli and Corynebacetrium glutamicum to produce MANT through a plant-based engineered metabolic pathway. The authors tuned the bacterial metabolic pathway by optimizing the levels of AAMT1, the key enzyme in the process. To maximize production of MANT, the authors tested six strategies, including increasing the supply of a precursor compound and enhancing the availability of a co-substrate. The most productive strategy proved to be a two-phase extractive culture, in which MANT was extracted into a solvent. This strategy produced MANT on the scale of 4.47 to 5.74 grams per liter, a significant amount, considering that engineered microbes produce most natural products at a scale of milligrams or micrograms per liter. According to the authors, the results suggest that MANT and other related molecules produced through industrial processes can be produced at scale by engineered microbes in a manner that would allow them to be marketed as natural one, instead of artificial one. This study, featured at the Proceeding of the National Academy of Sciences of the USA on May 13, was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT. (Image 2. Overview of the strategies applied for the microbial production of grape flavoring.)
2019.05.15
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Professor Hee-Sung Park Named Scientist of May
(Professor Hee-Sung Park) Professor Hee-Sung Park from the Department of Chemistry was named ‘Scientist of May’ sponsored by the Ministry of Science and ICT and the National Research Foundation of Korea. Professor Park was honored in recognition of his developing a tool to engineer designer proteins via diverse chemical modifications. This approach provides a novel platform for investigating numerous diseases such as cancer and dementia. His research focuses on the production of synthetic proteins and the generation of diverse protein functions as well as the designing and engineering of new translation machinery for genetic code expansion, and the application of synthetic biology techniques for basic cell biology and applied medical science. Post-translational modifications (PTMs) are constantly taking place during or after protein biosynthesis. PTMs play a vital role in expanding protein functional diversity and, as a result, critically affect numerous biological processes. Abnormal PTMs have been known to trigger various diseases including cancer and dementia. Therefore, this technology enables proteins to reproduce with specific modifications at selected residues and will significantly help establish experimental strategies to investigate fundamental biological mechanisms including the development of targeted cancer therapies. Professor Park also received 10 million KRW in prize money.
2018.05.04
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Professor Ju, to Receive Grants from HFSP
(Professor Young Seok Ju) Professor Young Seok Ju from the Graduate School of Medical Science and Engineering was selected as a young investigator to receive research funds from the Human Frontiers Science Program. The Human Frontiers Science Program (HFSP) was founded in 1989 with members of the G7 and European Union to stimulate innovative research in the field of life sciences. Professor Ju placed third out of the eight teams that were selected from 158 applicants representing 60 countries. He is now the fourth Korean to receive a research grant as a young investigator. Professor Jae Kyoung Kim from the Department of Mathematical Sciences also received this prize last year, hence KAIST has produced grant recipients for two consecutive years. Professor Ju is a medical doctor specializing in cancer genomics and computer biology. He has been studying somatic mutations and their functional consequences in human cancer in a bioinformatics way. He has published papers in international journals including Nature, Science, Genome Research, and Journal of Clinical Oncology. With a title ‘Tracing AID/APOBEC- and MSI-mediated hyper-mutagenesis in the clonal evolution of gastric cancer,’ Professor Ju will receive 1.05 million dollars for three years along with Professor Bon-Kyoung Koo from the Institute of Molecular Biotechnology at Austrian Academy of Sciences, and Sinppert Hugo from University Medical Center Utrecht. Professor Ju said, “As a young investigator, it is my great honor to receive this research fund from this organization. Through this internationally collaborative research, I will carry out groundbreaking research to understand the pathophysiology of cancers at a molecular level.”
2018.04.24
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Three Professors Named KAST Fellows
(Professor Dan Keun Sung at the center) (Professor Y.H. Cho at the center) (Professor K.H. Cho at the center) The Korean Academy of Science and Technology (KAST) inducted three KAIST professors as fellows at the New Year’s ceremony held at KAST on January 12. They were among the 24 newly elected fellows of the most distinguished academy in Korea. The new fellows are Professor Dan Keun Sung of the School of Electrical Engineering, Professor Kwang-Hyun Cho of the Department of Bio and Brain Engineering, and Professor Yong-Hoon Cho of the Department of Physics. Professor Sung was recognized for his lifetime academic achievements in fields related with network protocols and energy ICT. He also played a crucial role in launching the Korean satellites KITSAT-1,2,3 and the establishment of the Satellite Technology Research Center at KAIST. Professor Y.H.Cho has been a pioneer in the field of low-dimensional semiconductor-powered quantum photonics that enables quantum optical research in solid state. He has been recognized as a renowned scholar in this field internationally. Professor K.H.Cho has conducted original research that combines IT and BT in systems biology and has applied novel technologies of electronic modeling and computer simulation analysis for investigating complex life sciences. Professor Cho, who is in his 40s, is the youngest fellow among the newly inducted fellows.
2018.01.16
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Professor Jin Woo Kim Wins the 14th Macrogen Scientist Award
Professor Jin Woo Kim of the Department of Biological Sciences at KAIST received the 14th Macrogen Scientist Award at the 2017 KSMCB International Conference held in COEX on September 12, 2017. The award is given by the Korean Society for Molecular and Cellular Biology (KSMCB) and sponsored by Macrogen, a service provider of genome research. The award was established in 2004 to recognize biological scientists who have accomplished excellent performance in the field of basic life sciences. Professor Kim has achieved outstanding research performances on nerve development, such as identifying the cause of senile retinal degenerative disease and finding retinal nerve cells that distinguish light and darkness in dark conditions. Recently, he discovered intercellular communication, which controls the development of retinal neurons. His findings have contributed to addressing the principles of maintenance and regeneration of retinal neurons. Since joining KAIST, he has presented approximately 20 papers and published in numerous international journals including Cell Reports, Genes and Development, and EMBO Journal. Moreover, he delivered special lectures at international conferences, universities, and institutes around the world.
2017.09.14
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Distinguished Professor Lee Elected to the NAS
Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering was elected as a foreign associate to the US National Academy of Sciences (NAS) on May 2. The National Academy of Sciences elected 84 new members and 21 foreign associates in recognition of their distinguished and continuing achievements in their original research. Election to the Academy is widely regarded as one of the highest honors that a scientist can receive. Professor Lee was also elected in 2010 as a member of the US National Academy of Engineering (NAE) for his leadership in microbial biotechnology and metabolic engineering, including the development of fermentation processes for biodegradable polymers and organic acids. Until 2016, there are only 12 people worldwide who are foreign associates of both NAS and NAE. He is the first Korean elected to both prestigious academies, the NAS and the NAE in the US. Professor Lee is currently the dean of KAIST Institutes, the world leading institute for multi-and interdisciplinary research. He is also serving as co-chair of the Global Council on Biotechnology and member of the Global Future Council on the Fourth Industrial Revolution, the World Economic Forum.
2017.05.16
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Unveiling the Distinctive Features of Industrial Microorganism
KAIST researchers have sequenced the whole genome of Clostridium tyrobutyricum, which has a higher tolerance to toxic chemicals, such as 1-butanol, compared to other clostridial bacterial strains. Clostridium tyrobutyricum, a Gram-positive, anaerobic spore-forming bacterium, is considered a promising industrial host strain for the production of various chemicals including butyric acid which has many applications in different industries such as a precursor to biofuels. Despite such potential, C. tyrobutyricum has received little attention, mainly due to a limited understanding of its genotypic and metabolic characteristics at the genome level. A Korean research team headed by Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department at the Korea Advanced Institute of Science and Technology (KAIST) deciphered the genome sequence of C. tyrobutyricum and its proteome profiles during the course of batch fermentation. As a result, the research team learned that the bacterium is not only capable of producing a large amount of butyric acid but also can tolerate toxic compounds such as 1-butanol. The research results were published in mBio on June 14, 2016. The team adopted a genoproteomic approach, combining genomics and proteomics, to investigate the metabolic features of C. tyrobutyricum. Unlike Clostridium acetobutylicum, the most widely used organism for 1-butanol production, C. tyrobutyricum has a novel butyrate-producing pathway and various mechanisms for energy conservation under anaerobic conditions. The expression of various metabolic genes, including those involved in butyrate formation, was analyzed using the “shotgun” proteome approach. To date, the bio-based production of 1-butanol, a next-generation biofuel, has relied on several clostridial hosts including C. acetobutylicum and C. beijerinckii. However, these organisms have a low tolerance against 1-butanol even though they are naturally capable of producing it. C. tyrobutyricum cannot produce 1-butanol itself, but has a higher 1-butanol-tolerance and rapid uptake of monosaccharides, compared to those two species. The team identified most of the genes involved in the central metabolism of C. tyrobutyricum from the whole-genome and shotgun proteome data, and this study will accelerate the bacterium’s engineering to produce useful chemicals including butyric acid and 1-butanol, replacing traditional bacterial hosts. Professor Lee said, “The unique metabolic features and energy conservation mechanisms of C. tyrobutyricum can be employed in the various microbial hosts we have previously developed to further improve their productivity and yield. Moreover, findings on C. tyrobutyricum revealed by this study will be the first step to directly engineer this bacterium.” Director Jin-Woo Kim 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, “Over the years, Professor Lee’s team has researched the development of a bio-refinery system to produce natural and non-natural chemicals with the systems metabolic engineering of microorganisms. They were able to design strategies for the development of diverse industrial microbial strains to produce useful chemicals from inedible biomass-based carbon dioxide fixation. We believe the efficient production of butyric acid using a metabolic engineering approach will play an important role in the establishment of a bioprocess for chemical production.” The title of the research paper is “Deciphering Clostridium tyrobutyricum Metabolism Based on the Who-Genome Sequence and Proteome Analyses.” (DOI: 10.1128/mBio.00743-16) The lead authors are Joungmin Lee, a post-doctoral fellow in the BioProcess Research Center at KAIST, currently working in CJ CheilJedang Research Institute; Yu-Sin Jang, a research fellow in the BioProcess Research Center at KAIST, currently working at Gyeongsang National University as an assistant professor; and Mee-Jung Han, an assistant professor in the Environmental Engineering and Energy Department at Dongyang University. Jin Young Kim, a senior researcher at the Korea Basic Science Institute, also participated in the research. This research was supported by the Technology Development Program to Solve Climate Change’s research project entitled “Systems Metabolic Engineering for Biorefineries” from the Ministry of Science, ICT and Future Planning through the National Research Foundation of Korea (NRF-2012M1A2A2026556). Schematic Diagram of C. tyrobutyricum’s Genome Sequence and Its Proteome Profiles The picture below shows the complete genome sequence, global protein expression profiles, and the genome-based metabolic characteristics during batch fermentation of C. tyrobutyricum.
2016.06.20
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Special Lecture by Professor Sung-Hou Kim of UC Berkeley
As part of its special lecture series, the Department of Biological Sciences at KAIST has invited Professor Sung-Hou Kim of the Department of Chemistry at the University of California, Berkeley, to lecture on his research in structural biology. He will speak twice on May 23 and 30, respectively, on the topics “Origin of Universe and Earth—A Narrative” and “Origin of Life and Human Species—A Narrative.” Professor Kim's research addresses the structural basis of molecules to reveal how they communicate with each other to activate or inhibit particular processes in cell growth, cell differentiation, and cancer. Using the single-crystal X-ray diffraction technology, he discovered, for the first time in the world, the three-dimensional (3-D) structure of a transfer RNA (t-RNA) and received much praise for this work from the scientific community. Since then, he has been cited as a candidate for a Nobel Prize in Chemistry for many years. He also examined the 3-D structures of a RAS protein in normal and cancer cells and identified the mutations of the RAS protein as a cause for cancer. His work has assisted in the development of target drugs for cancer treatment. In recent years, he has adopted a computational biology approach to study the structure and function of biological genomics, with which he has tried to predict disease-sensitive genes. Professor Kim graduated from Seoul National University in 1962 and received his Ph.D. degree in chemistry from the University of Pittsburgh in the United States in 1966. He worked at the Massachusetts Institute of Technology (MIT) as a senior research scientist, and has taught at UC Berkeley since 1978.
2016.05.23
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Meditox Donates 600 Million KRW Scholarship
On February 17, a Korean biopharmaceutical company Meditox, headed by Chief Executive Officer (CEO) Hyun-Ho Jeong, signed a memorandum of understanding (MOU) with KAIST to establish the “Meditox Fellowship” and donated a total of 600 million Korean won (KRW) to the university to assist in promoting more scientists in the field of biology. Meditox CEO Hyun-Ho Jeong, KAIST President Steve Kang, Dean of Life Science and Bioengineering College Jung-Hoe Kim, and Dean of the Department of Biological Sciences Byung-Ha Oh participated in the agreement ceremony. According to the MOU, Meditox will donate 60,000,000 KRW over a ten year period, from which KAIST can draw on to grant scholarships for master’s and doctoral students. The “Meditox Fellowship” will support promising and enthusiastic students whose finances limit their studies. The first scholarship students for 2016 were: Kwang-Uk Min, In-suk Yeo, Sung-ryung- Lee, Si-on Lee, and Jung-hyun Kim. Meditox CEO Jeong, who graduated from KAIST’s Department of Biological Sciences, said, "I felt it was important to start the Meditox Fellowship at my alma mater to contribute to the cultivation of outstanding scientists in the field of biological sciences." He also said that he would plan to launch projects that aim to support not only those who receive the scholarship but also the development of Korea’s biological sciences in general. President Steve Kang (right) and Chief Executive Officer Hyun-Ho Jeong (left) of Meditox hold the signed memorandum of understanding together.
2016.02.18
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Professor Joonho Choe Appointed as the President of the KSMCB
Professor Joonho Choe of the Biological Sciences Department at KAIST has been elected the 25th president of Korean Society for Molecular and Cellular Biology (KSMCB). His presidency will last one year, beginning on January 1, 2016. Established in 1989, the Society has served as the largest academic gathering in the field of life sciences, holding an international conference every fall. It has more than 12,400 fellows. Professor Choe served as the vice president of KSMC as well as the editor of its journal, Molecules and Cells. He said, “The 2016 International Conference of the KSMCB will take place on October 12-14, 2016 at the COEX Convention and Exhibition Hall in Seoul. This year, we are preparing 20 symposiums and will invite four international renowned keynote speakers in the field including a Nobel Laureate. We hope many people, students and young researchers in particular, from academia and industry will join the conference.” Professor Choe received his doctoral degree from the University of California, Los Angeles (UCLA) after graduating from Seoul National University with his bachelor and master’s degrees.
2016.01.05
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Nature Biotechnology Nominates Sang Yup Lee of KAIST for Top 20 Translational Researchers of 2014
Nature Biotechnology, recognized as the most prestigious journal in the field of biotechnology, has released today its list of the Top 20 Translational Researchers of 2014. Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST (Korea Advanced Institute of Science and Technology) ranked seventh in the list. He is the only Asian researcher listed. The journal, in partnership with IP Checkups, a patent analytics firm, presents an annual ranking of researchers based on their paper and patent output. The list includes, among others, each researcher’s most-cited patent in the past five years and their H index, a measurement to evaluate the impact of a researcher’s published work utilizing citation analysis. (More details can be found at http://www.nature.com/bioent/2015/150801/full/bioe.2015.9.html.) American institutions made up the majority of the list, with 18 universities and research institutes, and the remainder was filled by KAIST in Korea and the Commonwealth Scientific and Industrial Research Organization (CSIRO) in Australia. Globally known as a leading researcher in systems metabolic engineering, Professor Lee has published more than 500 journal papers and 580 patents. He has received many awards, including the Citation Classic Award, Elmer Gaden Award, Merck Metabolic Engineering Award, ACS Marvin Johnson Award, SIMB Charles Thom Award, POSCO TJ Park Prize, Amgen Biochemical Engineering Award, and the Ho Am Prize in Engineering.
2015.08.27
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