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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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Distinguished Professor Sang Yup Lee Honored with the 23rd NAEK Award
(Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering) Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering was honored to be the laureate of the 23rd NAEK Award. The NAEK (National Academy of Engineering of Korea) Award was instituted in 1997 to honor and recognize engineers who have made significant contributions to the development of the engineering and technology field at universities, industries, and institutions. Every year, it is conferred to only one person who has achieved original and world-leading research that has led to national development. Distinguished Professor Lee is a pioneering scholar of the field of systems metabolic engineering and he was recognized for his significant achievements in the biochemical industry by developing novel microbial bioprocesses. In particular, he is globally renowned for biological plastic synthesis, making or decomposing polymers with microorganisms instead of using fossil resources. He has produced numerous high-quality research breakthroughs in metabolic and systems engineering. In 2016, he produced an easily degradable plastic with Escherichia coli (E. coli). In 2018, he successfully produced aromatic polyesters, the main material for PET (poly ethylene terephthalate) from E. coli strains. He also identified microorganism structures for PET degradation and improved its degradability with a novel variant. His research was ranked number one in the research and development division of Top Ten Science and Technology News 2018 announced by Korean Federation of Science & Technology Societies. He is one of highly cited researchers (HCR) ranked in the top 1% by citations for their field by the Clarivate Analytics.
2019.03.21
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KAIST and LG Electronics Team up for 6G Wireless Communications
(LG Electronics CTO Il-Pyung Park (left) and Dean of KAIST Institute Sang Yup Lee) KAIST and LG Electronics are working together to take the lead in next-generation wireless communications and launched the LG-KAIST 6G Research Center on January 28, 2019. KAIST Institute has been focusing on developing a new growth engine for the national economy through interdisciplinary research. In particular, its research work in the field of next-generation wireless communication was listed in the National Research and Development Excellence 100 in 2016 and 2017. LG Electronics has been a global leader in this field for many years. According to TechIPM, the company had the most 4G LTE/LTE-A patents from 2012 to 2016. Also, it first standardized the Cellular Vehicle-to-Everything, which is the core technology for autonomous vehicles. The new head of the research center, Professor Dong Ho Cho from the School of Electrical Engineering said, “We will work on developing source technology for sixth generation mobile communications, which will enhance national competence and prepare for the future industries.” CTO of LG Electronics Il-Pyung Park said, “We are hoping to take the lead in the global standardization of sixth generation wireless communications and secure new business opportunities.”
2019.01.29
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President Shin Speaks on Closing the Skills Gap at the WEF
(President Shin poses (far right) with the National University of Singapore President Tan Eng Chye (center) along with Distinguished Professor Sang Yup Lee in Davos last week.) President Sung-Chul Shin shared his ideas on how reskilling is a critical element of growth, dynamism, and competitiveness for countries during a session titled “Closing the Skills Gap: Creating a Reskilling Revolution” at the World Economic Forum on January 24 in Davos. While discussing a reskilling imperative alongside French Labor Minister Muriel Penicaud, he presented how the Korean government and KAIST are responding to the socio-economic transformation of workforces in the Fourth Industrial Revolution. After their presentation, Minister of Economy and Enterprise of Spain Nadia Calvirno Santamaria, Minister of Commerce and Industry of Oman Ali bin Masoud bin Ali Al Sunaidy, and Minister of Petroleum and Natural Gas, Skill Development, and Entrepreneurship of India Dharmendra Pradhan shared their views on the course of decision making regarding the proactive practices and policies they have applied for closing the gaps from their countries’ perspectives. President Shin presented how to upskill and reskill SMEs and startups, the real players who will jumpstart the economy in the Fourth Industrial Revolution. He explained that the government is striving to change the existing structure of the economy, which is dominated by a few giant conglomerates. He added that the Korean government is trying to support SMEs and startups in terms of both funding and technology reskilling in order to rejuvenate the economy. To better align itself with the government’s efforts, KAIST has introduced SME 4.0. SME 4.0 proposes to innovate the production process through the creation of a partnered platform between KAIST and SMEs across the country. With this platform, KAIST assists local SMEs for standardizing and systemizing all their processes of production, delivery, and management with enterprise resources planning (ERP) and manufacturing execution systems (MES). In addition, SME 4.0 offers retraining and re-tooling programs by linking the data generated through this platform in real time to better facilitate SMEs’ smart business. (President Shin shakes hands with H.E.Mohammed Al-Tuwairi, Minister of Economy and Planning of Saudi Arabia before holding a bilaterla meeting in Davos.) President Shin also explained about upskilling the leading corporations’ technological competitiveness, partnering with major leading corporations for upskilling their advanced technologies. He also held a series of bilateral meetings with dignitaries attending the WEF annual meeting to discuss partnerships and collaborations. He also attended the Global University Leaders Forum (GULF), a community composed of 28 presidents from the world’s top universities on January 23. President Shin, who is on the advisory board of the Center for Fourth Industrial Revolution (C4IR), also participated in the board meeting and discussed the upcoming launching of the Korea C4IR, which will open at KAIST in March.
2019.01.28
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A Comprehensive Metabolic Map for Bio-Based Chemicals Production
A KAIST research team completed a metabolic map that charts all available strategies and pathways of chemical reactions that lead to the production of various industrial bio-based chemicals. The team was led by Distinguished Professor Sang Yup Lee, who has produced high-quality metabolic engineering and systems engineering research for decades, and made the hallmark chemicals map after seven years of studies. The team presented a very detailed analysis on metabolic engineering for the production of a wide range of industrial chemicals, fuels, and materials. Surveying the current trends in the bio-based production of chemicals in industrial biotechnology, the team thoroughly examined the current status of industrial chemicals produced using biological and/or chemical reactions. This comprehensive map is expected to serve as a blueprint for the visual and intuitive inspection of biological and/or chemical reactions for the production of interest from renewable resources. The team also compiled an accompanying poster to visually present the synthetic pathways of chemicals in the context of their microbial metabolism. As metabolic engineering has become increasing powerful in addressing limited fossil resources, climate change, and other environmental issues, the number of microbially produced chemicals using biomass as a carbon source has increased substantially. The sustainable production of industrial chemicals and materials has been explored with micro-organisms as cell factories and renewable nonfood biomass as raw materials for alternative petroleum. The engineering of these micro-organism has increasingly become more efficient and effective with the help of metabolic engineering – a practice of engineering using the metabolism of living organisms to produce a desired metabolite. With the establishment of systems metabolic engineering – the integration of metabolic engineering with tools and strategies from systems biology, synthetic biology and evolutionary engineering – the speed at which micro-organisms are being engineered has reached an unparalleled pace. In order to evaluate the current state at which metabolically engineered micro-organisms can produce a large portfolio of industrial chemicals, the team conducted an extensive review of the literature and mapped them out on a poster. This resulting poster, termed the bio-based chemicals map, presents synthetic pathways for industrial chemicals, which consist of biological and/or chemical reactions. Industrial chemicals and their production routes are presented in the context of central carbon metabolic pathways as these key metabolites serve as precursors for the chemicals to be produced. The resulting biochemical map allows the detection and analysis of optimal synthetic pathways for a given industrial chemical. In addition to the poster, the authors have compiled a list of chemicals that have successfully been produced using micro-organisms and a list of the corresponding companies producing them commercially. This thorough review of the literature and the accompanying analytical summary will be an important resource for researchers interested in the production of chemicals from renewable biomass sources. Metabolically engineered micro-organisms have already made a huge contribution toward the sustainable production of chemicals using renewable resources. Professor Lee said he wanted a detailed survey of the current state and capacity of bio-based chemicals production. “We are so excited that this review and poster will expand further discussion on the production of important chemicals through engineered micro-organisms and also combined biological and chemical means in a more sustainable manner,” he explained. This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biofineries from the Ministry of Science and ICT through the National Research Foundation of Korea. For further information, Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST ( leesy@kaist.ac.kr , Tel: +82-42-350-3930) Figure: Bio-based chemicals production through biological and chemical routes. This metabolic map describes representative chemicals that can be produced either by biological and/or chemical means. Red arrows represent chemical routes and blue arrows represent biological routes. Intermediate metabolites in the metabolism of a living organism can serve as a platform toward the production of industrially relevant chemicals. A more comprehensive map presented by the team can be found as a poster in the review.
2019.01.15
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Distinguished Professor Lee Re-Appointed As Co-Chair of the Global Future Council on Biotechnology
(Distinguished Professor Sang Yup Lee) Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering was re-appointed as the co-chair of the Global Future Council on Biotechnology at the World Economic Forum during the annual GFC meeting in Dubai, UAE last week. Elizabeth O’Day, founder and CEO of Olaris Therapeutics, will co-chair the council with him for two years. Professor Lee served as the inaugural co-chair of the council for two years from 2016 with Professor Feng Zhang from the Broad Institute of MIT and Harvard. The World Economic Forum’s Global Future Councils on Biotechnology is comprised of 14 members and aims to identify policy opportunities to help accelerate new biotechnological discoveries and applications while guiding dialogue with consumers about their implications. Professor Lee, who has made significant research breakthroughs in the field of systems metabolic engineering, received the George Washington Carver Award, the PV Danckwerts Memorial Lecture Award, and the Eni Award this year.
2018.11.19
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A Novel Biosensor to Advance Diverse High-Level Production of Microbial Cell Factories
A research group at KAIST presented a novel biosensor which can produce diverse, high-level microbial cell factories. The biosensor monitors the concentration of products and even intermediates when new strains are being developed. This strategy provides a new platform for manufacturing diverse natural products from renewable resources. The team succeeded in creating four natural products of high-level pharmaceutical importance with this strategy. Malonyl-CoA is a major building block for many value-added chemicals including diverse natural products with pharmaceutical importance. However, due to the low availability of malonyl-CoA in bacteria, many malonyl-CoA-derived natural products have been produced by chemical synthesis or extraction from natural resources that are harmful to the environment and are unsustainable. For the sustainable biological production of malonyl-CoA-derived natural products, increasing the intracellular malonyl-CoA pool is necessary. To this end, the development of a robust and efficient malonyl-CoA biosensor was required to monitor the concentration of intracellular malonyl-CoA abundance as new strains are developed. Metabolic engineering researchers at KAIST addressed this issue. This research reports the development of a simple and robust malonyl-CoA biosensor by repurposing a type III polyketide synthase (also known as RppA), which produces flaviolin, a colorimetric indicator of malonyl-CoA. Subsequently, the RppA biosensor was used for the rapid and efficient colorimetric screening of gene manipulation targets enabling enhanced malonyl-CoA abundance. The screened beneficial gene targets were employed for the high-level production of four representative natural products derived from malonyl-CoA. Compared with the previous strategies, which were expensive and time-consuming, the new biosensor could be easily applied to industrially relevant bacteria including Escherichia coli, Pseudomonas putida, and Corynebacterium glutamicum to enable a one-step process. The study employs synthetic small regulatory RNA (sRNA) technology to rapidly and efficiently reduce endogenous target gene expression for improved malonyl-CoA production. The researchers constructed an E. coli genome-scale synthetic sRNA library targeting 1,858 genes covering all major metabolic genes in E. coli. This library was employed with the RppA biosensor to screen for gene targets which are believed to be beneficial for enhancing malonyl-CoA accumulation upon their expression knockdown. From this colorimetric screening, 14 gene targets were selected, all of which were successful at significantly increasing the production of four natural products (6-methylsalicylic acid, aloesone, resveratrol, and naringenin). Although specific examples are demonstrated in E. coli as a host, the researchers showed that the biosensor is also functional in P. putida and C. glutamicum, industrially important representative gram-negative and gram-positive bacteria, respectively. The malonyl-CoA biosensor developed in this research will serve as an efficient platform for the rapid development of strains capable of producing natural products crucial for the pharmaceutical, chemical, cosmetics, and food industries. An important aspect of this work is that the high-performance strains constructed in this research were developed rapidly and easily by utilizing the simple approach of colorimetric screening, without involving extensive metabolic engineering approaches. 6-Methylsalicylic acid (an antibiotic) could be produced to the highest titer reported for E. coli, and the microbial production of aloesone (a precursor of aloesin, an anti-inflammatory agent/whitening agent) was achieved for the first time. “A sustainable process for producing diverse natural products using renewable resources is of great interest. This study represents the development of a robust and efficient malonyl-CoA biosensor generally applicable to a wide range of industrially important bacteria. The capability of this biosensor for screening a large library was demonstrated to show that the rapid and efficient construction of high-performance strains is feasible. This research will be useful for further accelerating the development process of strains capable of producing valuable chemicals to industrially relevant levels,” said Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, who led the research. This study entitled “Repurposing type III polyketide synthase as a malonyl-CoA biosensor for metabolic engineering in bacteria,” was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on October 02. PhD students Dongsoo Yang and Won Jun Kim, MS student Shin Hee Ha, research staff Mun Hee Lee, Research Professor Seung Min Yoo, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering and Dr. Jong Hyun Choi of the Applied Microbiology Research Center at the Korea Research Institute of Bioscience and Biotechnology (KRIBB) participated in this research. Figure: Type III polyketide synthase (RppA) as a malonyl-CoA biosensor. RppA converts five molecules of malonyl-CoA into one molecule of red-colored flaviolin. This schematic diagram shows the overall conceptualization of the malonyl-CoA biosensor by indicating that higher malonyl-CoA abundance leads to higher production and secretion of flaviolin, resulting in a deeper red color of the culture. This system was employed for the enhanced production of four representative natural products (6-methylsalicylic acid, aloesone, resveratrol, and naringenin) from engineered E. coli strains.
2018.10.11
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Engineered E. coli Using Formic Acid and CO2 As a C1-Refinery Platform Strain
(Figure: Formic acid and CO2 assimilation pathways consisting of the reconstructed THF cycle and reverse glycine cleavage reaction. This schematic diagram shows the formic acid and CO2 assimilation procedure through the pathway. Plasmids used in this study and the genetic engineering performed in this study are illustrated.) A research group at KAIST has developed an engineered E. coli strain that converts formic acid and CO2 to pyruvate and produces cellular energy from formic acid through reconstructed one-carbon pathways. The strategy described in this study provides a new platform for producing value-added chemicals from one-carbon sources. Formic acid is a carboxylic acid composed of one carbon. Formic acid was produced from CO2 by the chemical method. Recently, the C1 Gas Refinery R&D Center has successfully developed a biological process that produces formic acid from carbon monoxide for the first time. Formic acid is in a liquid state when at room temperature and atmospheric pressure. In addition, it is chemically stable and less toxic, thus, easy to store and transport. Therefore, it can be used as an alternative carbon source in the microbial fermentation process. In order to produce value-added chemicals using formic acid, a metabolic pathway that converts formic acid into cellular molecules composed of multiple carbons is required. However, a metabolic pathway that can efficiently convert formic acid into cellular molecules has not been developed. This acted as an obstacle for the production of value-added chemicals using formic acid A research group of Ph.D. student Junho Bang and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering addressed this issue. This study, entitled “Assimilation of Formic Acid and CO2 by Engineered Escherichia coli Equipped with Reconstructed One-Carbon Assimilation Pathways”, has been published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on September 18. There has been increasing interest in utilizing formic acid as an alternative carbon source for the production of value-added chemicals. This research reports the development of an engineered E. coli strain that can convert formic acid and CO2 to pyruvate and produce cellular energy from formic acid through the reconstructed one-carbon pathways. The metabolic pathway that efficiently converts formic acid and CO2 into pyruvate was constructed by the combined use of the tetrahydrofolate cycle and reverse glycine cleavage reaction. The tetrahydrofolate cycle was reconstructed by utilizing Methylobacterium extorquens formate-THF ligase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase. The glycine cleavage reaction was reversed by knocking out the repressor gene (gcvR) and overexpressing the gcvTHP genes that encode enzymes related with the glycine cleavage reaction. Formic acid and CO2 conversion to pyruvate was increased via metabolic engineering of the E. coli strain equipped with the one-carbon assimilation pathway. In addition, in order to reduce glucose consumption and increase formic acid consumption, Candida boidnii formate dehydrogenase was additionally introduced to construct a cellular energy producing pathway from formic acid. This reduces glucose consumption and increases formic acid consumption. The reconstructed one-carbon pathways can supply cellular molecules and cellular energies from the formic acid and CO2. Thus, the engineered E. coli strain equipped with the formic acid and CO2 assimilation pathway and cellular energy producing pathway from formic acid showed cell growth from formic acid and CO2 without glucose. Cell growth was monitored and 13C isotope analysis was performed to confirm E. coli growth from the formic acid and CO2. It was found that the engineered E. coli strain sustained cell growth from the formic acid and CO2 without glucose. Professor Lee said, “To construct the C1-refinery system, a platform strain that can convert one-carbon materials to higher carbon materials needs to be developed. In this report, a one-carbon pathway that can efficiently convert formic acid and CO2 to pyruvate was developed and a cellular energy producing pathway from formic acid was introduced. This resulted in an engineered E. coli strain that can efficiently utilize formic acid as a carbon source while glucose consumption was reduced. The reconstructed one-carbon pathways in this research will be useful for the construction of the C1-refinery system.” This work was supported by the C1 Gas Refinery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2016M3D3A1A01913250). For further information: Sang Yup Lee, Distinguished Professor of Chemical and Biomolecular Engineering, KAIST (leesy@kaist.ac.kr, Tel: +82-42-350-3930)
2018.09.18
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Distinguished Professor Sang Yup Lee Announced as the Eni Award Recipient
(Distinguished Professor Sang Yup Lee) Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering will be awarded the 2018 Eni Advanced Environmental Solutions Prize in recognition of his innovations in the fields of energy and environment. The award ceremony will take place at the Quirinal Palace, the official residence of Italian President Sergio Mattarella, who will also be attending on October 22. Eni, an Italian multinational energy corporation established the Eni Award in 2008 to promote technological and research innovation of efficient and sustainable energy resources. The Advanced Environmental Solutions Prize is one of the three categories of the Eni Award. The other two categories are Energy Transition and Energy Frontiers. The Award for Advanced Environmental Solutions recognizes a researcher or group of scientists that has achieved internationally significant R&D results in the field of environmental protection and recovery. The Eni Award is referred to as the Nobel Award in the fields of energy and environment. Professor Lee, a pioneering leader in systems metabolic engineering was honored with the award for his developing engineered bacteria to produce chemical products, fuels, and non-food biomass materials sustainably and with a low environmental impact. He has leveraged the technology to develop microbial bioprocesses for the sustainable and environmentally friendly production of chemicals, fuels, and materials from non-food renewable biomass. The award committee said that they considered the following elements in assessing Professor Lee’s achievement: the scientific relevance and the research innovation level; the impact on the energy system in terms of sustainability as well as fairer and broader access to energy; and the adequacy between technological and economic aspects. Professor Lee, who already won two other distinguished prizes such as the George Washington Carver Award and the PV Danckwerts Memorial Lecture Award this year, said, “I am so glad that the international academic community as well as global industry leaders came to recognize our work that our students and research team has made for decades.” Dr. Lee’s lab has been producing a lot of chemicals in environmentally friendly ways. Among them, many were biologically produced for the first time and some of these processes have been already commercialized. “We will continue to strive for research outcomes with two objectives: First, to develop bio-based processes suitable for sustainable chemical industry. The other is to contribute to the human healthcare system through development of platform technologies integrating medicine and nutrition,” he added.
2018.09.12
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KAIST Core Technology Fair Accelerates Commercialization
(President Shin makes opening remarks at the KAIST Core Tech Transfer Day in Seoul.) Technology commercialization is the one of the innovation initiatives KAIST is strongly driving. KAIST showcased six core technologies developed by KAIST research teams during the 2018 KAIST Core Tech Transfer Day on September 10 at Coex in Seoul. More than 300 investors, buyers, and venture capitalists showed up for the fair. This is the second fair organized as one of the strategic innovation initiatives that KAIST is promoting. Developers of key technologies selected in the fields of bio, nano, AI, and semiconductors presented their distinct technological prowess to the attendees. The technologies are highly relevant for the new industrial environment trends in the Fourth Industrial Revolution. The 15-member committee comprised of patent attorneys, venture capitalists, and commercialization specialists selected the six core technologies based on their innovativeness, applicability, and marketability. The Office of University-Industry Cooperation (OUIC) plans to offer buyers various services for developing business models, business strategy analysis, and marketing at home and abroad. The six core technologies featured at the fair include: - Novel technology of a nano patterning platform by Professor Hee Tae Chung from the Department of Chemical and Biomolecular Engineering - Anticancer therapeutic candidate materials strengthening immune function by Professor Byung Sok Choi from the Department of Chemistry - Biofuel mass production using micro-organisms by Distinguished Professor Sang-Yup Lee from the Department of Chemical and Biomolecular Engineering - Compact single-shot hyperspectral camera technology by Min Hyuk Kim from the School of Computing - AI-powered high speed ultra-high definition upscaling technology by Professor Munchurl Kim from the School of Electrical Engineering - A radiation strong MOSFET device by Hee Chul Lee from the School of Electrical Engineering President Sung-Chul Shin stressed in his opening remarks that universities should make contributions to economic development through innovation. “Global leading universities are taking an instrumental role in creating new jobs and economic growth with their own technologies. KAIST, as the leading university in Korea, is accelerating the commercialization of technology produced internally to create a meaningful impact for the economy as well as the job market beyond Korea,” he said. “We are aiming for the global market, not just in Korea. I want KAIST to be a global value creator that can contribute to the betterment of the world through our innovations,” he added.
2018.09.10
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Metabolic Engineering of E. coli for the Secretory Production of Free Haem
Researchers of KAIST have defined a novel strategy for the secretory production of free haem using engineered Escherichia coli (E. coli) strains. They utilized the C5 pathway, the optimized downstream pathways, and the haem exporter to construct a recombinant micro-organism producing extracellular haem using fed-batch fermentation. This is the first report to extracellularly produce haem using engineered E. coli. This strategy will expedite the efficient production of free haem to serve as a bioavailable iron-supplying agent and an important prosthetic group of multiple hemoproteins for medical uses. This study, led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, was published in Nature Catalysis on Aug. 28. Haem, an organometallic compound complexed with a ferrous ion, is an essential molecule delivering oxygen in the blood of many animals. It is also a key component of electron transport chains responsible for the respiration of aerobic organisms including diverse bacteria. It is now being widely applied as a bioavailable iron-supplying agent in the healthcare and dietary supplement industries. The demand for haem and the need for the efficient production of this compound continue to grow. Many previous researchers have attempted to produce free haem using engineered E. coli. However, none of the studies was successful in producing free haem extracellularly, requiring an additional step to extract the accumulated haem from cells for subsequent uses. The secretion of haem in the form of haem peptides or proteins also requires an extraction step to isolate the free haem from the secreted products. Thus, the secretory production of free haem is an important task for the economical production of haem that is suitable for human consumption. Although some researchers could produce intracellular haem using recombinant E. coli strains, its final titer was extremely low, resulting from the use of sub-optimal metabolic pathways. Furthermore, the addition of the precursors L-glycine and succinate was deemed undesirable for massive industrial production. Thus, it is necessary to construct an optimized haem biosynthetic pathway to enable the efficient production of haem and examine the consequent secretion of free haem. To address this issue, the KAIST team used multiple strategies to produce extracellular free haem by enhancing its biosynthesis in E. coli. First, the capacities of the C4 and C5 pathways to produce aminolevulinate (ALA) without feeding precursors were examined. After confirming the superior performance of the C5 pathway over the C4 pathway, the metabolic genes of the C5 pathway and downstream pathways for haem biosynthesis were overexpressed. Then, the metabolic pathways were optimized by adjusting the expression levels of the relevant genes and disrupting the putative haem degradation enzyme encoded by the yfeX gene. Consequently, the resulting engineered strain secreted a significant amount of haem to the medium. Subsequent optimization of the cultivation conditions and the supplementation of nitrogen sources further increased both the titer of the total free haem and the amount of free haem secreted to the medium. Finally, the overexpression of the ccmABC genes encoding the haem exporter further enhanced the production and secretion of haem, producing the highest titer of haem both intracellularly and extracellularly from glucose. Professor Lee said, “The eco-friendly and sustainable chemical industry is a key global agenda every nation faces. We are conducting research to bio-synthesize high concentrations, high yields, and high productivity in natural products. This novel technology will serve as an opportunity to advance the biochemical industry moving forward.” This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea. Further Contact: Dr. Sang Yup Lee, Distinguished Professor, KAIST, Daejeon, Korea ( leesy@kaist.ac.kr+82-42-350-3930).
2018.08.28
View 4572
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