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Deep Learning-Powered 'DeepEC' Helps Accurately Understand Enzyme Functions
(Figure: Overall scheme of DeepEC) A deep learning-powered computational framework, ‘DeepEC,’ will allow the high-quality and high-throughput prediction of enzyme commission numbers, which is essential for the accurate understanding of enzyme functions. A team of Dr. Jae Yong Ryu, Professor Hyun Uk Kim, and Distinguished Professor Sang Yup Lee at KAIST reported the computational framework powered by deep learning that predicts enzyme commission (EC) numbers with high precision in a high-throughput manner. DeepEC takes a protein sequence as an input and accurately predicts EC numbers as an output. Enzymes are proteins that catalyze biochemical reactions and EC numbers consisting of four level numbers (i.e., a.b.c.d) indicate biochemical reactions. Thus, the identification of EC numbers is critical for accurately understanding enzyme functions and metabolism. EC numbers are usually given to a protein sequence encoding an enzyme during a genome annotation procedure. Because of the importance of EC numbers, several EC number prediction tools have been developed, but they have room for further improvement with respect to computation time, precision, coverage, and the total size of the files needed for the EC number prediction. DeepEC uses three convolutional neural networks (CNNs) as a major engine for the prediction of EC numbers, and also implements homology analysis for EC numbers if the three CNNs do not produce reliable EC numbers for a given protein sequence. DeepEC was developed by using a gold standard dataset covering 1,388,606 protein sequences and 4,669 EC numbers. In particular, benchmarking studies of DeepEC and five other representative EC number prediction tools showed that DeepEC made the most precise and fastest predictions for EC numbers. DeepEC also required the smallest disk space for implementation, which makes it an ideal third-party software component. Furthermore, DeepEC was the most sensitive in detecting enzymatic function loss as a result of mutations in domains/binding site residue of protein sequences; in this comparative analysis, all the domains or binding site residue were substituted with L-alanine residue in order to remove the protein function, which is known as the L-alanine scanning method. This study was published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 20, 2019, entitled “Deep learning enables high-quality and high-throughput prediction of enzyme commission numbers.” “DeepEC can be used as an independent tool and also as a third-party software component in combination with other computational platforms that examine metabolic reactions. DeepEC is freely available online,” said Professor Kim. Distinguished Professor Lee said, “With DeepEC, it has become possible to process ever-increasing volumes of protein sequence data more efficiently and more accurately.” 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 of Korea. This work was also funded by the Bio & Medical Technology Development Program of the National Research Foundation of Korea funded by the Korean government, the Ministry of Science and ICT. Profile: -Professor Hyun Uk Kim (email@example.com) https://sites.google.com/view/ehukim Department of Chemical and Biomolecular Engineering -Distinguished Professor Sang Yup Lee (firstname.lastname@example.org) Department of Chemical and Biomolecular Engineering http://mbel.kaist.ac.kr
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 email@example.com Distinguished Professor at the Department of Chemical and Biomolecular Engineering KAIST
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.)
MoU by KAIST-Seoul-Seocho-gu for the 4th Industrial Revolution
The opening ceremony of the Yangjae R&CD Innovation Hub was held in Seoul on December 5. More than 400 guests came to the ceremony from major institutes and companies that are based in the hub. KAIST President Sung-Chul Shin, the Mayor of Seoul, Won-soon Park, and the Mayor of Seocho-gu, Eun Hee Cho, signed an MoU for Seoul to be the leading city for successfully realizing the Fourth Industrial Revolution. The three organizations aim to cooperate with one another in various areas, including an economic boost for local job creation, technology development, and the promotion of projects through an industry-academia-institute network and fostering manpower. Yangjae R&CD is the first facility specializing in and dedicated for Artificial Intelligence, which is the major topic of the Fourth Industrial Revolution. The hub is comprised of enterprises specializing in AI, open co-work spaces, conference rooms, an open networking lounge, and spaces for fostering professional manpower. The hub will recruit additional enterprises and individuals who wish to move in. KAIST, an institute containing professors and researchers in the field of AI, and Modulabs, an organization becoming distinguished in AI research, will be in charge of operating the facility together. The Yangjae R&CD Innovation Hub will operate a professional training program with participation from KAIST professors, which aims to produce 500 professionals in AI research and development by 2020. It will also provide inexpensive space as well as consultations and venture capital to startup and venture companies. It plans to find and foster 50 innovation companies by 2020. In particular, the hub will operate a course for new AI business models 24 times over three years. The hub also offers job consultations, academic conferences, public space for companies residing in the hub, a free GPU cluster server, technical training, seminars, forums, investment attraction, overseas expansion, and one-to-one technical consultations. The Yangjae R&CD Zone is the place established for the Fourth Industrial Revolution by Seoul. R&CD is a concept combining Research and Development, Connection, Companies, Community, and Culture. Seoul aims to create the Yangjae Zone as an urban innovation hub for facilitating industry-academia linkage as well as establishing a startup-settlement-growth technical ecosystem.
Professor Duck-Joo Lee Awarded the 21st Century Grand Prize
Professor Duck-Joo Lee of the Department of Aerospace Engineering was awarded the 21st Century Grand Prize in the field of technology development by the New Industry Management Academy and the 21st Leaders Club on April 13. Professor Lee was honored in recognition of his contribution to the helicopter industry. He played a part in domestic helicopter development projects including the KUH-1 Surion (Korean Attack Helicopter), a twin-engine, transport utility helicopter as well as LAH (Light Armed Helicopter) and LCH (Light Civil Helicopter) projects. Since joining KAIST in 1988, Professor Lee supervised more than 26 PhDs and 27 MSs. He was responsible for hosting the 1st Asian-Australian Rotorcraft Forum and Exhibition and currently serves as vice president of the American Helicopter Society and the Korea Drone Industry Promotion Association. He also participated in open online courses on K-MOOC and Coursera. (Caption: Professor Lee (second from left in the first row) poses after receiving the award.)
EWB-KAIST Wraps up Five-Year Project in Nepal
‘Engineers Without Borders-KAIST (EWB-KAIST)’ led by Professor Tae-ho Song from the Department of Mechanical Engineering returned to Korea on January 10 after a two-week project in Nangi, Nepal. EWB-KAIST was established in 2012 by KAIST students and professors. Since then, the team visited Nangi, in the Annapurna region of Nepal, to engage in Appropriate Technology (AT) development projects. The projects included building passive houses and small hydroelectric power, and teaching science education. In particular, passive houses that use straw as an insulator received great a reception from the locals. This was their last visit to Nepal, since the five-year project has now come to an end. Future projects in Mongolia will be led by Professor Buhm Soon Park from the Graduate School of Science and Technology Policy. Professor Song commented, “I am glad that the Nepal project was successfully conducted over the last five years. To make sure the support does not end here, I will personally continue to visit the Himalayas to assist the villagers.” EWB-KAIST is a non-profit organization that conducts activities with the aim of AT development and providing support for less-developed countries in need of the benefits of technology. ( Passive house made of straws by EWB-KAIST team in Nangi, Nepal.)
An Electron Cloud Distribution Observed by the Scanning Seebeck Microscope
All matters are made of small particles, namely atoms. An atom is composed of a heavy nucleus and cloud-like, extremely light electrons. Korean researchers developed an electron microscopy technique that enables the accurate observation of an electron cloud distribution at room-temperature. The achievement is comparable to the invention of the quantum tunneling microscopy technique developed 33 years ago. Professor Yong-Hyun Kim of the Graduate School of Nanoscience and Technology at KAIST and Dr. Ho-Gi Yeo of the Korea Research Institute of Standards and Science (KRISS) developed the Scanning Seebeck Microscope (SSM). The SSM renders clear images of atoms, as well as an electron cloud distribution. This was achieved by creating a voltage difference via a temperature gradient. The development was introduced in the online edition of Physical Review Letters (April 2014), a prestigious journal published by the American Institute of Physics. The SSM is expected to be economically competitive as it gives high resolution images at an atomic scale even for graphene and semiconductors, both at room temperature. In addition, if the SSM is applied to thermoelectric material research, it will contribute to the development of high-efficiency thermoelectric materials. Through numerous hypotheses and experiments, scientists now believe that there exists an electron cloud surrounding a nucleus. IBM's Scanning Tunneling Microscope (STM) was the first to observe the electron cloud and has remained as the only technique to this day. The developers of IBM microscope, Dr. Gerd Binnig and Dr. Heinrich Rohrer, were awarded the 1986 Nobel Prize in Physics. There still remains a downside to the STM technique, however: it required high precision and extreme low temperature and vibration. The application of voltage also affects the electron cloud, resulting in a distorted image. The KAIST research team adopted a different approach by using the Seebeck effect which refers to the voltage generation due to a temperature gradient between two materials. The team placed an observation sample (graphene) at room temperature (37~57℃) and detected its voltage generation. This technique made it possible to observe an electron cloud at room temperature. Furthermore, the research team investigated the theoretical quantum mechanics behind the electron cloud using the observation gained through the Seebeck effect and also obtained by simulation capability to analyze the experimental results. The research was a joint research project between KAIST Professor Yong-Hyun Kim and KRISS researcher Dr. Ho-Gi Yeo. Eui-Seop Lee, a Ph.D. candidate of KAIST, and KRISS researcher Dr. Sang-Hui Cho also participated. The Ministry of Science, ICT, and Future Planning, the Global Frontier Initiative, and the Disruptive Convergent Technology Development Initiative funded the project in Korea. Picture 1: Schematic Diagram of the Scanning Seebeck Microscope (SSM) Picture 2: Electron cloud distribution observed by SSM at room temperature Picture 3: Professor Yong-Hyun Kim
World Research University Heads to Discuss Challenges in Global Financial Turmoil
About 70 leaders of the world"s major research universities will discuss how to better contribute to continued development of human society in global financial turmoil at a symposium organized by KAIST Monday (Sept. 21) at the Westin Chosun Hotel in Seoul. Participants of the 2nd International Presidential Forum on Global Research Universities are from 40 universities in 25 countries, including Stanford University and Georgia Institute of Technology of the United States, Berlin Institute of Technology of Germany, Paris Institute of Technology of France, Technical University of Denmark, National University of Singapore and Tokyo Institute of Technology. They include 20 presidents of Korean universities and two dozens of leaders from industry and the government. Under the main subject of "Challenges to Global Research Universities," the international symposium will proceed in four panel sessions. The subjects of each session and their keynote speakers are: -- "Institutional Management in Times of Financial Crisis" by Kurt Kutzler, President of Berlin Institute of Technology -- "Innovations in Education & Research" by Brian Cantor, Vice Chancellor of University of York -- "Globalization of Institutes of Higher Learning" by Gary Schuster, Provost and Executive Vice President of Georgia Institute of Technology -- "The Roles of Government, University and Industry in Green Technology Development" by KAIST President Nam-Pyo Suh KAIST President Suh said of the purpose of the conference: "The world has witnessed a global financial turmoil of unseen magnitude and many nations are still struggling under the devastating impacts. While universities were no exception in facing economic turmoil, they have realized renewed pressures and expectations from their respective communities to provide answers to the great challenges." "The conference will serve as an opportunity for the representatives of research universities to compare their visions of networking among theier institutions and initiate steps for new relationships. The conference I am sure will have a far-reaching influence on the course our research universities will take to shoulder greater responsibilities for building a better future of the mankind." For more information, visit forum.kaist.ac.kr
KAIST, KHNP Sign MOU on Nuclear Technology Development
KAIST signed a memorandum of understanding with the Korea Hydro & Nuclear Power Co. (KHNP) on Wednesday (May 6) to upgrade cooperation between the two organizations in nuclear power technology development. On hand at the signing ceremony at KAIST were KAIST President Nam-Pyo Suh, KHNP President Jong-Shin Kim and other related officials. The agreement calls for increased efficiency and synergy effect in the development of nuclear power generation by KAIST and KHNP to gain greater competitiveness in the exportation of nuclear power technologies. KHNP is responsible for the operation of all nuclear and hydraulic power plants in Korea which supply about 40 percent of the nation"s electric power demand. It is the largest among the six power generating subsidiaries that separated from Korea Electric Power Corporation (KEPCO) in April 2001.
KAIST Professor Exposes Structural Dynamics of Protein in Solution
-- Dr. Hyot-Cherl Ihee"s 3-Year Research Is Valuable in Pharmaceutical Application Prof. Hyot-Cherl Ihee and his team at the Department of Chemistry, KAIST, has successfully unveiled the structural dynamics of protein in solution as a result of more than three years" research work. Nature Methods, a sister publication of the authoritative science magazine Nature, published the treatise, titled "Tracking the structural dynamics of proteins in solution using time-resolved wide-angle X-ray scattering" in its Sept. 22 online edition. The research paper will be carried in the magazine"s printed version in its October edition, according to Dr. Lee who is its correspondence author. In May 2005, Prof. Ihee successfully photographed the structural dynamics of protein in solid state and his findings were published in the Proceedings of National Academy of Science of the United States. As protein normally exists in human body in solution, not in solid state, he directed his research to developing the technology to capture protein"s dynamics in resolved state. In July that year, Prof. Ihee succeeded in measuring the structural changes of simple organic molecules in real time. He further developed the technology to uncover the structural dynamics of hemoglobin, myoglobin and cytochrome C. Prof. Ihee"s research, helped with the Education-Science-Technology Ministry"s Creative Research Promotion Fund, can be applied to new pharmaceutical development projects as well as nanotechnology development, according to KAIST officials. Prof. Ihee who earned his doctorate at California Institute of Technology in 1994 began teaching at KAIST in 2003. He won the Young Scientist Award given by the Korean government in 2006.
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