THE
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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 (ehukim@kaist.ac.kr)
https://sites.google.com/view/ehukim
Department of Chemical and Biomolecular Engineering
-Distinguished Professor Sang Yup Lee (leesy@kaist.ac.kr)
Department of Chemical and Biomolecular Engineering
http://mbel.kaist.ac.kr
2019.07.09 View 36926 -
Wearable Robot 'WalkON Suit' Off to Cybathlon 2020
Standing upright and walking alone are very simple but noble motions that separate humans from many other creatures. Wearable and prosthetic technologies have emerged to augment human function in locomotion and manipulation. However, advances in wearable robot technology have been especially momentous to Byoung-Wook Kim, a triplegic for 22 years following a devastating car accident.
Kim rejoiced after standing upright and walking again by putting on the ‘WalkON Suit,’ the wearable robot developed by Professor Kyoungchul Kong’s team. Even more, Kim won third prize in the powered exoskeleton race at Cybathlon 2016, an international cyborg Olympics hosted by ETH Zurich.
Now Kim and Professor Kong’s team are all geared up for the Cybathlon Championship 2020. Professor Kong and his startup, Angel Robotics, held a kickoff ceremony for Cybathlon 2020 at KAIST on June 24. The 2020 championship will take place in Switzerland.
Only pilots with complete paralysis of the legs resulting from spinal cord injuries are eligible to participate in the Cybathlon, which takes place every four years. Pilots compete against each other while completing everyday tasks using technical assistance systems in six different disciplines: a brain-computer interface race, a functional electrical stimulation bike race, a powered arm prosthesis race, a powered leg prosthesis race, a powered exoskeleton race, and a powered wheelchair race. The 2016 championship drew 66 pilots from 56 teams representing 25 countries.
In the powered exoskeleton race, pilots complete everyday activities such as getting up from a sofa and overcoming obstacles such as stairs, ramps, or slopes and up to four pilots compete simultaneously on tracks to solve six tasks; and the pilot that solves the most tasks in the least amount of time wins the race.
(Kim, a triplegic for 22 years demonstrates walking and climbing the stairs (below photo) wearing the WalkOn Suit during the media day on June 21 at KAIST.)
Kim, who demonstrated walking and climbing the stairs wearing the WalkON Suit during the media day for the Cybathlon 2020 kickoff ceremony on June 21 at KAIST, said, “I have been confined to a wheelchair for more than 20 years. I am used to it so I feel like the wheelchair is one of my body parts. Actually, I don’t feel any big difficulties in doing everyday tasks in wheelchair. But whenever I face the fact that I will never be able to stand up with my own two legs again, I am so devastated.” He continued, “I still remember the day when I stood up with my own two legs by myself after 22 years. It was beyond description.”
The market for wearable robots, especially for exoskeleton robots, is continuing to grow as the aging population has been a major challenge in almost every advanced country. The global market for these robots expects to see annual growth of 41.2% to 8.3 billion US dollars by 2025. Healthcare wearable robots for the elderly and rehabilitation take up the half of the market share followed by wearable robots for industrial and defense purposes.
Professor Kong from the Department of Mechanical Engineering and his colleagues have developed two wearable robot systems in 2014: The "WalkON Suit" for complete paraplegics and “Angel Suit” for those with partial impairment in walking ability such as the elderly and rehabilitation patients.
Professor Kong said after 15 years of basic research, the team is now able to develop its own distinct technologies. He said their robots are powered by non-resistant precision drives with algorithms recognizing the user’s moving intention. Incorporated with prosthetic devices technology from the Severance Rehabilitation Hospital, their control technology has led to the production of a customizable robot suit optimized for each user’s physical condition.
The WalkON Suit, which boasts a maximum force of 250 Nm and maximum rotation speed of 45 RPM, gives the user high-energy efficiency modeled after the physiology of the human leg. It allows users to walk on flat ground and down stairs, climb up and down inclines, and sit and lie down. Currently the battery lasts five to six hours for locomotion and the approximate 25 kg of robot weight still remains a technical challenge to upgrade.
Professor Kong’s team has grafted AR glass technology into the WalkOn Suit that one of his pilots put on for the torch relay of the PyongChang Paralympics in 2018. His team is now upgrading the WalkON Suit 4.0 for next year’s competition. Severance Rehabilitation Hospital will help the seven pilots with their training.
Professor Kong said his goal is to make robots that can make people with disabilities much more independent. He stressed, “Wearable robots should be designed for each single user. We provide a very good graphical user interface so that we can design, check, and also verify our optimized design for users’ best performance.”
(Seven pilots and Professor Kong (fifth from left in second row) pose with guests who joined the Cybathlon 2020 kickoff ceremony. President Shin (fifth from right) made a congratulatory remarks during the ceremony.)
2019.06.25 View 40312 -
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 View 48772 -
Play Games With No Latency
One of the most challenging issues for game players looks to be resolved soon with the introduction of a zero-latency gaming environment. A KAIST team developed a technology that helps game players maintain zero-latency performance. The new technology transforms the shapes of game design according to the amount of latency.
Latency in human-computer interactions is often caused by various factors related to the environment and performance of the devices, networks, and data processing. The term ‘lag’ is used to refer to any latency during gaming which impacts the user’s performance.
Professor Byungjoo Lee at the Graduate School of Culture Technology in collaboration with Aalto University in Finland presented a mathematical model for predicting players' behavior by understanding the effects of latency on players. This cognitive model is capable of predicting the success rate of a user when there is latency in a 'moving target selection' task which requires button input in a time constrained situation.
The model predicts the players’ task success rate when latency is added to the gaming environment. Using these predicted success rates, the design elements of the game are geometrically modified to help players maintain similar success rates as they would achieve in a zero-latency environment. In fact, this research succeeded in modifying the pillar heights of the Flappy Bird game, allowing the players to maintain their gaming performance regardless of the added latency.
Professor Lee said, "This technique is unique in the sense that it does not interfere with a player's gaming flow, unlike traditional methods which manipulate the game clock by the amount of latency. This study can be extended to various games such as reducing the size of obstacles in the latent computing environment.”
This research, in collaboration with Dr. Sunjun Kim from Aalto University and led by PhD candidate Injung Lee, was presented during the 2019 CHI Conference on Human Factors in Computing Systems last month in Glasgow in the UK.
This research was supported by the National Research Foundation of Korea (NRF) (2017R1C1B2002101, 2018R1A5A7025409), and the Aalto University Seed Funding Granted to the GamerLab respectively.
Figure 1. Overview of Geometric Compensation
Publication:
Injung Lee, Sunjun Kim, and Byungjoo Lee. 2019. Geometrically Compensating Effect of End-to-End Latency in Moving-Target Selection Games. In Proceedings of the 2019 CHI Conference on Human Factors in Computing Systems (CHI’19) . ACM, New York, NY, USA, Article 560, 12 pages. https://doi.org/10.1145/3290605.3300790
Video Material:
https://youtu.be/TTi7dipAKJs
Profile: Prof. Byungjoo Lee, MD, PhD
byungjoo.lee@kaist.ac.kr
http://kiml.org/
Assistant Professor
Graduate School of Culture Technology (CT)
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Injung Lee, PhD Candidate
edndn@kaist.ac.kr
PhD Candidate
Interactive Media Lab
Graduate School of Culture Technology (CT)
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr
Daejeon 34141, Korea
Profile: Postdoc. Sunjun Kim, MD, PhD
kuaa.net@gmail.com
Postdoctoral Researcher
User Interfaces Group
Aalto University
https://www.aalto.fi Espoo 02150, Finland
(END)
2019.06.11 View 46425 -
Professor Cheol-Ho Jeong Honored with the DTU Lecturer of the Year
A KAIST alumnus and an associate professor at the Technical University of Denmark (DTU), Dr. Cheol-Ho Jeong was selected as the recipient of the Lecturer of the Year 2019 Award by DTU.
Professor Jeong received his B.S., M.Sc., and Ph. D. degrees from KAIST’s Department of Mechanical Engineering in August 2007 under the supervision of Professor Jeong-Guon Ih, and has been serving as an assistant followed by associate professor at DTU’s Department of Electrical Engineering since October 2007. His research covers wide arrays of architectural acoustics, environmental acoustics, psychoacoustics, and structural acoustics. Every year, the students at DTU nominate one or two lecturer(s) of the year. The award celebrates and honors the selected lecturers for showing great commitment not only to education itself, but also to their communication and engagement with the students.
This year, the DTU student union Polyteknisk Forening nominated Professor Jeong for his outstanding course evaluations for his excellent teaching over the years. One of the student testimonies for the award read, "Professor Jeong is one of the best teachers I have ever had at DTU. He is very humane and approachable."
The awards ceremony was held on May 3 at DTU during the 2019 Annual Commemoration Party and Professor Jeong was warmly congratulated by the Crown Prince Couple of Denmark. The other award was given to Professor Robert Madsen from DTU’s Chemistry department.
©Photo and Quote: Ulrik Jantzen, Büro Jantzen, Camilla Christiane Hermann.
2019.05.30 View 7128 -
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 View 54905 -
Professor Park at UPC-Barcelona Tech Receives Jeong Hun Cho Award
Professor Hyuk Park was honored to be the recipient of the Jeong Hun Cho Award which was presented at the Universitat Politècnica de Catalunya Barcelona Tech. The award recognizes young scientists in the field of aerospace engineering.
Professor Park, a graduate of KAIST’s Department of Mechanical Engineering in 2001, earned his MS and PhD at the Gwangju Institute of Science and Technology, and works at the Castelldefels School of Telecommunications and Aerospace Engineering at UPC-Barcelona Tech. He won this year’s award, which honors former PhD candidate Jeong Hun Cho at the Aerospace Engineering Department who died in a lab accident in 2003. Professor Park also received 25 million KRW prize money. Cho’s family endowed the award and scholarship in his memory. Since 2005, the scholarship has selected three young scholars every year who specialize in aerospace engineering from Cho’s alma maters of KAIST, Korea University, and Kongju National University High School.
Professor Park was selected as this year’s awardee in recognition of his studies of synthetic-aperture radar (SAR) satellite radiometer system, remote sensing radio frequency interference reduction system development, and 3CAT series research.
The Award Committee also chose three students for scholarships: PhD candidate Sang-Woo Chung from the Department of Aerospace Engineering at KAIST with 4 million KRW, PhD candidate Eun-Hee Kang from the School of Mechanical Engineering at Korea University with 4 million KRW, and Chan-Ho Song from Kongju National University High School with 3 million KRW.
2019.05.14 View 7704 -
KAIST Develops Core Technology for Ultra-small 3D Image Sensor
(from left: Dr. Jong-Bum Yo, PhD candidate Seong-Hwan Kimand Professor Hyo-Hoon Park)
A KAIST research team developed a silicon optical phased array (OPA) chip, which can be a core component for three-dimensional image sensors. This research was co-led by PhD candidate Seong-Hwan Kim and Dr. Jong-Bum You from the National Nanofab Center (NNFC).
A 3D image sensor adds distance information to a two-dimensional image, such as a photo, to recognize it as a 3D image. It plays a vital role in various electronics including autonomous vehicles, drones, robots, and facial recognition systems, which require accurate measurement of the distance from objects.
Many automobile and drone companies are focusing on developing 3D image sensor systems, based on mechanical light detection and ranging (LiDAR) systems. However, it can only get as small as the size of a fist and has a high possibility of malfunctioning because it employs a mechanical method for laser beam-steering.
OPAs have gained a great attention as a key component to implement solid-state LiDAR because it can control the light direction electronically without moving parts. Silicon-based OPAs are small, durable, and can be mass-produced through conventional Si-CMOS processes.
However, in the development of OPAs, a big issue has been raised about how to achieve wide beam-steering in transversal and longitudinal directions. In the transversal direction, a wide beam-steering has been implemented, relatively easily, through a thermo-optic or electro-optic control of the phase shifters integrated with a 1D array. But the longitudinal beam-steering has been remaining as a technical challenge since only a narrow steering was possible with the same 1D array by changing the wavelengths of light, which is hard to implement in semiconductor processes.
If a light wavelength is changed, characteristics of element devices consisting the OPA can vary, which makes it difficult to control the light direction with reliability as well as to integrate a wavelength-tunable laser on a silicon-based chip. Therefore, it is essential to devise a new structure that can easily adjust the radiated light in both transversal and longitudinal directions.
By integrating tunable radiator, instead of tunable laser in a conventional OPA, Professor Hyo-Hoon Park from the School of Electrical Engineering and his team developed an ultra-small, low-power OPA chip that facilitates a wide 2D beam-steering with a monochromatic light source.
This OPA structure allows the minimizing of the 3D image sensors, as small as a dragonfly’s eye.
According to the team, the OPA can function as a 3D image sensor and also as a wireless transmitter sending the image data to a desired direction, enabling high-quality image data to be freely communicated between electronic devices.
Kim said, “It’s not an easy task to integrate a tunable light source in the OPA structures of previous works. We hope our research proposing a tunable radiator makes a big step towards commercializing OPAs.”
Dr. You added, “We will be able to support application researches of 3D image sensors, especially for facial recognition with smartphones and augmented reality services. We will try to prepare a processing platform in NNFC that provides core technologies of the 3D image sensor fabrication.”
This research was published in Optics Letters on January 15.
Figure 1.The manufactured OPA chip
Figure 2. Schematic feature showing an application of the OPA to a 3D image sensor
2019.02.08 View 6885 -
A Novel Material for Transparent and Flexible Displays
(Research team led by Professor Sang Youl Kim from the Department of Chemistry)
The next generation of flexible and transparent displays will require a high-performing and flexible polymeric material that has the optical and thermal properties of glass. The material must be transparent to visible light and have a low coefficient of thermal expansion (CTE). Unfortunately, such a polymeric material has not been available. A KAIST research team has succeeded in making a new polymeric material with an exceptionally low CTE value while retaining high transparency and excellent thermal and mechanical properties. The method developed for amorphous polymers with a controlled CTE can be applied to control the thermal expansion of organic materials as well.
Most of objects expands upon heating and shrinks by cooling, and organic polymers have a relatively large CTE compared to that of ceramics or metals. Thin, light-weight planar substrates for semiconductor devices should have a similar CTE of ceramics. Otherwise, the device can be cracked due to the stress caused by thermal expansion and contraction. Therefore, matching the CTE of the semiconductor device and the substrate is crucial for successful manufacturing of display devices. Forming a network structure by connecting polymer chains is a well-known method of reducing the CTE of amorphous polymers. However, polymers with a network structure eventually lose their flexibility and becomes brittle.
As an alternative method, Professor Sang Youl Kim from the Department of Chemistry and his team chose to adjust the distance and interaction between polymer chains. Thermal expansion and contraction of polymer films can be minimized by introducing interaction forces between the polymer chains and by arranging the direction of the force perpendicularly. The team successfully implemented this approach by appropriately designing the chemical structure of a transparent polymeric material. It is called poly (amide-imide) film, which is a transparent, flexible, and high-performing polymeric material. It is thermally stable enough to be used in the AMOLED (active-matrix organic light-emitting diode) fabrication process (stable at >400℃) with a low CTE (4ppm/℃).
The team made IGZO TFT (Indium Gallium Zinc Oxide Thin Film Transistor) devices on the newly synthesized transparent poly(amide-imide) film, and confirmed that the device could indeed operate normally even when it is folded down to a radius of 1mm.
Professor Kim said, “Our results suggest a way of controlling the thermal expansion of amorphous polymers similar to a level of glass without chemical cross-linking, which has long been regarded as a challenging problem. At the same time, we succeeded in making the polymer transparent and flexible. We expect that it can be applied to controlling the thermal expansion of various organic materials.”
This research, led by researchers Sun Dal Kim and Byungyoung Lee, was published in Science Advances on October 26. (DOI: 10.1126/sciadv.aau1956v)
2019.01.24 View 6411 -
Professor Jeong-Ho Lee Named the KAISTian of 2018
(Professor Jeong-Ho Lee (right) poses with President Sung-Chul Shin)
Professor Jeong-Ho Lee from the Graduate School of Medical Science and Engineering was selected as the KAISTian of the Year of 2018. The award was established in 2001 and recognizes the most outstanding scholars who have made significant research and scholastic achievements during the year. Professor Lee was awarded during the New Year ceremony held in the auditorium on January 2.
Professor Lee has investigated mutations arising in the brain for decades and has published in renowned journals such as Nature, Nature Medicine, and Cell. Last August, Professor Lee reported breakthrough research on glioblastoma in Nature, giving insight into understanding how the mutation causing glioblastoma starts and suggested novel ways to treat glioblastoma, which was thought to be incurable. (Click for more)
Professor Lee’s Translational Neurogenetics Laboratory lab is investigating innovative diagnostics and therapeutics for untreatable brain disorders including intractable epilepsy and glioblastoma. To commercialize his technology, he established the tech-startup SoVarGen and now works as its CTO.
Professor Lee credited all his lab colleagues and staff. “I know all of this research would not have possible without their sweat and effort. I am happy to receive this honorable award on behalf of them.”
Remembering the beginning of his career at KAIST in 2012, Professor Lee said “KAIST seemed to be a very high and formidable barrier for me, after completing my medical education in Korea. I thank my department professors and colleagues who led me to focus on the research path that I really wanted. They provided everything for my research environment to help make good results.”
“I will continue to strive for promoting the well-being of humanity by addressing various incurable diseases as well as developing novel therapeutics. That will be the way to promote the stature of KAIST at home and abroad,” he added.
2019.01.02 View 5805 -
Professor Baik Awarded Sangsan Young Mathematician Prize
(Professor Hyungryul Baik)
Professor Hyungryul Baik from the Department of Mathematical Sciences was honored as the recipient of the 2018 Sangsan Prize for Young Mathematicians by the Korean Mathematical Society (KMS).
The Sangsan Prize recognizes young mathematicians who finished their degree within the previous five years and have begun an outstanding research career. Professor Baik was recognized for his studies in the fields of low-dimensional topology, geophysical mathematics, and geometric theory. In particular, his Ph.D. dissertation presented a new criterion that completely identifies the hyperbolic surface group, making an inference about the nature of the hyperbolic manifold group.
Recently, Professor Baik co-published a paper entitled Spaces of Invariant Circular Orders of Groups with Professor Eric Samperton at the University of California Santa Barbara in the renowned academic journal Groups, Geometry, and Dynamics in 2018.
Professor Baik earned his BS at KAIST and finished his MS and Ph.D. in mathematics in 2014 at Cornell University. He joined KAIST as a faculty member last year.
2018.10.30 View 6476 -
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 View 9647