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KAIST Researchers Suggest an Extraordinary Alternative to Petroleum-based PET - Bacteria!
< (From left) Dr. Cindy Pricilia, Ph.D. Candidate Cheon Woo Moon, Distinguished Professor Sang Yup Lee >
Currently, the world is suffering from environmental problems caused by plastic waste. The KAIST research team has succeeded in producing a microbial-based plastic that is biodegradable and can replace existing PET bottles, making it a hot topic.
Our university announced on the 7th of November that the research team of Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering has succeeded in developing a microbial strain that efficiently produces pseudoaromatic polyester monomer to replace polyethylene terephthalate (PET) using systems metabolic engineering.
Pseudoaromatic dicarboxylic acids have better physical properties and higher biodegradability than aromatic polyester (PET) when synthesized as polymers, and are attracting attention as an eco-friendly monomer* that can be synthesized into polymers. The production of pseudoaromatic dicarboxylic acids through chemical methods has the problems of low yield and selectivity, complex reaction conditions, and the generation of hazardous waste.
*Monomer: A material for making polymers, which is used to synthesize polymers by polymerizing monomers together
< Figure. Overview of pseudoaromatic dicarboxylic acid production using metabolically engineered C. glutamicum. >
To solve this problem, Professor Sang Yup Lee's research team used metabolic engineering to develop a microbial strain that efficiently produces five types of pseudoaromatic dicarboxylic acids, including 2-pyrone-4,6-dicarboxylic acid and four types of pyridine dicarboxylic acids (2,3-, 2,4-, 2,5-, 2,6-pyridine dicarboxylic acids), in Corynebacterium, a bacterium mainly used for amino acid production.
The research team used metabolic engineering techniques to build a platform microbial strain that enhances the metabolic flow of protocatechuic acid, which is used as a precursor for several pseudoaromatic dicarboxylic acids, and prevents the loss of precursors.
Based on this, the genetic manipulation target was discovered through transcriptome analysis, producing 76.17 g/L of 2-pyrone-4,6-dicarboxylic acid, and by newly discovering and constructing three types of pyridine dicarboxylic acid production metabolic pathways, successfully producing 2.79 g/L of 2,3-pyridine dicarboxylic acid, 0.49 g/L of 2,4-pyridine dicarboxylic acid, and 1.42 g/L of 2,5-pyridine dicarboxylic acid.
In addition, the research team confirmed the production of 15.01 g/L through the construction and reinforcement of the 2,6-pyridine dicarboxylic acid biosynthesis pathway, successfully producing a total of five similar aromatic dicarboxylic acids with high efficiency.
In conclusion, the team succeeded in producing 2,4-, 2,5-, and 2,6-pyridine dicarboxylic acids at the world's highest concentration. In particular, 2,4-, 2,5-pyridine dicarboxylic acid achieved production on the scale of g/L, which was previously produced in extremely small amounts (mg/L).
Based on this study, it is expected that it will be applied to various polyester production industrial processes, and it is also expected that it will be actively utilized in research on the production of similar aromatic polyesters.
Professor Sang Yup Lee, the corresponding author, said, “The significance lies in the fact that we have developed an eco-friendly technology that efficiently produces similar aromatic polyester monomers based on microorganisms,” and “This study will help the microorganism-based bio-monomer industry replace the petrochemical-based chemical industry in the future.”
The results of this study were published in the international academic journal, the Proceedings of the National Academy of Sciences of United States of America (PNAS) on October 30th.
※ Paper title: Metabolic engineering of Corynebacterium glutamicum for the production of pyrone and pyridine dicarboxylic acids
※ Author information: Jae Sung Cho (co-first author), Zi Wei Luo (co-first author), Cheon Woo Moon (co-first author), Cindy Prabowo (co-author), Sang Yup Lee (corresponding author) - a total of 5 people
This study was conducted with the support of the Development of Next-generation Biorefinery Platform Technologies for Leading Bio-based Chemicals Industry Project and the Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project (Project leader: Professor Sang Yup Lee) from the National Research Foundation supported by the Ministry of Science and Technology and ICT of Korea.
2024.11.08 View 778 -
KAIST Proposes a New Way to Circumvent a Long-time Frustration in Neural Computing
The human brain begins learning through spontaneous random activities even before it receives sensory information from the external world. The technology developed by the KAIST research team enables much faster and more accurate learning when exposed to actual data by pre-learning random information in a brain-mimicking artificial neural network, and is expected to be a breakthrough in the development of brain-based artificial intelligence and neuromorphic computing technology in the future.
KAIST (President Kwang-Hyung Lee) announced on the 23rd of October that Professor Se-Bum Paik 's research team in the Department of Brain Cognitive Sciences solved the weight transport problem*, a long-standing challenge in neural network learning, and through this, explained the principles that enable resource-efficient learning in biological brain neural networks.
*Weight transport problem: This is the biggest obstacle to the development of artificial intelligence that mimics the biological brain. It is the fundamental reason why large-scale memory and computational work are required in the learning of general artificial neural networks, unlike biological brains.
Over the past several decades, the development of artificial intelligence has been based on error backpropagation learning proposed by Geoffery Hinton, who won the Nobel Prize in Physics this year. However, error backpropagation learning was thought to be impossible in biological brains because it requires the unrealistic assumption that individual neurons must know all the connected information across multiple layers in order to calculate the error signal for learning.
< Figure 1. Illustration depicting the method of random noise training and its effects >
This difficult problem, called the weight transport problem, was raised by Francis Crick, who won the Nobel Prize in Physiology or Medicine for the discovery of the structure of DNA, after the error backpropagation learning was proposed by Hinton in 1986. Since then, it has been considered the reason why the operating principles of natural neural networks and artificial neural networks will forever be fundamentally different.
At the borderline of artificial intelligence and neuroscience, researchers including Hinton have continued to attempt to create biologically plausible models that can implement the learning principles of the brain by solving the weight transport problem.
In 2016, a joint research team from Oxford University and DeepMind in the UK first proposed the concept of error backpropagation learning being possible without weight transport, drawing attention from the academic world. However, biologically plausible error backpropagation learning without weight transport was inefficient, with slow learning speeds and low accuracy, making it difficult to apply in reality.
KAIST research team noted that the biological brain begins learning through internal spontaneous random neural activity even before experiencing external sensory experiences. To mimic this, the research team pre-trained a biologically plausible neural network without weight transport with meaningless random information (random noise).
As a result, they showed that the symmetry of the forward and backward neural cell connections of the neural network, which is an essential condition for error backpropagation learning, can be created. In other words, learning without weight transport is possible through random pre-training.
< Figure 2. Illustration depicting the meta-learning effect of random noise training >
The research team revealed that learning random information before learning actual data has the property of meta-learning, which is ‘learning how to learn.’ It was shown that neural networks that pre-learned random noise perform much faster and more accurate learning when exposed to actual data, and can achieve high learning efficiency without weight transport.
< Figure 3. Illustration depicting research on understanding the brain's operating principles through artificial neural networks >
Professor Se-Bum Paik said, “It breaks the conventional understanding of existing machine learning that only data learning is important, and provides a new perspective that focuses on the neuroscience principles of creating appropriate conditions before learning,” and added, “It is significant in that it solves important problems in artificial neural network learning through clues from developmental neuroscience, and at the same time provides insight into the brain’s learning principles through artificial neural network models.”
This study, in which Jeonghwan Cheon, a Master’s candidate of KAIST Department of Brain and Cognitive Sciences participated as the first author and Professor Sang Wan Lee of the same department as a co-author, will be presented at the 38th Neural Information Processing Systems (NeurIPS), the world's top artificial intelligence conference, to be held in Vancouver, Canada from December 10 to 15, 2024. (Paper title: Pretraining with random noise for fast and robust learning without weight transport)
This study was conducted with the support of the National Research Foundation of Korea's Basic Research Program in Science and Engineering, the Information and Communications Technology Planning and Evaluation Institute's Talent Development Program, and the KAIST Singularity Professor Program.
2024.10.23 View 814 -
Professor Jimin Park and Dr. Inho Kim join the ranks of the 2024 "35 Innovators Under 35" by the MIT Technology Review
< (From left) Professor Jimin Park of the Department of Chemical and Biomolecular Engineering and Dr. Inho Kim, a graduate of the Department of Materials Science and Engineering >
KAIST (represented by President Kwang-Hyung Lee) announced on the 13th of September that Professor Jimin Park from KAIST’s Department of Chemical and Biomolecular Engineering and Dr. Inho Kim, a graduate from the Department of Materials Science and Engineering (currently a postdoctoral researcher at Caltech), were selected by the MIT Technology Review as the 2024 "35 Innovators Under 35”.
The MIT Technology Review, first published in 1899 by the Massachusetts Institute of Technology, is the world’s oldest and most influential magazine on science and technology, offering in-depth analysis across various technology fields, expanding knowledge and providing insights into cutting-edge technology trends.
Since 1999, the magazine has annually named 35 innovators under the age of 35, recognizing young talents making groundbreaking contributions in modern technology fields. The recognition is globally considered a prestigious honor and a dream for young researchers in the science and technology community.
< Image 1. Introduction for Professor Jimin Park at the Meet 35 Innovators Under 35 Summit 2024 >
Professor Jimin Park is developing next-generation bio-interfaces that link artificial materials with living organisms, and is engaged in advanced research in areas such as digital healthcare and carbon-neutral compound manufacturing technologies. In 2014, Professor Park was also recognized as one of the ‘Asia Pacific Innovators Under 35’ by the MIT Technology Review, which highlights young scientists in the Asia-Pacific region.
Professor Park responded, “It’s a great honor to be named as one of the young innovators by the MIT Technology Review, a symbol of innovation with a long history. I will continue to pursue challenging, interdisciplinary research to develop next-generation interfaces that seamlessly connect artificial materials and living organisms, from atomic to system levels.”
< Image 2. Introduction for Dr. Inho Kim as the 2024 Innovator of Materials Science for 35 Innovators Under 35 >
Dr. Inho Kim, who earned his PhD from KAIST in 2020 under the supervision of Professor Sang Ouk Kim from the Department of Materials Science and Engineering, recently succeeded in developing a new artificial muscle using composite fibers. This new material is considered the most human-like muscle ever reported in scientific literature, while also being 17 times stronger than natural human muscle.
Dr. Kim is researching the application of artificial muscle fibers in next-generation wearable assistive devices that move more naturally, like humans or animals, noting that the fibers are lightweight, flexible, and exhibit conductivity during contraction, enabling real-time feedback. Recognized for this potential, Dr. Inho Kim was named one of the '35 Innovators Under 35' this year, making him the first researcher to win the honor with the research conducted at KAIST and a PhD earned from Korea.
Dr. Kim stated, “I aim to develop robots using these new materials that can replace today’s expensive and heavy exoskeleton suits by eliminating motors and rigid frames. This will significantly reduce costs and allow for better customization, making cutting-edge technology more accessible to those who need it most, like children with cerebral palsy.”
2024.09.13 View 1617 -
KAIST finds ways for Bacteria to produce PET-like materials
Among various eco-friendly polymers, polyhydroxyalkanoates (PHA) stand out for their excellent biodegradability and biocompatibility. They decompose naturally in soil and marine environments and are used in applications such as food packaging and medical products. However, natural PHA produced to date has faced challenges meeting various physical property requirements, such as durability and thermal stability, and has been limited in its commercial application due to low production concentrations. In light of this, KAIST researchers have recently developed a technology that could play a crucial role in solving the environmental pollution problem caused by plastics.
KAIST (represented by President Kwang-Hyung Lee) announced on August 26th that a research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering, including Dr. Youngjoon Lee and master's student Minju Kang, has successfully developed a microbial strain that efficiently produces aromatic polyester* using systems metabolic engineering.
※ Aromatic polyester: A polymer containing aromatic compounds (specific carbon ring structures like benzene) and ester bonds.
In this study, the research team used metabolic engineering to enhance the metabolic flux of the biosynthetic pathway for the aromatic monomer phenyllactate (PhLA) in E. coli. They manipulated the metabolic pathway to increase the polymer fraction accumulated within the cells and employed computer simulations to predict the structure of PHA synthase and improve the enzyme based on the structure-function relationship.
Through subsequent fermentation optimization, the team achieved the world’s highest concentration (12.3±0.1 g/L) for the efficient production of poly (PhLA) and successfully produced polyester through a 30L scale fed-batch fermentation, demonstrating the possibility of industrial-level production. The produced aromatic polyesters showed enhanced thermal properties, improved mechanical properties, and potential for use as drug delivery carriers.
< Figure 1. Development schematics of aromatic polyester producing microorganisms >
The research team also demonstrated that an exogenous phasin protein* plays a crucial role in increasing the intracellular polymer accumulation fraction, which is directly related to the economic feasibility and efficiency of non-natural PHA production. They improved PHA synthase using a rational enzyme design approach, predicting the three-dimensional structure of the enzyme through homology modeling (a method of predicting the three-dimensional structure of a new protein based on the structure of similar proteins) followed by molecular docking simulations (simulations that predict how well a monomer can bind to an enzyme) and molecular dynamics simulations (simulations that predict how molecules move and interact over time) to upgrade the enzyme into a mutant enzyme with enhanced monomer polymerization efficiency.
※ Exogenous phasin protein: Phasin is a protein related to PHA production, interacting with the cytoplasmic environment on the surface of granules of PHA, and playing a role in polymer accumulation and controlling the number and size of granules. In this study, genes encoding phasin proteins derived from various natural PHA-producing microorganisms were selected and introduced.
Dr. Youngjoon Lee, co-first author of the paper, explained, "The significance of this study lies in the fact that we have achieved the world's highest concentration of microbial-based aromatic polyester production using eco-friendly materials and methods. This technology is expected to play a crucial role in addressing the environmental pollution caused by plastics." Distinguished Professor Sang Yup Lee added, "This study, which presents various strategies for the high-efficiency production of useful polymers via systems metabolic engineering, is expected to make a significant contribution to solving climate change issues, particularly the recent plastic problem."
< Figure 2. Detailed development strategy for aromatic polyester producing microorganisms >
The research findings were published on August 21st in Trends in Biotechnology, published by Cell, an international academic journal.
※ Paper Title: “Microbial production of an aromatic homopolyester”
※ Author Information: Youngjoon Lee (KAIST, co-first author), Minju Kang (KAIST, co-first author), Woo Dae Jang (KAIST, second author), So Young Choi (KAIST, third author), Jung Eun Yang (KAIST, fourth author), Sang Yup Lee (KAIST, corresponding author), totaling six authors.
This research was supported by the "Development of Next-Generation Biorefinery Platform Technologies for Leading the Bio-based Chemicals Industry" project led by Distinguished Professor Sang Yup Lee at KAIST, under the eco-friendly chemical technology development project aimed at substituting petroleum, funded by the Ministry of Science and ICT. It was also supported by the "Development of Platform Technology for the Production of Novel Aromatic Bioplastic Using Microbial Cell Factories" project (Project Leader: Si Jae Park, Ewha Woman’s University).
2024.08.28 View 1856 -
KAIST Research Team Creates the Scent of Jasmine from Microorganisms
The fragrance of jasmine and ylang-ylang, used widely in the manufacturing of cosmetics, foods, and beverages, can be produced by direct extraction from their respective flowers. In reality, this makes it difficult for production to meet demand, so companies use benzyl acetate, a major aromatic component of the two fragrances that is chemically synthesized from raw materials derived from petroleum.
On February 26, a KAIST research team led by Research Professor Kyeong Rok Choi from the BioProcess Engineering Research Center and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering revealed the development of the first microbial process to effectively produce benzyl acetate, an industrially useful compound, from renewable carbon sources such as glucose. The results were published in their paper titled “A microbial process for the production of benzyl acetate”.
< Figure 1. Production of benzyl acetate through co-culture of upstream and downstream strains harboring the benzoic acid-dependent pathway. >
The team, led by Distinguished Professor Lee, aimed to produce benzyl acetate through an environmentally friendly and sustainable method, and developed an Escherichia coli strand to convert glucose into benzyl acetate through system metabolic engineering*.
*System metabolic engineering: a field of research founded by Distinguished Professor Lee to effectively develop microbial cell plants, a core component of the bio-industry that will replace the existing chemical industry, which is highly dependent on petroleum.
The research team developed a metabolic pathway that biosynthesizes benzyl acetate from benzoic acid derived from glucose, and successfully produced benzyl acetate by co-culturing** the strain.
**co-culture: simultaneously synthesizing two or more types of microorganisms in a mixture
However, it has been confirmed that the enzyme used to convert benzoic acid into benzyl acetate in this co-culturing technique acts non-specifically on an intermediate product during benzoic acid biosynthesis, producing a by-product called cinnamyl acetate. This process consumes the intermediate product needed for benzoic acid biosynthesis, thereby reducing the production efficiency of the target compound, benzyl acetate.
To overcome this problem, Distinguished Professor Lee and his team devised a delayed co-culture method, where they first produced benzoic acid in the earlier stages of fermentation by only culturing the top strain that produces benzoic acid from glucose, and later inoculated the bottom strain to convert the accumulated benzoic acid in the culture medium into benzyl acetate.
By applying this co-culture technique, the team suppressed the formation of by-products without further strain improvement or applying additional enzymes, and multiplied the concentration of the target compound by 10 times, producing 2.2 g/L of benzyl acetate. In addition, the team confirmed its potential for the commercial production of benzyl acetate through a technical economic analysis on this microbial process.
< Figure 2. Delayed co-culture of the Bn1 and Bn-BnAc3 strains for improved production of benzyl acetate through the benzoic acid-independent pathway.>
Research Professor Keyong Rok Choi, who was the first author of this paper, said, “This work is significant in that we have developed an effective microbial process to produce the industrially useful compound benzyl acetate, and also in that we have suggested a new approach to overcome the target chemical efficiency diminution and by-product formation issues caused commonly through non-specific enzyme activities during metabolic engineering.”
Distinguished Professor Lee said, “If we can increase the variety and number of microbial processes that produce useful chemicals through sustainable methods and at the same time develop effective strategies to solve chronic and inevitable problems that arise during microbial strain development, we will be able to accelerate the transition from the petrochemical industry into the eco-friendly and sustainable bio-industry.
This work was published online in Nature Chemical Engineering, issued by Nature.
This research was supported by the ‘Implementation of Intelligent Cell Factory Technology (PI: Distinguished Professor Sang Yup Lee) Project by the Ministry of Science and ICT, and the ‘Development of Protein Production Technology from Inorganic Substances through Microbiological Metabolic System Control’ (PI: Research Professor Kyeong Rok Choi) by the Agricultural Microbiological Project Group at the Rural Development Administration.
2024.03.05 View 3446 -
KAIST to begin Joint Research to Develop Next-Generation LiDAR System with Hyundai Motor Group
< (From left) Jong-Soo Lee, Executive Vice President at Hyundai Motor, Sang-Yup Lee, Senior Vice President for Research at KAIST >
The ‘Hyundai Motor Group-KAIST On-Chip LiDAR Joint Research Lab’ was opened at KAIST’s main campus in Daejeon to develop LiDAR sensors for advanced autonomous vehicles.
The joint research lab aims to develop high-performance and compact on-chip sensors and new signal detection technology, which are essential in the increasingly competitive autonomous driving market. On-chip sensors, which utilize semiconductor manufacturing technology to add various functions, can reduce the size of LiDAR systems compared to conventional methods and secure price competitiveness through mass production using semiconductor fabrication processes.
The joint research lab will consist of about 30 researchers, including the Hyundai-Kia Institute of Advanced Technology Development research team and KAIST professors Sanghyeon Kim, Sangsik Kim, Wanyeong Jung, and Hamza Kurt from KAIST’s School of Electrical Engineering, and will operate for four years until 2028.
KAIST will be leading the specialized work of each research team, such as for the development of silicon optoelectronic on-chip LiDAR components, the fabrication of high-speed, high-power integrated circuits to run the LiDAR systems, and the optimization and verification of LiDAR systems.
Hyundai Motor and Kia, together with Hyundai NGV, a specialized industry-academia cooperation institution, will oversee the operation of the joint research lab and provide support such as monitoring technological trends, suggesting research directions, deriving core ideas, and recommending technologies and experts to enhance research capabilities.
A Hyundai Motor Group official said, "We believe that this cooperation between Hyundai Motor Company and Kia, the leader in autonomous driving technology, and KAIST, the home of world-class technology, will hasten the achievement of fully autonomous driving." He added, "We will do our best to enable the lab to produce tangible results.”
Professor Sanghyeon Kim said, "The LiDAR sensor, which serves as the eyes of a car, is a core technology for future autonomous vehicle development that is essential for automobile companies to internalize."
2024.02.27 View 4382 -
KAIST presents strategies for environmentally friendly and sustainable polyamides production
- Provides current research trends in bio-based polyamide production
- Research on bio-based polyamides production gains importance for achieving a carbon-neutral society
Global industries focused on carbon neutrality, under the slogan "Net-Zero," are gaining increasing attention. In particular, research on microbial production of polymers, replacing traditional chemical methods with biological approaches, is actively progressing.
Polyamides, represented by nylon, are linear polymers widely used in various industries such as automotive, electronics, textiles, and medical fields. They possess beneficial properties such as high tensile strength, electrical insulation, heat resistance, wear resistance, and biocompatibility. Since the commercialization of nylon in 1938, approximately 7 million tons of polyamides are produced worldwide annually. Considering their broad applications and significance, producing polyamides through bio-based methods holds considerable environmental and industrial importance.
KAIST (President Kwang-Hyung Lee) announced that a research team led by Distinguished Professor Sang Yup Lee, including Dr. Jong An Lee and doctoral candidate Ji Yeon Kim from the Department of Chemical and Biomolecular Engineering, published a paper titled "Current Advancements in Bio-Based Production of Polyamides”. The paper was featured on the cover of the monthly issue of "Trends in Chemistry” by Cell Press.
As part of climate change response technologies, bio-refineries involve using biotechnological and chemical methods to produce industrially important chemicals and biofuels from renewable biomass without relying on fossil resources. Notably, systems metabolic engineering, pioneered by KAIST's Distinguished Professor Sang Yup Lee, is a research field that effectively manipulates microbial metabolic pathways to produce valuable chemicals, forming the core technology for bio-refineries. The research team has successfully developed high-performance strains producing a variety of compounds, including succinic acid, biodegradable plastics, biofuels, and natural products, using systems metabolic engineering tools and strategies.
The research team predicted that if bio-based polyamide production technology, which is widely used in the production of clothing and textiles, becomes widespread, it will attract attention as a future technology that can respond to the climate crisis due to its environment-friendly production technology. In this study, the research team comprehensively reviewed the bio-based polyamide production strategies. They provided insights into the advancements in polyamide monomer production using metabolically engineered microorganisms and highlighted the recent trends in bio-based polyamide advancements utilizing these monomers. Additionally, they reviewed the strategies for synthesizing bio-based polyamides through chemical conversion of natural oils and discussed the biodegradability and recycling of the polyamides. Furthermore, the paper presented the future direction in which metabolic engineering can be applied for the bio-based polyamide production, contributing to environmentally friendly and sustainable society.
Ji Yeon Kim, the co-first author of this paper from KAIST, stated "The importance of utilizing systems metabolic engineering tools and strategies for bio-based polyamides production is becoming increasingly prominent in achieving carbon neutrality."
Professor Sang Yup Lee emphasized, "Amid growing concerns about climate change, the significance of environmentally friendly and sustainable industrial development is greater than ever. Systems metabolic engineering is expected to have a significant impact not only on the chemical industry but also in various fields."
< [Figure 1] A schematic overview of the overall process for polyamides production >
This paper by Dr. Jong An Lee, PhD student Ji Yeon Kim, Dr. Jung Ho Ahn, and Master Yeah-Ji Ahn from the Department of Chemical and Biomolecular Engineering at KAIST was published in the December issue of 'Trends in Chemistry', an authoritative review journal in the field of chemistry published by Cell. It was published on December 7 as the cover paper and featured review.
※ Paper title: Current advancements in the bio-based production of polyamides
※ Author information: Jong An Lee, Ji Yeon Kim, Jung Ho Ahn, Yeah-Ji Ahn, and Sang Yup Lee
This research was conducted with the support from the development of platform technologies of microbial cell factories for the next-generation biorefineries project and C1 gas refinery program by Korean Ministry of Science and ICT.
< [Figure 2] Cover paper of the December issue of Trends in Chemistry >
2023.12.21 View 3747 -
KAIST proposes alternatives to chemical factories through “iBridge”
- A computer simulation program “iBridge” was developed at KAIST that can put together microbial cell factories quickly and efficiently to produce cosmetics and food additives, and raw materials for nylons
- Eco-friendly and sustainable fermentation process to establish an alternative to chemical plants
As climate change and environmental concerns intensify, sustainable microbial cell factories garner significant attention as candidates to replace chemical plants. To develop microorganisms to be used in the microbial cell factories, it is crucial to modify their metabolic processes to induce efficient target chemical production by modulating its gene expressions. Yet, the challenge persists in determining which gene expressions to amplify and suppress, and the experimental verification of these modification targets is a time- and resource-intensive process even for experts. The challenges were addressed by a team of researchers at KAIST (President Kwang-Hyung Lee) led by Distinguished Professor Sang Yup Lee.
It was announced on the 9th by the school that a method for building a microbial factory at low cost, quickly and efficiently, was presented by a novel computer simulation program developed by the team under Professor Lee’s guidance, which is named “iBridge”. This innovative system is designed to predict gene targets to either overexpress or downregulate in the goal of producing a desired compound to enable the cost-effective and efficient construction of microbial cell factories specifically tailored for producing the chemical compound in demand from renewable biomass.
Systems metabolic engineering is a field of research and engineering pioneered by KAIST’s Distinguished Professor Sang Yup Lee that seeks to produce valuable compounds in industrial demands using microorganisms that are re-configured by a combination of methods including, but not limited to, metabolic engineering, synthetic biology, systems biology, and fermentation engineering.
In order to improve microorganisms’ capability to produce useful compounds, it is essential to delete, suppress, or overexpress microbial genes. However, it is difficult even for the experts to identify the gene targets to modify without experimental confirmations for each of them, which can take up immeasurable amount of time and resources.
The newly developed iBridge identifies positive and negative metabolites within cells, which exert positive and/or negative impact on formation of the products, by calculating the sum of covariances of their outgoing (consuming) reaction fluxes for a target chemical. Subsequently, it pinpoints "bridge" reactions responsible for converting negative metabolites into positive ones as candidates for overexpression, while identifying the opposites as targets for downregulation.
The research team successfully utilized the iBridge simulation to establish E. coli microbial cell factories each capable of producing three of the compounds that are in high demands at a production capacity that has not been reported around the world. They developed E. coli strains that can each produce panthenol, a moisturizing agent found in many cosmetics, putrescine, which is one of the key components in nylon production, and 4-hydroxyphenyllactic acid, an anti-bacterial food additive. In addition to these three compounds, the study presents predictions for overexpression and suppression genes to construct microbial factories for 298 other industrially valuable compounds.
Dr. Youngjoon Lee, the co-first author of this paper from KAIST, emphasized the accelerated construction of various microbial factories the newly developed simulation enabled. He stated, "With the use of this simulation, multiple microbial cell factories have been established significantly faster than it would have been using the conventional methods. Microbial cell factories producing a wider range of valuable compounds can now be constructed quickly using this technology."
Professor Sang Yup Lee said, "Systems metabolic engineering is a crucial technology for addressing the current climate change issues." He added, "This simulation could significantly expedite the transition from resorting to conventional chemical factories to utilizing environmentally friendly microbial factories."
< Figure. Conceptual diagram of the flow of iBridge simulation >
The team’s work on iBridge is described in a paper titled "Genome-Wide Identification of Overexpression and Downregulation Gene Targets Based on the Sum of Covariances of the Outgoing Reaction Fluxes" written by Dr. Won Jun Kim, and Dr. Youngjoon Lee of the Bioprocess Research Center and Professors Hyun Uk Kim and Sang Yup Lee of the Department of Chemical and Biomolecular Engineering of KAIST. The paper was published via peer-review on the 6th of November on “Cell Systems” by Cell Press.
This research was conducted with the support from the Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project (Project Leader: Distinguished Professor Sang Yup Lee, KAIST) and Development of Platform Technology for the Production of Novel Aromatic Bioplastic using Microbial Cell Factories Project (Project Leader: Research Professor So Young Choi, KAIST) of the Korean Ministry of Science and ICT.
2023.11.09 View 4306 -
KAIST holds its first ‘KAIST Tech Fair’ in New York, USA
< Photo 1. 2023 KAIST Tech Fair in New York >
KAIST (President Kwang-Hyung Lee) announced on the 11th that it will hold the ‘2023 KAIST Tech Fair in New York’ at the Kimmel Center at New York University in Manhattan, USA, on the 22nd of this month. It is an event designed to be the starting point for KAIST to expand its startup ecosystem into the global stage, and it is to attract investments and secure global customers in New York by demonstrating the technological value of KAIST startup companies directly at location.
< Photo 2. President Kwang Hyung Lee at the 2023 KAIST Tech Fair in New York >
KAIST has been holding briefing sessions for technology transfer in Korea every year since 2018, and this year is the first time to hold a tech fair overseas for global companies.
KAIST Institute of Technology Value Creation (Director Sung-Yool Choi) has prepared for this event over the past six months with the Korea International Trade Association (hereinafter KITA, CEO Christopher Koo) to survey customer base and investment companies to conduct market analysis.
Among the companies founded with the technologies developed by the faculty and students of KAIST and their partners, 7 companies were selected to be matched with companies overseas that expressed interests in these technologies. Global multinational companies in the fields of IT, artificial intelligence, environment, logistics, distribution, and retail are participating as demand agencies and are testing the marketability of the start-up's technology as of September.
Daim Research, founded by Professor Young Jae Jang of the Department of Industrial and Systems Engineering, is a company specializing in smart factory automation solutions and is knocking on the door of the global market with a platform technology optimized for automated logistics systems.
< Photo 3. Presentation by Professor Young Jae Jang for DAIM Research >
It is a ‘collaborative intelligence’ solution that maximizes work productivity by having a number of robots used in industrial settings collaborate with one another. The strength of their solution is that logistics robots equipped with AI reinforced learning technology can respond to processes and environmental changes on their own, minimizing maintenance costs and the system can achieve excellent performance even with a small amount of data when it is combined with the digital twin technology the company has developed on its own.
A student startup, ‘Aniai’, is entering the US market, the home of hamburgers, with hamburger patty automation equipments and solutions. This is a robot kitchen startup founded by its CEO Gunpil Hwang, a graduate of KAIST’s School of Electrical Engineering which gathered together the experts in the fields of robot control, design, and artificial intelligence and cognitive technology to develop technology to automatically cook hamburger patties.
At the touch of a button, both sides of the patty are cooked simultaneously for consistent taste and quality according to the set condition. Since it can cook about 200 dishes in an hour, it is attracting attention as a technology that can not only solve manpower shortages but also accelerate the digital transformation of the restaurant industry.
Also, at the tech fair to be held at the Kimmel Center of New York University on the 22nd, the following startups who are currently under market verification in the U.S. will be participating: ▴'TheWaveTalk', which developed a water quality management system that can measure external substances and metal ions by transferring original technology from KAIST; ▴‘VIRNECT’, which helps workers improve their skills by remotely managing industrial sites using XR*; ▴‘Datumo’, a solution that helps process and analyze artificial intelligence big data, ▴‘VESSL AI’, the provider of a solution to eliminate the overhead** of machine learning systems; and ▴ ‘DolbomDream’, which developed an inflatable vest that helps the psychological stability of people with developmental disabilities.
* XR (eXtended Reality): Ultra-realistic technology that enhances immersion by utilizing augmented reality, virtual reality, and mixed reality technologies
** Overhead: Additional time required for stable processing of the program
In addition, two companies (Plasmapp and NotaAI) that are participating in the D-Unicorn program with the support of the Daejeon City and two companies (Enget and ILIAS Biologics) that are receiving support from the Scale Up Tips of the Ministry of SMEs and Startups, three companies (WiPowerOne, IDK Lab, and Artificial Photosynthesis Lab) that are continuing to realize the sustainable development goals for a total of 14 KAIST startups, will hold a corporate information session with about 100 invited guests from global companies and venture capital.
< Photo 4. Presentation for AP Lab >
Prior to this event, participating startups will be visiting the New York Economic Development Corporation and large law firms to receive advice on U.S. government support programs and on their attemps to enter the U.S. market. In addition, the participating companies plan to visit a startup support investment institution pursuing sustainable development goals and the Leslie eLab, New York University's one-stop startup support space, to lay the foundation for KAIST's leap forward in global technology commercialization.
< Photo 5. Sung-Yool Choi, the Director of KAIST Institute of Technology Value Creation (left) at the 2023 KAIST Tech Fair in New York with the key participants >
Sung-Yool Choi, the Director of KAIST Institute of Technology Value Creation, said, “KAIST prepared this event to realize its vision of being a leading university in creating global value.” He added, “We hope that our startups founded with KAIST technology would successfully completed market verification to be successful in securing global demands and in attracting investments for their endeavors.”
2023.09.11 View 9677 -
A KAIST Research Team Produces Eco-Friendly Nylon with Engineered Bacterium
With worsening climate change and environmental issues, in recent years, there has been increased interest in the eco-friendly production of polymers like nylon.
On August 10, Dr. Taehee Han from a KAIST research team led by Distinguished Professor Sang Yup Lee in the Department of Chemical and Biomolecular Engineering revealed the successful development of a microbial strain that produces valerolactam, a monomer of nylon-5.
Valerolactam is an important monomer that constitutes nylon-5 and nylon-6,5. Nylon is the oldest synthetic polymer, and nylon-5 is one of its derivatives composed of monomers with five carbons, while nylon-5,6 is composed of two types of monomers with either five or six carbons. They not only have excellent processability, but are also light and tough, which allows them to be applied in a wide range of industrial sectors including clothing, badminton rackets, fishing nets, tents, and gear parts. Monomers are materials that can be built into polymers, and synthetic processes are what connects them into a polymer.
The chemical production of valerolactam, however, is based on petrochemistry, where extreme reaction conditions are required and toxic waste is produced. To solve these problems, efforts are being made to develop environmentally friendly and highly efficient microbial cell factories for lactam production. Systems metabolic engineering, a key strategy for effective microbial strain development, is a research field pioneered by Professor Sang Yup Lee.
Professor Lee’s team used metabolic engineering, a technique for manipulating microbial metabolic pathways, to construct a synthetic metabolic pathway for valerolactam production in Corynebacteriam glutamicum, a bacterium commonly used for amino acid production. With this, they successfully developed a microbial strain that utilizes biomass-derived glucose as a carbon source to produce high-value valerolactam.
In 2017, the team suggested a novel method that metabolically manipulates Escherichia coli to produce valerolactam. However, there were several limitations at the time including low producibility and the generation of harmful byproducts.
< Figure 1. Schematic graphical representation of the development of microorganisms that produce valerolactam, a nylon-5 monomer >
In this research, the team improved valerolactam producibility and incorporated an additional systems metabolic strategy to the developed microbial strain while eliminating the harmful byproducts. By removing the gene involved in the production of the main byproduct and through gene screening, the team successfully converted 5-aminovaleric acid, a byproduct and a precursor, into valerolactam.
Furthermore, by employing a strategy where the 5-aminovaleric acid-converting gene is inserted multiple times into the genome, the team strengthened the metabolic flux for valerolactam production. As a result, they reached a world-record concentration of 76.1 g/L, which is 6.17 times greater than what was previously reported.
This study was published in Metabolic Engineering on July 12, under the title, “Metabolic engineering of Corynebacterium glutamicum for the high-level production of valerolactam, a nylon-5 monomer”.
Dr. Taehee Han, the first author of the paper, said, “The significance of this research lies in our development of an environmentally friendly technology that efficiently produces monomer lactam for nylon production using microorganisms.” She added, “Through this technology, we will be able to take a step forward in replacing the petrochemical industry with a microorganism-based biopolymer industry.”
This work was supported by the “Development of Next-Generation Biofinery Platform Technologies for Leading Bio-based Chemicals Industry Project” funded by the Korean Ministry of Science and ICT.
2023.08.24 View 3566 -
Professor Joseph J. Lim of KAIST receives the Best System Paper Award from RSS 2023, First in Korea
- Professor Joseph J. Lim from the Kim Jaechul Graduate School of AI at KAIST and his team receive an award for the most outstanding paper in the implementation of robot systems.
- Professor Lim works on AI-based perception, reasoning, and sequential decision-making to develop systems capable of intelligent decision-making, including robot learning
< Photo 1. RSS2023 Best System Paper Award Presentation >
The team of Professor Joseph J. Lim from the Kim Jaechul Graduate School of AI at KAIST has been honored with the 'Best System Paper Award' at "Robotics: Science and Systems (RSS) 2023".
The RSS conference is globally recognized as a leading event for showcasing the latest discoveries and advancements in the field of robotics. It is a venue where the greatest minds in robotics engineering and robot learning come together to share their research breakthroughs. The RSS Best System Paper Award is a prestigious honor granted to a paper that excels in presenting real-world robot system implementation and experimental results.
< Photo 2. Professor Joseph J. Lim of Kim Jaechul Graduate School of AI at KAIST >
The team led by Professor Lim, including two Master's students and an alumnus (soon to be appointed at Yonsei University), received the prestigious RSS Best System Paper Award, making it the first-ever achievement for a Korean and for a domestic institution.
< Photo 3. Certificate of the Best System Paper Award presented at RSS 2023 >
This award is especially meaningful considering the broader challenges in the field. Although recent progress in artificial intelligence and deep learning algorithms has resulted in numerous breakthroughs in robotics, most of these achievements have been confined to relatively simple and short tasks, like walking or pick-and-place. Moreover, tasks are typically performed in simulated environments rather than dealing with more complex, long-horizon real-world tasks such as factory operations or household chores. These limitations primarily stem from the considerable challenge of acquiring data required to develop and validate learning-based AI techniques, particularly in real-world complex tasks.
In light of these challenges, this paper introduced a benchmark that employs 3D printing to simplify the reproduction of furniture assembly tasks in real-world environments. Furthermore, it proposed a standard benchmark for the development and comparison of algorithms for complex and long-horizon tasks, supported by teleoperation data. Ultimately, the paper suggests a new research direction of addressing complex and long-horizon tasks and encourages diverse advancements in research by facilitating reproducible experiments in real-world environments.
Professor Lim underscored the growing potential for integrating robots into daily life, driven by an aging population and an increase in single-person households. As robots become part of everyday life, testing their performance in real-world scenarios becomes increasingly crucial. He hoped this research would serve as a cornerstone for future studies in this field.
The Master's students, Minho Heo and Doohyun Lee, from the Kim Jaechul Graduate School of AI at KAIST, also shared their aspirations to become global researchers in the domain of robot learning. Meanwhile, the alumnus of Professor Lim's research lab, Dr. Youngwoon Lee, is set to be appointed to the Graduate School of AI at Yonsei University and will continue pursuing research in robot learning.
Paper title: Furniture Bench: Reproducible Real-World Benchmark for Long-Horizon Complex Manipulation. Robotics: Science and Systems.
< Image. Conceptual Summary of the 3D Printing Technology >
2023.07.31 View 5294 -
KAIST presents a microbial cell factory as a source of eco-friendly food and cosmetic coloring
Despite decades of global population growth, global food crisis seems to be at hand yet again because the food productivity is cut severely due to prolonged presence of abnormal weather from intensifying climate change and global food supply chain is deteriorated due to international conflicts such as wars exacerbating food shortages and nutritional inequality around the globe. At the same time, however, as awareness of the environment and sustainability rises, an increase in demand for more eco-friendly and high-quality food and beauty products is being observed not without a sense of irony. At a time like this, microorganisms are attracting attention as a key that can handle this couple of seemingly distant problems.
KAIST (President Kwang-Hyung Lee) announced on the 26th that Kyeong Rok Choi, a research professor of the Bioprocess Research Center and Sang Yup Lee, a Distinguished Professor of the Department of Chemical and Biomolecular Engineering, published a paper titled “Metabolic Engineering of Microorganisms for Food and Cosmetics Production” upon invitation by “Nature Reviews Bioengineering” to be published online published by Nature after peer review.
※ Paper title: Systems metabolic engineering of microorganisms for food and cosmetics production
※ Author information: Kyeong Rok Choi (first author) and Sang Yup Lee (corresponding author)
Systems metabolic engineering is a research field founded by Distinguished Professor Sang Yup Lee of KAIST to more effectively develop microbial cell factories, the core factor of the next-generation bio industry to replace the existing chemical industry that relies heavily on petroleum. By applying a systemic metabolic engineering strategy, the researchers have developed a number of high-performance microbial cell factories that produce a variety of food and cosmetic compounds including natural substances like heme and zinc protoporphyrin IX compounds which can improve the flavor and color of synthetic meat, lycopene and β-carotene which are functional natural pigments that can be widely used in food and cosmetics, and methyl anthranilate, a grape-derived compound widely used to impart grape flavor in food and beverage manufacturing.
In this paper written upon invitation by Nature, the research team covered remarkable cases of microbial cell factory that can produce amino acids, proteins, fats and fatty acids, vitamins, flavors, pigments, alcohols, functional compounds and other food additives used in various foods and cosmetics and the companies that have successfully commercialized these microbial-derived materials Furthermore, the paper organized and presents systems metabolic engineering strategies that can spur the development of industrial microbial cell factories that can produce more diverse food and cosmetic compounds in an eco-friendly way with economic feasibility.
< Figure 1. Examples of production of food and cosmetic compounds using microbial cell factories >
For example, by producing proteins or amino acids with high nutritional value through non-edible biomass used as animal feed or fertilizer through the microbial fermentation process, it will contribute to the increase in production and stable supply of food around the world. Furthermore, by contributing to developing more viable alternative meat, further reducing dependence on animal protein, it can also contribute to reducing greenhouse gases and environmental pollution generated through livestock breeding or fish farming.
In addition, vanillin or methyl anthranilate, which give off vanilla or grape flavor, are widely added to various foods, but natural products isolated and refined from plants are low in production and high in production cost, so in most cases, petrochemicals substances derived from vanillin and methylanthranilic acid are added to food. These materials can also be produced through an eco-friendly and human-friendly method by borrowing the power of microorganisms.
Ethical and resource problems that arise in producing compounds like Calmin (cochineal pigment), a coloring added to various cosmetics and foods such as red lipstick and strawberry-flavored milk, which must be extracted from cochineal insects that live only in certain cacti. and Hyaluronic acid, which is widely consumed as a health supplement, but is only present in omega-3 fatty acids extracted from shark or fish livers, can also be resolved when they can be produced in an eco-friendly way using microorganisms.
KAIST Research Professor Kyeong Rok Choi, the first author of this paper, said, “In addition to traditional fermented foods such as kimchi and yogurt, foods produced with the help of microorganisms like cocoa butter, a base ingredient for chocolate that can only be obtained from fermented cacao beans, and monosodium glutamate, a seasoning produced through microbial fermentation are already familiar to us”. “In the future, we will be able to acquire a wider variety of foods and cosmetics even more easily produced in an eco-friendly and sustainable way in our daily lives through microbial cell factories.” he added.
< Figure 2. Systems metabolic engineering strategy to improve metabolic flow in microbial cell factories >
Distinguished Professor Sang Yup Lee said, “It is engineers’ mission to make the world a better place utilizing science and technology.” and added, “Continuous advancement and active use of systems metabolic engineering will contribute greatly to easing and resolving the problems arising from both the food crisis and the climate change."
This research was carried out as a part of the “Development of Protein Production Technology from Inorganic Substances through Control of Microbial Metabolism System Project” (Project Leader: Kyeong Rok Choi, KAIST Research Professor) of the the Center for Agricultural Microorganism and Enzyme (Director Pahn-Shick Chang) supported by the Rural Development Administration and the “Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project” (Project Leader: Sang Yup Lee, KAIST Distinguished Professor) of the Petroleum-Substitute Eco-friendly Chemical Technology Development Program supported by the Ministry of Science and ICT.
2023.07.28 View 4939