Sang+Yup+Lee
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KAIST provides a comprehensive resource on microbial cell factories for sustainable chemical production
In silico analysis of five industrial microorganisms identifies optimal strains and metabolic engineering strategies for producing 235 valuable chemicals
Climate change and the depletion of fossil fuels have raised the global need for sustainable chemical production. In response to these environmental challenges, microbial cell factories are gaining attention as eco-friendly platforms for producing chemicals using renewable resources, while metabolic engineering technologies to enhance these cell factories are becoming crucial tools for maximizing production efficiency. However, difficulties in selecting suitable microbial strains and optimizing complex metabolic pathways continue to pose significant obstacles to practical industrial applications.
KAIST (President Kwang-Hyung Lee) announced on 27th of March that Distinguished Professor Sang Yup Lee’s research team in the Department of Chemical and Biomolecular Engineering comprehensively evaluated the production capabilities of various industrial microbial cell factories using in silico simulations and, based on these findings, identified the most suitable microbial strains for producing specific chemicals as well as optimal metabolic engineering strategies.
Previously, researchers attempted to determine the best strains and efficient metabolic engineering strategies among numerous microbial candidates through extensive biological experiments and meticulous verification processes. However, this approach required substantial time and costs. Recently, the introduction of genome-scale metabolic models (GEMs), which reconstruct the metabolic networks within an organism based on its entire genome information, has enabled systematic analysis of metabolic fluxes via computer simulations. This development offers a new way to overcome limitations of conventional experimental approaches, revolutionizing both strain selection and metabolic pathway design.
Accordingly, Professor Lee’s team at the Department of Chemical and Biomolecular Engineering, KAIST, evaluated the production capabilities of five representative industrial microorganisms—Escherichia coli, Saccharomyces cerevisiae, Bacillus subtilis, Corynebacterium glutamicum, and Pseudomonas putida—for 235 bio-based chemicals. Using GEMs, the researchers calculated both the maximum theoretical yields and the maximum achievable yields under industrial conditions for each chemical, thereby establishing criteria to identify the most suitable strains for each target compound.
< Figure 1. Outline of the strategy for improving microbial cell factories using a genome-scale metabolic model (GEM) >
The team specifically proposed strategies such as introducing heterologous enzyme reactions derived from other organisms and exchanging cofactors used by microbes to expand metabolic pathways. These strategies were shown to increase yields beyond the innate metabolic capacities of the microorganisms, resulting in higher production of industrially important chemicals such as mevalonic acid, propanol, fatty acids, and isoprenoids.
Moreover, by applying a computational approach to analyze metabolic fluxes in silico, the researchers suggested strategies for improving microbial strains to maximize the production of various chemicals. They quantitatively identified the relationships between specific enzyme reactions and target chemical production, as well as the relationships between enzymes and metabolites, determining which enzyme reactions should be up- or down-regulated. Through this, the team presented strategies not only to achieve high theoretical yields but also to maximize actual production capacities.
< Figure 2. Comparison of production routes and maximum yields of useful chemicals using representative industrial microorganisms >
Dr. Gi Bae Kim, the first author of this paper from the KAIST BioProcess Engineering Research Center, explained, “By introducing metabolic pathways derived from other organisms and exchanging cofactors, it is possible to design new microbial cell factories that surpass existing limitations. The strategies presented in this study will play a pivotal role in making microbial-based production processes more economical and efficient.” In addition, Distinguished Professor Sang Yup Lee noted, “This research serves as a key resource in the field of systems metabolic engineering, reducing difficulties in strain selection and pathway design, and enabling more efficient development of microbial cell factories. We expect it to greatly contribute to the future development of technologies for producing various eco-friendly chemicals, such as biofuels, bioplastics, and functional food materials.”
This research was conducted with the support from the Development of platform technologies of microbial cell factories for the next-generation biorefineries project and Development of advanced synthetic biology source technologies for leading the biomanufacturing industry project (Project Leader: Distinguished Professor Sang Yup Lee, KAIST) from National Research Foundation supported by the Korean Ministry of Science and ICT.
2025.03.27 View 256 -
KAIST Develops Eco-Friendly, Nylon-Like Plastic Using Microorganisms
Poly(ester amide) amide is a next-generation material that combines the advantages of PET (polyester) and nylon (polyamide), two widely used plastics. However, it could only be produced from fossil fuels, which posed environmental concerns. Using microorganisms, KAIST researchers have successfully developed a new bio-based plastic to replace conventional plastic.
KAIST (represented by President Kwang Hyung Lee) announced on the 20th of March that a research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering has developed microbial strains through systems metabolic engineering to produce various eco-friendly, bio-based poly(ester amide)s. The team collaborated with researchers from the Korea Research Institute of Chemical Technology (KRICT, President Young-Kook Lee) to analyze and confirm the properties of the resulting plastic.
Professor Sang Yup Lee’s research team designed new metabolic pathways that do not naturally exist in microorganisms, and developed a platform microbial strain capable of producing nine different types of poly(ester amide)s, including poly(3-hydroxybutyrate-ran-3-aminopropionate) and poly(3-hydroxybutyrate-ran-4-aminobutyrate).
Using glucose derived from abundant biomass sources such as waste wood and weeds, the team successfully produced poly(ester amide)s in an eco-friendly manner. The researchers also confirmed the potential for industrial-scale production by demonstrating high production efficiency (54.57 g/L) using fed-batch fermentation of the engineered strain.
In collaboration with researchers Haemin Jeong and Jihoon Shin from KRICT, the KAIST team analyzed the properties of the bio-based plastic and found that it exhibited characteristics similar to high-density polyethylene (HDPE). This means the new plastic is not only eco-friendly but also strong and durable enough to replace conventional plastics.
The engineered strains and strategies developed in this study are expected to be useful not only for producing various poly(ester amide)s but also for constructing metabolic pathways for the biosynthesis of other types of polymers.
Professor Sang Yup Lee stated, “This study is the first to demonstrate the possibility of producing poly(ester amide)s (plastics) through a renewable bio-based chemical process rather than relying on the petroleum-based chemical industry. We plan to further enhance the production yield and efficiency through continued research.”
The study was published online on March 17 in the international journal Nature Chemical Biology.
·Title: Biosynthesis of poly(ester amide)s in engineered Escherichia coli
·DOI: 10.1038/s41589-025-01842-2
·Authors: A total of seven authors including Tong Un Chae (KAIST, first author), So Young Choi (KAIST, second author), Da-Hee Ahn (KAIST, third author), Woo Dae Jang (KAIST, fourth author), Haemin Jeong (KRICT, fifth author), Jihoon Shin (KRICT, sixth author), and Sang Yup Lee (KAIST, corresponding author).
This research was supported by the Ministry of Science and ICT (MSIT) under the Eco-Friendly Chemical Technology Development Project as part of the "Next-Generation Biorefinery Technology Development to Lead the Bio-Chemical Industry" initiative (project led by Distinguished Professor Sang Yup Lee at KAIST).
2025.03.24 View 746 -
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 5506 -
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 4042 -
KAIST Develops Microbial Liquid Egg Substitute
A team of researchers published a paper on developing a substitute for eggs using microorganisms, grabbing international attention. It is expected that the development of egg substitutes using non-animal raw materials will solve the problems of factory farming, which causes problems like increased emission of greenhouse gas and waste, and contribute to building a sustainable food system that allows easy protein intake.
KAIST (President Kwang-Hyung Lee) announced that Research Professor Kyeong Rok Choi from the Biological Process Research Center and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering have published a paper on the development of an "Eco-Friendly Liquid Egg Substitute Derived from Microorganisms."
Eggs play a crucial role in various culinary applications due to their unique physicochemical properties such as gelling, foaming, and emulsifying, while also providing essential nutrients. However, traditional egg production is not only unethical and resource-intensive but also has significant environmental impacts such as greenhouse gas emissions and waste issues. Additionally, factors such as wars and trade regulations have led to significant increases in egg prices, highlighting food security concerns. In response to these issues, there has been growing interest in egg substitutes made from non-animal sources to establish a sustainable food system.
Although there has been progress in developing non-animal protein-based egg substitutes, no substitute has been able to fully replicate the essential functional properties of liquid eggs, such as gelling and foaming, while also providing complete nutrition. In this context, the research team aimed to develop a liquid egg substitute using microbial biomass, which has a protein content comparable to that of meat per unit dry mass. Various microorganisms, such as yeast, Bacillus, lactic acid bacteria, and other probiotics, have been proven safe through long-term human consumption. Microbial biomass requires fewer resources like water and land during production, and possesses high-quality nutrients, making it a promising sustainable food resource.
< Figure 1. Comparison of heat treatment results of microbial pellets and microbial lysates >
However, the semi-solid microbial biomass recovered through microbial cultivation was observed to turn liquid upon heating, unlike liquid egg. To address this, the research team devised a microbial lysate by breaking down the cell walls and cell membranes of microorganisms, which correspond to the eggshell. They found that the microbial lysate's proteins coagulated when heated and formed a gel similar to that of liquid egg. The gel formed from the heated microbial lysate was found to have microscopic structures and physical properties similar to those of boiled eggs. The addition of microbial-derived edible enzymes or plant-based materials allowed for the adjustment of its properties, enabling the creation of various textures.
Furthermore, the researchers demonstrated that the microbial lysate could form stable foams widely used in baking, such as meringues (made from egg whites). They successfully baked meringue cookies using this lysate, showing its potential as a functional liquid egg substitute.
Distinguished Professor Sang Yup Lee stated, "This substitute has excellent nutritional components, making it suitable for regular food consumption. It is especially promising as emergency food for long-term space travel, wartime situations, and other emergencies. More importantly, it contributes to securing a sustainable food system."
< Figure 2. Example of foaming ability of microbial lysate and meringue cookie production >
< Figure 3. Example of foaming ability of microbial lysate and meringue cookie production >
The paper was published online in the journal npj Science of Food, issued by Nature.
- Paper Title: Microbial lysates repurposed as liquid egg substitutes
- Authors: Kyeong Rok Choi (first author), Da-Hee Ahn, Seok Yeong Jung, YuHyun Lee, and Sang Yup Lee (corresponding author)
This research was supported by the Ministry of Science and ICT's project for developing eco-friendly chemical technologies to replace petroleum (Project Leader: Distinguished Professor Sang Yup Lee, KAIST) and the Rural Development Administration's Agricultural Microorganisms Project Group (Director: Professor Pan-sik Jang, Seoul National University) for developing protein production technology from inorganic substances through microbial metabolic system control (Project Leader: Research Professor Kyeong Rok Choi, KAIST).
2024.07.05 View 4841 -
KAIST introduces microbial food as a strategy food production of the future
The global food crisis is increasing due to rapid population growth and declining food productivity to climate change. Moreover, today's food production and supply system emit a huge amount of carbon dioxide, reaching 30% of the total amount emitted by humanity, aggravating climate change. Sustainable and nutritious microbial food is attracting attention as a key to overcoming this impasse.
KAIST (President Kwang Hyung Lee) announced on April 12th that Research Professor Kyeong Rok Choi of the BioProcess Engineering Research Center and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering published a paper that proposes a direction of research on ‘microbial food production from sustainable raw materials.’
Microbial food refers to various foods and food ingredients produced using microorganisms. Microbial biomass contains a large amount of protein per unit in dry mass, comparable to that of meat, and emits the smallest amount of carbon dioxide and is required to produce a unit mass compared to various livestock, fish, shellfish, and crops. Since the amount of water and space requirement is small, it can be an eco-friendly, sustainable and highly nutritious food resource.
Fermented foods are the most readily available microbial foods around us. Although the proportion of microbial biomass in fermented foods is small, compounds with relatively low nutritional value, such as carbohydrates, are consumed during the fermentation process, and as microorganisms proliferate, the content of nutrients with higher nutritional value, such as proteins and vitamins, increases.
Various food compounds isolated and purified from biomass or culture media obtained through microbial culture are also a branch of microbial food. Examples that can be found around us include various amino acids, including monosodium glutamate, food proteins, enzymes, flavoring compounds, food colorings, and bioactive substances.
< Figure 1. Schematic diagram portraying various microbial biomass production strategies utlizing sustainable feedstocks >
Lastly, the most ultimate and fundamental form of microbial food can be said to be microbial biomass or extracts produced through microbial culture and foods cooked using them. A representative example is single-cell protein, which collectively refers to microbial biomass or microbial proteins extracted from it.
In this paper, the researchers comprehensively covered various non-edible raw materials and strategies for using them that can be used to produce microbial food in a more sustainable way. Furthermore, it covers various microbial foods that are actually produced in the industry using the relevant raw materials and their characteristics, as well as prospects for the production and generalization of sustainable microbial foods.
Research Professor Kyeong Rok Choi, the first author of this paper, said, “Microbial foods produced from various sustainable raw materials will soon be commonly encountered at our tables.” Second author Seok Yeong Jung, a doctoral student, also said, “Microbial foods of the future will not be limited foods consumed only out of a sense of obligation to the environment, but will be complete foods that are consumed by choice because of their nutritional value and taste.” In addition, Distinguished Professor Sang Yup Lee said, “It is time for the industry and academia, as well as the public and private sectors, to cooperate more closely so that more diverse microbial foods can be developed and supplied in order to create a sustainable society for ourselves and our descendants.”
< Figure 2. Compositions and environmental footprints of animal, plant and microbial biomass. >
This paper was published online on April 9 in ‘Nature Microbiology’ published by Nature.
※ Paper title: From sustainable feedstocks to microbial foods
※ Author information: Kyeong Rok Choi (first author), Seok Yeong Jung (second author) and Sang Yup Lee (corresponding author)
This research was conducted under the development of platform technologies of microbial cell factories for the next-generation biorefineries project (project leader KAIST Distinguished Professor Sang Yup Lee) supported by the Ministry of Science and ICT and the Cooperative Research Program for Agriculture Science and Technology Development (Project leader KAIST Research Professor Kyeong Rok Choi) of the Agricultural Microbiology Project Group (Director, Professor Pahn-Shick Chang) supported by the Rural Development Administration.
2024.04.12 View 5543 -
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 5114 -
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 7161 -
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 5410 -
KAIST introduces eco-friendly technologies for plastic production and biodegradation
- A research team under Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering published a paper in Nature Microbiology on the overview and trends of plastic production and degradation technology using microorganisms.
- Eco-friendly and sustainable plastic production and degradation technology using microorganisms as a core technology to achieve a plastic circular economy was presented.
Plastic is one of the important materials in modern society, with approximately 460 million tons produced annually and with expected production reaching approximately 1.23 billion tons in 2060. However, since 1950, plastic waste totaling more than 6.3 billion tons has been generated, and it is believed that more than 140 million tons of plastic waste has accumulated in the aquatic environment. Recently, the seriousness of microplastic pollution has emerged, not only posing a risk to the marine ecosystem and human health, but also worsening global warming by inhibiting the activity of marine plankton, which play an important role in lowering the Earth's carbon dioxide concentration.
KAIST President Kwang-Hyung Lee announced on December 11 that a research team under Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering had published a paper titled 'Sustainable production and degradation of plastics using microbes', which covers the latest technologies for producing plastics and processing waste plastics in an eco-friendly manner using microorganisms.
As the international community moves to solve this plastic problem, various efforts are being made, including 175 countries participating to conclude a legally binding agreement with the goal of ending plastic pollution by 2024. Various technologies are being developed for sustainable plastic production and processing, and among them, biotechnology using microorganisms is attracting attention.
Microorganisms have the ability to naturally produce or decompose certain compounds, and this ability is maximized through biotechnologies such as metabolic engineering and enzyme engineering to produce plastics from renewable biomass resources instead of fossil raw materials and to decompose waste plastics.
Accordingly, the research team comprehensively analyzed the latest microorganism-based technologies for the sustainable production and decomposition of plastics and presented how they actually contribute to solving the plastic problem. Based on this, they presented limitations, prospects, and research directions of the technologies for achieving a circular economy for plastics.
Microorganism-based technologies for various plastics range from widely used synthetic plastics such as polyethylene (PE) to promising bioplastics such as natural polymers derived from microorganisms (polyhydroxyalkanoate (PHA)) that are completely biodegradable in the natural environment and do not pose a risk of microplastic generation. Commercialization statuses and latest technologies were also discussed. In addition, the technology to decompose these plastics using microorganisms and their enzymes and the upcycling technology to convert them into other useful compounds after decomposition were introduced, highlighting the competitiveness and potential of technology using microorganisms.
First author So Young Choi, a research assistant professor in the Department of Chemical and Biomolecular Engineering at KAIST, said, “In the future, we will be able to easily find eco-friendly plastics made using microorganisms all around us,” and corresponding author Distinguished Professor Sang Yup Lee said, “Plastic can be made more sustainable. It is important to use plastics responsibly to protect the environment and simultaneously achieve economic and social development through the new plastics industry, and we look forward to the improved performance of microbial metabolic engineering technology.”
This paper was published on November 30th in the online edition of Nature Microbiology.
※ Paper Title : Sustainable production and degradation of plastics using microbes
Authors: So Young Choi, Youngjoon Lee, Hye Eun Yu, In Jin Cho, Minju Kang & Sang Yup Lee
2023.12.11 View 5457 -
KAIST-UCSD researchers build an enzyme discovering AI
- A joint research team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering and Bernhard Palsson of UCSD developed ‘DeepECtransformer’, an artificial intelligence that can predict Enzyme Commission (EC) number of proteins.
- The AI is tasked to discover new enzymes that have not been discovered yet, which would allow prediction for a total of 5,360 types of Enzyme Commission (EC) numbers
- It is expected to be used in the development of microbial cell factories that produce environmentally friendly chemicals as a core technology for analyzing the metabolic network of a genome.
While E. coli is one of the most studied organisms, the function of 30% of proteins that make up E. coli has not yet been clearly revealed. For this, an artificial intelligence was used to discover 464 types of enzymes from the proteins that were unknown, and the researchers went on to verify the predictions of 3 types of proteins were successfully identified through in vitro enzyme assay.
KAIST (President Kwang-Hyung Lee) announced on the 24th that a joint research team comprised of Gi Bae Kim, Ji Yeon Kim, Dr. Jong An Lee and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST, and Dr. Charles J. Norsigian and Professor Bernhard O. Palsson of the Department of Bioengineering at UCSD has developed DeepECtransformer, an artificial intelligence that can predict the enzyme functions from the protein sequence, and has established a prediction system by utilizing the AI to quickly and accurately identify the enzyme function.
Enzymes are proteins that catalyze biological reactions, and identifying the function of each enzyme is essential to understanding the various chemical reactions that exist in living organisms and the metabolic characteristics of those organisms. Enzyme Commission (EC) number is an enzyme function classification system designed by the International Union of Biochemistry and Molecular Biology, and in order to understand the metabolic characteristics of various organisms, it is necessary to develop a technology that can quickly analyze enzymes and EC numbers of the enzymes present in the genome.
Various methodologies based on deep learning have been developed to analyze the features of biological sequences, including protein function prediction, but most of them have a problem of a black box, where the inference process of AI cannot be interpreted. Various prediction systems that utilize AI for enzyme function prediction have also been reported, but they do not solve this black box problem, or cannot interpret the reasoning process in fine-grained level (e.g., the level of amino acid residues in the enzyme sequence).
The joint team developed DeepECtransformer, an AI that utilizes deep learning and a protein homology analysis module to predict the enzyme function of a given protein sequence. To better understand the features of protein sequences, the transformer architecture, which is commonly used in natural language processing, was additionally used to extract important features about enzyme functions in the context of the entire protein sequence, which enabled the team to accurately predict the EC number of the enzyme. The developed DeepECtransformer can predict a total of 5360 EC numbers.
The joint team further analyzed the transformer architecture to understand the inference process of DeepECtransformer, and found that in the inference process, the AI utilizes information on catalytic active sites and/or the cofactor binding sites which are important for enzyme function. By analyzing the black box of DeepECtransformer, it was confirmed that the AI was able to identify the features that are important for enzyme function on its own during the learning process.
"By utilizing the prediction system we developed, we were able to predict the functions of enzymes that had not yet been identified and verify them experimentally," said Gi Bae Kim, the first author of the paper. "By using DeepECtransformer to identify previously unknown enzymes in living organisms, we will be able to more accurately analyze various facets involved in the metabolic processes of organisms, such as the enzymes needed to biosynthesize various useful compounds or the enzymes needed to biodegrade plastics." he added.
"DeepECtransformer, which quickly and accurately predicts enzyme functions, is a key technology in functional genomics, enabling us to analyze the function of entire enzymes at the systems level," said Professor Sang Yup Lee. He added, “We will be able to use it to develop eco-friendly microbial factories based on comprehensive genome-scale metabolic models, potentially minimizing missing information of metabolism.”
The joint team’s work on DeepECtransformer is described in the paper titled "Functional annotation of enzyme-encoding genes using deep learning with transformer layers" written by Gi Bae Kim, Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering of KAIST and their colleagues. The paper was published via peer-review on the 14th of November on “Nature Communications”.
This research was conducted with the support by “the Development of next-generation biorefinery platform technologies for leading bio-based chemicals industry project (2022M3J5A1056072)” and by “Development of platform technologies of microbial cell factories for the next-generation biorefineries project (2022M3J5A1056117)” from National Research Foundation supported by the Korean Ministry of Science and ICT (Project Leader: Distinguished Professor Sang Yup Lee, KAIST).
< Figure 1. The structure of DeepECtransformer's artificial neural network >
2023.11.24 View 4565 -
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 6329