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KAIST Unveils New Possibilities for Treating Intractable Brain Tumors
< Photo 1. (From left) Professor Heung Kyu Lee, KAIST Department of Biological Sciences, and Dr. Keun Bon Ku >
Immunotherapy, which enhances the immune system's T cell response to eliminate cancer cells, has emerged as a key approach in cancer treatment. However, in the case of glioblastoma, an aggressive and treatment-resistant brain tumor, numerous clinical trials have failed to confirm their efficacy. Korean researchers have recently analyzed the mechanisms that cause T cell exhaustion, which is characterized by a loss of function or a weakened response following prolonged exposure to antigens in such intractable cancers, identifying key control factors in T cell activation and clarifying the mechanisms that enhance therapeutic effectiveness.
KAIST (represented by President Kwang Hyung Lee) announced on the 6th of November that Professor Heung Kyu Lee’s team from the Department of Biological Sciences, in collaboration with the Korea Research Institute of Chemical Technology (represented by President Young Kuk Lee), has confirmed improved survival rates in a glioblastoma mouse model. By removing the inhibitory Fc gamma receptor (FcγRIIB), the research team was able to restore the responsiveness of cytotoxic T cells to immune checkpoint inhibitors, leading to enhanced anticancer activity.
The research team examined the effect of FcγRIIB, an inhibitory receptor recently found in cytotoxic T cells, on tumor-infiltrating T cells and the therapeutic effectiveness of the anti-PD-1 immune checkpoint inhibitor.
< Figure 1. Study results on improved survival rate due to increased antitumor activity of anti-PD-1 treatment in inhibitory Fc gamma receptor(Fcgr2b) ablation mice with murine glioblastoma. >
Their findings showed that deleting FcγRIIB induced the increase of tumor antigen-specific memory T cells, which helps to suppress exhaustion, enhances stem-like qualities, and reactivates T cell-mediated antitumor immunity, particularly in response to anti-PD-1 treatment. Furthermore, FcγRIIB deletion led to an increase in antigen-specific memory T cells that maintained continuous infiltration into the tumor tissue.
This study presents a new therapeutic target for tumors unresponsive to immune checkpoint inhibitors and demonstrates that combining FcγRIIB inhibition with anti-PD-1 treatment can produce synergistic effects, potentially improving therapeutic outcomes for tumors like glioblastoma, which typically show resistance to anti-PD-1 therapy.
< Figure 2. Overview of the study on the enhanced response to anti-PD-1 therapy for glioblastoma brain tumors upon deletion of the inhibitory Fc gamma receptor (FcγRIIB) in tumor microenvironment. When the inhibitory Fc gamma receptor (FcγRIIB) of cytotoxic T cells is deleted, an increase in tumor-specific memory T cells (Ttsms) was observed. In addition, this T cell subset is identified as originating from the tumor-draining lymph nodes(TdLNs) and leads to persistent infiltration into the tumor tissue. Anti-PD-1 therapy leads to an increased anti-tumor immune response via Ttsms, which is confirmed by increased tumor cell toxicity and increased cell division and decreased cell de-migration indices. Ultimately, the increased cytotoxic T cell immune response leads to an increase in the survival rate of glioblastoma. >
Professor Heung Kyu Lee explained, "This study offers a way to overcome clinical failures in treating brain tumors with immune checkpoint therapy and opens possibilities for broader applications to other intractable cancers. It also highlights the potential of utilizing cytotoxic T cells for tumor cell therapy."
The study, led by Dr. Keun Bon Ku of KAIST (currently a senior researcher at the Korea Research Institute of Chemical Technology's Center for Infectious Disease Diagnosis and Prevention), along with Chae Won Kim, Yumin Kim, Byeong Hoon Kang, Jeongwoo La, In Kang, Won Hyung Park, Stephen Ahn, and Sung Ki Lee, was published online on October 26 in the Journal for ImmunoTherapy of Cancer, an international journal in tumor immunology and therapy from the Society for Immunotherapy of Cancer. (Paper title: “Inhibitory Fcγ receptor deletion enhances CD8 T cell stemness increasing anti-PD-1 therapy responsiveness against glioblastoma,” http://dx.doi.org/10.1136/jitc-2024-009449).
This research received support from the National Research Foundation of Korea, the Bio & Medical Technology Development Program, and the Samsung Science & Technology Foundation.
2024.11.15 View 240 -
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 818 -
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 1630 -
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 1873 -
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 3287 -
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 3798 -
A KAIST-SNUH Team Devises a Way to Make Mathematical Predictions to find Metabolites Related to Somatic Mutations in Cancers
Cancer is characterized by abnormal metabolic processes different from those of normal cells. Therefore, cancer metabolism has been extensively studied to develop effective diagnosis and treatment strategies. Notable achievements of cancer metabolism studies include the discovery of oncometabolites* and the approval of anticancer drugs by the U.S. Food and Drug Administration (FDA) that target enzymes associated with oncometabolites. Approved anticancer drugs such as ‘Tibsovo (active ingredient: ivosidenib)’ and ‘Idhifa (active ingredient: enasidenib)’ are both used for the treatment of acute myeloid leukemia. Despite such achievements, studying cancer metabolism, especially oncometabolites, remains challenging due to time-consuming and expensive methodologies such as metabolomics. Thus, the number of confirmed oncometabolites is very small although a relatively large number of cancer-associated gene mutations have been well studied.
*Oncometabolite: A metabolite that shows pro-oncogenic function when abnormally accumulated in cancer cells. An oncometabolite is often generated as a result of gene mutations, and this accumulation promotes the growth and survival of cancer cells. Representative oncometabolites include 2-hydroxyglutarate, succinate, and fumarate.
On March 18th, a KAIST research team led by Professor Hyun Uk Kim from the Department of Chemical and Biomolecular Engineering developed a computational workflow that systematically predicts metabolites and metabolic pathways associated with somatic mutations in cancer through collaboration with research teams under Prof Youngil Koh, Prof. Hongseok Yun, and Prof. Chang Wook Jeong from Seoul National University Hospital.
The research teams have successfully reconstructed patient-specific genome-scale metabolic models (GEMs)* for 1,043 cancer patients across 24 cancer types by integrating publicly available cancer patients’ transcriptome data (i.e., from international cancer genome consortiums such as PCAWG and TCGA) into a generic human GEM. The resulting patient-specific GEMs make it possible to predict each patient’s metabolic phenotypes.
*Genome-scale metabolic model (GEM): A computational model that mathematically describes all of the biochemical reactions that take place inside a cell. It allows for the prediction of the cell’s metabolic phenotypes under various genetic and/or environmental conditions.
< Figure 1. Schematic diagram of a computational methodology for predicting metabolites and metabolic pathways associated with cancer somatic mutations. of a computational methodology for predicting metabolites and metabolic pathways associated with cancer somatic mutations. >
The team developed a four-step computational workflow using the patient-specific GEMs from 1,043 cancer patients and somatic mutation data obtained from the corresponding cancer patients. This workflow begins with the calculation of the flux-sum value of each metabolite by simulating the patient-specific GEMs. The flux-sum value quantifies the intracellular importance of a metabolite. Next, the workflow identifies metabolites that appear to be significantly associated with specific gene mutations through a statistical analysis of the predicted flux-sum data and the mutation data. Finally, the workflow selects altered metabolic pathways that significantly contribute to the biosynthesis of the predicted oncometabolite candidates, ultimately generating metabolite-gene-pathway sets as an output.
The two co-first authors, Dr. GaRyoung Lee (currently a postdoctoral fellow at the Dana-Farber Cancer Institute and Harvard Medical School) and Dr. Sang Mi Lee (currently a postdoctoral fellow at Harvard Medical School) said, “The computational workflow developed can systematically predict how genetic mutations affect cellular metabolism through metabolic pathways. Importantly, it can easily be applied to different types of cancer based on the mutation and transcriptome data of cancer patient cohorts.”
Prof. Kim said, “The computational workflow and its resulting prediction outcomes will serve as the groundwork for identifying novel oncometabolites and for facilitating the development of various treatment and diagnosis strategies”.
This study, which was supported by the National Research Foundation of Korea, has been published online in Genome Biology, a representative journal in the field of biotechnology and genetics, under the title "Prediction of metabolites associated with somatic mutations in cancers by using genome‑scale metabolic models and mutation data".
2024.03.18 View 3271 -
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 3452 -
A KAIST Research Team Observes the Processes of Memory and Cognition in Real Time
The human brain contains approximately 86 billion neurons and 600 trillion synapses that exchange signals between the neurons to help us control the various functions of the brain including cognition, emotion, and memory. Interestingly, the number of synapses decrease with age or as a result of diseases like Alzheimer’s, and research on synapses thus attracts a lot of attention. However, limitations have existed in observing the dynamics of synapse structures in real time.
On January 9, a joint research team led by Professor Won Do Heo from the KAIST Department of Biological Sciences, Professor Hyung-Bae Kwon from Johns Hopkins School of Medicine, and Professor Sangkyu Lee from the Institute for Basic Science (IBS) revealed that they have developed the world’s first technique to allow a real-time observation of synapse formation, extinction, and alterations.
Professor Heo’s team conjugated dimerization-dependent fluorescent proteins (ddFP) to synapses in order to observe the process in which synapses create connections between neurons in real time. The team named this technique SynapShot, by combining the words ‘synapse’ and snapshot’, and successfully tracked and observed the live formation and extinction processes of synapses as well as their dynamic changes.
< Figure 1. To observe dynamically changing synapses, dimerization-dependent fluorescent protein (ddFP) was expressed to observe flourescent signals upon synapse formation as ddFP enables fluorescence detection through reversible binding to pre- and postsynaptic terminals. >
Through a joint research project, the teams led by Professor Heo and Professor Sangkyu Lee at IBS together designed a SynapShot with green and red fluorescence, and were able to easily distinguish the synapse connecting two different neurons. Additionally, by combining an optogenetic technique that can control the function of a molecule using light, the team was able to observe the changes in the synapses while simultaneously inducing certain functions of the neurons using light.
Through more joint research with the team led by Professor Hyung-Bae Kwon at the Johns Hopkins School of Medicine, Professor Heo’s team induced several situations on live mice, including visual discrimination training, exercise, and anaesthesia, and used SynapShot to observe the changes in the synapses during each situation in real time. The observations revealed that each synapse could change fairly quickly and dynamically. This was the first-ever case in which the changes in synapses were observed in a live mammal.
< Figure 2. Microscopic photos observed through changes of the flourescence of the synapse sensor (SynapShot) by cultivating the neurons of an experimental rat and expressing the SynapShot. The changes in the synapse that is created when the pre- and post-synaptic terminals come into contact and the synapse that disappears after a certain period of time are measured by the fluorescence of the SynapShot. >
Professor Heo said, “Our group developed SynapShot through a collaboration with domestic and international research teams, and have opened up the possibility for first-hand live observations of the quick and dynamic changes of synapses, which was previously difficult to do. We expect this technique to revolutionize research methodology in the neurological field, and play an important role in brightening the future of brain science.”
This research, conducted by co-first authors Seungkyu Son (Ph.D. candidate), Jinsu Lee (Ph.D. candidate) and Dr. Kanghoon Jung from Johns Hopkins, was published in the online edition of Nature Methods on January 8 under the title “Real-time visualization of structural dynamics of synapses in live cells in vivo”, and will be printed in the February volume.
< Figure 3. Simultaneous use of green-SynapShot and red-SynapShot to distinguish and observe synapses with one post-terminal and different pre-terminals. >
< Figure 4. Dimer-dependent fluorescent protein (ddFP) exists as a green fluorescent protein as well as a red fluorescent protein, and can be applied together with blue light-activated optogenetic technology. After activating Tropomyosin receptor kinase B (TrkB) by blue light using optogenetic technology, the strengthening of synaptic connections through signals of brain-derived neurotrophic factor is observed using red-SynapShot. >
< Figure 5. Micrographs showing real-time changing synapses in the visual cortex of mice trained through visual training using in vivo imaging techniques such as two-photon microscopy as well as at the cellular level. >
This research was supported by Mid-Sized Research Funds and the Singularity Project from KAIST, and by IBS.
2024.01.18 View 3649 -
A KAIST Research Team Develops High-Performance Stretchable Solar Cells
With the market for wearable electric devices growing rapidly, stretchable solar cells that can function under strain have received considerable attention as an energy source. To build such solar cells, it is necessary that their photoactive layer, which converts light into electricity, shows high electrical performance while possessing mechanical elasticity. However, satisfying both of these two requirements is challenging, making stretchable solar cells difficult to develop.
On December 26, a KAIST research team from the Department of Chemical and Biomolecular Engineering (CBE) led by Professor Bumjoon Kim announced the development of a new conductive polymer material that achieved both high electrical performance and elasticity while introducing the world’s highest-performing stretchable organic solar cell.
Organic solar cells are devices whose photoactive layer, which is responsible for the conversion of light into electricity, is composed of organic materials. Compared to existing non-organic material-based solar cells, they are lighter and flexible, making them highly applicable for wearable electrical devices. Solar cells as an energy source are particularly important for building electrical devices, but high-efficiency solar cells often lack flexibility, and their application in wearable devices have therefore been limited to this point.
The team led by Professor Kim conjugated a highly stretchable polymer to an electrically conductive polymer with excellent electrical properties through chemical bonding, and developed a new conductive polymer with both electrical conductivity and mechanical stretchability. This polymer meets the highest reported level of photovoltaic conversion efficiency (19%) using organic solar cells, while also showing 10 times the stretchability of existing devices. The team thereby built the world’s highest performing stretchable solar cell that can be stretched up to 40% during operation, and demonstrated its applicability for wearable devices.
< Figure 1. Chemical structure of the newly developed conductive polymer and performance of stretchable organic solar cells using the material. >
Professor Kim said, “Through this research, we not only developed the world’s best performing stretchable organic solar cell, but it is also significant that we developed a new polymer that can be applicable as a base material for various electronic devices that needs to be malleable and/or elastic.”
< Figure 2. Photovoltaic efficiency and mechanical stretchability of newly developed polymers compared to existing polymers. >
This research, conducted by KAIST researchers Jin-Woo Lee and Heung-Goo Lee as first co-authors in cooperation with teams led by Professor Taek-Soo Kim from the Department of Mechanical Engineering and Professor Sheng Li from the Department of CBE, was published in Joule on December 1 (Paper Title: Rigid and Soft Block-Copolymerized Conjugated Polymers Enable High-Performance Intrinsically-Stretchable Organic Solar Cells).
This research was supported by the National Research Foundation of Korea.
2024.01.04 View 5009 -
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 3755 -
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 3880