KAIST Produces Eco-Friendly Core Nylon Precursors Used from Clothing to Automobiles with Microbes
<(From Left) Dr. Da-Hee Ahn, Distinguished Professor Sang Yup Lee>
Nylon is a representative plastic material used throughout our daily lives, from clothing to automobiles. However, most of its raw materials have been produced through petrochemical processes, resulting in large carbon emissions. KAIST researchers have developed a technology that can produce key nylon precursors in an eco-friendly way using microbes.
KAIST (President Kwang Hyung Lee) announced on the 31st of May that a research team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering has developed an Escherichia coli-based modular platform capable of producing three key monomers (basic molecular units that make up polymers) of “nylon 6,6” and “nylon 6” — adipic acid, hexamethylenediamine, and epsilon-caprolactam — from “glycerol (an eco-friendly bio-based byproduct generated during biodiesel production),” a renewable carbon source, using systems metabolic engineering (a technology that designs and optimizes microbial metabolic pathways to maximize the production of desired substances).
“Nylon 6” is highly flexible and is used in clothing and films, while “nylon 6,6” has excellent strength and heat resistance and is used in automobiles and machinery parts. The numbers after the nylon name indicate the number of carbon atoms contained in the raw material molecules.
The core of this study is that the biosynthetic pathway was divided into upstream and downstream modules, with E. coli strains assigned different roles. The upstream strain was designed to produce adipic acid from glycerol, while the downstream strain was designed to convert it into hexamethylenediamine or epsilon-caprolactam, respectively. Through this, the research team succeeded in producing adipic acid and hexamethylenediamine, the key raw materials of nylon 6,6, and epsilon-caprolactam, the key raw material of nylon 6, within a single integrated platform.
To improve production efficiency, the researchers compared and validated various enzymes (proteins that promote chemical reactions in living organisms), including carboxylic acid reductases and transaminases, and applied the optimal combination, thereby improving hexamethylenediamine titer. In addition, in the epsilon-caprolactam production process, they designed a flexible-linker fusion enzyme that enhances reaction efficiency through efficient cofactor regeneration.In the upstream module, the team reconstructed the biosynthetic pathway (a series of reaction processes through which compounds are produced in living organisms) and improved the performance of key enzymes using artificial intelligence (AI), increasing production titer. As a result, they succeeded in producing adipic acid at a level of 6 grams per liter (g/L) in a fed-batch fermentation process.
The research team also applied a “delayed inoculation” strategy (time-staggered co-culture), in which the second strain is introduced later after sufficient adipic acid has first been produced, rather than adding the two types of E. coli simultaneously. This is a method of sequentially introducing microbes with different roles at different times.
When this strategy was applied to a fed-batch fermentation process (a fermentation method that increases productivity by supplying nutrients step by step), the team produced 230 milligrams per liter (mg/L) of hexamethylenediamine and 808 micrograms per liter (μg/L) of epsilon-caprolactam using only glycerol. Although the production amounts are not yet high, the research team explained that these results represent world-class performance among cases of direct production from glycerol.
<Schematic Diagram>
This technology is significant in that it presents the possibility of producing nylon raw materials, which have relied on petrochemical processes, through bio-based methods.
The research team plans to further improve titer by combining AI-based enzyme design with additional systems metabolic engineering, and to expand the platform to produce various polymer raw materials (substances formed by the repeated bonding of multiple monomers).
Distinguished Professor Sang Yup Lee stated, “This study is meaningful in that it presents a modular microbial platform capable of producing key monomers required for nylon 6 and nylon 6,6 production from renewable carbon sources,” adding, “We will continue to advance enzyme and metabolic flux engineering to improve titer and develop this into a core platform for sustainably producing various bio-based polymer raw materials.”
The results of this study were published on May 4 in the Proceedings of the National Academy of Sciences (PNAS), with Dr. Da-Hee Ahn of the Department of Chemical and Biomolecular Engineering as the first author.
※ Paper title: “Metabolic engineering of Escherichia coli for the biosynthesis of nylon 6 and nylon 6,6 monomers”
Authors: Sang Yup Lee (KAIST, corresponding author), Da-Hee Ahn (KAIST, first author), Tong Un Chae (KAIST, second author), total of 3 authors
DOI: https://doi.org/10.1073/pnas.2535786123
This research was supported by the “Development of Platform Technologies of Microbial Cell Factories for the Next-Generation Biorefineries” project under the Petroleum Replacement Eco-Friendly Chemical Technology Development Program supported by the Ministry of Science and ICT, and by the “Development of Advanced Synthetic Biology Source Technologies for Leading the Biomanufacturing Industry” project under the Core Synthetic Biology Technology Development Program.
KAIST, Making Pharmaceuticals with Light and Air… Solving a Long-Standing Challenge in Chemical Synthesis
<(From Left) Professor Sang Woo Han, Researcher Jin Wook Baek>
In chemical processes for producing pharmaceuticals, catalysts are the key to determine production speed and cost. However, until now, there has been a trade-off between “precise but disposable catalysts” and “reusable catalysts.” A KAIST research team has developed an eco-friendly catalytic technology that combines these two types, operating with light and air. This opens a pathway to producing pharmaceutical ingredients more cheaply and cleanly, with expected reductions in carbon emissions and environmental pollution.
KAIST (President Kwang Hyung Lee) announced on the 30th of March that a research team led by Professor Sang Woo Han of the Department of Chemistry has succeeded in combining two different types of catalysts into one system. One is a silver (Ag)-based catalyst that operates in a solid state, and the other is an organic photocatalyst, DDQ (a substance that triggers chemical reactions upon absorbing light), which operates in solution. By enabling these two catalysts to function together, the team made it possible to carry out previously difficult reactions more efficiently.
< Schematic diagram of the operation of a heterogeneous–homogeneous hybrid photocatalytic system >
Using this technology, the researchers successfully produced amines—key raw materials for pharmaceuticals—through an environmentally friendly process using light and air. This demonstrated that the desired substances can be synthesized without additional chemical reagents, proving the practicality of the technology.
Conventional organic photocatalysis required additional chemicals to reuse catalysts after reactions, or suffered from reduced efficiency due to slow reaction rates when using oxygen from air.
To address this, the research team proposed a method of reusing byproducts generated during the reaction. These byproducts restore the catalyst to a reusable state, while oxygen in the air helps sustain this cycle. In other words, instead of being used once and discarded, the catalyst regenerates itself and continues operating in a “cyclic system.”
As a result, they established a “cyclic catalytic system” that continues functioning without the need for additional chemical inputs. Notably, this system operates with light and air. Light activates the catalyst to initiate the reaction, while air restores the used catalyst to its active state. In essence, the catalyst continuously “recharges” and operates repeatedly. Since air leaves only water as a byproduct in this process, the environmental burden is significantly reduced.
In addition, to solve the issue of reduced performance when different catalysts interact, the team introduced lithium salt (LiClO₄). This substance helps regulate interactions between the two catalysts, significantly improving their stability and lifespan.
< A hybrid catalyst powered by light and air as energy sources >
Professor Sang Woo Han stated, “This research is the first to successfully integrate an inorganic photochemical loop system—where a metal-based catalyst reacts under light and returns to its original state—into the field of organic synthesis,” adding, “It represents an important advancement that combines the advantages of different catalytic systems to dramatically reduce the carbon footprint of the chemical industry.” He further noted, “It opens a new pathway for producing high-value compounds, such as pharmaceutical ingredients, in the most environmentally friendly way.”
This research was conducted with Jin Wook Baek of the KAIST Department of Chemistry as the first author, and the results were published on March 18 in the Journal of the American Chemical Society (JACS), a leading journal in chemistry.
※ Paper title: “Merger of heterogeneous and homogeneous photocatalysis for arene C–H Amination”
※ DOI: 10.1021/jacs.5c20824
This research was supported by the National Research Foundation of Korea’s Mid-career Researcher Program.
KAIST Develops Bioelectrosynthesis Platform for Switch-Like Precision Control of Cell Signaling
<(From left)Professor Jimin Park, Ph.D candidate Myeongeun Lee, Ph.D cadidate Jaewoong Lee,Professor Jihan Kim>
Cells use various signaling molecules to regulate the nervous, immune, and vascular systems. Among these, nitric oxide (NO) and ammonia (NH₃) play important roles, but their chemical instability and gaseous nature make them difficult to generate or control externally. A KAIST research team has developed a platform that generates specific signaling molecules in situ from a single precursor under an applied electrical signal, enabling switch-like, precise spatiotemporal control of cellular responses. This approach could provide a foundation for future medical technologies such as electroceuticals, electrogenetics, and personalized cell therapies.
KAIST (President Kwang Hyung Lee) announced on August 11 that a research team led by Professor Jimin Park from the Department of Chemical and Biomolecular Engineering, in collaboration with Professor Jihan Kim's group, has developed a 'Bioelectrosynthesis Platform' capable of producing either nitric oxide or ammonia on demand using only an electrical signal. The platform allows control over the timing, spatial range, and duration of cell responses.
Inspired by enzymes involved in nitrite reduction, the researchers implemented an electrochemical strategy that selectively produces nitric oxide or ammonia from a single precursor, nitrite (NO₂⁻). By changing the catalyst, the team generated ammonia or nitric oxide from nitrite using a copper-molybdenum-sulfur catalyst (Cu2MoS4) and an iron-incorporated catalyst (FeCuMS4), respectively.
Through electrochemical measurements and computer simulations, the team revealed that Fe sites in the FeCuMoS4 catalyst bind nitric oxide intermediates more strongly, shifting product selectivity toward nitric oxide. Under the same electrical conditions, the Fe-containing catalyst preferentially produces nitric oxide, whereas the Cu2MoS4 catalyst favors ammonia production.
<Figure 1. Schematic diagram of a bio-electrosynthesis platform that synthesizes a desired signaling substance with an electrical signal (left) and the results of precise cell control using it (right)>
The research team demonstrated biological functionality by using the platform to activate ion channels in human cells. Specifically, electrochemically produced nitric oxide activated TRPV1 channels (responsive to heat and chemical stimuli), while electrochemically produced ammonia induced intracellular alkalinization and activated OTOP1 proton channels. By tuning the applied voltage and electrolysis duration, the team modulated the onset time, spatial extent, and termination of cellular responses, which effectively turned cellular signaling on and off like a switch.
<Figure 2. Experimental results showing the change in the production ratio of nitric oxide and ammonia signaling substances according to the type of catalyst (left) and computational simulation results showing the strong bond between iron and nitric oxide (right)>
Professor Jimin Park said, "This work is significant because it enables precise cellular control by selectively producing signaling molecules with electricity. We believe it has strong potential for applications in electroceutical technologies targeting the nervous system or metabolic disorders."
Myeongeun Lee and Jaewoong Lee, Ph.D. students in the Department of Chemical and Biomolecular Engineering at KAIST, served as the co-first authors. Professor Jihan Kim is a co-author. The paper was published online in 'Angewandte Chemie International Edition' on July 8, 2025 (DOI: 10.1002/ange.202508192).
Reference: https://doi.org/10.1002/ange.202508192
Authors: Myeongeun Lee†, Jaewoong Lee†, Yongha Kim, Changho Lee, Sang Yeon Oh, Prof. Jihan Kim, Prof. Jimin Park*
†These authors contributed equally. *Corresponding author.
KAIST holds its first ‘KAIST Tech Fair’ in New York, USA
< Photo 1. 2023 KAIST Tech Fair in New York >
KAIST (President Kwang-Hyung Lee) announced on the 11th that it will hold the ‘2023 KAIST Tech Fair in New York’ at the Kimmel Center at New York University in Manhattan, USA, on the 22nd of this month. It is an event designed to be the starting point for KAIST to expand its startup ecosystem into the global stage, and it is to attract investments and secure global customers in New York by demonstrating the technological value of KAIST startup companies directly at location.
< Photo 2. President Kwang Hyung Lee at the 2023 KAIST Tech Fair in New York >
KAIST has been holding briefing sessions for technology transfer in Korea every year since 2018, and this year is the first time to hold a tech fair overseas for global companies.
KAIST Institute of Technology Value Creation (Director Sung-Yool Choi) has prepared for this event over the past six months with the Korea International Trade Association (hereinafter KITA, CEO Christopher Koo) to survey customer base and investment companies to conduct market analysis.
Among the companies founded with the technologies developed by the faculty and students of KAIST and their partners, 7 companies were selected to be matched with companies overseas that expressed interests in these technologies. Global multinational companies in the fields of IT, artificial intelligence, environment, logistics, distribution, and retail are participating as demand agencies and are testing the marketability of the start-up's technology as of September.
Daim Research, founded by Professor Young Jae Jang of the Department of Industrial and Systems Engineering, is a company specializing in smart factory automation solutions and is knocking on the door of the global market with a platform technology optimized for automated logistics systems.
< Photo 3. Presentation by Professor Young Jae Jang for DAIM Research >
It is a ‘collaborative intelligence’ solution that maximizes work productivity by having a number of robots used in industrial settings collaborate with one another. The strength of their solution is that logistics robots equipped with AI reinforced learning technology can respond to processes and environmental changes on their own, minimizing maintenance costs and the system can achieve excellent performance even with a small amount of data when it is combined with the digital twin technology the company has developed on its own.
A student startup, ‘Aniai’, is entering the US market, the home of hamburgers, with hamburger patty automation equipments and solutions. This is a robot kitchen startup founded by its CEO Gunpil Hwang, a graduate of KAIST’s School of Electrical Engineering which gathered together the experts in the fields of robot control, design, and artificial intelligence and cognitive technology to develop technology to automatically cook hamburger patties.
At the touch of a button, both sides of the patty are cooked simultaneously for consistent taste and quality according to the set condition. Since it can cook about 200 dishes in an hour, it is attracting attention as a technology that can not only solve manpower shortages but also accelerate the digital transformation of the restaurant industry.
Also, at the tech fair to be held at the Kimmel Center of New York University on the 22nd, the following startups who are currently under market verification in the U.S. will be participating: ▴'TheWaveTalk', which developed a water quality management system that can measure external substances and metal ions by transferring original technology from KAIST; ▴‘VIRNECT’, which helps workers improve their skills by remotely managing industrial sites using XR*; ▴‘Datumo’, a solution that helps process and analyze artificial intelligence big data, ▴‘VESSL AI’, the provider of a solution to eliminate the overhead** of machine learning systems; and ▴ ‘DolbomDream’, which developed an inflatable vest that helps the psychological stability of people with developmental disabilities.
* XR (eXtended Reality): Ultra-realistic technology that enhances immersion by utilizing augmented reality, virtual reality, and mixed reality technologies
** Overhead: Additional time required for stable processing of the program
In addition, two companies (Plasmapp and NotaAI) that are participating in the D-Unicorn program with the support of the Daejeon City and two companies (Enget and ILIAS Biologics) that are receiving support from the Scale Up Tips of the Ministry of SMEs and Startups, three companies (WiPowerOne, IDK Lab, and Artificial Photosynthesis Lab) that are continuing to realize the sustainable development goals for a total of 14 KAIST startups, will hold a corporate information session with about 100 invited guests from global companies and venture capital.
< Photo 4. Presentation for AP Lab >
Prior to this event, participating startups will be visiting the New York Economic Development Corporation and large law firms to receive advice on U.S. government support programs and on their attemps to enter the U.S. market. In addition, the participating companies plan to visit a startup support investment institution pursuing sustainable development goals and the Leslie eLab, New York University's one-stop startup support space, to lay the foundation for KAIST's leap forward in global technology commercialization.
< Photo 5. Sung-Yool Choi, the Director of KAIST Institute of Technology Value Creation (left) at the 2023 KAIST Tech Fair in New York with the key participants >
Sung-Yool Choi, the Director of KAIST Institute of Technology Value Creation, said, “KAIST prepared this event to realize its vision of being a leading university in creating global value.” He added, “We hope that our startups founded with KAIST technology would successfully completed market verification to be successful in securing global demands and in attracting investments for their endeavors.”
A biohybrid system to extract 20 times more bioplastic from CO2 developed by KAIST researchers
As the issues surrounding global climate change intensify, more attention and determined efforts are required to re-grasp the issue as a state of “crisis” and respond to it properly. Among the various methods of recycling CO2, the electrochemical CO2 conversion technology is a technology that can convert CO2 into useful chemical substances using electrical energy. Since it is easy to operate facilities and can use the electricity from renewable sources like the solar cells or the wind power, it has received a lot of attention as an eco-friendly technology can contribute to reducing greenhouse gases and achieve carbon neutrality.
KAIST (President Kwang Hyung Lee) announced on the 30th that the joint research team led by Professor Hyunjoo Lee and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering succeeded in developing a technology that produces bioplastics from CO2 with high efficiency by developing a hybrid system that interlinked the electrochemical CO2 conversion and microbial bio conversion methods together. The results of the research, which showed the world's highest productivity by more than 20 times compared to similar systems, were published online on March 27th in the "Proceedings of the National Academy of Sciences (PNAS)".
※ Paper title: Biohybrid CO2 electrolysis for the direct synthesis of polyesters from CO2
※ Author information: Jinkyu Lim (currently at Stanford Linear Accelerator Center, co-first author), So Young Choi (KAIST, co-first author), Jae Won Lee (KAIST, co-first author), Hyunjoo Lee (KAIST, corresponding author), Sang Yup Lee (KAIST, corresponding author)
For the efficient conversion of CO2, high-efficiency electrode catalysts and systems are actively being developed. As conversion products, only compounds containing one or up to three carbon atoms are produced on a limited basis. Compounds of one carbon, such as CO, formic acid, and ethylene, are produced with relatively high efficiency. Liquid compounds of several carbons, such as ethanol, acetic acid, and propanol, can also be produced by these systems, but due to the nature of the chemical reaction that requires more electrons, there are limitations involving the conversion efficiency and the product selection.
Accordingly, a joint research team led by Professor Hyunjoo Lee and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST developed a technology to produce bioplastics from CO2 by linking electrochemical conversion technology with bioconversion method that uses microorganisms.
This electrochemical-bio hybrid system is in the form of having an electrolyzer, in which electrochemical conversion reactions occur, connected to a fermenter, in which microorganisms are cultured. When CO2 is converted to formic acid in the electrolyzer, and it is fed into the fermenter in which the microbes like the Cupriavidus necator, in this case, consumes the carbon source to produce polyhydroxyalkanoate (PHA), a microbial-derived bioplastic.
According to the research results of the existing hybrid concepts, there was a disadvantage of having low productivity or stopping at a non-continuous process due to problems of low efficiency of the electrolysis and irregular results arising from the culturing conditions of the microbes.
In order to overcome these problems, the joint research team made formic acid with a gas diffusion electrode using gaseous CO2. In addition, the team developed a 'physiologically compatible catholyte' that can be used as a culture medium for microorganisms as well as an electrolyte that allows the electrolysis to occur sufficiently without inhibiting the growth of microorganisms, without having to have a additional separation and purification process, which allowed the acide to be supplied directly to microorganisms.
Through this, the electrolyte solution containing formic acid made from CO2 enters the fermentation tank, is used for microbial culture, and enters the electrolyzer to be circulated, maximizing the utilization of the electrolyte solution and remaining formic acid. In addition, a filter was installed to ensure that only the electrolyte solution with any and all microorganisms that can affect the electrosis filtered out is supplied back to the electrolyzer, and that the microorganisms exist only in the fermenter, designing the two system to work well together with utmost efficiency.
Through the developed hybrid system, the produced bioplastic, poly-3-hydroxybutyrate (PHB), of up to 83% of the cell dry weight was produced from CO2, which produced 1.38g of PHB from a 4 cm2 electrode, which is the world's first gram(g) level production and is more than 20 times more productive than previous research. In addition, the hybrid system is expected to be applied to various industrial processes in the future as it shows promises of the continuous culture system.
The corresponding authors, Professor Hyunjoo Lee and Distinguished Professor Sang Yup Lee noted that “The results of this research are technologies that can be applied to the production of various chemical substances as well as bioplastics, and are expected to be used as key parts needed in achieving carbon neutrality in the future.”
This research was received and performed with the supports from the CO2 Reduction Catalyst and Energy Device Technology Development Project, the Heterogeneous Atomic Catalyst Control Project, and the Next-generation Biorefinery Source Technology Development Project to lead the Biochemical Industry of the Oil-replacement Eco-friendly Chemical Technology Development Program by the Ministry of Science and ICT.
Figure 1. Schematic diagram and photo of the biohybrid CO2 electrolysis system.
(A) A conceptual scheme and (B) a photograph of the biohybrid CO2 electrolysis system. (C) A detailed scheme of reaction inside the system. Gaseous CO2 was converted to formate in the electrolyzer, and the formate was converted to PHB by the cells in the fermenter. The catholyte was developed so that it is compatible with both CO2 electrolysis and fermentation and was continuously circulated.
A KAIST Research Team Develops Diesel Reforming Catalyst Enabling Hydrogen Production for Future Mobile Fuel Cells
This catalyst capability allowing stable hydrogen production from commercial diesel is expected to be applied in mobile fuel cell systems in the future hydrogen economy
On August 16, a joint research team led by Professors Joongmyeon Bae and Kang Taek Lee of KAIST’s Department of Mechanical Engineering and Dr. Chan-Woo Lee of Korea Institute of Energy Research (KIER) announced the successful development of a highly active and durable reforming catalyst allowing hydrogen production from commercial diesel.
Fuel reforming is a hydrogen production technique that extracts hydrogen from hydrocarbons through catalytic reactions. Diesel, being a liquid fuel, has a high storage density for hydrogen and is easy to transport and store. There have therefore been continuous research efforts to apply hydrogel supply systems using diesel reformation in mobile fuel cells, such as for auxiliary power in heavy trucks or air-independent propulsion (AIP) systems in submarines.
However, diesel is a mixture of high hydrocarbons including long-chained paraffin, double-bonded olefin, and aromatic hydrocarbons with benzene groups, and it requires a highly active catalyst to effectively break them down. In addition, the catalyst must be extremely durable against caulking and sintering, as they are often the main causes of catalyst degradation. Such challenges have limited the use of diesel reformation technologies to date.
The joint research team successfully developed a highly active and durable diesel reforming catalyst through elution (a heat treatment method used to uniformly grow active metals retained in an oxide support as ions in the form of metal nanoparticles), forming alloy nanoparticles. The design was based on the fact that eluted nanoparticles strongly interact with the support, allowing a high degree of dispersion at high temperatures, and that producing an alloy from dissimilar metals can increase the performance of catalysts through a synergistic effect.
The research team introduced a solution combustion synthesis method to produce a multi-component catalyst with a trace amount of platinum (Pt) and ruthenium (Ru) penetrated into a ceria (CeO2) lattice, which is a structure commonly used as a support for catalysts in redox reactions. When exposed to a diesel reforming reaction environment, the catalyst induces Pt-Ru alloy nanoparticle formation upon Pt and Ru elution onto the support surface.
In addition to the catalyst analysis, the research team also succeeded in characterizing the behaviour of active metal elution and alloy formation from an energetic perspective using a density functional theory-based calculation. In a performance comparison test between the Pt-Ru alloy catalyst against existing single-metal catalysts, the reforming activity was shown to have improved, as it showed a 100% fuel conversion rate even at a low temperature (600oC, compared to the original 800oC). In a long-term durability test (800oC, 200 hours), the catalyst showed commercial stability by successfully producing hydrogen from commercial diesel without performance degradation.
The study was conducted by Ph.D. candidate Jaemyung Lee of KAIST’s Department of Mechanical Engineering as the first author. Ph.D. candidate Changho Yeon of KIER, Dr. Jiwoo Oh of KAIST’s Department of Mechanical Engineering, Dr. Gwangwoo Han of KIER, Ph.D. candidate Jeong Do Yoo of KAIST’s Department of Mechanical Engineering, and Dr. Hyung Joong Yun of the Korea Basic Science Institute contributed as co-authors. Dr. Chan-Woo Lee of KIER and Professors Kang Taek Lee and Joongmyeon Bae of KAIST’s Department of Mechanical Engineering contributed as corresponding authors. The research was published in the online version of Applied Catalysis B: Environmental (IF 24.319, JCR 0.93%) on June 17, under the title “Highly Active and Stable Catalyst with Exsolved PtRu Alloy Nanoparticles for Hydrogen Production via Commercial Diesel Reforming”.
Professor Joongmyeon Bae said, “The fact that hydrogen can be stably produced from commercial diesel makes this a very meaningful achievement, and we look forward to this technology contributing to the active introduction of mobile fuel cell systems in the early hydrogen economy.” He added, “Our approach to catalyst design may be applied not only to reforming reactions, but also in various other fields.”
This research was supported by the National Research Foundation of Korea through funding from the Ministry of Science, ICT and Future Planning.
Figure. Schematic diagram of high-performance diesel reforming catalyst with eluted platinum-ruthenium alloy nanoparticles and long-term durability verification experiment results for commercial diesel reforming reaction
Interactive Map of Metabolical Synthesis of Chemicals
An interactive map that compiled the chemicals produced by biological, chemical and combined reactions has been distributed on the web
- A team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, organized and distributed an all-inclusive listing of chemical substances that can be synthesized using microorganisms
- It is expected to be used by researchers around the world as it enables easy assessment of the synthetic pathway through the web.
A research team comprised of Woo Dae Jang, Gi Bae Kim, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST reported an interactive metabolic map of bio-based chemicals. Their research paper “An interactive metabolic map of bio-based chemicals” was published online in Trends in Biotechnology on August 10, 2022.
As a response to rapid climate change and environmental pollution, research on the production of petrochemical products using microorganisms is receiving attention as a sustainable alternative to existing methods of productions. In order to synthesize various chemical substances, materials, and fuel using microorganisms, it is necessary to first construct the biosynthetic pathway toward desired product by exploration and discovery and introduce them into microorganisms. In addition, in order to efficiently synthesize various chemical substances, it is sometimes necessary to employ chemical methods along with bioengineering methods using microorganisms at the same time. For the production of non-native chemicals, novel pathways are designed by recruiting enzymes from heterologous sources or employing enzymes designed though rational engineering, directed evolution, or ab initio design.
The research team had completed a map of chemicals which compiled all available pathways of biological and/or chemical reactions that lead to the production of various bio-based chemicals back in 2019 and published the map in Nature Catalysis. The map was distributed in the form of a poster to industries and academia so that the synthesis paths of bio-based chemicals could be checked at a glance.
The research team has expanded the bio-based chemicals map this time in the form of an interactive map on the web so that anyone with internet access can quickly explore efficient paths to synthesize desired products. The web-based map provides interactive visual tools to allow interactive visualization, exploration, and analysis of complex networks of biological and/or chemical reactions toward the desired products. In addition, the reported paper also discusses the production of natural compounds that are used for diverse purposes such as food and medicine, which will help designing novel pathways through similar approaches or by exploiting the promiscuity of enzymes described in the map. The published bio-based chemicals map is also available at http://systemsbiotech.co.kr.
The co-first authors, Dr. Woo Dae Jang and Ph.D. student Gi Bae Kim, said, “We conducted this study to address the demand for updating the previously distributed chemicals map and enhancing its versatility.” “The map is expected to be utilized in a variety of research and in efforts to set strategies and prospects for chemical production incorporating bio and chemical methods that are detailed in the map.”
Distinguished Professor Sang Yup Lee said, “The interactive bio-based chemicals map is expected to help design and optimization of the metabolic pathways for the biosynthesis of target chemicals together with the strategies of chemical conversions, serving as a blueprint for developing further ideas on the production of desired chemicals through biological and/or chemical reactions.”
The interactive metabolic map of bio-based chemicals.
Professor Jung Receives the Hansong Science Award
Professor Yousung Jung of the Department of Chemical and Biomolecular Engineering has been selected as the recipient of the 5th Hansong Science Award in Chemistry. The award recognizes young and mid-career scholars who made outstanding achievement in physics, chemistry, and life sciences. Recipients receive 50 million KRW in prize money.
Professor Jung was recognized for finding a new way to predict synthesis potentials when designing data-based materials and molecules through AI-powered inverse technology. Conventionally, new material discovery mainly relied on a method where the new materials were proposed by an expert’s intuition or experimental trial, then synthesized to measure the properties of the material before it was used. However, this method took a lot of time, which resulted in an inefficient discovery process.
Professor Jung’s AI reverse design technology is reported to be more efficient for discovering new materials by finding crystal structures with desired properties using data and AI algorithms.
"AI reverse design technology can accelerate the development of new materials and new drugs," Professor Jung said. "It can be used as an algorithm for future autonomous laboratories implemented by robots, algorithms, and data without human intervention," he added.
Microbial Production of a Natural Red Colorant Carminic Acid
Metabolic engineering and computer-simulated enzyme engineering led to the production of carminic acid, a natural red colorant, from bacteria for the first time
A research group at KAIST has engineered a bacterium capable of producing a natural red colorant, carminic acid, which is widely used for food and cosmetics. The research team reported the complete biosynthesis of carminic acid from glucose in engineered Escherichia coli. The strategies will be useful for the design and construction of biosynthetic pathways involving unknown enzymes and consequently the production of diverse industrially important natural products for the food, pharmaceutical, and cosmetic industries.
Carminic acid is a natural red colorant widely being used for products such as strawberry milk and lipstick. However, carminic acid has been produced by farming cochineals, a scale insect which only grows in the region around Peru and Canary Islands, followed by complicated multi-step purification processes. Moreover, carminic acid often contains protein contaminants that cause allergies so many people are unwilling to consume products made of insect-driven colorants. On that account, manufacturers around the world are using alternative red colorants despite the fact that carminic acid is one of the most stable natural red colorants.
These challenges inspired the metabolic engineering research group at KAIST to address this issue. Its members include postdoctoral researchers Dongsoo Yang and Woo Dae Jang, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering. This study entitled “Production of carminic acid by metabolically engineered Escherichia coli” was published online in the Journal of the American Chemical Society (JACS) on April 2.
This research reports for the first time the development of a bacterial strain capable of producing carminic acid from glucose via metabolic engineering and computer simulation-assisted enzyme engineering. The research group optimized the type II polyketide synthase machinery to efficiently produce the precursor of carminic acid, flavokermesic acid.
Since the enzymes responsible for the remaining two reactions were neither discovered nor functional, biochemical reaction analysis was performed to identify enzymes that can convert flavokermesic acid into carminic acid. Then, homology modeling and docking simulations were performed to enhance the activities of the two identified enzymes. The team could confirm that the final engineered strain could produce carminic acid directly from glucose. The C-glucosyltransferase developed in this study was found to be generally applicable for other natural products as showcased by the successful production of an additional product, aloesin, which is found in aloe leaves.
“The most important part of this research is that unknown enzymes for the production of target natural products were identified and improved by biochemical reaction analyses and computer simulation-assisted enzyme engineering,” says Dr. Dongsoo Yang. He explained the development of a generally applicable C-glucosyltransferase is also useful since C-glucosylation is a relatively unexplored reaction in bacteria including Escherichia coli. Using the C-glucosyltransferase developed in this study, both carminic acid and aloesin were successfully produced from glucose.
“A sustainable and insect-free method of producing carminic acid was achieved for the first time in this study. Unknown or inefficient enzymes have always been a major problem in natural product biosynthesis, and here we suggest one effective solution for solving this problem. As maintaining good health in the aging society is becoming increasingly important, we expect that the technology and strategies developed here will play pivotal roles in producing other valuable natural products of medical or nutritional importance,” said Distinguished Professor Sang Yup Lee.
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries of the Ministry of Science and ICT (MSIT) through the National Research Foundation (NRF) of Korea and the KAIST Cross-Generation Collaborative Lab project; Sang Yup Lee and Dongsoo Yang were also supported by Novo Nordisk Foundation in Denmark.
Publication:
Dongsoo Yang, Woo Dae Jang, and Sang Yup Lee. Production of carminic acid by metabolically engineered Escherichia coli. at the Journal of the American Chemical Society. https://doi.org.10.1021/jacs.0c12406
Profile:
Sang Yup Lee, PhD
Distinguished Professor
leesy@kaist.ac.kr
http://mbel.kaist.ac.kr
Metabolic &Biomolecular Engineering National Research Laboratory
Department of Chemical and Biomolecular Engineering
KAIST
Expanding the Biosynthetic Pathway via Retrobiosynthesis
- Researchers reports a new strategy for the microbial production of multiple short-chain primary amines via retrobiosynthesis. -
KAIST metabolic engineers presented the bio-based production of multiple short-chain primary amines that have a wide range of applications in chemical industries for the first time. The research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering designed the novel biosynthetic pathways for short-chain primary amines by combining retrobiosynthesis and a precursor selection step.
The research team verified the newly designed pathways by confirming the in vivo production of 10 short-chain primary amines by supplying the precursors. Furthermore, the platform Escherichia coli strains were metabolically engineered to produce three proof-of-concept short-chain primary amines from glucose, demonstrating the possibility of the bio-based production of diverse short-chain primary amines from renewable resources. The research team said this study expands the strategy of systematically designing biosynthetic pathways for the production of a group of related chemicals as demonstrated by multiple short-chain primary amines as examples.
Currently, most of the industrial chemicals used in our daily lives are produced with petroleum-based products. However, there are several serious issues with the petroleum industry such as the depletion of fossil fuel reserves and environmental problems including global warming. To solve these problems, the sustainable production of industrial chemicals and materials is being explored with microorganisms as cell factories and renewable non-food biomass as raw materials for alternative to petroleum-based products. The engineering of these microorganisms has increasingly become more efficient and effective with the help of systems metabolic engineering – a practice of engineering the metabolism of a living organism toward the production of a desired metabolite. In this regard, the number of chemicals produced using biomass as a raw material has substantially increased.
Although the scope of chemicals that are producible using microorganisms continues to expand through advances in systems metabolic engineering, the biological production of short-chain primary amines has not yet been reported despite their industrial importance. Short-chain primary amines are the chemicals that have an alkyl or aryl group in the place of a hydrogen atom in ammonia with carbon chain lengths ranging from C1 to C7. Short-chain primary amines have a wide range of applications in chemical industries, for example, as a precursor for pharmaceuticals (e.g., antidiabetic and antihypertensive drugs), agrochemicals (e.g., herbicides, fungicides and insecticides), solvents, and vulcanization accelerators for rubber and plasticizers. The market size of short-chain primary amines was estimated to be more than 4 billion US dollars in 2014.
The main reason why the bio-based production of short-chain primary amines was not yet possible was due to their unknown biosynthetic pathways. Therefore, the team designed synthetic biosynthetic pathways for short-chain primary amines by combining retrobiosynthesis and a precursor selection step. The retrobiosynthesis allowed the systematic design of a biosynthetic pathway for short-chain primary amines by using a set of biochemical reaction rules that describe chemical transformation patterns between a substrate and product molecules at an atomic level.
These multiple precursors predicted for the possible biosynthesis of each short-chain primary amine were sequentially narrowed down by using the precursor selection step for efficient metabolic engineering experiments.
“Our research demonstrates the possibility of the renewable production of short-chain primary amines for the first time. We are planning to increase production efficiencies of short-chain primary amines. We believe that our study will play an important role in the development of sustainable and eco-friendly bio-based industries and the reorganization of the chemical industry, which is mandatory for solving the environmental problems threating the survival of mankind,” said Professor Lee.
This paper titled “Microbial production of multiple short-chain primary amines via retrobiosynthesis” was published in Nature Communications. This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea.
-Publication
Dong In Kim, Tong Un Chae, Hyun Uk Kim, Woo Dae Jang, and Sang Yup Lee. Microbial production of multiple short-chain primary amines via retrobiosynthesis. Nature Communications ( https://www.nature.com/articles/s41467-020-20423-6)
-Profile
Distinguished Professor Sang Yup Lee
leesy@kaist.ac.kr
Metabolic &Biomolecular Engineering National Research Laboratory
http://mbel.kaist.ac.kr
Department of Chemical and Biomolecular Engineering
KAIST
Professor Il-Doo Kim Named Scientist of the Year by the Journalists
Professor Il-Doo Kim from the Department of Materials Science and Engineering was named the 2019 Scientist of the Year by Korean science journalists. The award was conferred at the 2019 Science Press Night ceremony of the Korea Science Journalists Association (KSJA) on November 29.
Professor Kim focuses on developing nanofiber gas sensors for diagnosing diseases in advance by analyzing exhaled biomarkers with electrospinning technology. His outstanding research was praised and selected as one of the top 10 nanotechnology of 2019 by the Korea Nano Technology Research Society (KoNTRS), the Ministry of Science and ICT (MSIT), and the Ministry of Trade, Industry and Energy (MOTIE).
Professor Kim was honored with the QIAN Baojun Fiber Award, which is awarded every two years by Donghua University in Shanghai, China to recognize outstanding contributions in fiber science and technology. Professor Kim was also elected as an academician of the Asia Pacific Academy of Materials (APAM) on November 21 in Guangzhou, China.
In May, Professor Kim was appointed as an associate editor of ACS Nano, a leading international research journal in the field of nanoscience. In his editorial published in the May issue of ACS Nano, Professor Kim introduced and shared the history of KAIST and its vision for the future with other members of the journal. He hopes this will help with promoting a closer relationship between the members of the journal and KAIST moving forward.
“Above all,” he said in his acceptance speech, “the greatest news for me as an educator is that the first PhD graduate from our lab, Dr. Seonjin Choi, was appointed as the youngest professor in the Division of Materials Science and Engineering at Hanyang University on September 1.”
Gallium-Based Solvating Agent Efficiently Analyzes Optically Active Alcohols
A KAIST research team has developed a gallium-based metal complex enabling the rapid chiral analysis of alcohols. A team working under Professor Hyunwoo Kim reported the efficient new alcohol analysis method using nuclear magnetic resonance (NMR) spectroscopy in iScience.
Enantiopure chiral alcohols are ubiquitous in nature and widely utilized as pharmaceuticals. This importance of chirality in synthetic and medicinal chemistry has advanced the search for rapid and facile methods to determine the enantiomeric purities of compounds. To date, chiral analysis has been performed using high-performance liquid chromatography (HPLC) with chiral columns.
Along with the HPLC technique, chiral analysis using NMR spectroscopy has gained tremendous attention as an alternative to traditionally employed chromatographic methods due to its simplicity and rapid detection for real-time measurement. However, this method carries drawbacks such as line-broadening, narrow substrate scope, and poor resolution. Thus, compared with popular methods of chromatographic analysis, NMR spectroscopy is infrequently used for chiral analysis.
In principle, a chiral solvating agent is additionally required for the NMR measurement of chiral alcohols to obtain two distinct signals. However, NMR analysis of chiral alcohols has been challenging due to weak binding interactions with chiral solvating agents. To overcome the intrinsic difficulty of relatively weak molecular interactions that are common for alcohols, many researchers have used multifunctional alcohols to enhance interactions with solvating agents.
Instead, the KAIST team successfully varied the physical properties of metal complexes to induce stronger interactions with alcohols rather than the strategy of using multifunctional analytes, in the hopes of developing a universal chiral solvating agent for alcohols. Compared to the current method of chiral analysis used in the pharmaceutical industry, alcohols that do not possess chromophores can also be directly analyzed with the gallium complexes.
Professor Kim said that this method could be a complementary chiral analysis technique at the industry level in the near future. He added that since the developed gallium complex can determine enantiomeric excess within minutes, it can be further utilized to monitor asymmetric synthesis. This feature will benefit a large number of researchers in the organic chemistry community, as well as the pharmaceutical industry.
(Figure: Schematic view of the in-situ direct 1H NMR chiral analysis.)
-Profile:
Professor Hyunwoo Kim
Department of Chemistry
KAIST
http://mdos.kaist.ac.kr
hwk34@kaist.ac.kr
For more on this article,
please go to https://doi.org/10.1016/j.isci2019.07051