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KAIST Researchers Suggest an Extraordinary Alternative to Petroleum-based PET - Bacteria!
< (From left) Dr. Cindy Pricilia, Ph.D. Candidate Cheon Woo Moon, Distinguished Professor Sang Yup Lee >
Currently, the world is suffering from environmental problems caused by plastic waste. The KAIST research team has succeeded in producing a microbial-based plastic that is biodegradable and can replace existing PET bottles, making it a hot topic.
Our university announced on the 7th of November that the research team of Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering has succeeded in developing a microbial strain that efficiently produces pseudoaromatic polyester monomer to replace polyethylene terephthalate (PET) using systems metabolic engineering.
Pseudoaromatic dicarboxylic acids have better physical properties and higher biodegradability than aromatic polyester (PET) when synthesized as polymers, and are attracting attention as an eco-friendly monomer* that can be synthesized into polymers. The production of pseudoaromatic dicarboxylic acids through chemical methods has the problems of low yield and selectivity, complex reaction conditions, and the generation of hazardous waste.
*Monomer: A material for making polymers, which is used to synthesize polymers by polymerizing monomers together
< Figure. Overview of pseudoaromatic dicarboxylic acid production using metabolically engineered C. glutamicum. >
To solve this problem, Professor Sang Yup Lee's research team used metabolic engineering to develop a microbial strain that efficiently produces five types of pseudoaromatic dicarboxylic acids, including 2-pyrone-4,6-dicarboxylic acid and four types of pyridine dicarboxylic acids (2,3-, 2,4-, 2,5-, 2,6-pyridine dicarboxylic acids), in Corynebacterium, a bacterium mainly used for amino acid production.
The research team used metabolic engineering techniques to build a platform microbial strain that enhances the metabolic flow of protocatechuic acid, which is used as a precursor for several pseudoaromatic dicarboxylic acids, and prevents the loss of precursors.
Based on this, the genetic manipulation target was discovered through transcriptome analysis, producing 76.17 g/L of 2-pyrone-4,6-dicarboxylic acid, and by newly discovering and constructing three types of pyridine dicarboxylic acid production metabolic pathways, successfully producing 2.79 g/L of 2,3-pyridine dicarboxylic acid, 0.49 g/L of 2,4-pyridine dicarboxylic acid, and 1.42 g/L of 2,5-pyridine dicarboxylic acid.
In addition, the research team confirmed the production of 15.01 g/L through the construction and reinforcement of the 2,6-pyridine dicarboxylic acid biosynthesis pathway, successfully producing a total of five similar aromatic dicarboxylic acids with high efficiency.
In conclusion, the team succeeded in producing 2,4-, 2,5-, and 2,6-pyridine dicarboxylic acids at the world's highest concentration. In particular, 2,4-, 2,5-pyridine dicarboxylic acid achieved production on the scale of g/L, which was previously produced in extremely small amounts (mg/L).
Based on this study, it is expected that it will be applied to various polyester production industrial processes, and it is also expected that it will be actively utilized in research on the production of similar aromatic polyesters.
Professor Sang Yup Lee, the corresponding author, said, “The significance lies in the fact that we have developed an eco-friendly technology that efficiently produces similar aromatic polyester monomers based on microorganisms,” and “This study will help the microorganism-based bio-monomer industry replace the petrochemical-based chemical industry in the future.”
The results of this study were published in the international academic journal, the Proceedings of the National Academy of Sciences of United States of America (PNAS) on October 30th.
※ Paper title: Metabolic engineering of Corynebacterium glutamicum for the production of pyrone and pyridine dicarboxylic acids
※ Author information: Jae Sung Cho (co-first author), Zi Wei Luo (co-first author), Cheon Woo Moon (co-first author), Cindy Prabowo (co-author), Sang Yup Lee (corresponding author) - a total of 5 people
This study was conducted with the support of the Development of Next-generation Biorefinery Platform Technologies for Leading Bio-based Chemicals Industry Project and the Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project (Project leader: Professor Sang Yup Lee) from the National Research Foundation supported by the Ministry of Science and Technology and ICT of Korea.
2024.11.08 View 854 -
KAIST Proposes a New Way to Circumvent a Long-time Frustration in Neural Computing
The human brain begins learning through spontaneous random activities even before it receives sensory information from the external world. The technology developed by the KAIST research team enables much faster and more accurate learning when exposed to actual data by pre-learning random information in a brain-mimicking artificial neural network, and is expected to be a breakthrough in the development of brain-based artificial intelligence and neuromorphic computing technology in the future.
KAIST (President Kwang-Hyung Lee) announced on the 23rd of October that Professor Se-Bum Paik 's research team in the Department of Brain Cognitive Sciences solved the weight transport problem*, a long-standing challenge in neural network learning, and through this, explained the principles that enable resource-efficient learning in biological brain neural networks.
*Weight transport problem: This is the biggest obstacle to the development of artificial intelligence that mimics the biological brain. It is the fundamental reason why large-scale memory and computational work are required in the learning of general artificial neural networks, unlike biological brains.
Over the past several decades, the development of artificial intelligence has been based on error backpropagation learning proposed by Geoffery Hinton, who won the Nobel Prize in Physics this year. However, error backpropagation learning was thought to be impossible in biological brains because it requires the unrealistic assumption that individual neurons must know all the connected information across multiple layers in order to calculate the error signal for learning.
< Figure 1. Illustration depicting the method of random noise training and its effects >
This difficult problem, called the weight transport problem, was raised by Francis Crick, who won the Nobel Prize in Physiology or Medicine for the discovery of the structure of DNA, after the error backpropagation learning was proposed by Hinton in 1986. Since then, it has been considered the reason why the operating principles of natural neural networks and artificial neural networks will forever be fundamentally different.
At the borderline of artificial intelligence and neuroscience, researchers including Hinton have continued to attempt to create biologically plausible models that can implement the learning principles of the brain by solving the weight transport problem.
In 2016, a joint research team from Oxford University and DeepMind in the UK first proposed the concept of error backpropagation learning being possible without weight transport, drawing attention from the academic world. However, biologically plausible error backpropagation learning without weight transport was inefficient, with slow learning speeds and low accuracy, making it difficult to apply in reality.
KAIST research team noted that the biological brain begins learning through internal spontaneous random neural activity even before experiencing external sensory experiences. To mimic this, the research team pre-trained a biologically plausible neural network without weight transport with meaningless random information (random noise).
As a result, they showed that the symmetry of the forward and backward neural cell connections of the neural network, which is an essential condition for error backpropagation learning, can be created. In other words, learning without weight transport is possible through random pre-training.
< Figure 2. Illustration depicting the meta-learning effect of random noise training >
The research team revealed that learning random information before learning actual data has the property of meta-learning, which is ‘learning how to learn.’ It was shown that neural networks that pre-learned random noise perform much faster and more accurate learning when exposed to actual data, and can achieve high learning efficiency without weight transport.
< Figure 3. Illustration depicting research on understanding the brain's operating principles through artificial neural networks >
Professor Se-Bum Paik said, “It breaks the conventional understanding of existing machine learning that only data learning is important, and provides a new perspective that focuses on the neuroscience principles of creating appropriate conditions before learning,” and added, “It is significant in that it solves important problems in artificial neural network learning through clues from developmental neuroscience, and at the same time provides insight into the brain’s learning principles through artificial neural network models.”
This study, in which Jeonghwan Cheon, a Master’s candidate of KAIST Department of Brain and Cognitive Sciences participated as the first author and Professor Sang Wan Lee of the same department as a co-author, will be presented at the 38th Neural Information Processing Systems (NeurIPS), the world's top artificial intelligence conference, to be held in Vancouver, Canada from December 10 to 15, 2024. (Paper title: Pretraining with random noise for fast and robust learning without weight transport)
This study was conducted with the support of the National Research Foundation of Korea's Basic Research Program in Science and Engineering, the Information and Communications Technology Planning and Evaluation Institute's Talent Development Program, and the KAIST Singularity Professor Program.
2024.10.23 View 861 -
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 1644 -
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 1888 -
KAIST proposes alternatives to chemical factories through “iBridge”
- A computer simulation program “iBridge” was developed at KAIST that can put together microbial cell factories quickly and efficiently to produce cosmetics and food additives, and raw materials for nylons
- Eco-friendly and sustainable fermentation process to establish an alternative to chemical plants
As climate change and environmental concerns intensify, sustainable microbial cell factories garner significant attention as candidates to replace chemical plants. To develop microorganisms to be used in the microbial cell factories, it is crucial to modify their metabolic processes to induce efficient target chemical production by modulating its gene expressions. Yet, the challenge persists in determining which gene expressions to amplify and suppress, and the experimental verification of these modification targets is a time- and resource-intensive process even for experts. The challenges were addressed by a team of researchers at KAIST (President Kwang-Hyung Lee) led by Distinguished Professor Sang Yup Lee.
It was announced on the 9th by the school that a method for building a microbial factory at low cost, quickly and efficiently, was presented by a novel computer simulation program developed by the team under Professor Lee’s guidance, which is named “iBridge”. This innovative system is designed to predict gene targets to either overexpress or downregulate in the goal of producing a desired compound to enable the cost-effective and efficient construction of microbial cell factories specifically tailored for producing the chemical compound in demand from renewable biomass.
Systems metabolic engineering is a field of research and engineering pioneered by KAIST’s Distinguished Professor Sang Yup Lee that seeks to produce valuable compounds in industrial demands using microorganisms that are re-configured by a combination of methods including, but not limited to, metabolic engineering, synthetic biology, systems biology, and fermentation engineering.
In order to improve microorganisms’ capability to produce useful compounds, it is essential to delete, suppress, or overexpress microbial genes. However, it is difficult even for the experts to identify the gene targets to modify without experimental confirmations for each of them, which can take up immeasurable amount of time and resources.
The newly developed iBridge identifies positive and negative metabolites within cells, which exert positive and/or negative impact on formation of the products, by calculating the sum of covariances of their outgoing (consuming) reaction fluxes for a target chemical. Subsequently, it pinpoints "bridge" reactions responsible for converting negative metabolites into positive ones as candidates for overexpression, while identifying the opposites as targets for downregulation.
The research team successfully utilized the iBridge simulation to establish E. coli microbial cell factories each capable of producing three of the compounds that are in high demands at a production capacity that has not been reported around the world. They developed E. coli strains that can each produce panthenol, a moisturizing agent found in many cosmetics, putrescine, which is one of the key components in nylon production, and 4-hydroxyphenyllactic acid, an anti-bacterial food additive. In addition to these three compounds, the study presents predictions for overexpression and suppression genes to construct microbial factories for 298 other industrially valuable compounds.
Dr. Youngjoon Lee, the co-first author of this paper from KAIST, emphasized the accelerated construction of various microbial factories the newly developed simulation enabled. He stated, "With the use of this simulation, multiple microbial cell factories have been established significantly faster than it would have been using the conventional methods. Microbial cell factories producing a wider range of valuable compounds can now be constructed quickly using this technology."
Professor Sang Yup Lee said, "Systems metabolic engineering is a crucial technology for addressing the current climate change issues." He added, "This simulation could significantly expedite the transition from resorting to conventional chemical factories to utilizing environmentally friendly microbial factories."
< Figure. Conceptual diagram of the flow of iBridge simulation >
The team’s work on iBridge is described in a paper titled "Genome-Wide Identification of Overexpression and Downregulation Gene Targets Based on the Sum of Covariances of the Outgoing Reaction Fluxes" written by Dr. Won Jun Kim, and Dr. Youngjoon Lee of the Bioprocess Research Center and Professors Hyun Uk Kim and Sang Yup Lee of the Department of Chemical and Biomolecular Engineering of KAIST. The paper was published via peer-review on the 6th of November on “Cell Systems” by Cell Press.
This research was conducted with the support from the Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project (Project Leader: Distinguished Professor Sang Yup Lee, KAIST) and Development of Platform Technology for the Production of Novel Aromatic Bioplastic using Microbial Cell Factories Project (Project Leader: Research Professor So Young Choi, KAIST) of the Korean Ministry of Science and ICT.
2023.11.09 View 4330 -
KAIST holds its first ‘KAIST Tech Fair’ in New York, USA
< Photo 1. 2023 KAIST Tech Fair in New York >
KAIST (President Kwang-Hyung Lee) announced on the 11th that it will hold the ‘2023 KAIST Tech Fair in New York’ at the Kimmel Center at New York University in Manhattan, USA, on the 22nd of this month. It is an event designed to be the starting point for KAIST to expand its startup ecosystem into the global stage, and it is to attract investments and secure global customers in New York by demonstrating the technological value of KAIST startup companies directly at location.
< Photo 2. President Kwang Hyung Lee at the 2023 KAIST Tech Fair in New York >
KAIST has been holding briefing sessions for technology transfer in Korea every year since 2018, and this year is the first time to hold a tech fair overseas for global companies.
KAIST Institute of Technology Value Creation (Director Sung-Yool Choi) has prepared for this event over the past six months with the Korea International Trade Association (hereinafter KITA, CEO Christopher Koo) to survey customer base and investment companies to conduct market analysis.
Among the companies founded with the technologies developed by the faculty and students of KAIST and their partners, 7 companies were selected to be matched with companies overseas that expressed interests in these technologies. Global multinational companies in the fields of IT, artificial intelligence, environment, logistics, distribution, and retail are participating as demand agencies and are testing the marketability of the start-up's technology as of September.
Daim Research, founded by Professor Young Jae Jang of the Department of Industrial and Systems Engineering, is a company specializing in smart factory automation solutions and is knocking on the door of the global market with a platform technology optimized for automated logistics systems.
< Photo 3. Presentation by Professor Young Jae Jang for DAIM Research >
It is a ‘collaborative intelligence’ solution that maximizes work productivity by having a number of robots used in industrial settings collaborate with one another. The strength of their solution is that logistics robots equipped with AI reinforced learning technology can respond to processes and environmental changes on their own, minimizing maintenance costs and the system can achieve excellent performance even with a small amount of data when it is combined with the digital twin technology the company has developed on its own.
A student startup, ‘Aniai’, is entering the US market, the home of hamburgers, with hamburger patty automation equipments and solutions. This is a robot kitchen startup founded by its CEO Gunpil Hwang, a graduate of KAIST’s School of Electrical Engineering which gathered together the experts in the fields of robot control, design, and artificial intelligence and cognitive technology to develop technology to automatically cook hamburger patties.
At the touch of a button, both sides of the patty are cooked simultaneously for consistent taste and quality according to the set condition. Since it can cook about 200 dishes in an hour, it is attracting attention as a technology that can not only solve manpower shortages but also accelerate the digital transformation of the restaurant industry.
Also, at the tech fair to be held at the Kimmel Center of New York University on the 22nd, the following startups who are currently under market verification in the U.S. will be participating: ▴'TheWaveTalk', which developed a water quality management system that can measure external substances and metal ions by transferring original technology from KAIST; ▴‘VIRNECT’, which helps workers improve their skills by remotely managing industrial sites using XR*; ▴‘Datumo’, a solution that helps process and analyze artificial intelligence big data, ▴‘VESSL AI’, the provider of a solution to eliminate the overhead** of machine learning systems; and ▴ ‘DolbomDream’, which developed an inflatable vest that helps the psychological stability of people with developmental disabilities.
* XR (eXtended Reality): Ultra-realistic technology that enhances immersion by utilizing augmented reality, virtual reality, and mixed reality technologies
** Overhead: Additional time required for stable processing of the program
In addition, two companies (Plasmapp and NotaAI) that are participating in the D-Unicorn program with the support of the Daejeon City and two companies (Enget and ILIAS Biologics) that are receiving support from the Scale Up Tips of the Ministry of SMEs and Startups, three companies (WiPowerOne, IDK Lab, and Artificial Photosynthesis Lab) that are continuing to realize the sustainable development goals for a total of 14 KAIST startups, will hold a corporate information session with about 100 invited guests from global companies and venture capital.
< Photo 4. Presentation for AP Lab >
Prior to this event, participating startups will be visiting the New York Economic Development Corporation and large law firms to receive advice on U.S. government support programs and on their attemps to enter the U.S. market. In addition, the participating companies plan to visit a startup support investment institution pursuing sustainable development goals and the Leslie eLab, New York University's one-stop startup support space, to lay the foundation for KAIST's leap forward in global technology commercialization.
< Photo 5. Sung-Yool Choi, the Director of KAIST Institute of Technology Value Creation (left) at the 2023 KAIST Tech Fair in New York with the key participants >
Sung-Yool Choi, the Director of KAIST Institute of Technology Value Creation, said, “KAIST prepared this event to realize its vision of being a leading university in creating global value.” He added, “We hope that our startups founded with KAIST technology would successfully completed market verification to be successful in securing global demands and in attracting investments for their endeavors.”
2023.09.11 View 9704 -
A KAIST Research Team Produces Eco-Friendly Nylon with Engineered Bacterium
With worsening climate change and environmental issues, in recent years, there has been increased interest in the eco-friendly production of polymers like nylon.
On August 10, Dr. Taehee Han from a KAIST research team led by Distinguished Professor Sang Yup Lee in the Department of Chemical and Biomolecular Engineering revealed the successful development of a microbial strain that produces valerolactam, a monomer of nylon-5.
Valerolactam is an important monomer that constitutes nylon-5 and nylon-6,5. Nylon is the oldest synthetic polymer, and nylon-5 is one of its derivatives composed of monomers with five carbons, while nylon-5,6 is composed of two types of monomers with either five or six carbons. They not only have excellent processability, but are also light and tough, which allows them to be applied in a wide range of industrial sectors including clothing, badminton rackets, fishing nets, tents, and gear parts. Monomers are materials that can be built into polymers, and synthetic processes are what connects them into a polymer.
The chemical production of valerolactam, however, is based on petrochemistry, where extreme reaction conditions are required and toxic waste is produced. To solve these problems, efforts are being made to develop environmentally friendly and highly efficient microbial cell factories for lactam production. Systems metabolic engineering, a key strategy for effective microbial strain development, is a research field pioneered by Professor Sang Yup Lee.
Professor Lee’s team used metabolic engineering, a technique for manipulating microbial metabolic pathways, to construct a synthetic metabolic pathway for valerolactam production in Corynebacteriam glutamicum, a bacterium commonly used for amino acid production. With this, they successfully developed a microbial strain that utilizes biomass-derived glucose as a carbon source to produce high-value valerolactam.
In 2017, the team suggested a novel method that metabolically manipulates Escherichia coli to produce valerolactam. However, there were several limitations at the time including low producibility and the generation of harmful byproducts.
< Figure 1. Schematic graphical representation of the development of microorganisms that produce valerolactam, a nylon-5 monomer >
In this research, the team improved valerolactam producibility and incorporated an additional systems metabolic strategy to the developed microbial strain while eliminating the harmful byproducts. By removing the gene involved in the production of the main byproduct and through gene screening, the team successfully converted 5-aminovaleric acid, a byproduct and a precursor, into valerolactam.
Furthermore, by employing a strategy where the 5-aminovaleric acid-converting gene is inserted multiple times into the genome, the team strengthened the metabolic flux for valerolactam production. As a result, they reached a world-record concentration of 76.1 g/L, which is 6.17 times greater than what was previously reported.
This study was published in Metabolic Engineering on July 12, under the title, “Metabolic engineering of Corynebacterium glutamicum for the high-level production of valerolactam, a nylon-5 monomer”.
Dr. Taehee Han, the first author of the paper, said, “The significance of this research lies in our development of an environmentally friendly technology that efficiently produces monomer lactam for nylon production using microorganisms.” She added, “Through this technology, we will be able to take a step forward in replacing the petrochemical industry with a microorganism-based biopolymer industry.”
This work was supported by the “Development of Next-Generation Biofinery Platform Technologies for Leading Bio-based Chemicals Industry Project” funded by the Korean Ministry of Science and ICT.
2023.08.24 View 3579 -
Professor Joseph J. Lim of KAIST receives the Best System Paper Award from RSS 2023, First in Korea
- Professor Joseph J. Lim from the Kim Jaechul Graduate School of AI at KAIST and his team receive an award for the most outstanding paper in the implementation of robot systems.
- Professor Lim works on AI-based perception, reasoning, and sequential decision-making to develop systems capable of intelligent decision-making, including robot learning
< Photo 1. RSS2023 Best System Paper Award Presentation >
The team of Professor Joseph J. Lim from the Kim Jaechul Graduate School of AI at KAIST has been honored with the 'Best System Paper Award' at "Robotics: Science and Systems (RSS) 2023".
The RSS conference is globally recognized as a leading event for showcasing the latest discoveries and advancements in the field of robotics. It is a venue where the greatest minds in robotics engineering and robot learning come together to share their research breakthroughs. The RSS Best System Paper Award is a prestigious honor granted to a paper that excels in presenting real-world robot system implementation and experimental results.
< Photo 2. Professor Joseph J. Lim of Kim Jaechul Graduate School of AI at KAIST >
The team led by Professor Lim, including two Master's students and an alumnus (soon to be appointed at Yonsei University), received the prestigious RSS Best System Paper Award, making it the first-ever achievement for a Korean and for a domestic institution.
< Photo 3. Certificate of the Best System Paper Award presented at RSS 2023 >
This award is especially meaningful considering the broader challenges in the field. Although recent progress in artificial intelligence and deep learning algorithms has resulted in numerous breakthroughs in robotics, most of these achievements have been confined to relatively simple and short tasks, like walking or pick-and-place. Moreover, tasks are typically performed in simulated environments rather than dealing with more complex, long-horizon real-world tasks such as factory operations or household chores. These limitations primarily stem from the considerable challenge of acquiring data required to develop and validate learning-based AI techniques, particularly in real-world complex tasks.
In light of these challenges, this paper introduced a benchmark that employs 3D printing to simplify the reproduction of furniture assembly tasks in real-world environments. Furthermore, it proposed a standard benchmark for the development and comparison of algorithms for complex and long-horizon tasks, supported by teleoperation data. Ultimately, the paper suggests a new research direction of addressing complex and long-horizon tasks and encourages diverse advancements in research by facilitating reproducible experiments in real-world environments.
Professor Lim underscored the growing potential for integrating robots into daily life, driven by an aging population and an increase in single-person households. As robots become part of everyday life, testing their performance in real-world scenarios becomes increasingly crucial. He hoped this research would serve as a cornerstone for future studies in this field.
The Master's students, Minho Heo and Doohyun Lee, from the Kim Jaechul Graduate School of AI at KAIST, also shared their aspirations to become global researchers in the domain of robot learning. Meanwhile, the alumnus of Professor Lim's research lab, Dr. Youngwoon Lee, is set to be appointed to the Graduate School of AI at Yonsei University and will continue pursuing research in robot learning.
Paper title: Furniture Bench: Reproducible Real-World Benchmark for Long-Horizon Complex Manipulation. Robotics: Science and Systems.
< Image. Conceptual Summary of the 3D Printing Technology >
2023.07.31 View 5317 -
KAIST presents a microbial cell factory as a source of eco-friendly food and cosmetic coloring
Despite decades of global population growth, global food crisis seems to be at hand yet again because the food productivity is cut severely due to prolonged presence of abnormal weather from intensifying climate change and global food supply chain is deteriorated due to international conflicts such as wars exacerbating food shortages and nutritional inequality around the globe. At the same time, however, as awareness of the environment and sustainability rises, an increase in demand for more eco-friendly and high-quality food and beauty products is being observed not without a sense of irony. At a time like this, microorganisms are attracting attention as a key that can handle this couple of seemingly distant problems.
KAIST (President Kwang-Hyung Lee) announced on the 26th that Kyeong Rok Choi, a research professor of the Bioprocess Research Center and Sang Yup Lee, a Distinguished Professor of the Department of Chemical and Biomolecular Engineering, published a paper titled “Metabolic Engineering of Microorganisms for Food and Cosmetics Production” upon invitation by “Nature Reviews Bioengineering” to be published online published by Nature after peer review.
※ Paper title: Systems metabolic engineering of microorganisms for food and cosmetics production
※ Author information: Kyeong Rok Choi (first author) and Sang Yup Lee (corresponding author)
Systems metabolic engineering is a research field founded by Distinguished Professor Sang Yup Lee of KAIST to more effectively develop microbial cell factories, the core factor of the next-generation bio industry to replace the existing chemical industry that relies heavily on petroleum. By applying a systemic metabolic engineering strategy, the researchers have developed a number of high-performance microbial cell factories that produce a variety of food and cosmetic compounds including natural substances like heme and zinc protoporphyrin IX compounds which can improve the flavor and color of synthetic meat, lycopene and β-carotene which are functional natural pigments that can be widely used in food and cosmetics, and methyl anthranilate, a grape-derived compound widely used to impart grape flavor in food and beverage manufacturing.
In this paper written upon invitation by Nature, the research team covered remarkable cases of microbial cell factory that can produce amino acids, proteins, fats and fatty acids, vitamins, flavors, pigments, alcohols, functional compounds and other food additives used in various foods and cosmetics and the companies that have successfully commercialized these microbial-derived materials Furthermore, the paper organized and presents systems metabolic engineering strategies that can spur the development of industrial microbial cell factories that can produce more diverse food and cosmetic compounds in an eco-friendly way with economic feasibility.
< Figure 1. Examples of production of food and cosmetic compounds using microbial cell factories >
For example, by producing proteins or amino acids with high nutritional value through non-edible biomass used as animal feed or fertilizer through the microbial fermentation process, it will contribute to the increase in production and stable supply of food around the world. Furthermore, by contributing to developing more viable alternative meat, further reducing dependence on animal protein, it can also contribute to reducing greenhouse gases and environmental pollution generated through livestock breeding or fish farming.
In addition, vanillin or methyl anthranilate, which give off vanilla or grape flavor, are widely added to various foods, but natural products isolated and refined from plants are low in production and high in production cost, so in most cases, petrochemicals substances derived from vanillin and methylanthranilic acid are added to food. These materials can also be produced through an eco-friendly and human-friendly method by borrowing the power of microorganisms.
Ethical and resource problems that arise in producing compounds like Calmin (cochineal pigment), a coloring added to various cosmetics and foods such as red lipstick and strawberry-flavored milk, which must be extracted from cochineal insects that live only in certain cacti. and Hyaluronic acid, which is widely consumed as a health supplement, but is only present in omega-3 fatty acids extracted from shark or fish livers, can also be resolved when they can be produced in an eco-friendly way using microorganisms.
KAIST Research Professor Kyeong Rok Choi, the first author of this paper, said, “In addition to traditional fermented foods such as kimchi and yogurt, foods produced with the help of microorganisms like cocoa butter, a base ingredient for chocolate that can only be obtained from fermented cacao beans, and monosodium glutamate, a seasoning produced through microbial fermentation are already familiar to us”. “In the future, we will be able to acquire a wider variety of foods and cosmetics even more easily produced in an eco-friendly and sustainable way in our daily lives through microbial cell factories.” he added.
< Figure 2. Systems metabolic engineering strategy to improve metabolic flow in microbial cell factories >
Distinguished Professor Sang Yup Lee said, “It is engineers’ mission to make the world a better place utilizing science and technology.” and added, “Continuous advancement and active use of systems metabolic engineering will contribute greatly to easing and resolving the problems arising from both the food crisis and the climate change."
This research was carried out as a part of the “Development of Protein Production Technology from Inorganic Substances through Control of Microbial Metabolism System Project” (Project Leader: Kyeong Rok Choi, KAIST Research Professor) of the the Center for Agricultural Microorganism and Enzyme (Director Pahn-Shick Chang) supported by the Rural Development Administration and the “Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project” (Project Leader: Sang Yup Lee, KAIST Distinguished Professor) of the Petroleum-Substitute Eco-friendly Chemical Technology Development Program supported by the Ministry of Science and ICT.
2023.07.28 View 4965 -
A KAIST Research Team Identifies a Cancer Reversion Mechanism
Despite decades of intensive cancer research by numerous biomedical scientists, cancer still holds its place as the number one cause of death in Korea. The fundamental reason behind the limitations of current cancer treatment methods is the fact that they all aim to completely destroy cancer cells, which eventually allows the cancer cells to acquire immunity. In other words, recurrences and side-effects caused by the destruction of healthy cells are inevitable. To this end, some have suggested anticancer treatment methods based on cancer reversion, which can revert cancer cells back to normal or near-normal cells under certain conditions. However, the practical development of this idea has not yet been attempted.
On June 8, a KAIST research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering reported to have successfully identified the fundamental principle of a process that can revert cancer cells back to normal cells without killing the cells.
Professor Cho’s team focused on the fact that unlike normal cells, which react according to external stimuli, cancer cells tend to ignore such stimuli and only undergo uncontrolled cell division. Through computer simulation analysis, the team discovered that the input-output (I/O) relationships that were distorted by genetic mutations could be reverted back to normal I/O relationships under certain conditions. The team then demonstrated through molecular cell experiments that such I/O relationship recovery also occurred in real cancer cells.
The results of this study, written by Dr. Jae Il Joo and Dr. Hwa-Jeong Park, were published in Wiley’s Advanced Science online on June 2 under the title, "Normalizing input-output relationships of cancer networks for reversion therapy."
< Image 1. Input-output (I/O) relationships in gene regulatory networks >
Professor Kwang-Hyun Cho's research team classified genes into four types by simulation-analyzing the effect of gene mutations on the I/O relationship of gene regulatory networks. (Figure A-J) In addition, by analyzing 18 genes of the cancer-related gene regulatory network, it was confirmed that when mutations occur in more than half of the genes constituting each network, reversibility is possible through appropriate control. (Figure K)
Professor Cho’s team uncovered that the reason the distorted I/O relationships of cancer cells could be reverted back to normal ones was the robustness and redundancy of intracellular gene control networks that developed over the course of evolution. In addition, they found that some genes were more promising as targets for cancer reversion than others, and showed through molecular cell experiments that controlling such genes could revert the distorted I/O relationships of cancer cells back to normal ones.
< Image 2. Simulation results of restoration of bladder cancer gene regulation network and I/O relationship of bladder cancer cells. >
The research team classified the effects of gene mutations on the I/O relationship in the bladder cancer gene regulation network by simulation analysis and classified them into 4 types. (Figure A) Through this, it was found that the distorted input-output relationship between bladder cancer cell lines KU-1919 and HCT-1197 could be restored to normal. (Figure B)
< Image 3. Analysis of survival of bladder cancer patients according to reversible gene mutation and I/O recovery experiment of bladder cancer cells. >
As predicted through network simulation analysis, Professor Kwang-Hyun Cho's research team confirmed through molecular cell experiments that the response to TGF-b was normally restored when AKT and MAP3K1 were inhibited in the bladder cancer cell line KU-1919. (Figure A-G) In addition, it was confirmed that there is a difference in the survival rate of bladder cancer patients depending on the presence or absence of a reversible gene mutation. (Figure H)
The results of this research show that the reversion of real cancer cells does not happen by chance, and that it is possible to systematically explore targets that can induce this phenomenon, thereby creating the potential for the development of innovative anticancer drugs that can control such target genes.
< Image 4. Cancer cell reversibility principle >
The research team analyzed the reversibility, redundancy, and robustness of various networks and found that there was a positive correlation between them. From this, it was found that reversibility was additionally inherent in the process of evolution in which the gene regulatory network acquired redundancy and consistency.
Professor Cho said, “By uncovering the fundamental principles of a new cancer reversion treatment strategy that may overcome the unresolved limitations of existing chemotherapy, we have increased the possibility of developing new and innovative drugs that can improve both the prognosis and quality of life of cancer patients.”
< Image 5. Conceptual diagram of research results >
The research team identified the fundamental control principle of cancer cell reversibility through systems biology research. When the I/O relationship of the intracellular gene regulatory network is distorted by mutation, the distorted I/O relationship can be restored to a normal state by identifying and adjusting the reversible gene target based on the redundancy of the molecular circuit inherent in the complex network.
After Professor Cho’s team first suggested the concept of reversion treatment, they published their results for reverting colorectal cancer in January 2020, and in January 2022 they successfully re-programmed malignant breast cancer cells back into hormone-treatable ones. In January 2023, the team successfully removed the metastasis ability from lung cancer cells and reverted them back to a state that allowed improved drug reactivity. However, these results were case studies of specific types of cancer and did not reveal what common principle allowed cancer reversion across all cancer types, making this the first revelation of the general principle of cancer reversion and its evolutionary origins.
This research was funded by the Ministry of Science and ICT of the Republic of Korea and the National Research Foundation of Korea.
2023.06.20 View 4952 -
KAIST Holds 2023 Commencement Ceremony
< Photo 1. On the 17th, KAIST held the 2023 Commencement Ceremony for a total of 2,870 students, including 691 doctors. >
KAIST held its 2023 commencement ceremony at the Sports Complex of its main campus in Daejeon at 2 p.m. on February 27. It was the first commencement ceremony to invite all its graduates since the start of COVID-19 quarantine measures.
KAIST awarded a total of 2,870 degrees including 691 PhD degrees, 1,464 master’s degrees, and 715 bachelor’s degrees, which adds to the total of 74,999 degrees KAIST has conferred since its foundation in 1971, which includes 15,772 PhD, 38,360 master’s and 20,867 bachelor’s degrees.
This year’s Cum Laude, Gabin Ryu, from the Department of Mechanical Engineering received the Minister of Science and ICT Award. Seung-ju Lee from the School of Computing received the Chairman of the KAIST Board of Trustees Award, while Jantakan Nedsaengtip, an international student from Thailand received the KAIST Presidential Award, and Jaeyong Hwang from the Department of Physics and Junmo Lee from the Department of Industrial and Systems Engineering each received the President of the Alumni Association Award and the Chairman of the KAIST Development Foundation Award, respectively.
Minister Jong-ho Lee of the Ministry of Science and ICT awarded the recipients of the academic awards and delivered a congratulatory speech.
Yujin Cha from the Department of Bio and Brain Engineering, who received a PhD degree after 19 years since his entrance to KAIST as an undergraduate student in 2004 gave a speech on behalf of the graduates to move and inspire the graduates and the guests.
After Cha received a bachelor’s degree from the Department of Nuclear and Quantum Engineering, he entered a medical graduate school and became a radiation oncology specialist. But after experiencing the death of a young patient who suffered from osteosarcoma, he returned to his alma mater to become a scientist. As he believes that science and technology is the ultimate solution to the limitations of modern medicine, he started as a PhD student at the Department of Bio and Brain Engineering in 2018, hoping to find such solutions.
During his course, he identified the characteristics of the decision-making process of doctors during diagnosis, and developed a brain-inspired AI algorithm. It is an original and challenging study that attempted to develop a fundamental machine learning theory from the data he collected from 200 doctors of different specialties.
Cha said, “Humans and AI can cooperate by humans utilizing the unique learning abilities of AI to develop our expertise, while AIs can mimic us humans’ learning abilities to improve.” He added, “My ultimate goal is to develop technology to a level at which humans and machines influence each other and ‘coevolve’, and applying it not only to medicine, but in all areas.”
Cha, who is currently an assistant professor at the KAIST Biomedical Research Center, has also written Artificial Intelligence for Doctors in 2017 to help medical personnel use AI in clinical fields, and the book was selected as one of the 2018 Sejong Books in the academic category.
During his speech at this year’s commencement ceremony, he shared that “there are so many things in the world that are difficult to solve and many things to solve them with, but I believe the things that can really broaden the horizons of the world and find fundamental solutions to the problems at hand are science and technology.”
Meanwhile, singer-songwriter Sae Byul Park who studied at the KAIST Graduate School of Culture Technology will also receive her PhD degree.
Natural language processing (NLP) is a field in AI that teaches a computer to understand and analyze human language that is actively being studied. An example of NLP is ChatGTP, which recently received a lot of attention. For her research, Park analyzed music rather than language using NLP technology.
To analyze music, which is in the form of sound, using the methods for NLP, it is necessary to rebuild notes and beats into a form of words or sentences as in a language. For this, Park designed an algorithm called Mel2Word and applied it to her research.
She also suggested that by converting melodies into texts for analysis, one would be able to quantitatively express music as sentences or words with meaning and context rather than as simple sounds representing a certain note.
Park said, “music has always been considered as a product of subjective emotion, but this research provides a framework that can calculate and analyze music.”
Park’s study can later be developed into a tool to measure the similarities between musical work, as well as a piece’s originality, artistry and popularity, and it can be used as a clue to explore the fundamental principles of how humans respond to music from a cognitive science perspective.
Park began her Ph.D. program in 2014, while carrying on with her musical activities as well as public and university lectures alongside, and dealing with personally major events including marriage and childbirth during the course of years. She already met the requirements to receive her degree in 2019, but delayed her graduation in order to improve the level of completion of her research, and finally graduated with her current achievements after nine years.
Professor Juhan Nam, who supervised Park’s research, said, “Park, who has a bachelor’s degree in psychology, later learned to code for graduate school, and has complete high-quality research in the field of artificial intelligence.” He added, “Though it took a long time, her attitude of not giving up until the end as a researcher is also excellent.”
Sae Byul Park is currently lecturing courses entitled Culture Technology and Music Information Retrieval at the Underwood International College of Yonsei University.
Park said, “the 10 or so years I’ve spent at KAIST as a graduate student was a time I could learn and prosper not only academically but from all angles of life.” She added, “having received a doctorate degree is not the end, but a ‘commencement’. Therefore, I will start to root deeper from the seeds I sowed and work harder as a both a scholar and an artist.”
< Photo 2. From left) Yujin Cha (Valedictorian, Medical-Scientist Program Ph.D. graduate), Saebyeol Park (a singer-songwriter, Ph.D. graduate from the Graduate School of Culture and Technology), Junseok Moon and Inah Seo (the two highlighted CEO graduates from the Department of Management Engineering's master’s program) >
Young entrepreneurs who dream of solving social problems will also be wearing their graduation caps. Two such graduates are Jun-seok Moon and Inah Seo, receiving their master’s degrees in social entrepreneurship MBA from the KAIST College of Business.
Before entrance, Moon ran a café helping African refugees stand on their own feet. Then, he entered KAIST to later expand his business and learn social entrepreneurship in order to sustainably help refugees in the blind spots of human rights and welfare.
During his master’s course, Moon realized that he could achieve active carbon reduction by changing the coffee alone, and switched his business field and founded Equal Table. The amount of carbon an individual can reduce by refraining from using a single paper cup is 10g, while changing the coffee itself can reduce it by 300g.
1kg of coffee emits 15kg of carbon over the course of its production, distribution, processing, and consumption, but Moon produces nearly carbon-neutral coffee beans by having innovated the entire process. In particular, the company-to-company ESG business solution is Moon’s new start-up area. It provides companies with carbon-reduced coffee made by roasting raw beans from carbon-neutral certified farms with 100% renewable energy, and shows how much carbon has been reduced in its making. Equal Table will launch the service this month in collaboration with SK Telecom, its first partner.
Inah Seo, who also graduated with Moon, founded Conscious Wear to start a fashion business reducing environmental pollution. In order to realize her mission, she felt the need to gain the appropriate expertise in management, and enrolled for the social entrepreneurship MBA.
Out of the various fashion industries, Seo focused on the leather market, which is worth 80 trillion won. Due to thickness or contamination issues, only about 60% of animal skin fabric is used, and the rest is discarded. Heavy metals are used during such processes, which also directly affects the environment.
During the social entrepreneurship MBA course, Seo collaborated with SK Chemicals, which had links through the program, and launched eco-friendly leather bags. The bags used discarded leather that was recycled by grinding and reprocessing into a biomaterial called PO3G. It was the first case in which PO3G that is over 90% biodegradable was applied to regenerated leather. In other words, it can reduce environmental pollution in the processing and disposal stages, while also reducing carbon emissions and water usage by one-tenth compared to existing cowhide products.
The social entrepreneurship MBA course, from which Moon and Seo graduated, will run in integration with the Graduate School of Green Growth as an Impact MBA program starting this year. KAIST plans to steadily foster entrepreneurs who will lead meaningful changes in the environment and society as well as economic values through innovative technologies and ideas.
< Photo 3. NYU President Emeritus John Sexton (left), who received this year's honorary doctorate of science, poses with President Kwang Hyung Lee >
Meanwhile, during this day’s commencement ceremony, KAIST also presented President Emeritus John Sexton of New York University with an honorary doctorate in science. He was recognized for laying the foundation for the cooperation between KAIST and New York University, such as promoting joint campuses.
< Photo 4. At the commencement ceremony of KAIST held on the 17th, President Kwang Hyung Lee is encouraging the graduates with his commencement address. >
President Kwang Hyung Lee emphasized in his commencement speech that, “if you can draw up the future and work hard toward your goal, the future can become a work of art that you create with your own hands,” and added, “Never stop on the journey toward your dreams, and do not give up even when you are met with failure. Failure happens to everyone, all the time. The important thing is to know 'why you failed', and to use those elements of failure as the driving force for the next try.”
2023.02.20 View 12893 -
Phage resistant Escherichia coli strains developed to reduce fermentation failure
A genome engineering-based systematic strategy for developing phage resistant Escherichia coli strains has been successfully developed through the collaborative efforts of a team led by Professor Sang Yup Lee, Professor Shi Chen, and Professor Lianrong Wang. This study by Xuan Zou et al. was published in Nature Communications in August 2022 and featured in Nature Communications Editors’ Highlights. The collaboration by the School of Pharmaceutical Sciences at Wuhan University, the First Affiliated Hospital of Shenzhen University, and the KAIST Department of Chemical and Biomolecular Engineering has made an important advance in the metabolic engineering and fermentation industry as it solves a big problem of phage infection causing fermentation failure.
Systems metabolic engineering is a highly interdisciplinary field that has made the development of microbial cell factories to produce various bioproducts including chemicals, fuels, and materials possible in a sustainable and environmentally friendly way, mitigating the impact of worldwide resource depletion and climate change. Escherichia coli is one of the most important chassis microbial strains, given its wide applications in the bio-based production of a diverse range of chemicals and materials. With the development of tools and strategies for systems metabolic engineering using E. coli, a highly optimized and well-characterized cell factory will play a crucial role in converting cheap and readily available raw materials into products of great economic and industrial value.
However, the consistent problem of phage contamination in fermentation imposes a devastating impact on host cells and threatens the productivity of bacterial bioprocesses in biotechnology facilities, which can lead to widespread fermentation failure and immeasurable economic loss. Host-controlled defense systems can be developed into effective genetic engineering solutions to address bacteriophage contamination in industrial-scale fermentation; however, most of the resistance mechanisms only narrowly restrict phages and their effect on phage contamination will be limited.
There have been attempts to develop diverse abilities/systems for environmental adaptation or antiviral defense. The team’s collaborative efforts developed a new type II single-stranded DNA phosphorothioation (Ssp) defense system derived from E. coli 3234/A, which can be used in multiple industrial E. coli strains (e.g., E. coli K-12, B and W) to provide broad protection against various types of dsDNA coliphages. Furthermore, they developed a systematic genome engineering strategy involving the simultaneous genomic integration of the Ssp defense module and mutations in components that are essential to the phage life cycle. This strategy can be used to transform E. coli hosts that are highly susceptible to phage attack into strains with powerful restriction effects on the tested bacteriophages. This endows hosts with strong resistance against a wide spectrum of phage infections without affecting bacterial growth and normal physiological function. More importantly, the resulting engineered phage-resistant strains maintained the capabilities of producing the desired chemicals and recombinant proteins even under high levels of phage cocktail challenge, which provides crucial protection against phage attacks.
This is a major step forward, as it provides a systematic solution for engineering phage-resistant bacterial strains, especially industrial bioproduction strains, to protect cells from a wide range of bacteriophages. Considering the functionality of this engineering strategy with diverse E. coli strains, the strategy reported in this study can be widely extended to other bacterial species and industrial applications, which will be of great interest to researchers in academia and industry alike.
Fig. A schematic model of the systematic strategy for engineering phage-sensitive industrial E. coli strains into strains with broad antiphage activities. Through the simultaneous genomic integration of a DNA phosphorothioation-based Ssp defense module and mutations of components essential for the phage life cycle, the engineered E. coli strains show strong resistance against diverse phages tested and maintain the capabilities of producing example recombinant proteins, even under high levels of phage cocktail challenge.
2022.08.23 View 8993