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 Develops Eco-Friendly, Nylon-Like Plastic Using Microorganisms
Poly(ester amide) amide is a next-generation material that combines the advantages of PET (polyester) and nylon (polyamide), two widely used plastics. However, it could only be produced from fossil fuels, which posed environmental concerns. Using microorganisms, KAIST researchers have successfully developed a new bio-based plastic to replace conventional plastic.
KAIST (represented by President Kwang Hyung Lee) announced on the 20th of March that a research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering has developed microbial strains through systems metabolic engineering to produce various eco-friendly, bio-based poly(ester amide)s. The team collaborated with researchers from the Korea Research Institute of Chemical Technology (KRICT, President Young-Kook Lee) to analyze and confirm the properties of the resulting plastic.
Professor Sang Yup Lee’s research team designed new metabolic pathways that do not naturally exist in microorganisms, and developed a platform microbial strain capable of producing nine different types of poly(ester amide)s, including poly(3-hydroxybutyrate-ran-3-aminopropionate) and poly(3-hydroxybutyrate-ran-4-aminobutyrate).
Using glucose derived from abundant biomass sources such as waste wood and weeds, the team successfully produced poly(ester amide)s in an eco-friendly manner. The researchers also confirmed the potential for industrial-scale production by demonstrating high production efficiency (54.57 g/L) using fed-batch fermentation of the engineered strain.
In collaboration with researchers Haemin Jeong and Jihoon Shin from KRICT, the KAIST team analyzed the properties of the bio-based plastic and found that it exhibited characteristics similar to high-density polyethylene (HDPE). This means the new plastic is not only eco-friendly but also strong and durable enough to replace conventional plastics.
The engineered strains and strategies developed in this study are expected to be useful not only for producing various poly(ester amide)s but also for constructing metabolic pathways for the biosynthesis of other types of polymers.
Professor Sang Yup Lee stated, “This study is the first to demonstrate the possibility of producing poly(ester amide)s (plastics) through a renewable bio-based chemical process rather than relying on the petroleum-based chemical industry. We plan to further enhance the production yield and efficiency through continued research.”
The study was published online on March 17 in the international journal Nature Chemical Biology.
·Title: Biosynthesis of poly(ester amide)s in engineered Escherichia coli
·DOI: 10.1038/s41589-025-01842-2
·Authors: A total of seven authors including Tong Un Chae (KAIST, first author), So Young Choi (KAIST, second author), Da-Hee Ahn (KAIST, third author), Woo Dae Jang (KAIST, fourth author), Haemin Jeong (KRICT, fifth author), Jihoon Shin (KRICT, sixth author), and Sang Yup Lee (KAIST, corresponding author).
This research was supported by the Ministry of Science and ICT (MSIT) under the Eco-Friendly Chemical Technology Development Project as part of the "Next-Generation Biorefinery Technology Development to Lead the Bio-Chemical Industry" initiative (project led by Distinguished Professor Sang Yup Lee at KAIST).
KAIST presents strategies for environmentally friendly and sustainable polyamides production
- Provides current research trends in bio-based polyamide production
- Research on bio-based polyamides production gains importance for achieving a carbon-neutral society
Global industries focused on carbon neutrality, under the slogan "Net-Zero," are gaining increasing attention. In particular, research on microbial production of polymers, replacing traditional chemical methods with biological approaches, is actively progressing.
Polyamides, represented by nylon, are linear polymers widely used in various industries such as automotive, electronics, textiles, and medical fields. They possess beneficial properties such as high tensile strength, electrical insulation, heat resistance, wear resistance, and biocompatibility. Since the commercialization of nylon in 1938, approximately 7 million tons of polyamides are produced worldwide annually. Considering their broad applications and significance, producing polyamides through bio-based methods holds considerable environmental and industrial importance.
KAIST (President Kwang-Hyung Lee) announced that a research team led by Distinguished Professor Sang Yup Lee, including Dr. Jong An Lee and doctoral candidate Ji Yeon Kim from the Department of Chemical and Biomolecular Engineering, published a paper titled "Current Advancements in Bio-Based Production of Polyamides”. The paper was featured on the cover of the monthly issue of "Trends in Chemistry” by Cell Press.
As part of climate change response technologies, bio-refineries involve using biotechnological and chemical methods to produce industrially important chemicals and biofuels from renewable biomass without relying on fossil resources. Notably, systems metabolic engineering, pioneered by KAIST's Distinguished Professor Sang Yup Lee, is a research field that effectively manipulates microbial metabolic pathways to produce valuable chemicals, forming the core technology for bio-refineries. The research team has successfully developed high-performance strains producing a variety of compounds, including succinic acid, biodegradable plastics, biofuels, and natural products, using systems metabolic engineering tools and strategies.
The research team predicted that if bio-based polyamide production technology, which is widely used in the production of clothing and textiles, becomes widespread, it will attract attention as a future technology that can respond to the climate crisis due to its environment-friendly production technology. In this study, the research team comprehensively reviewed the bio-based polyamide production strategies. They provided insights into the advancements in polyamide monomer production using metabolically engineered microorganisms and highlighted the recent trends in bio-based polyamide advancements utilizing these monomers. Additionally, they reviewed the strategies for synthesizing bio-based polyamides through chemical conversion of natural oils and discussed the biodegradability and recycling of the polyamides. Furthermore, the paper presented the future direction in which metabolic engineering can be applied for the bio-based polyamide production, contributing to environmentally friendly and sustainable society.
Ji Yeon Kim, the co-first author of this paper from KAIST, stated "The importance of utilizing systems metabolic engineering tools and strategies for bio-based polyamides production is becoming increasingly prominent in achieving carbon neutrality."
Professor Sang Yup Lee emphasized, "Amid growing concerns about climate change, the significance of environmentally friendly and sustainable industrial development is greater than ever. Systems metabolic engineering is expected to have a significant impact not only on the chemical industry but also in various fields."
< [Figure 1] A schematic overview of the overall process for polyamides production >
This paper by Dr. Jong An Lee, PhD student Ji Yeon Kim, Dr. Jung Ho Ahn, and Master Yeah-Ji Ahn from the Department of Chemical and Biomolecular Engineering at KAIST was published in the December issue of 'Trends in Chemistry', an authoritative review journal in the field of chemistry published by Cell. It was published on December 7 as the cover paper and featured review.
※ Paper title: Current advancements in the bio-based production of polyamides
※ Author information: Jong An Lee, Ji Yeon Kim, Jung Ho Ahn, Yeah-Ji Ahn, and Sang Yup Lee
This research was conducted with the support from the development of platform technologies of microbial cell factories for the next-generation biorefineries project and C1 gas refinery program by Korean Ministry of Science and ICT.
< [Figure 2] Cover paper of the December issue of Trends in Chemistry >
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.