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KAIST Brings the Era of Microbial Cell Factories One Step Closer
The era of "biomanufacturing", in which microbes, not petroleum, produce chemical products, is one step closer. A KAIST research team has analyzed the key challenges limiting the commercialization of biomanufacturing and proposed an AI-driven strategy for industrialization.
KAIST (President Choongsik Bae) announced on the 14th of July that a research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering has comprehensively analyzed the key bottlenecks to commercializing biomanufacturing and proposed an industrialization strategy and a roadmap for future growth to address them.
Most chemical products today — including plastics, textiles, and pharmaceutical raw materials — are produced from petroleum. But as concerns over carbon emissions and environmental pollution grow, biomanufacturing, which uses microbes to produce chemicals, is drawing attention as a next-generation manufacturing technology. Still, scaling up lab-developed technologies into economically viable mass production at actual factories remains a major challenge.
Systems metabolic engineering, a core technology in biomanufacturing, designs and optimizes microbial metabolic pathways to build "microbial cell factories" that produce desired chemicals. But technologies that show high productivity in the lab often perform worse once moved to industrial settings — productivity drops, production costs rise, and many fail to achieve price competitiveness, ultimately failing to commercialize.
The research team analyzed succinic acid, a bio-based chemical feedstock, and polyhydroxyalkanoate (PHA), a biodegradable plastic, as representative cases illustrating this "gap between the lab and industry," often called the "valley of death."
Succinic acid is a key raw material for producing eco-friendly plastics and various chemical materials. The team explained that for succinic acid to compete with existing petrochemical products, competitiveness depends not just on production volume, but also on raw material and separation/purification costs, the fermentation process, and market size — all of which must be weighed together. The team also suggested that a phased strategy — entering high-value markets such as pharmaceuticals, cosmetics, and food ingredients first — could be a realistic solution.
PHA is a biodegradable plastic that microbes accumulate inside their cells, an eco-friendly material that breaks down naturally in the environment after use. But PHA is currently less price-competitive than conventional plastics due to high production and recovery costs, and its intrinsic material properties pose a separate barrier: the archetypal polymer P(3HB) is highly crystalline, becomes brittle with age, and has a narrow window between its melting and decomposition temperatures, meaning PHAs are generally not suitable as direct "drop-in" replacements.The team found that a phased approach is needed — simplifying the production process and first applying it to high-value fields such as medical applications and food packaging before expanding into general-purpose markets.
The team predicted that artificial intelligence will become a key to industrializing biomanufacturing going forward. AI can optimize the entire biomanufacturing process — from enzyme and microbial design to digital twins that virtually simulate production processes, and technologies that simultaneously analyze economic feasibility and environmental impact. The team explained that this can shorten development timelines, reduce production costs, and increase the likelihood of successful commercialization.
The team also proposed that techno-economic analysis (TEA) and life cycle assessment (LCA) should be applied as design criteria from the earliest stages of research, rather than as evaluations conducted only after research is complete. The team further emphasized that supply chain resilience — accounting for raw material availability and shifts in the international landscape — should be considered a new design standard for biomanufacturing.
This study is significant not for developing a new production technology, but for comprehensively analyzing the conditions for successful biomanufacturing industrialization and presenting an industrialization roadmap spanning the entire cycle — from securing raw materials to microbial design, fermentation, separation and purification, and market entry. The team expects the study to accelerate the commercialization of the bio-based chemical industry and, over the long term, contribute to shifting the petroleum-centered chemical industry toward an eco-friendly bioeconomy.
The paper, with Ji Yeon Kim and Hye Eun Yu as co-first authors, both Ph.D. candidates in KAIST's Department of Chemical and Biomolecular Engineering, was published online on May 30 in the international journal Nature Communications.
※ Paper title: Beyond petrochemicals: challenges and opportunities in industrial-scale biomanufacturing
※ DOI: 10.1038/s41467-026-73835-1
※ Authors: Ji Yeon Kim (KAIST, co-first author), Hye Eun Yu (KAIST, co-first author), Min Ho Kim (KAIST), Sang Yup Lee (KAIST, corresponding author)
This research was supported by the National Research Foundation of Korea, funded by the Ministry of Science and ICT, through the “Development of Platform Technologies of Microbial Cell Factories for Next-Generation Biorefineries” project (Project No. 2022M3J5A1056117) and the “Development of Advanced Synthetic Biology Source Technologies for Leading the Biomanufacturing Industry” project (Project No. RS-2024-00399424).
2026.07.14 View 733 -
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 14927