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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.
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A research team led by Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering comprehensively analyzed the key bottlenecks to commercializing biomanufacturing and proposed an industrialization strategy and roadmap for future growth to address them. 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 in Nature Communications.
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 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 when 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, separation and 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 because of 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 key to industrializing biomanufacturing. 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.
More information: Ji Yeon Kim et al, Beyond petrochemicals: challenges and opportunities in industrial-scale biomanufacturing, Nature Communications (2026). DOI: 10.1038/s41467-026-73835-1
Provided by The Korea Advanced Institute of Science and Technology (KAIST)
This story was originally published on Phys.org.
