A research team led by Professor Joongoo Lee in the Department of Chemical Engineering at POSTECH (Pohang University of Science and Technology) has developed an automated, modular method for assembling reconstituted cell-free systems, which are test-tube systems that can produce proteins outside living cells. The findings were published online on June 6, 2026, in Trends in Biotechnology (Impact Factor: 16.6), an international journal in the fields of biotechnology and synthetic biology.
Compared with commercially available kits, this platform reduced preparation costs by 95%, improved cell-free protein synthesis performance by 5-fold, and cut preparation time from 4 days to 2 days.
A simple way to understand cell-free protein synthesis is to think of a 3-in-1 instant coffee. Coffee, sugar, and creamer are already mixed in a fixed ratio. All we need to do is add hot water. Cell-free protein synthesis works on a similar principle. Instead of relying on living cells, the translational machinery is prepared in advance, and researchers simply add the DNA, which is the recipe for the protein they want to produce.
The problem is that this instant coffee for protein synthesis has been extremely expensive. Only a small number of suppliers provide ready-to-use systems, and preparing them in the lab has involved labor-intensive and time-consuming processes that highly depend on the skill of the experimenter.
To overcome this challenge, the POSTECH research team shifted the production of key components outside living cells. Using an E. coli lysate-based cell-free protein synthesis platform, the researchers produced the translation factors directly from the test tubes and integrated the process with an automated liquid handling system. This reduced hands-on time, streamlined the workflow, and made the system more reproducible from batch to batch.
Another key advantage of the system is its modular design. Researchers can add or remove individual components depending on their experiments. Using this flexibility, the POSTECH research team successfully incorporated non-canonical amino acids into peptides and proteins. This capability could be useful for biologically engineering high-value therapeutics, including antibody-drug conjugates, in which drug payloads are linked to antibodies.
This advance is especially relevant to biofoundries, which are automated infrastructures that use robotics, and artificial intelligence to design, build, test and learn from large numbers of experiments. A lower-cost, customizable, cell-free system could help overcome one of the practical bottlenecks in drug discovery and enzyme engineering.
Professor Joongoo Lee of POSTECH, who led the study, explained the significance of the work: "We have built an automated platform that makes cell-free protein synthesis dramatically faster and cheaper, while allowing its components to be freely customized depending on the application."
This research was supported by the Bio and Medical Technology Development Program of the National Research Foundation (NRF), funded by the Korean government (MSIT). This research was also supported by a grant from the Korea–US Collaborative Research Fund (KUCRF), funded by the Ministry of Science and ICT and the Ministry of Health and Welfare. This research also supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea. This work made use of the Green Bio Foundry facility at Pohang Technopark, established with funding from the Ministry of Agriculture, Food and Rural Affairs of Korea, Gyeongsangbuk-do Province, and Pohang City.
