KAIST develops gene regulator that works in bacteria and yeast simultaneously

South Korean researchers have developed a universal gene-regulatory platform that allows a single genetic design to be applied and compared across multiple microorganisms at the same time — a tool expected to help identify which microorganism is best suited for producing a desired substance.

KAIST announced Monday that a research team led by Professor Lee Ju-young of the Graduate School of Engineering Biology has developed a "hybrid promoter," a gene-regulatory device that functions in both E. coli and yeast — two microorganisms of entirely different types.

For a microorganism to produce a target substance, the genes required for that production must be active. A promoter is the segment of DNA positioned in front of a gene that controls how actively the gene operates.

The challenge is that E. coli and yeast read genes differently. A promoter that works well in E. coli may not function in yeast. As a result, researchers trying to produce the same substance in a different microorganism have had to select a compatible promoter and recalibrate gene expression levels from scratch.

The newly developed hybrid promoter merges DNA elements that each microorganism can recognize into a single construct. Even though the two microorganisms read genes in different ways, the device is designed so that each can find the signal it needs — effectively a shared regulatory tool. The research team created multiple variants by changing the combination of DNA elements, ranging from devices that drive weak gene expression to those that drive strong expression.

In experiments, the promoters functioned in both E. coli and yeast. Combinations that drove strong expression in E. coli generally did the same in yeast. This does not mean the two microorganisms produced identical quantities of a substance — rather, it means researchers can gauge which combinations are relatively stronger or weaker even when switching between microorganisms.

The team also sought to confirm that the new device could be used for actual substance production, not just activating a single gene. To test this, they chose a green pigment that requires three genes to operate in sequence. When the stronger regulatory device was used, pigment output was about 3.1 times higher in E. coli and about 2.6 times higher in yeast compared with the weaker device — demonstrating that the system can regulate production levels across both microorganisms. The team also confirmed that the promoter functioned in other bacterial and yeast species.

As the research advances, it could help streamline the process of identifying which microorganism is best suited for producing a desired substance, since the same gene-regulatory design can be applied across multiple microorganisms and their outputs compared directly. The approach has the potential to reduce the burden of redesigning regulatory devices from scratch each time a microorganism is changed, though additional fine-tuning tailored to each microorganism will still be needed to boost actual production levels.

The technology could be applied to the development of microbial cell factories that produce a wide range of substances, including pharmaceuticals, biotech chemicals, pigments, fuels and food ingredients. It is particularly expected to prove useful for automated, high-throughput design in biofoundry settings, where the same genetic design must be applied across multiple microorganisms and performance compared rapidly.

"This research is significant in that it presents a common design principle that allows the relative strength of a promoter to be predicted even when the microorganism changes," Lee said. "We expect it to be used to design and compare diverse microbial cell factories more quickly, accelerating the pace of biomanufacturing development."

The findings were published in the international journal Nucleic Acids Research on Sept. 23.