Microbial cell factories that produce pharmaceutical ingredients and other useful compounds include both the bacterium Escherichia coli and yeast, the organism used to leaven bread and ferment alcohol. The two organisms turn genes on by different rules, so a production design built for one has been hard to transfer to the other. A KAIST research team has now built a gene control element that works in both and tested it using a green pigment whose production requiresseveral genes working together. The work is expected to help researchers select the microbe best suited to producing a target compound.

KAIST (President Choongsik Bae) announced on September 28 that a research team led by Professor Juyoung Lee from the Graduate School of Engineering Biology has developed a "hybrid promoter," a gene control element that works in both E. coli and yeast, two very different types of microorganism.

For a microbe to make a target compound, the genes responsible for producing it must be turned on. A promoter is the stretch of DNA located in front of a gene that controls how strongly that gene works.

The challenge is that E. coli and yeast turn genes on in different ways, and a promoter that performs well in E. coli may not work at all in yeast. Making the same compound in a different microbe has therefore requiredt choosing a promoter suited to that host and retuning the output of each gene from the beginning.

The team's hybrid promoter combines, within a single sequence, DNA elements that E. coli and yeast each recognize. It is, in effect, a shared control elementdesigned so that each organism can find the signals it needs even though the two read genes differently. By varying the combination of these elements, the researchers built a series of promoters spanning a range of strength from weak to strong.

The promoters worked in both hosts, and combinations that were strong in E. coli were generally strong in yeast as well. That does not mean the two microbes make equal amounts of a compound; it means the relative ranking of promoter strengths from weak to strong is preserved across hosts.

The team then tested whether the new control element could do more than turn on a single gene and could also be used for actual compound production. For this, they chose a green pigment whose production requires three genes acting in sequence. Under the strong control element, pigment output was about 3.1 times higher in E. coli and about 2.6 times higher in yeast than under the weak one. The result shows that the system can control the amount of a compound produced in both microbes. The team also confirmed that the promoters worked in other typesof bacteria and yeast.

The approach could help researchers identify which microbe is best suited to producing a given compound, since the same gene control design can be applied across several microbes and the production results can be compared. It may reduce the need to redesign control elements from scratch whenever the host changes, although improving actual output will still requir host-specific tuning.

"What matters about this work is that it gives us a common design principle, one that lets us predict a promoter's relative strength even when the microbe changes," said Professor Juyoung Lee. She added that she expects the approach to speed up biomanufacturing by making it faster to design and compare a range of microbial cell factories.

So-Hee Son, Soo Young Moon, and Nan-Yeong An of KAIST are co-first authors on the paper, which was published in Nucleic Acids Research on September 23 and first appeared online on September 8.

※ Paper title: Modular synthetic cross-kingdom promoters enable coordinated expression in Escherichia coli and Saccharomyces cerevisiae, DOI: https://doi.org/10.1093/nar/gkag868
This work was supported by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF) through the Bio & Medical Technology Development Program (RS-2024-00445145) and the Basic Science Research Program (RS-2025-00518119), with additional support from the Korea-US Collaborative Research Fund (KUCRF), funded by MSIT and the Ministry of Health & Welfare (RS-2024-00468410).