Plants are a rich and renewable source of compounds used in medicines, food ingredients, and cosmetics. Since growing an entire plant just to extract a few specific compounds is rather inefficient, scientists are turning to plant cell cultures as a more sustainable alternative. Cultured plant cells can act as ideal 'biofactories' that multiply quickly indoors and are unaffected by weather or seasons. Unfortunately, this strategy faces a long-standing problem: although plant cells contain thousands of genes capable of making diverse chemicals, only a small fraction of them are active under standard culture conditions.
One possible strategy to unlock these hidden metabolic pathways comes from the concept of microbial co-cultures, a method where different organisms are grown together so their interactions trigger the production of compounds that are previously unattainable when grown alone. Although this technique has transformed natural product discovery and synthesis in bacteria and fungi, it remains challenging in plant cells. Most bacteria either inhibit plant cell growth or kill plant cultures outright. As a result, very few safe microbial partners that can stimulate plant metabolism are known. Could endophytic bacteria, which naturally live inside plants without causing harm, be the solution?
In a recent study published in Volume 19, Issue 1 of the journal Microbial Biotechnology on January 8, 2026, a research team led by Professor Toshiki Furuya from the Department of Applied Biological Science, Tokyo University of Science (TUS), Japan, investigated this possibility using endophytic bacteria previously isolated from Japanese mustard spinach (komatsuna) and Japanese radish (daikon). The researchers tested whether these bacteria could coexist with plant cell cultures and activate new metabolic pathways. Other members of the team included Mr. Yui Aikawa (completed Master's program in 2022), Ms. Ayano Yabuuchi (completed Master's program in 2024), and Mr. Hiroki Kaneko (completed Master's program in 2022), as well as Assistant Professor Takafumi Hashimoto, all from TUS at the time of the research.
"Through the analysis of komatsuna, we came up with the idea that endophytic bacteria that originally live symbiotically within plants might be able to coexist favorably with plant-cultured cells," shares Prof. Furuya as the core idea behind the study.
The researchers focused first on tobacco BY-2 cells, a widely used model plant cell line. They introduced an endophytic bacterium called Delftia sp. BR1R-2 into the culture and compared its effects with those of common bacteria. As expected, pathogenic bacteria and even the most commonly found Escherichia coli quickly suppressed plant cell growth and caused cell death. In contrast, BR1R-2 grew alongside the plant cells without harming them.
Interestingly, chemical analysis confirmed major metabolic changes. Using high-performance liquid chromatography, the team detected increased levels of acetophenone derivatives—small molecules known for antimicrobial and pesticidal activities. At the same time, another compound (N-caffeoylputrescine), normally abundant in tobacco cells, decreased, indicating that metabolic resources had been redirected. Extracts from the co-cultured cells also inhibited the growth of a plant pathogen, demonstrating that the newly produced molecules were biologically active.
The team conducted gene expression analyses to look further into the changes caused by co-culturing. They found that microbial growth switched on various defense-related pathways controlled by plant hormones involved in immune responses. The researchers also proved that physical contact between plant cells and bacteria was required to trigger these effects. Importantly, similar results were obtained with another endophyte from radish (Pseudomonas sp. RS1P-1) and in Arabidopsis cultured cells. This suggests the effect is not limited to one species. "Although our study used model plants for proof-of-concept, extending the method to other plant species could enable exploitation of previously inaccessible plant metabolic pathways," highlights Prof. Furuya.
Overall, the findings of this work point to a new way to safely stimulate plant cell metabolism using bacteria that naturally coexist with plants. "Plant immunity–activating endophytic bacteria exhibit great potential for use in altering the metabolic profile of cultured plant cells for the production of valuable phytochemicals," notes Prof. Furuya. Thus, this promising approach may help expand the range of plant-derived compounds available through cell-based production, opening new avenues for the synthesis of more affordable pharmaceuticals, cosmetics, food additives, and functional materials.
