Genome-edited perilla plants (left) showing a striking color change from red to green and enhanced accumulation of the health-promoting flavonoid luteolin.
Photo Credit: Matsushita et al. / Hiroshima Prefectural Technology Research Institute
Scientific Frontline: Extended "At a Glance" Summary: Perilla Genome Editing
The Core Concept: Hiroshima University researchers successfully used CRISPR-Cas9 genome editing to disrupt the flavanone 3-hydroxylase (F3H) gene in red perilla (Perilla frutescens), creating a green-leafed variant with a significantly altered metabolic profile.
Key Distinction/Mechanism: By disabling the F3H enzyme—a critical branching point in the flavonoid biosynthetic pathway—researchers diverted metabolic flux away from anthocyanin production and toward the synthesis of beneficial flavones, specifically increasing luteolin concentrations by approximately sixfold.
Major Frameworks/Components:
- CRISPR-Cas9: The primary gene-editing technology used for precise DNA modification.
- Metabolic Engineering: The systematic redirection of plant metabolic pathways to increase the yield of high-value secondary metabolites.
- Non-Transgenic Breeding: The generation of stable, edited plant lines that contain no foreign DNA, facilitating easier regulatory and commercial adoption.
- Phenylpropanoid Metabolism: The broader biochemical pathway influenced by the F3H disruption, which also resulted in elevated levels of rosmarinic acid.
Branch of Science: Genetics, Plant Biology, Biochemistry, and Food Science.
Future Application: These findings provide a scalable blueprint for developing high-performance "functional" crops, allowing the food and pharmaceutical industries to cultivate plants enriched with natural antioxidants and anti-inflammatory compounds.
Why It Matters: This study demonstrates that precise genome editing can "reinvent" traditional culinary herbs to maximize their nutritional and medicinal potential without the complexities associated with transgenic methods.
From traffic lights to fashion trends, changing from red to green can signal much more than a shift in color.
Now, Hiroshima University researchers have shown that the same is true for perilla. Using genome editing, they transformed red perilla into a green look-alike and simultaneously restructured the plant’s chemistry to boost levels of compounds prized for their potential health benefits. The findings point to a new strategy for developing high-value crops for the food and pharmaceutical industries.
Perilla, a member of the mint family, is cultivated throughout Asia and is known by many names, including shiso in Japan, kkaennip in Korea, and tía tô in Vietnam. The plant is broadly classified into red and green varieties based on leaf color, a trait that strongly influences its culinary uses, market value, and consumer appeal. In Japan, red perilla is valued for imparting a distinctive color and flavor to pickled plums, whereas green perilla is commonly consumed fresh for its aroma and taste.
While best known as a culinary herb, perilla also carries a range of health-benefiting properties.
“Perilla contains more than 400 bioactive compounds, including anthocyanins, luteolin, rosmarinic acid, and perillaldehyde, which have been associated with antioxidant, anti-inflammatory, antibacterial, and other health-promoting effects,” said Hidemasa Bono, professor at Hiroshima University’s Graduate School of Integrated Sciences for Life and a corresponding author of the study.
The genetic mechanisms controlling the production and balance of these compounds, however, have remained largely unknown.
Seeking an answer, the researchers turned to CRISPR-Cas9, a genome-editing technology that allows scientists to precisely modify DNA. In red perilla, the team disabled a gene called flavanone 3-hydroxylase (F3H), which encodes an enzyme that acts as a key branching point in the flavonoid biosynthetic pathway.
The result was immediately visible.
“Plants edited at the F3H gene lost their characteristic red pigmentation and developed green leaves that were virtually indistinguishable in appearance from conventional green perilla varieties,” Bono said.
Chemical analyses revealed that the color change reflected a major metabolic shift. The edited plants produced far lower amounts of anthocyanins, the pigments responsible for red coloration, while accumulating substantially higher levels of flavones, a class of plant compounds associated with multiple health benefits. In particular, concentrations of luteolin, a flavone known for its antioxidant and anti-inflammatory properties, increased approximately sixfold compared with unedited plants.
The researchers also detected elevated levels of rosmarinic acid, another bioactive metabolite linked to potential health benefits, suggesting that editing F3H influences not only flavonoid production but broader phenylpropanoid metabolism.
Importantly, the team generated stable edited lines that no longer contained foreign DNA from the genome-editing process. This demonstrates the feasibility of producing nontransgenic perilla varieties with tailored metabolic profiles.
“By modifying a single enzyme gene in red perilla, we have successfully changed the plant’s metabolism to increase its health-promoting compounds,” Bono said. “Genome editing makes it possible to develop high-performance perilla with enhanced value for food and pharmaceutical applications.”
The team plans to use the newly developed lines to further investigate the complex biological functions of perilla and deepen understanding of how its diverse metabolites are regulated.
“We hope to translate these findings into the development of high-value functional foods enriched with beneficial compounds and to explore the use of perilla as a new source of naturally derived pharmaceutical materials,” Bono said.
Funding: The study was supported by the Hiroshima Prefectural Government's "Hiroshima Health and Medical-Related Industry Creation Support Project" and the Center of Innovation for Bio-Digital Transformation (BioDX), an open innovation platform for industry-academia co-creation of JST (COI-NEXT, JPMJPF2010).
Published in journal: Frontiers in Plant Science
Authors: Shuji Matsushita, Michiharu Nakano, Suguru Chokyuu, Masaki Kurao, Ayane Fujita, Junko Kimura, Chinatsu Nagata, Takeshi Ishikawa, Keita Tamura, and Hidemasa Bono
Source/Credit: Hiroshima University
Edited by: Scientific Frontline
Reference Number: gen071626_01
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