Purdue plant scientists find anti-cancer compound in herbs

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atalia Dudareva, distinguished professor of biochemistry in Purdue’s College of Agriculture, stands in her laboratory. Dudareva led a team of researchers that mapped the biosynthetic pathway of an anti-cancer compound found in oregano and thyme, opening the door to potential pharmaceutical use. (Purdue University photo/Tom Campbell)

WEST LAFAYETTE — While herbs like thyme and oregano possess an anti-cancer compound that has been found to suppress tumor development, the only real way to unlock the benefit within the plants is by amplifying the amount of that compound created or by synthesizing the compound.

Researchers at Purdue University were able to take the first step towards using the compound in drug development by mapping its biosynthetic pathway, or in simpler terms — by finding and following its recipe.

“These plants contain important compounds, but the amount is very low and extraction won’t be enough,” said Purdue’s Natalia Dudareva, who co-led the project, in a press release. “By understanding how these compounds are formed, we open a path to engineering plants with higher levels of them or to synthesizing the compounds in microorganisms for medical use. It is an amazing time for plant science right now. We have tools that are faster, cheaper and provide much more insight. It is like looking inside the cell; it is almost unbelievable.”

Thyme, oregano, sage, basil, mint, rosemary, lavender and many other herbs are part of the Lamiaceae family of plants, all containing flavor compounds, antibacterial, anti-inflammatory, antioxidants and other health beneficial properties. One of these compounds, thymohydroquinone, is particularly of interest because of its anti-cancer properties, according to Dudareva.

They collaborated with scientists at Michigan State University and at Martin Luther University Halle-Wittenberg in Germany. Together, they uncovered the biosynthetic pathway — the recipe — for thymohydroquinone.

“These findings provide new targets for engineering high-value compounds in plants and other organisms,” said Pan Liao, co-first author of the paper detailing this work and a postdoctoral researcher in Dudareva’s lab. “Not only do many plants contain medicinal properties, but the compounds within them are used as food additives and for perfumes, cosmetics and other products.”

Now that there is a known recipe, plant scientists could develop methods of cultivation and produce more of the beneficial compounds, or it could be incorporated into microorganisms for production like yeast is. Like yeast, the latter method would require a fermentation process in order to obtain the compounds. Liao said this was true for many plant-based products.

The research was supported by a $5 million grant from the National Science Foundation. When using RNA sequencing and correlation analysis, the team had screened more than 80,000 genes from plant samples and identified the genes that were needed for developing and producing thymohydroquinone. Based on what was already known about the compound structure and through testing, the team was able to discover the recipe.

“The intermediate formed in the pathway was not what had been predicted,” Liao said. “We found that the aromatic backbone of both thymol and carvacrol is formed from γ-terpinene by a P450 monooxygenase in combination with a dehydrogenase via two unstable intermediates, but not p-cymene, as was proposed.”

Dudareva said that more pathways — more recipes — are being discovered now using this technique. The results of this research will also be useful for those in biochemistry and plant sciences research of other species of plants.

“We, as scientists, are always comparing pathways in different systems and plants,” Dudareva said. “We are always in pursuit of new possibilities. The more we learn, the more we are able to recognize the similarities and differences that could be key to the next breakthrough.”

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