Thyme and oregano possess an anti-cancer compound that suppresses tumor development, but adding more to your tomato sauce isn’t enough to gain significant benefit. The key to unlocking the power of these plants is in amplifying the amount of the compound created or synthesizing the compound for drug development.
And exciting for the field of fermentation: extracting those beneficial compounds from the plant is done through fermentation.
“The fermentation process is so important to food and beverage, pharmaceutical and biofuels production that Purdue now offers a fermentation science major,” reads a press release from Purdue University.
Researchers at Purdue took the first step in using the compound in pharmaceuticals by mapping its biosynthetic pathway, a sort of molecular recipe of the ingredients and steps needed.
“These plants contain important compounds, but the amount is very low and extraction won’t be enough,” said Natalia Dudareva, distinguished professor of biochemistry in Purdue’s College of Agriculture and director of Purdue’s Center for Plant Biology, who co-led the project. “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.”
Thymol, carvacrol and thymohydroquinone are flavor compounds in thyme, oregano and other plants in the Lamiaceae family. They have antibacterial, anti-inflammatory, antioxidant and other properties beneficial to human health. Thymohydroquinone has been shown to have anti-cancer properties and is particularly of interest, said Dudareva..
In collaboration with scientists from Martin Luther University Halle-Wittenberg in Germany and Michigan State University, the Purdue team uncovered the entire biosynthetic pathway to thymohydroquinone, including the formation of its precursors thymol and carvacrol, and the short-lived intermediate compounds along the way.
The findings alter previous views of the formation of this class of compounds, called phenolic or aromatic monoterpenes, for which only a few biosynthetic pathways have been discovered in other plants, she said. The study results were published in the Proceedings of the National Academy of Sciences.
“These findings provide new targets for engineering high-value compounds in plants and other organisms,” said Pan Liao, co-first author of the paper 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 this pathway is known, plant scientists could develop cultivars that produce more of the beneficial compounds, or it could be incorporated — using fermentation — into microorganisms like yeast for production.
A $5 million grant from the National Science Foundation supported the research. Using RNA sequencing and correlation analysis, the team screened more than 80,000 genes from plant tissue samples and identified the genes needed for thymohydroquinone production. Based on what was known about the compound structure and through metabolite profiling and biochemical testing, the team identified the biosynthetic pathway.
“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.”
More pathways are now being discovered, thanks to the availability of RNA sequencing to perform high-throughput gene expression analysis, according to Dudareva.
“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.”