Yeast Engineered To Create Ashwagandha Compounds Raises Promise And Questions

Scientists at Northeastern University, a research university in Boston, Massachusetts, have said that they have successfully engineered yeast cells to produce withanolides—the compounds widely associated with the therapeutic properties of ashwagandha (Withania somnifera). The study, published in Nature Plants, suggests that microbial production might one day reduce dependence on cultivation of the slow-growing medicinal shrub.

However, while the researchers described their work as a potential gateway to manufacturing precision versions of the molecules for research and drug development, experts from India’s traditional medicine community have called for caution and stated that it was too early to reach such a conclusion.

“We not only discovered the pathway through this yeast engineering approach, but we have a prototype yeast strain that can be industrialized to produce withanolides,” said Jing-Ke Weng, bioengineer at Northeastern University and corresponding author of the study.

The team sequenced the plant’s genome and identified six genes believed to function together like an assembly line for withanolide synthesis. When transferred into yeast, the organism began producing the compounds within days.

“Yeast and plants diverged a billion years ago, but when we put these six genes in the yeast genome, the yeast basically starts to make withanolides,” Dr. Weng said. “We were actually very surprised it worked.”

Although current yields remain small—in milligrams per litre—the authors called it an important starting point for eventual industrial scale-up.

“In the future, we can foresee that we don't have to grow the plants to get withanolides,” he said. “We can simply engineer and optimize this yeast strain to produce the very precise analog we want. Then it really opens the doors for all kinds of drug discovery research in the future.”

Ashwagandha has been used in Ayurveda for centuries and has witnessed a dramatic global surge in popularity in recent years as a supplement marketed for stress, sleep, and vitality.

However, Indian experts have cautioned that the herb’s clinical action cannot be narrowed to a single class of chemicals. Dr. (Prof.) Rama Kant Yadava, Department of Ayurveda Medicine, All India Institute of Ayurveda, Delhi, described the findings as scientifically interesting but premature in terms of application.

“Focusing only on withanolides may give an incomplete picture,” he said. “There are several other substances in the plant that work in combination. We still do not fully understand how this synergy happens.”

According to him, traditional formulations rely on the interaction among multiple constituents that together shape therapeutic outcomes.

Another major issue is how purified or highly concentrated molecules might behave in the body.

If withanolides are produced outside the natural matrix of the herb, their pharmacological action could change, Dr. Yadava warned. Some animal experiments already suggest that compounds such as withanone or withanolide A may produce toxicity beyond certain limits.

Because of this, he said, any future therapeutic use would require a long pathway of laboratory validation, toxicology studies, animal research, and phased human clinical trials under regulatory supervision.

“At best, in the distant future, if proven safe, very small quantities of such compounds might be used to fortify foods or beverages,” Dr. Yadava said. “But that possibility remains theoretical for now.”

“This is promising science,” he added, “but we must wait for evidence on effectiveness and safety. That journey is long.”

Dr. R.P. Parasher, National President of the All India Doctors Association of Indian System of Medicine (ISM), said history offers cautionary lessons about isolating single alkaloids from complex medicinal plants.

“Each and every plant has a number of compounds and alkaloids which collectively produce the desired mode of action,” he said. “Roots, stem, leaves, bark, or flowers of a plant have different alkaloids and are used accordingly. When we separate a particular alkaloid, it may or may not have the same effect. Further, it may result in some side effects.”

He cited Rauwolfia serpentina (Sarpagandha), long used for hypertension and mental health conditions.

“When the active ingredients for hypertension were separated from the plant Sarpagandha, the single alkaloid led to suicidal tendency in the users. Therefore, consuming a separated particular alkaloid may prove harmful,” Dr. Parasher said.

Even if fermentation technology matures, the Indian experts believe it is unlikely to fully replace naturally cultivated ashwagandha.