Dr. Zhen Wang's research project aims to pinpoint the genes that plants use to produce medicinal compounds could enable scientists to explore faster, more efficient methods of manufacturing these substances. This could include genetically engineering microbes to synthesize the drugs. One goal of the project is to decipher how the foxglove plant Digitalis lanata makes compounds called cardenolides, which have pharmaceutical relevance. See feature by UB Now.
UB biologists are hunting for the genes that help foxglove plants make medicinal compounds. Here, scientists insert promising foxglove genes into the leaves of a tobacco plant. If the tobacco plant starts producing the foxglove compounds or closely related molecules, it’s a sign that the research is on the right track.
Left to right: Zhen Q. Wang, assistant professor of biological sciences, is leading the project. The goal is to decipher how the foxglove plant Digitalis lanata makes compounds called cardenolides, which have pharmaceutical relevance. Lab members include PhD students Indu Raghavan and Emily Carroll, and undergraduate researcher Zahin Hossain, who has since graduated.
Carroll introduces foxglove genes into a tobacco plant. The syringe holds a solution of agrobacteria that helps to transfer the foreign genes into the leaves.
The focus is on injecting the solution into the undersides of the tobacco leaves, which have a larger number of pores called stomata.
Pinpointing the genes that plants use to produce medicinal compounds could enable scientists to explore faster, more efficient methods of manufacturing these substances, Wang says. This could include genetically engineering microbes to synthesize the drugs.
In a related project, Wang’s team is testing the hypothesis that foxglove plants release cardenolides as a defensive mechanism, in response to stress. Here, Raghavan injects a stress-inducing substance into the leaves of a foxglove plant.
After injecting a stress-inducing substance into a foxglove plant, Raghavan will analyze leaves to see whether the plant produced more cardenolides than usual under stress.
The darkened areas of the leaf are spots where the foxglove plant has absorbed the stress-inducing substance.
Published August 15, 2022
Healing with medicinal plants is as old as humankind itself. Even today, some of the most extensively used drugs such as aspirin, morphine, and quinine are directly extracted from plants. Unlike synthetic drugs, plant natural products are evolutionarily pre-selected chemicals against a wide spectrum of pathogens and other stresses in the environment. However, most plant-based medicines, although biologically effective, have not entered the realm of modern medicine. The biggest challenge is the lack of effective and sustainable methods for producing plant-based medicines because they are present at extremely low concentrations, sometimes less than 0.0001% of fresh weight. The current strategy of farming host plants is unlikely to meet the increasing demand for plant-derived drugs. In addition, these natural products usually have complex chemical structures, and conventional drug synthesis has not been able to produce them in a cost-effective manner.
The long-term goal in my laboratory is to provide alternative solutions for the sustainable and economical production of plant-based medicines through metabolic engineering and synthetic biology. In particular, we build novel metabolic pathways and reroute native pathways in microorganisms such as E. coli and yeast for the production of plant-derived drugs. Our current focus is terpene, the largest family of plant natural products. Many essential medicines including anti-cancer drug paclitaxel, vinblastine, and vincristine, are terpenes or terpene derivatives. Moreover, a complete understanding of biosynthesis pathways in host plants precedes any engineering efforts for scalable production of plant-based medicines. To this end, we are investigating the missing genes in the biosynthesis of digoxin—an important medicine on the World Health Organization’s (WHO) list of essential medicines for the treatment of heart failure. With the unprecedented technological advancement including DNA synthesis, -omics tools, and genome editing in recent years, we hope to tap into the great diversity of plant natural products to benefit the human health."