Salicylic acid, a compound chemically similar to aspirin, is found in willow tree bark and is made by the plant as a chemical defense against pathogens. By mimicking the chemical production processes of plants, scientists have been able to synthetically produce and engineer many important alkaloid drug products, including caffeine, atropine (an anti-spasmodic used to treat heart arrhythmia), nicotine, morphine, and quinine.
The trick, however, is to understand how a plant produces these compounds and then transports them through the plant. In a recent Proceedings of the National Academy of Sciences (PNAS) publication entitled “A tobacco nicotine uptake permease effects alkaloid metabolism,” a team of Virginia Tech and Purdue University scientists identified a distinct transporter used by tobacco plant cells for nicotine metabolism.
John Jelesko, associate professor of plant pathology, physiology, and weed science, and Sakiko Okumoto, assistant professor of plant pathology, physiology, and weed science, were the lead Virginia Tech scientists working on the project.
Both are affiliated faculty members with the Fralin Life Science Institute at Virginia Tech.
The transporter, called nicotine uptake permease, or NUP1 for short, allows alkaloids — nitrogen-containing compounds — to pass into plant cells. The transporter is a tubular structure found in the outer boundary of the plant cell, known as the plasma membrane. Passage of alkaloids from one cell to another in an assembly line fashion is crucial to the biosynthesis of many medicinal plant alkaloids. However, prior to the study, it was not known exactly how the alkaloids were able to move either in or out of the cell.
“We knew that the general process of going in and out is important for alkaloid metabolism, but we didn’t know the details,” said Jelesko.”The NUP1 transporter is very specific for nicotine — other closely related alkaloids don’t use this transporter. That degree of specificity is rather unusual.”
Identification of the transporter is a first step in understanding details about how the tobacco plant manages nicotine transport processes. So far, it is known that the chemical is made in the roots of tobacco plants, as a response to a pathogen attack. When ingested by insects and other organisms, it is a powerful neurotoxin, causing paralysis. Once produced in the roots, it is transported up through the rest of the plant by tube-like passageways called xylem and accumulates in the leaves. Tobacco farmers harvest nicotine by collecting the plant’s leaves.
The NUP1 gene was identified by looking for genes that were turned up or down in concert with known nicotine biosynthesis genes, Jelesko explained. The discovery of the transporter helps scientists gain new insight into the overarching field of medicinal alkaloid production in plants, Jelesko said. Understanding the complete process could enable bioengineering of medicinal plants to produce an optimal amount of compounds beneficial for treatment.
Research team leaders were Jelesko, Okumoto, and Angus Murphy, professor of horticulture at Purdue University. Co-authors in order are Sherry B. Hildreth, a postdoctoral associate in biological sciences at Virginia Tech who received her Ph.D. in plant pathology, physiology and weed science at Tech in 2009; Elizabeth A. Gehman, a former technician in plant pathology, physiology, and weed science at Virginia Tech, now with the Battelle National Biodefense Institute, National Biodefense Analysis and Countermeasures Center; Haibing Yang, a research scientist with the horticulture department at Purdue; Rong-He Lu, former technician in plant pathology, physiology and weed science at Virginia Tech; Ritesh KC, research specialist in plant pathology, physiology and weed science at Virginia Tech; Kim Harich, analytical chemist in the biochemistry department at Virginia Tech; Shi Yu, Ph.D. student in plant pathology, physiology and weed science at Virginia Tech; Jinshan Lin, Ph.D. student in horticulture at Purdue; Jackson L. Sandoe, a former undergraduate studnet in biological sciences at Virginia Tech, now a graduate student in molecular and cellular biology at Harvard University; Okumoto, Murphy, and Jelesko.
Seven Virginia Tech institutes support research and creative scholarship in strategically important areas, drawing upon the university’s established strengths. The Virginia Tech Carilion School of Medicine and Research Institute, the Virginia Tech Transportation Institute, and the Virginia Bioinformatics Institute focus on national research priorities, including translational health and medical research, national security, and safe infrastructure. The Institute for Critical Technology and Applied Science, Fralin Life Science Institute, and the Institute for Society, Culture, and Environment provide organizational and financial support to develop opportunities at the intersection of engineering, science, and medicine; target infectious disease; and advance human development. The Institute for Creativity, Arts, and Technology promotes creativity, critical thinking, and life-long learning.