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Reviving Extinct Plant Genes: Implications for Drug Development
Researchers at Northeastern University have successfully resurrected an extinct gene from the coyote tobacco plant, unlocking new insights into plant evolution and creating possibilities for drug discovery.
Under the leadership of Jing-Ke Weng, a professor specializing in chemistry, chemical biology, and bioengineering, the team focused on repairing a non-functional gene in the coyote tobacco species. Their findings, detailed in a recent publication in the Proceedings of the National Academy of Sciences, reveal the presence of an innovative type of cyclic peptide named nanamin. According to Weng, this discovery represents a significant advancement in drug development capabilities.
“This provides chemical biologists with additional tools necessary for developing new peptide-based treatments for cancer, discovering new antibiotics, and even enhancing agricultural defenses against pathogens and pests,” Weng explains.
Historically, plants have been instrumental in the evolution of pharmaceuticals. Weng notes a trend that favors human-synthesized compounds, which often lack the efficacy derived from the natural evolutionary processes of plants. “Creating drug-like compounds from random structures can be challenging. Nature has refined these processes over millions of years, so molecules like nanamin likely serve distinct roles in their ecosystems. We aim to harness this evolutionary knowledge for new drug discoveries,” he adds.
Cyclic peptides offer unique opportunities for drug creation. These small molecules, composed of modest chains of amino acids, possess properties that align well with pharmaceutical needs. “Cyclic peptides are diminutive, combining features characteristic of proteins while being easier to engineer,” Weng remarks. “We can construct vast libraries of these peptides to facilitate drug screening efficiently.”
The research team’s previous explorations into cyclic peptides led them to investigate the genetic material of the coyote tobacco. In doing so, they identified a pseudogene that had lost its functionality over time due to genetic drift. Although this gene had originally encoded the cyclic peptide nanamin, the passage of time had rendered it useless. Nevertheless, the researchers persevered and discovered that a functional version of the gene still existed in related plant species. Through a novel technique known as molecular gene resurrection, they successfully cloned and repaired this gene.
“To our astonishment, we managed to restore the ancestral function of this gene,” Weng states. “We are attempting to accelerate an evolutionary process that would usually unfold over millions of years, achieving it instead in a matter of months or years in the laboratory.”
Weng emphasizes that their work not only brings new life to extinct genes but also highlights the potential of cyclic peptides and nanamin in various applications. Already, his lab is harnessing the properties of nanamin to identify new cancer treatments. Additionally, in 2024, a partnership was established with Bayer Crop Science to leverage cyclic peptides in developing insect resistance for corn and bean crops. The potential to easily engineer these peptides into crops marks a fresh approach to enhancing agricultural resilience amidst climate variability.
The focus on the genetic and chemical attributes of coyote tobacco has allowed the research team to witness “evolution in action,” ultimately enriching our understanding of plant life that often goes unnoticed in our surroundings. “Plants are extraordinary chemists,” Weng concludes. “They have evolved to produce a multitude of compounds as forms of communication with their environment. This research exemplifies that capability.”
More information: Elliot M. Suh et al, The emergence and loss of cyclic peptides in Nicotiana illuminate dynamics and mechanisms of plant metabolic evolution, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2425055122
Source
phys.org