The work done by Northeastern University researchers opens the doors to develop new cancer treatments, antibiotics and insect protection for crops.
Northeastern University researchers resurrected an extinct plant gene, turning back the evolutionary clock to pave a path forward for the development and discovery of new drugs.
Specifically, the team, led by Jing-Ke Weng, a professor of chemistry, chemical biology and bioengineering at Northeastern, repaired a defunct gene in the coyote tobacco plant. In a new paper, they detail their discovery of a previously unknown kind of cyclic peptide, or mini protein, called nanamin that is easy to bioengineer, making it “a platform with huge potential for drug discovery,” Weng says.
“It will provide chemical biologists with other tools to develop new peptide-based cancer treatments, for discovering new antibiotics and also for agricultural applications for defense against pathogens and insects,” Weng says.
Plants have driven countless innovations in the discovery and development of new drugs. However, Weng says there has been a more recent turn toward human-synthesized compounds that are not nearly as efficient as using a plant’s natural evolutionary process.
“If you start with random compounds, it’s actually pretty hard to get it to be druglike,” Weng says. “Evolution over hundreds of millions of years has done its job, so very likely nanamin and its analogs are already playing certain roles in nature. We’re just leveraging that and using that for drug discovery.”
That’s where cyclic peptides present an opportunity. Made up of short strings of amino acids, cyclic peptides are very small and almost tailor-made for use in drug development.
“Cyclic peptides are much smaller, so it’s like a small molecule drug but has the chemical features of a protein. You can also engineer it,” Weng says. “We can easily generate a library that produces millions of these peptides that can be used for drug screening.”
Weng’s Institute for Plant-Human Interface previously discovered that cyclic peptides exist in plants, which brought him to coyote tobacco, which is common in the Western United States. As Weng and his team delved into the genetic code of this plant, they discovered a pseudogene that was no longer functional.
This particular gene had previously encoded the cyclic peptide nanamin in coyote tobacco, but over time, due to adaptive mutations, it had faded away into the evolutionary past. But that didn’t stop Weng and his team.
They found that this gene still existed in related plant species and, using a new method called molecular gene resurrection, cloned the gene and corrected the mutation.
“To our surprise, we were able to recover the ancestral function of this gene,” Weng says. “We are trying to game the process that otherwise would take tens of millions of years to occur naturally, to be able to do it within just months or years in a lab.”
Beyond resurrecting an extinct gene, Weng says their research proves the viability of cyclic peptides, and nanamin specifically, as the foundation for a number of novel uses.
Nanamin’s size and chemical mutability makes it an asset for discovering new drugs; Weng and his lab are already using it to discover new drugs for cancer treatment. However, its uses extend to agriculture as well, he says.
In 2024, his lab started a collaboration with Bayer Crop Science and they are using cyclic peptides to develop anti-insect traits in corn and bean crops. The ease with which they can be easily coded and transplanted into crops from their original host plant is a novel approach to building crop resilience in a changing climate.
More broadly, delving into the genetics and chemical traits of coyote tobacco helped the researchers “capture evolution in action” in a way that could help us understand and appreciate the plants we walk by almost every day, he explains.
“The whole lifestyle for plants is to be a very good chemist,” Weng says. “They’re masters of chemistry. They have to evolve to produce so many compounds as their unique languages to communicate with the outside world. … This is one example we’re uncovering here.”