Scientists from the Leibniz Institute for Natural Product Research and Infection Biology in Jena, Germany (Leibniz-HKI) have identified three natural compounds with incredibly effective fungicidal capabilities.
In fact, these compounds are so skilled at taking out fungi that they’ve been named after the legendary actor Keanu Reeves, known for his roles in action movies like John Wick and The Matrix.
Meet keanumycins, the mean, green, fungi-killing machines.
A threat to human and plant health
Recently, fungal infections have been a trending topic, especially after HBO’s release of The Last of Us, which suggests the severity of these infections and how they can spread at a rapid rate. Although none of the infections we currently face will send us spiraling into a post-apocalyptic society, several fungi still pose a severe threat to human and plant health. Every year, there are over 150 million cases of severe fungal infections worldwide, leading to almost 1.7 million deaths. These numbers continue to rise as fungi become more drug-resistant due to the long-term therapeutic use of antifungal drugs (1).
Additionally, fungal infections destroy around 125 million tons of our top food crops (wheat, corn, rice, potatoes, and soy), costing global agriculture almost $60 billion in losses annually (2). Unfortunately, there are not many drugs against fungal infections on the market, and many fungicides can be harmful to both human and environmental health. Though statistics seem grim, perhaps the discovery and development of naturally occurring compounds like keanumycins can push us forward in the direction of a more effective solution.
The discovery of keanumycins
The discovery of the compounds all comes down to a genus of bacteria called Pseudomonas, which is commonly found all over the environment, primarily in soil and water. Many species within this bacterial family are incredibly toxic to the amoebas that feed off of them. According to a report from CNN, researchers were studying Pseudomonas for their ability to fight off harmful amoebas when they discovered a natural byproduct with antimicrobial compounds called lipopeptides. Since amoebas have a comparable cell structure to fungi, scientists tested out the newly discovered compounds and found that they were just as effective at taking out fungi. As explained by the study’s coauthor, Sebastian Götze, “The lipopeptides kill so efficiently that we named them after Keanu Reeves because he, too, is extremely deadly in his roles.” As a result, the three nonribosomal peptides became known as keanumycins A, B, and C.
Research on keanumycins shows promising results
A study posted in the Journal of the American Chemical Society noted that the keanumycin compounds were tested in several ways to prove their capabilities as a natural pesticide (3). In one experiment, keanumycin A was tested against a common plant pathogen called gray mold rot. The fungus, Botrytis cinerea, initially develops on flowers or leaves, then quickly spreads to other areas of the plant. Over 200 flowering species and possibly another thousand other plant species can be impacted by the fungus (4). Some of the most common horticultural crops affected are vegetables like broccoli, lettuce, and beans, as well as fruit crops like grapes, strawberries, and raspberries.
For the test, researchers inoculated the fungi on hydrangea leaves, which are highly susceptible to the fungal disease. They recorded photos of the leaves three and five days after the incubation and found that keanumycin A reduced the fungal rotting significantly in comparison to the control group. These results are promising, considering that the compound can fight against the fungus in very low concentrations. With further research, scientists could discover how to potentially harness the abilities of keanumycin as a commercial fungicide.
Researchers conducted further tests to see how keanumycins impact pathogenic fungi, such as Candida albicans, a yeast that manifests as a harmful fungal infection in humans. Although Canidida lives inside and on the body, an overgrowth can lead to a severe yeast infection. If the infection enters the bloodstream, it can lead to serious health complications, not only in the blood but also in internal organs. According to testing, keanumycins were also successful at significantly inhibiting the growth of this fungus (5). Though testing is still in its early stages, there’s a possibility that keanumycins can pave the way for a range of diverse antifungal agents in the future.
A green alternative to traditional fungicides and antimycotics
With overwhelming evidence that demonstrates the potential of keanumycins, these compounds could one day be a natural and more efficient substitute for the chemical antifungal agents that we currently use. Researchers hope that keanumycins achieve what traditional antimycotics fall short on. Since plant and animal pathogens are continuously evolving resistance to the chemicals we use on them, it is only a matter of time before our current methods are no longer effective. There is a growing concern among scientists, including Götze, regarding the dilemma. As Götze explains in an interview with the Washington Post that “Not many new antibiotics, at the moment, are being developed, and the same also goes for antifungals.” Götze also emphasizes the severity of the situation to a German research institution, Phys.org, expressing that “We have a crisis in anti-infectives… Many human-pathogenic fungi are now resistant to antimycotics (antifungals) — partly because they are used in large quantities in agricultural fields.” With more resistant fungi on the rise, researchers are left scrambling for solutions to help protect the health of plants and humans from dangerous fungal diseases. Götze’s comments are an important reminder that there is a current, urgent need to address this crisis before it becomes even more severe.
Fortunately, the study of kanamycin found that they are “good lead structure candidates for the development of antifungal drugs," as stated by researcher Dr. Matt Nelsen from Chicago’s Field Museum.
Rather than using chemical pesticides that can be harmful to human and ecological health, kanamycins are an environmentally friendly alternative for farms that lose millions of dollars annually to fungal diseases.
In addition, since the compounds are relatively harmless to human cells, they could be used as a more natural option that potentially works better than any antifungals currently used to treat these serious diseases.
Keanu’s response to the naming
During a recent Reddit Q&A session, Keanu Reeves was asked about his thoughts on being named after a scientific compound. In reply, Keanu shared his appreciation for the unique honor, saying, “they should’ve called it John Wick…but that’s pretty cool and surreal for me. He also expresses his gratitude towards the scientific community for their efforts in seeking better alternatives for the well-being of others. “Thanks, scientist people,” he remarks, “Good luck, and thank you for helping us.”
Keanu’s humble yet witty response proves just how fitting he is to be named after such an impressive scientific discovery. Further tests will be conducted on the compound to hopefully prove that keanumycins truly live up to their villain-busting title.
References
- Kainz, Katharina, Maria A. Bauer, Frank Madeo, and Didac Carmona-Gutierrez. 2020. “Fungal Infections in Humans: The Silent Crisis.” Microbial Cell 7 (6): 143–45. https://doi.org/10.15698/mic2020.06.718.
- Fisher, Matthew C., Daniel. A. Henk, Cheryl J. Briggs, John S. Brownstein, Lawrence C. Madoff, Sarah L. McCraw, and Sarah J. Gurr. 2012. “Emerging Fungal Threats to Animal, Plant and Ecosystem Health.” Nature 484 (7393): 186–94. https://doi.org/10.1038/nature10947.
- Mitchinson, Andrew. 2023. “Bacterial Defence Repurposed to Fight Blight.” Nature 614 (7946): 39–39. https://doi.org/10.1038/d41586-023-00195-x.
- Boddy, Lynne. 2016. “Botrytis Cinerea – an Overview | ScienceDirect Topics.” Sciencedirect.com. 2016. https://www.sciencedirect.com/topics/neuroscience/botrytis-cinerea.
- Götze, Sebastian, Raghav Vij, Katja Burow, Nicola Thome, Lennart Urbat, Nicolas Schlosser, Sebastian Pflanze, et al. 2023. “Ecological Niche-Inspired Genome Mining Leads to the Discovery of Crop-Protecting Nonribosomal Lipopeptides Featuring a Transient Amino Acid Building Block.” Journal of the American Chemical Society 145 (4): 2342–53. https://doi.org/10.1021/jacs.2c11107.