The newly discovered natural product group of keanumycins in bacteria has been shown to be effective against the plant pest Botrytis cinerea, which causes grey mould rot and massive harvest losses every year. However, the active ingredient also inhibits dangerous fungi to humans, such as Candida albicans. Previous research has shown that it is safe for both plant and human cells.
Keanumycins could thus be an environmentally friendly alternative to chemical pesticides, as well as an option in the fight against resistant fungi. “There is an anti-infective crisis,” says Sebastian Götze, first author of the study and postdoc at Leibniz-HKI. “Many human-pathogenic fungi are now resistant to antimycotics, owing in part to their widespread use in agricultural fields.”
As lethal as John Wick
It is no coincidence that the researchers have discovered a new active ingredient in bacteria of the genus Pseudomonas. “We’ve been working with pseudomonads for a while and know that many of these bacterial species are extremely toxic to amoebae, which eat bacteria,” says study leader Pierre Stallforth. He is the head of the Paleobiotechnology department at Leibniz-HKI, as well as a professor of Bioorganic Chemistry and Paleobiotechnology at Friedrich Schiller University in Jena.
It appears that several toxins, of which only one was previously identified, are responsible for the bacteria’s lethal effect. The researchers discovered biosynthesis genes for the newly discovered natural products, keanumycins A, B, and C, in the bacteria’s genome. This natural product category includes nonribosomal lipopeptides having soap-like characteristics.
The researchers were successful in isolating one of the keanumycins and conducted additional experiments with colleagues at the Leibniz-Bio HKI’s Pilot Plant. “We called the lipopeptides after Keanu Reeves because he, too, is highly lethal in his roles,” Götze adds with a smile.
The researchers believed that keanumycins may also kill fungi, which resemble amoebas in certain ways. This assumption was proven in collaboration with the University of Applied Sciences Erfurt’s Research Centre for Horticultural Crops. Keanumycin was shown to be efficient against grey mould rot on hydrangea leaves in that study. In this example, culture fluid that no longer included bacterial cells was enough to dramatically restrict fungal development.
“In theory, the keanumycin-containing supernatant from Pseudomonas cells may be utilised directly for plants,” Götze explains. Further testing will be carried out in collaboration with colleagues in Erfurt. Because keanumycin is biodegradable, no long-lasting leftovers should occur in the soil. This suggests that the natural substance has the potential to be a safer alternative to chemical pesticides.
Every year, fungal infections such as Botrytis cinerea, which causes grey mould rot, cause enormous harvest losses in fruit and vegetable crops. Strawberry and immature grapes are among the more than 200 fruit and vegetable varieties impacted.
Human applications are possible.
“Furthermore, we tested the isolated compound against a variety of human-infecting fungus. Among other things, we discovered that it substantially suppresses the harmful fungus Candida albicans “explains Götze.
Keanumycin might potentially be utilised in people instead of plants. According to preliminary testing, the natural substance is not very hazardous to human cells and is already effective against fungus at extremely low quantities. As a result, it is an excellent candidate for the pharmacological development of novel antimycotics. These are also desperately required, since there are relatively few medications available to treat fungal infections.
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