Full Time Professor
Bioengineering Department
When we think that reality is stranger than fiction, these news appear that change our perspective. Scientists from the Department of Paleobiotechnology at the Leibniz Institute for Research on Natural Products and Infection Biology (Leibniz-HKI) have recently discovered a number of new molecules that could prove effective against both fungal plant diseases and human pathogenic fungi. . But so far, what does the actor Keanu Reeves have to do with this discovery?
The group of molecules was named keanumycins in honor of the actor and his characters, mainly John Wick.
As reported by Pierre Stallforth, head of the Paleobiotechnology department, investigation of the ecological context of predator-prey microbial interactions allows the identification of microorganisms that produce multiple secondary metabolites to evade predation or kill the predator. In addition, genome searching combined with molecular biology methods can be used to identify more biosynthetic gene pools that produce new antimicrobials to combat the antimicrobial crisis. By contrast, classical sensing based approaches have limitations, as they do not claim to unlock the full biosynthetic potential of a given organism.
In a new study published by the American Chemical Society (ACS) the team of researchers describe the genomics-based identification of keanumycins A–C. These molecules are nonribosomal peptides that allow bacteria of the genus Pseudomonas to evade predation by amoebae. While amebicidal at the nanomolar level, these compounds also exhibit strong antifungal activity, particularly against the devastating plant pathogen Botrytis cinerea , and dramatically inhibit infection of Hydrangea macrophylla leaves using only Pseudomonas culture supernatants . Finally, a detailed microarray analysis of the whole genome of Candida albicans exposed to keanumycin A shed light on the mode of action of this potential product that will help the development of new pharmaceutical and agrochemical antifungals.
Nuclear magnetic resonance techniques, tandem mass spectrometry, and degradation experiments were used to obtain the molecular structures, revealing an unprecedented terminal imine motif in keanumycin C that extends the non-ribosomal amino acid family by a building block. highly reactive. According to the study, the deadly effect of bacteria of the genus Pseudomonas resides in these toxins, the keanumycins, of which only one type was known up to now, but of which scientists have now discovered 3 different classes: the so-called keanumycin A, B and C.
The researchers were able to isolate one of these keanumycins and conduct further testing. “This group of natural molecules belongs to the non-ribosomal lipopeptides with soapy properties,” explained Götze, one of the researchers and project leaders in statements to the media. He added: “Lipopeptides kill so efficiently that we named them after Keanu Reeves because he is also extremely lethal in his roles.”
According to tests carried out so far, the natural product is not highly toxic to human cells and is already effective against fungi at very low concentrations. This makes it a good candidate for pharmaceutical development of new antifungals, something that is urgently needed as very few antifungal drugs are currently on the market.
References:
Götze, S., Vij, R., Burow, K., Thome, N., Urbat, L., Schlosser, N., Pflanze, S., Müller, R., Hänsch, V. G., Schlabach, K., Fazlikhani, L., Walther, G., Dahse, H.-M., Regestein, L., Brunke, S., Hube, B., Hertweck, C., Franken, P., & Stallforth, P. (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), 2342–2353. https://doi.org/10.1021/jacs.2c11107
Rodríguez, H., Editor y periodista especializado en ciencia y naturaleza, & Berg, E. van den. (2023, February 10). La Molécula Keanu Reeves, Una Aliada letal en la Lucha Microbiana. www.nationalgeographic.com.es. Retrieved April 4, 2023, from https://www.nationalgeographic.com.es/ciencia/molecula-keanu-reeves-aliada-letal-lucha-microbiana_19489
Simmons, L. (2023, February 7). New Keanu Reeves molecules are deadly weapon in the fight against fungi. IFLScience. Retrieved April 4, 2023, from https://www.iflscience.com/new-keanu-reeves-molecules-a-deadly-weapon-in-the-fight-against-fungi-67424
Images:
Genome mining_Gotze_2023 – American Chemical Society
Keanu Reeves – IMDb
Keanu mycin – IFLScience
