BioTechniques News
Beatrice Bowlby
Lurking within two deadly blooms, researchers have discovered a suite of enzymes that catalyze the production of an essential metabolite, potentially opening the door to new medicines.
From a spinach-based treatment for dry eye disease to biosynthesis breakthroughs with therapeutic potential, scientists are constantly taking inspiration from the plant kingdom when designing novel medicines. Now, a serendipitous collaboration between scientists at Michigan State University (MI, USA) and the Czech Academy of Sciences (Prague, Czechia) has joined these ranks, focusing on two poisonous plants to identify crucial steps in the biosynthesis of atisinium, an alkaloid that may hold promise for the treatment of pain, malaria and cancer.
To support their defense, interactions with other organisms and ecological adaptation, plants have evolved a sophisticated arsenal of chemical weapons. These specialized compounds frequently prove to be biologically relevant and are fundamental to the discovery of novel drugs; for example, morphine, the anti-malarial artemisinin and the cancer drug paclitaxel are all derived from plants. In the words of study author Björn Hamberger: “plants are the best chemists around.”
At present, there is growing interest in diterpenoid alkaloids – metabolites with a wide range of bioactivities found primarily within the Aconitum and Delphinium genera. However, their structural complexity has long puzzled scientists and presented a barrier for chemical synthesis. Uncovering the biosynthetic pathways that underlie the production of these compounds would help mitigate some of the challenges, but so far, little progress has been made in this area.
That tide could be set to turn thanks to the researchers’ study of larkspur and wolfsbane, two related and highly toxic plants. To identify how they produce their diterpenoid alkaloids, the team conducted transcriptome sequencing on Delphinium grandiflorum, Aconitum plicatum and Aconitum lycoctonum, and used public data to assemble transcriptomes of four other Aconitum species, all of which are known to accumulate diterpenoid alkaloids. This allowed for comparative transcriptomics, which revealed several promising genetic candidates that the team then expressed in tobacco plants (Nicotiana benthamiana).
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Ultimately, this led to the identification of six enzymes that are active in the biosynthesis of the diterpenoid alkaloid atisinium. Key to the pathway is a reductase that selectively incorporates ethanolamine over ethylamine, supporting the formation of atisinium.
Moreover, isotope labeling in Aconitum callus cultures combined with computational metabolomics revealed that ethanolamine is the unexpected yet preferred source of nitrogen for these compounds.
By furthering our understanding of the biochemistry behind atisinium production, the researchers hope their breakthrough could result in promising medical applications for this molecule and the wider diterpenoid alkaloid family.
“In an ideal scenario, this could eventually help create new drugs inspired by these natural products,” concluded co-first author Lana Mutabdžija.
“Our vision is to provide green, sustainable tools that will allow us harness these plants’ natural power,” Hamberger added.
The post Deadly flowers may unlock the secret to synthesizing potent new medicines appeared first on BioTechniques.
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