A team of researchers from the Max Planck Institute for Chemical Ecology in Jena revealed the complete biosynthetic path for the development of strychnine in the plant types Strychnos nux-vomica (poison nut). The scientists led by Benke Hong and Sarah OConnor from the Department of Natural Product Biosynthesis not just had to discover one missing out on link, however they had to unwind the entire chain of biosynthetic events that lead to the development of strychnine in the toxin nut tree. Benke Hongs group has now tackled this massive task: “Our crucial concern was how to discover the genes accountable for the biosynthesis of strychnine in the toxin nut. As a first action, we compared the expression of genes (transcriptome) from 2 types of the same genus (Strychnos), however of which just the toxin nut tree produces strychnine. The scientists were not able to find a corresponding enzyme that catalyzed the last action of strychnine biosynthesis, the conversion of prestrychnine to strychnine.
Toxin nut tree Strychnos nux-vomica. Credit: Danny Kessler, Max Planck Institute for Chemical Ecology
Researchers from Jena demonstrate how the toxin nut tree forms strychnine.
A group of researchers from limit Planck Institute for Chemical Ecology in Jena disclosed the total biosynthetic path for the development of strychnine in the plant species Strychnos nux-vomica (toxin nut). After identifying all genes associated with the biosynthesis of strychnine and other metabolites, the researchers expressed them in the model plant Nicotiana benthamiana. This demonstrated that these incredibly complex and pharmacologically essential particles can be synthesized utilizing “metabolic engineering” techniques.
Strychnine is something many people know about from criminal activity books, reports, or films. Agatha Christie had several of her victims die of strychnine poisoning.
In science, also, investigative impulse and detective work are sometimes needed. The scientists led by Benke Hong and Sarah OConnor from the Department of Natural Product Biosynthesis not only needed to find one missing link, but they needed to unwind the whole chain of biosynthetic events that result in the development of strychnine in the poison nut tree. Remain in the language of crime literature, one could state: They have actually resolved the case!
Robert Robinson, the chemist and Nobel Prize winner, who was among the first to clarify the structure of strychnine in the 1940s, as soon as explained this monoterpene indole alkaloid as the most complex chemical substance for its molecular size. Numerous chemists were captivated by the architecture of the strychnine molecule and developed ways to produce this molecule utilizing chemical synthesis. Remarkably, nevertheless, nobody had yet prospered in figuring out how plants produce this natural item.
Contrast of gene activity
Benke Hongs group has actually now tackled this mammoth job: “Our key concern was how to discover the genes accountable for the biosynthesis of strychnine in the toxin nut. As a very first step, we compared the expression of genes (transcriptome) from 2 species of the very same genus (Strychnos), however of which only the poison nut tree produces strychnine. We chose candidate genes for each step based upon the proposed chemical transformation, which we did not understand was appropriate or not,” Benke Hong explains.
The upstream genes of strychnine biosynthesis to the formation of a crucial intermediate (geissoschizine) have been fully elucidated in the medicinal plant Catharanthus roseus (Madagascar periwinkle), which is likewise being studied in Sarah OConnors department, and the homologous genes have been determined in the poison nut tree.
Chemical reasoning
“You might state that chemistry directed the discovery of the genes in our study. Based on chemical structures and systems, each action in the metabolic pathway yielded a proposed chemical change.
As evidence that the determined genes were responsible for the proposed biosynthetic actions, the researchers customized tobacco plants (Nicotiana benthamiana) to temporarily produce the enzymes from Strychnos. After including the proper feed materials, they then investigated whether the assumed item was produced by the transformed tobacco plant. This method permitted high-throughput testing of multiple genes concurrently, which shortened the time needed to solve the puzzle.
Prestrychnine converts to strychnine.
The researchers were not able to discover a corresponding enzyme that catalyzed the last step of strychnine biosynthesis, the conversion of prestrychnine to strychnine. With the secret of the last step solved, the researchers were therefore able to elucidate the complete biosynthetic path of strychnine, as well as the related molecules brucine and diaboline. While brucine is likewise produced by the toxin nut, diaboline is produced by a related species of the genus Strychnos, that does not produce either strychnine or brucine.
The elucidation of plant metabolite biosynthesis and the biotechnological use of the genetic basis for the formation of clinically important plant substances in design plants are appealing research fields. The current research study opens up new possibilities for the production of previously unidentified plant natural products utilizing “metabolic engineering” techniques.
Referral: “Biosynthesis of strychnine” by Benke Hong, Dagny Grzech, Lorenzo Caputi, Prashant Sonawane, Carlos E. Rodríguez López, Mohamed Omar Kamileen, Néstor J. Hernández Lozada, Veit Grabe and Sarah E. OConnor, 6 July 2022, Nature.DOI: 10.1038/ s41586-022-04950-4.