Case Solved: The Biosynthesis of Strychnine
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Loading... - Darcelle Nke
- 15 Aug 2022
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Researchers show how the poison nut tree forms strychnine.
A team of scientists from the Max Planck Institute for Chemical Ecology disclosed the complete biosynthetic pathway for the formation of strychnine in the plant species Strychnos nux-vomica (poison nut). After identifying all genes involved in the biosynthesis of strychnine and other metabolites, the researchers expressed them in the model plant Nicotiana benthamiana. This demonstrated that these extremely complex and pharmacologically important molecules can be synthesized using “metabolic engineering” methods.
Strychnine is something many people know about from crime reports, novels, or films. For example, Agatha Christie had several of her victims die of strychnine poisoning. In her first novel “The Mysterious Affair at Style,” she described what is probably the best-known fictional murder case involving the highly toxic alkaloid used as rat poison. The final clue to solving the case was found by the legendary detective character Hercule Poirot in his first literary appearance.
In science, as well, investigative instinct and detective work are sometimes required. The scientists led by Benke Hong and Sarah O’Connor from the Department of Natural Product Biosynthesis not only had to find one missing link, but they had to unravel the entire chain of biosynthetic events that lead to the formation of strychnine in the poison nut tree. Stay in the language of crime literature, one could say: They have solved the case!
Robert Robinson, the chemist and Nobel Prize winner, who was one of the first to elucidate the structure of strychnine in the 1940s, once described this monoterpene indole alkaloid as the most complex chemical substance for its molecular size. Many chemists were intrigued by the architecture of the strychnine molecule and developed ways to produce this molecule using chemical synthesis. Surprisingly, however, no one had yet succeeded in determining how plants produce this natural product.
Comparison of gene activity
Benke Hong’s team has now tackled this mammoth task: “Our key question was how to find the genes responsible for the biosynthesis of strychnine in the poison nut. As a first step, we compared the expression of genes (transcriptome) from two species of the same genus (Strychnos), but of which only the poison nut tree produces strychnine. We selected candidate genes for each step based on the proposed chemical transformation, which we did not know was correct or not,” Benke Hong explains. Read More...
