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Area of Science:

  • Natural Product Chemistry
  • Organic Synthesis
  • Plant Biochemistry

Background:

  • Strychnine, a complex natural product, has significantly influenced organic chemistry.
  • Its potent neurotoxicity leads to its use as a rodenticide.
  • The biosynthesis of strychnine in plants remains unelucidated.

Purpose of the Study:

  • To elucidate the biosynthetic pathway of strychnine and related alkaloids (brucine, diaboline).
  • To demonstrate the feasibility of recapitulating this biosynthesis in a heterologous system.

Main Methods:

  • Isolation and structural elucidation of natural products.
  • Synthetic chemistry approaches to understand molecular construction.
  • Metabolic engineering in *Nicotiana benthamiana*.

Main Results:

  • The complete biosynthetic pathway for strychnine, brucine, and diaboline was determined.
  • Successful recapitulation of the biosynthesis of these alkaloids in *Nicotiana benthamiana* from an upstream intermediate was achieved.

Conclusions:

  • The study reveals how plants produce the complex strychnine scaffold.
  • Metabolic engineering offers a new avenue for harnessing the production of these pharmacologically active compounds.