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Related Experiment Video

Updated: Aug 12, 2025

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
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Complex scaffold remodeling in plant triterpene biosynthesis.

Ricardo De La Peña1, Hannah Hodgson2, Jack Chun-Ting Liu3

  • 1Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.

Science (New York, N.Y.)
|January 26, 2023
PubMed
Summary

Researchers discovered 22 enzymes enabling the complete biosynthesis of limonoids, like kihadalactone A and azadirone. This breakthrough unlocks access to valuable plant compounds and aids in understanding complex triterpene pathways.

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Area of Science:

  • Plant biochemistry
  • Natural product biosynthesis
  • Enzymology

Background:

  • Triterpenes, including limonoids, are prevalent in plants with significant commercial value.
  • Limonoids are known for their bitter taste in citrus and insecticidal properties in neem oil.
  • A complete biosynthetic pathway for limonoids has remained elusive.

Purpose of the Study:

  • To elucidate the complete biosynthetic route of limonoids.
  • To identify the enzymes involved in the complex skeletal rearrangements and oxidations of triterpenes.
  • To enable the production of valuable limonoids like kihadalactone A and azadirone.

Main Methods:

  • Discovery and characterization of 22 novel enzymes.
  • Identification of a pair of neofunctionalized sterol isomerases.
  • Reconstitution of the total biosynthesis pathway for specific limonoids.

Main Results:

  • Detailed the complete biosynthetic pathway for kihadalactone A and azadirone.
  • Identified 12 distinct enzymatic reactions, including novel sterol isomerizations.
  • Demonstrated the feasibility of accessing complex limonoids through enzymatic synthesis.

Conclusions:

  • The discovered enzyme set provides a complete biosynthetic route for key limonoids.
  • This work offers a framework for discovering and reconstructing other plant triterpene pathways.
  • Enables biotechnological production of valuable limonoids and related compounds.