Complex scaffold remodeling in plant triterpene biosynthesis

Author:

De La Peña Ricardo1ORCID,Hodgson Hannah2ORCID,Liu Jack Chun-Ting3ORCID,Stephenson Michael J.4ORCID,Martin Azahara C.5ORCID,Owen Charlotte2ORCID,Harkess Alex6ORCID,Leebens-Mack Jim7ORCID,Jimenez Luis E.1ORCID,Osbourn Anne2ORCID,Sattely Elizabeth S.18ORCID

Affiliation:

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

2. Department of Biochemistry and Metabolism, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.

3. Department of Chemistry, Stanford University, Stanford, CA 94305, USA.

4. School of Chemistry, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.

5. Department of Crop Genetics, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.

6. HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.

7. Department of Plant Biology, 4505 Miller Plant Sciences, University of Georgia, Athens, GA 30602, USA.

8. Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.

Abstract

Triterpenes with complex scaffold modifications are widespread in the plant kingdom. Limonoids are an exemplary family that are responsible for the bitter taste in citrus (e.g., limonin) and the active constituents of neem oil, a widely used bioinsecticide (e.g., azadirachtin). Despite the commercial value of limonoids, a complete biosynthetic route has not been described. We report the discovery of 22 enzymes, including a pair of neofunctionalized sterol isomerases, that catalyze 12 distinct reactions in the total biosynthesis of kihadalactone A and azadirone, products that bear the signature limonoid furan. These results enable access to valuable limonoids and provide a template for discovery and reconstitution of triterpene biosynthetic pathways in plants that require multiple skeletal rearrangements and oxidations.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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