Complex scaffold remodeling in plant triterpene biosynthesis

Ricardo De La Pena; Hannah Hodgson; Chun-Ting Liu; Michael J Stephenson; Azahara Carmen Martin; Charlotte Owen; Alex Harkess; James Leebens-Mack; Luis Jimenez; Anne Osbourn; Elizabeth Sattely

doi:10.1126/science.adf1017

Complex scaffold remodeling in plant triterpene biosynthesis

Ricardo De La Pena, Hannah Hodgson, Chun-Ting Liu, Michael J Stephenson, Azahara Carmen Martin, Charlotte Owen, Alex Harkess, James Leebens-Mack, Luis Jimenez, Anne Osbourn, Elizabeth Sattely

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	361-368
Number of pages	8
Journal	Science
Volume	379
Issue number	6630
DOIs	https://doi.org/10.1126/science.adf1017
Publication status	Published - 27 Jan 2023

Keywords

Biosynthesis
Triterpenoids
Limonoids
Transient expression

Access to Document

10.1126/science.adf1017

adf1017_ArticleContent_v3Accepted author manuscript, 1.28 MB
adf1017_SupplementalMaterial_v3Accepted author manuscript, 7.39 MB

Cite this

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title = "Complex scaffold remodeling in plant triterpene biosynthesis",

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.",

keywords = "Biosynthesis, Triterpenoids, Limonoids, Transient expression",

author = "Pena, {Ricardo De La} and Hannah Hodgson and Chun-Ting Liu and Stephenson, {Michael J} and Martin, {Azahara Carmen} and Charlotte Owen and Alex Harkess and James Leebens-Mack and Luis Jimenez and Anne Osbourn and Elizabeth Sattely",

year = "2023",

month = jan,

day = "27",

doi = "10.1126/science.adf1017",

language = "English",

volume = "379",

pages = "361--368",

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T1 - Complex scaffold remodeling in plant triterpene biosynthesis

AU - Pena, Ricardo De La

AU - Hodgson, Hannah

AU - Liu, Chun-Ting

AU - Stephenson, Michael J

AU - Martin, Azahara Carmen

AU - Owen, Charlotte

AU - Harkess, Alex

AU - Leebens-Mack, James

AU - Jimenez, Luis

AU - Osbourn, Anne

AU - Sattely, Elizabeth

PY - 2023/1/27

Y1 - 2023/1/27

N2 - 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.

AB - 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.

KW - Biosynthesis

KW - Triterpenoids

KW - Limonoids

KW - Transient expression

U2 - 10.1126/science.adf1017

DO - 10.1126/science.adf1017

M3 - Article

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SP - 361

EP - 368

JO - Science

JF - Science

SN - 0036-8075

IS - 6630

ER -