Advanced search
2 files | 3.91 MB Add to list

CYP712K4 catalyzes the C-29 oxidation of friedelin in the Maytenus ilicifolia quinone methide triterpenoid biosynthesis pathway

(2019) PLANT AND CELL PHYSIOLOGY. 60(11). p.2510-2522
Author
Organization
Abstract
The native Brazilian plant Maytenus ilicifolia accumulates a set of quinone methide triterpenoids with important pharmacological properties, of which maytenin, pristimerin and celastrol accumulate exclusively in the root bark of this medicinal plant. The first committed step in the quinone methide triterpenoid biosynthesis is the cyclization of 2,3-oxidosqualene to friedelin, catalyzed by the oxidosqualene cyclase friedelin synthase (FRS). In this study, we produced heterologous friedelin by the expression of M. ilicifolia FRS in Nicotiana benthamiana leaves and in a Saccharomyces cerevisiae strain engineered using CRISPR/Cas9. Furthermore, friedelin-producing N. benthamiana leaves and S. cerevisiae cells were used for the characterization of CYP712K4, a cytochrome P450 from M. ilicifolia that catalyzes the oxidation of friedelin at the C-29 position, leading to maytenoic acid, an intermediate of the quinone methide triterpenoid biosynthesis pathway. Maytenoic acid produced in N. benthamiana leaves was purified and its structure was confirmed using high-resolution mass spectrometry and nuclear magnetic resonance analysis. The three-step oxidation of friedelin to maytenoic acid by CYP712K4 can be considered as the second step of the quinone methide triterpenoid biosynthesis pathway, and may form the basis for further discovery of the pathway and heterologous production of friedelanes and ultimately quinone methide triterpenoids.
Keywords
Celastrol, CYP712K4, Friedelin, Maytenoic acid, Maytenus ilicifolia, Quinone methide triterpenoids, TRANSIENT EXPRESSION, VECTORS, PLANTS, YEAST, PLATFORM, PROTEIN, SYSTEM

Downloads

  • Bicalho pcz144.pdf
    • full text (Accepted manuscript)
    • |
    • open access
    • |
    • PDF
    • |
    • 2.27 MB
  • (...).pdf
    • full text (Published version)
    • |
    • UGent only
    • |
    • PDF
    • |
    • 1.64 MB

Citation

Please use this url to cite or link to this publication:

MLA
Bicalho, Keylla, et al. “CYP712K4 Catalyzes the C-29 Oxidation of Friedelin in the Maytenus Ilicifolia Quinone Methide Triterpenoid Biosynthesis Pathway.” PLANT AND CELL PHYSIOLOGY, vol. 60, no. 11, 2019, pp. 2510–22, doi:10.1093/pcp/pcz144.
APA
Bicalho, K., Santoni, M. M., Arendt, P., Zanelli, C. F., Furlan, M., Goossens, A., & Pollier, J. (2019). CYP712K4 catalyzes the C-29 oxidation of friedelin in the Maytenus ilicifolia quinone methide triterpenoid biosynthesis pathway. PLANT AND CELL PHYSIOLOGY, 60(11), 2510–2522. https://doi.org/10.1093/pcp/pcz144
Chicago author-date
Bicalho, Keylla, Mariana M. Santoni, Philipp Arendt, Cleslei F. Zanelli, Maysa Furlan, Alain Goossens, and Jacob Pollier. 2019. “CYP712K4 Catalyzes the C-29 Oxidation of Friedelin in the Maytenus Ilicifolia Quinone Methide Triterpenoid Biosynthesis Pathway.” PLANT AND CELL PHYSIOLOGY 60 (11): 2510–22. https://doi.org/10.1093/pcp/pcz144.
Chicago author-date (all authors)
Bicalho, Keylla, Mariana M. Santoni, Philipp Arendt, Cleslei F. Zanelli, Maysa Furlan, Alain Goossens, and Jacob Pollier. 2019. “CYP712K4 Catalyzes the C-29 Oxidation of Friedelin in the Maytenus Ilicifolia Quinone Methide Triterpenoid Biosynthesis Pathway.” PLANT AND CELL PHYSIOLOGY 60 (11): 2510–2522. doi:10.1093/pcp/pcz144.
Vancouver
1.
Bicalho K, Santoni MM, Arendt P, Zanelli CF, Furlan M, Goossens A, et al. CYP712K4 catalyzes the C-29 oxidation of friedelin in the Maytenus ilicifolia quinone methide triterpenoid biosynthesis pathway. PLANT AND CELL PHYSIOLOGY. 2019;60(11):2510–22.
IEEE
[1]
K. Bicalho et al., “CYP712K4 catalyzes the C-29 oxidation of friedelin in the Maytenus ilicifolia quinone methide triterpenoid biosynthesis pathway,” PLANT AND CELL PHYSIOLOGY, vol. 60, no. 11, pp. 2510–2522, 2019.
@article{8625739,
  abstract     = {{The native Brazilian plant Maytenus ilicifolia accumulates a set of quinone methide triterpenoids with important pharmacological properties, of which maytenin, pristimerin and celastrol accumulate exclusively in the root bark of this medicinal plant. The first committed step in the quinone methide triterpenoid biosynthesis is the cyclization of 2,3-oxidosqualene to friedelin, catalyzed by the oxidosqualene cyclase friedelin synthase (FRS). In this study, we produced heterologous friedelin by the expression of M. ilicifolia FRS in Nicotiana benthamiana leaves and in a Saccharomyces cerevisiae strain engineered using CRISPR/Cas9. Furthermore, friedelin-producing N. benthamiana leaves and S. cerevisiae cells were used for the characterization of CYP712K4, a cytochrome P450 from M. ilicifolia that catalyzes the oxidation of friedelin at the C-29 position, leading to maytenoic acid, an intermediate of the quinone methide triterpenoid biosynthesis pathway. Maytenoic acid produced in N. benthamiana leaves was purified and its structure was confirmed using high-resolution mass spectrometry and nuclear magnetic resonance analysis. The three-step oxidation of friedelin to maytenoic acid by CYP712K4 can be considered as the second step of the quinone methide triterpenoid biosynthesis pathway, and may form the basis for further discovery of the pathway and heterologous production of friedelanes and ultimately quinone methide triterpenoids.}},
  author       = {{Bicalho, Keylla and Santoni, Mariana M. and Arendt, Philipp and Zanelli, Cleslei F. and Furlan, Maysa and Goossens, Alain and Pollier, Jacob}},
  issn         = {{0032-0781}},
  journal      = {{PLANT AND CELL PHYSIOLOGY}},
  keywords     = {{Celastrol,CYP712K4,Friedelin,Maytenoic acid,Maytenus ilicifolia,Quinone methide triterpenoids,TRANSIENT EXPRESSION,VECTORS,PLANTS,YEAST,PLATFORM,PROTEIN,SYSTEM}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{2510--2522}},
  title        = {{CYP712K4 catalyzes the C-29 oxidation of friedelin in the Maytenus ilicifolia quinone methide triterpenoid biosynthesis pathway}},
  url          = {{http://dx.doi.org/10.1093/pcp/pcz144}},
  volume       = {{60}},
  year         = {{2019}},
}

Altmetric
View in Altmetric
Web of Science
Times cited: