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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

CYP712K4 Catalyzes the C-29 Oxidation of Friedelin in the Maytenus ilicifolia Quinone Methide Triterpenoid Biosynthesis Pathway

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Author(s):
Bicalho, Keylla U. [1, 2, 3, 4] ; Santoni, Mariana M. [2, 4] ; Arendt, Philipp [1, 3] ; Zanelli, Cleslei F. [2] ; Furlan, Maysa [4] ; Goossens, Alain [1, 3] ; Pollier, Jacob [1, 3, 5]
Total Authors: 7
Affiliation:
[1] Univ Ghent, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent - Belgium
[2] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Biol Sci, Araraquara, SP - Brazil
[3] VIB Ctr Plant Syst Biol, B-9052 Ghent - Belgium
[4] Sao Paulo State Univ UNESP, Inst Chem, Dept Organ Chem, Araraquara, SP - Brazil
[5] VIB Metabol Core, B-9052 Ghent - Belgium
Total Affiliations: 5
Document type: Journal article
Source: Plant and Cell Physiology; v. 60, n. 11, p. 2510-2522, NOV 2019.
Web of Science Citations: 0
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. (AU)

FAPESP's process: 14/50926-0 - INCT 2014: biodiversity and natural products
Grantee:Vanderlan da Silva Bolzani
Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
Grantee:Glaucius Oliva
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 15/25175-3 - Cloning and characterization of cytochrome P450 oxidoreductase type from Maytenus ilicifolia and their effect on increasing the production of quinonamethide triterpenes by heterologous expression in Saccharomyces ceravisiae
Grantee:Keylla Utherdyany Bicalho
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 17/10911-1 - Combinatorial biosynthesis of triterpenes in Saccharomyces cerevisiae and Nicotiana benthamiana systems using P450 enzymes on friedelin substrate
Grantee:Keylla Utherdyany Bicalho
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 16/16970-7 - Study of the impact of the role of eIF5A in the cell proteomic profile using Saccharomyces cerevisiae as a model
Grantee:Cleslei Fernando Zanelli
Support Opportunities: Regular Research Grants