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Production of highly bioactive resveratrol analogues pterostilbene and piceatannol in metabolically engineered grapevine cell cultures

Martínez‐Márquez, Ascensión ; Morante‐Carriel, Jaime A. ; Ramírez‐Estrada, Karla ; Cusidó, Rosa M. ; Palazon, Javier ; Bru‐Martínez, Roque

Plant biotechnology journal, 2016-09, Vol.14 (9), p.1813-1825 [Periódico revisado por pares]

England: John Wiley & Sons, Inc

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Título:
Production of highly bioactive resveratrol analogues pterostilbene and piceatannol in metabolically engineered grapevine cell cultures
Autor: Martínez‐Márquez, Ascensión ; Morante‐Carriel, Jaime A. ; Ramírez‐Estrada, Karla ; Cusidó, Rosa M. ; Palazon, Javier ; Bru‐Martínez, Roque
Assuntos: Bioavailability ; Biological activity ; Biotechnology ; Cancer ; Carbon ; Cell culture ; Cell Culture Techniques ; Cultiu cel·lular ; Cyclodextrin ; Cyclodextrins ; Cytochrome ; Cytochrome P450 ; Cytochromes P450 ; Derivatives ; Dextrins ; Enginyeria genètica vegetal ; Feasibility studies ; Gene Expression Regulation, Plant ; Grapes ; grapevine cell culture ; Hydroxylase ; Kinases ; Metabolic Engineering ; Metabolism ; Metabolisme de les plantes ; Metabolites ; Methyl jasmonate ; Methyltransferase ; Nicotiana benthamiana ; Phosphorylation ; Piceatannol ; Plant genetic engineering ; Plant metabolism ; Plants, Genetically Modified - genetics ; Plants, Genetically Modified - metabolism ; pterostilbene ; Resveratrol ; Stilbene ; Stilbene synthase ; Stilbenes - chemistry ; Stilbenes - metabolism ; Tobacco ; Vineyards ; Vinyes ; Vitaceae ; Vitis - cytology ; Vitis - genetics ; Vitis - metabolism ; Vitis vinifera
É parte de: Plant biotechnology journal, 2016-09, Vol.14 (9), p.1813-1825
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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This article is part of Ascensión Martínez‐Márquez's PhD thesis.
Descrição: Summary Grapevine stilbenes, particularly trans‐resveratrol, have a demonstrated pharmacological activity. Other natural stilbenes derived from resveratrol such as pterostilbene or piceatannol, display higher oral bioavailability and bioactivity than the parent compound, but are far less abundant in natural sources. Thus, to efficiently obtain these bioactive resveratrol derivatives, there is a need to develop new bioproduction systems. Grapevine cell cultures are able to produce large amounts of easily recoverable extracellular resveratrol when elicited with methylated cyclodextrins and methyl jasmonate. We devised this system as an interesting starting point of a metabolic engineering‐based strategy to produce resveratrol derivatives using resveratrol‐converting enzymes. Constitutive expression of either Vitis vinifera resveratrol O‐methyltransferase (VvROMT) or human cytochrome P450 hydroxylase 1B1 (HsCYP1B1) led to pterostilbene or piceatannol, respectively, after the engineered cell cultures were treated with the aforementioned elicitors. Functionality of both gene products was first assessed in planta by Nicotiana benthamiana agroinfiltration assays, in which tobacco cells transiently expressed stilbene synthase and VvROMT or HsCYP1B1. Grapevine cell cultures transformed with VvROMT produced pterostilbene, which was detected in both intra‐ and extracellular compartments, at a level of micrograms per litre. Grapevine cell cultures transformed with HsCYP1B1 produced about 20 mg/L culture of piceatannol, displaying a sevenfold increase in relation to wild‐type cultures, and reaching an extracellular distribution of up to 45% of total production. The results obtained demonstrate the feasibility of this novel system for the bioproduction of natural and more bioactive resveratrol derivatives and suggest new ways for the improvement of production yields.
Editor: England: John Wiley & Sons, Inc
Idioma: Inglês

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Production of highly bioactive resveratrol analogues pterostilbene and piceatannol in metabolically engineered grapevine cell cultures

Martínez‐Márquez, Ascensión ; Morante‐Carriel, Jaime A. ; Ramírez‐Estrada, Karla ; Cusidó, Rosa M. ; Palazon, Javier ; Bru‐Martínez, Roque

England: John Wiley & Sons, Inc

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