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Title: Production of highly bioactive resveratrol analogues pterostilbene and piceatannol in metabolically engineered grapevine cell cultures
Author: Martínez Márquez, Ascensión
Morante Carriel, Jaime A
Ramírez Estrada, Karla
Cusidó Vidal, Rosa M.
Palazón Barandela, Javier
Bru Martínez, Roque
Keywords: Cultiu cel·lular
Metabolisme de les plantes
Enginyeria genètica vegetal
Cell culture
Plant metabolism
Plant genetic engineering
Issue Date: 11-Jan-2016
Publisher: John Wiley & Sons
Abstract: 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 resveratrolconverting 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
Note: Reproducció del document publicat a:
It is part of: Plant Biotechnology Journal, 2016, vol. 14, p. 1813-1825
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ISSN: 1467-7644
Appears in Collections:Articles publicats en revistes (Biologia, Sanitat i Medi Ambient)

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