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

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Title: Production of highly bioactive resveratrol analogues pterostilbene and piceatannol in metabolically engineered grapevine cell cultures
Authors: Martínez Márquez, Ascensión | Morante Carriel, Jaime | Ramírez-Estrada, Karla | Cusidó, Rosa M. | Palazon, Javier | Bru-Martinez, Roque
Research Group/s: Proteómica y Genómica Funcional de Plantas
Center, Department or Service: Universidad de Alicante. Departamento de Agroquímica y Bioquímica
Keywords: Grapevine cell culture | Metabolic engineering | Piceatannol | Pterostilbene | Resveratrol | Vitis vinifera
Knowledge Area: Bioquímica y Biología Molecular
Issue Date: Sep-2016
Publisher: Society for Experimental Biology | Association of Applied Biologists | John Wiley & Sons
Citation: Plant Biotechnology Journal. 2016, 14(9): 1813-1825. doi:10.1111/pbi.12539
Abstract: 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.
Sponsor: This work has been supported by grants from the Spanish Ministry of Science and Innovation (BIO2011-29856-C02-01, BIO2011-29856-C02-02 and BIO2014-51861-R), Generalitat de Catalunya (2014SGR215) and European Funds for Regional Development (FEDER) and Conselleria d’Educacio, Cultura i Sport de la Generalitat Valenciana (FPA/2013/A/074). J.M.C. acknowledges a postdoctoral and research grants from SENESCYT GOVERNMENT OF ECUADOR (006-IECE-SMG5-GPLR-2012 and Programa1-Senescyt-2014) and a grant from UTEQ (UTEQAmbiental-9-FCAmb-IFOR-2014-FOCICYT002).
URI: http://hdl.handle.net/10045/57636
ISSN: 1467-7644 (Print) | 1467-7652 (Online)
DOI: 10.1111/pbi.12539
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Peer Review: si
Publisher version: http://dx.doi.org/10.1111/pbi.12539
Appears in Collections:INV - Proteómica y Genómica Funcional de Plantas - Artículos de Revistas

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