Production of Anthocyanins in Grape Cell Cultures: A potential Source of Raw Material for Pharmaceutical, Food, and Cosmetic Industries

Research continues to show that many artificial pigments are actually detrimental to our health. According to [1], there is an increasing consumer preference for healthy foods, which has invit‐ ed considerable demand for the use of anthocyanins as natural colorants, because of their natu‐ ral pedigree and healthful properties. Anthocyanins are the most widely distributed group of water-soluble plant pigments in nature. They are mainly responsible for the mauve, red, blue, and purple colors in flowers, fruits, leaves, seeds and other organs in most of the flowering plants. The other important class of water-soluble pigments are betalains, which are present on‐ ly in plants belonging to 13 families of Caryophyllales order [2-5]. An interesting phenomenon is the existence of mutual exclusiveness of anthocyanins and betalains in plant kingdom [3, 5-9]. Recent research demonstrated that simultaneous production of anthocyanins and betalains is possible in cell cultures and seedlings of anthocyanin producing plants by introduction and ex‐ pression of genes encoding dihydroxyphenylalanine (L-DOPA) dioxygenases in combination with substrate precursor feeding [10]. However, the co-occurrence of both pigments in the same plant species have never been found in nature and the plants which produce anthocyanins nev‐ er produce betalains and vice versa [6]. The commercial production of anthocyanin pigments is one of the fastest growing segments of the food colorant industry [2, 11]. The only industrial sources for anthocyanin pigments are from whole plant extracts [1], with the most common source being grape skins from the wine industry. According to [1], the demand of natural colo‐ rants continues to rise by 5-15% every year and this translated to the sales of anthocyanins isolat‐ ed from grape skins in 2002, which was estimated to be US$200 million worldwide. The increase

[1]  R. Bino,et al.  The light-hyperresponsive high pigment-2dg mutation of tomato: alterations in the fruit metabolome. , 2005, The New phytologist.

[2]  J. Mérillon,et al.  Condensed tannin and anthocyanin production in Vitis vinifera cell suspension cultures , 1996, Plant Cell Reports.

[3]  E. Peterlunger,et al.  Transcriptional regulation of anthocyanin biosynthesis in ripening fruits of grapevine under seasonal water deficit. , 2007, Plant, cell & environment.

[4]  A. Mortensen Carotenoids and other pigments as natural colorants , 2006 .

[5]  E. Grotewold,et al.  Different Mechanisms Participate in the R-dependent Activity of the R2R3 MYB Transcription Factor C1* , 2004, Journal of Biological Chemistry.

[6]  M. Giusti,et al.  Anthocyanins: natural colorants with health-promoting properties. , 2010, Annual review of food science and technology.

[7]  Linda Chalker-Scott,et al.  Environmental Significance of Anthocyanins in Plant Stress Responses , 1999 .

[8]  P. Broun Transcriptional control of flavonoid biosynthesis: a complex network of conserved regulators involved in multiple aspects of differentiation in Arabidopsis. , 2005, Current opinion in plant biology.

[9]  S. Conn,et al.  Purification, molecular cloning, and characterization of glutathione S-transferases (GSTs) from pigmented Vitis vinifera L. cell suspension cultures as putative anthocyanin transport proteins , 2008, Journal of experimental botany.

[10]  A. Azuma,et al.  Flavonoid biosynthesis-related genes in grape skin are differentially regulated by temperature and light conditions , 2012, Planta.

[11]  P. Bordallo,et al.  Synchronized somatic embryo development in embryogenic suspensions of grapevine Muscadinia rotundifolia (Michx.) Small , 2015 .

[12]  N. Stanietsky,et al.  The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity , 2009, Proceedings of the National Academy of Sciences.

[13]  K. Gould,et al.  Flavonoid functions in plants. , 2006 .

[14]  Phillip D. Zamore,et al.  RNA Interference , 2000, Science.

[15]  Wei Zhang,et al.  Manipulating anthocyanin composition in Vitis vinifera suspension cultures by elicitation with jasmonic acid and light irradiation , 2003, Biotechnology Letters.

[16]  K. Davies,et al.  Plant pigments and their manipulation. , 2004 .

[17]  A. Marchev,et al.  Two-phase temporary immersion system for Agrobacterium rhizogenes genetic transformation of sage (Salvia tomentosa Mill.) , 2011, Biotechnology Letters.

[18]  K. Roubelakis-Angelakis Molecular biology & biotechnology of the grapevine , 2001 .

[19]  T. Ferrier,et al.  The Transcription Factor VvMYB5b Contributes to the Regulation of Anthocyanin and Proanthocyanidin Biosynthesis in Developing Grape Berries12[W] , 2008, Plant Physiology.

[20]  Hirohiko Hirochika,et al.  Retrotransposon-Induced Mutations in Grape Skin Color , 2004, Science.

[21]  R. D. Stefano,et al.  Caractérisation variétale de cépages musqués à raisin coloré au moyen de paramètres ampélographiques descriptifs et biochimiques , 2015 .

[22]  Fei He,et al.  Biosynthesis of Anthocyanins and Their Regulation in Colored Grapes , 2010, Molecules.

[23]  Kazuo Tsugane,et al.  Efficient gene targeting by homologous recombination in rice , 2002, Nature Biotechnology.

[24]  W. Steyn Prevalence and Functions of Anthocyanins in Fruits , 2008 .

[25]  A. Bovy,et al.  Improving the nutritional content of tomatoes through reprogramming their flavonoid biosynthetic pathway , 2004, Phytochemistry Reviews.

[26]  A. Miyao,et al.  Target Site Specificity of the Tos17 Retrotransposon Shows a Preference for Insertion within Genes and against Insertion in Retrotransposon-Rich Regions of the Genome Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.012559. , 2003, The Plant Cell Online.

[27]  W. Schwab,et al.  A double mutation in the anthocyanin 5-O-glucosyltransferase gene disrupts enzymatic activity in Vitis vinifera L. , 2009, Journal of agricultural and food chemistry.

[28]  Giovanni Agati,et al.  Rapid and non‐destructive method to assess in the vineyard grape berry anthocyanins under different seasonal and water conditions* , 2011 .

[29]  P. Williams,et al.  Identification of anthocyanins in muscadine grapes with HPLC-ESI-MS , 2009 .

[30]  J. Yoder,et al.  Lc as a non‐destructive visual reporter and transposition excision marker gone for tomato , 1996 .

[31]  N. Goto-Yamamoto,et al.  Structure and transcription of three chalcone synthase genes of grapevine (Vitis vinifera) , 2002 .

[32]  N. Ramsay,et al.  MYB-bHLH-WD40 protein complex and the evolution of cellular diversity. , 2005, Trends in plant science.

[33]  John M Leavitt,et al.  Regulation of the anthocyanin biosynthetic pathway by the TTG1/bHLH/Myb transcriptional complex in Arabidopsis seedlings. , 2008, The Plant journal : for cell and molecular biology.

[34]  C. Bowler,et al.  Fruit-specific RNAi-mediated suppression of DET1 enhances carotenoid and flavonoid content in tomatoes , 2005, Nature Biotechnology.

[35]  C. Ulrichs,et al.  Specific Poly-phenolic Compounds in Cell Culture of Vitis vinifera L. cv. Gamay Fréaux , 2011, Applied biochemistry and biotechnology.

[36]  R. Dixon,et al.  Flavonoids and isoflavonoids - a gold mine for metabolic engineering. , 1999, Trends in plant science.

[37]  D. Gray,et al.  Effects of exogenous abscisic acid on antioxidant capacities, anthocyanins, and flavonol contents of muscadine grape (Vitis rotundifolia) skins , 2011 .

[38]  R. Hall,et al.  Metabolic engineering of flavonoids in tomato (Solanum lycopersicum): the potential for metabolomics , 2007, Metabolomics.

[39]  T. Bley,et al.  Betalain production in plant in vitro systems , 2008, Acta Physiologiae Plantarum.

[40]  M. Oren-Shamir,et al.  Increased accumulation and decreased catabolism of anthocyanins in red grape cell suspension culture following magnesium treatment , 2011, Planta.

[41]  David Lamb,et al.  PA—Precision Agriculture: Remote-Sensing and Mapping of Weeds in Crops , 2001 .

[42]  V. Walbot,et al.  Impact of low-temperature stress on general phenylpropanoid and anthocyanin pathways: Enhancement of transcript abundance and anthocyanin pigmentation in maize seedlings , 1994, Planta.

[43]  Simon C. Deroles,et al.  Anthocyanin Biosynthesis in Plant Cell Cultures: A Potential Source of Natural Colourants , 2008 .

[44]  K. Gould,et al.  Anthocyanic vacuolar inclusions--their nature and significance in flower colouration. , 2000, Phytochemistry.

[45]  M. Sakuta,et al.  Effect of phosphate deficiency on the content and biosynthesis of anthocyanins and the expression of related genes in suspension-cultured grape (Vitis sp.) cells. , 2012, Plant physiology and biochemistry : PPB.

[46]  Simcha Lev-Yadun,et al.  Role of Anthocyanins in Plant Defence , 2008 .

[47]  P. Waterhouse,et al.  Role of short RNAs in gene silencing. , 2001, Trends in plant science.

[48]  H. Honda,et al.  Enhancement of anthocyanin production from grape (Vitis vinifera) callus in a viscous additive-supplemented medium , 2001 .

[49]  C. Santos-Buelga,et al.  Recent Advances in Polyphenol Research , 2008 .

[50]  P. Boss,et al.  Molecular Biology of Sugar and Anthocyanin Accumulation in Grape Berries , 2001 .

[51]  S. Conn,et al.  Characterization of anthocyanic vacuolar inclusions in Vitis vinifera L. cell suspension cultures , 2010, Planta.

[52]  E. Schijlen,et al.  Modification of flavonoid biosynthesis in crop plants. , 2004, Phytochemistry.

[53]  E. Grotewold The genetics and biochemistry of floral pigments. , 2006, Annual review of plant biology.

[54]  T. Holton,et al.  Genetics and Biochemistry of Anthocyanin Biosynthesis. , 1995, The Plant cell.

[55]  S. Iida,et al.  Isolation of cDNAs for R2R3-MYB, bHLH and WDR transcriptional regulators and identification of c and ca mutations conferring white flowers in the Japanese morning glory. , 2006, Plant & cell physiology.

[56]  H. Budzinski,et al.  Production of highly 13C-labeled polyphenols in Vitis vinifera cell bioreactor cultures. , 2004, Journal of biotechnology.

[57]  D. R. Wagner,et al.  Activation Tagging in Tomato Identifies a Transcriptional Regulator of Anthocyanin Biosynthesis, Modification, and Transport Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.012963. , 2003, The Plant Cell Online.

[58]  F. Meins RNA degradation and models for post-transcriptional gene silencing , 2000, Plant Molecular Biology.

[59]  M. Krsnik-Rasol,et al.  Complex Biochemistry and Biotechnological Production of Betalains , 2011 .

[60]  C. Napoli,et al.  Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans. , 1990, The Plant cell.

[61]  D. Lewis,et al.  Betalain production is possible in anthocyanin-producing plant species given the presence of DOPA-dioxygenase and L-DOPA , 2012, BMC Plant Biology.

[62]  L. Gény,et al.  ABA Initiates Anthocyanin Production in Grape Cell Cultures , 2011, Journal of Plant Growth Regulation.

[63]  J. Mol,et al.  Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression. , 1990, The Plant cell.

[64]  R. Koes,et al.  Flavonoids: a colorful model for the regulation and evolution of biochemical pathways. , 2005, Trends in plant science.

[65]  James F Harbertson,et al.  Modulation of flavonoid biosynthetic pathway genes and anthocyanins due to virus infection in grapevine (Vitis vinifera L.) leaves , 2010, BMC Plant Biology.

[66]  Masahiko Suzuki Enhancement of Anthocyanin Accumulation by High Osmotic Stress and Low pH in Grape Cells (Vitis hybrids) , 1995 .

[67]  Ø. M. Andersen Recent Advances in the Field of Anthocyanins – Main Focus on Structures , 2009 .

[68]  de C.H. Vos,et al.  Increasing antioxidant levels in tomatoes through modification of the flavonoid biosynthetic pathway. , 2002, Journal of experimental botany.

[69]  P. Neubauer,et al.  Elicitation and precursor feeding influence phenolic acids composition in Vitis vinifera suspension culture , 2012 .

[70]  A. Mercadante Anthocyanins in Foods: Occurrence and Physicochemical Properties , 2007 .

[71]  S. Lund,et al.  Characterization of a Vitis vinifera cv. Cabernet Sauvignon 3',5'-O-methyltransferase showing strong preference for anthocyanins and glycosylated flavonols. , 2010, Phytochemistry.

[72]  Masahiko Kitayama,et al.  Loss of anthocyanins in red-wine grape under high temperature. , 2007, Journal of experimental botany.

[73]  A. S. Duque,et al.  Cell suspension cultures , 2006 .

[74]  C. Napoli,et al.  Modification of Flower Color in Florist's Chrysanthemum: Production of a White–Flowering Variety Through Molecular Genetics , 1994, Bio/Technology.

[75]  A. Vardi,et al.  Aloe vera transformation: the role of Amberlite XAD-4 resin and antioxidants during selection and regeneration , 2010, In Vitro Cellular & Developmental Biology - Plant.

[76]  F. Vardar-Sukan,et al.  Large scale cultivation of plant cell and tissue culture in bioreactors , 2010 .

[77]  G. Mazza,et al.  Anthocyanins in grapes and grape products. , 1995, Critical reviews in food science and nutrition.

[78]  O. Paredes-López,et al.  Natural Colorants for Food and Nutraceutical Uses , 2002 .

[79]  M. Shiraishi,et al.  Genomic and genetic analysis of Myb-related genes that regulate anthocyanin biosynthesis in grape berry skin , 2008, Theoretical and Applied Genetics.

[80]  Yoshikazu Tanaka,et al.  Biosynthesis of plant pigments: anthocyanins, betalains and carotenoids. , 2008, The Plant journal : for cell and molecular biology.

[81]  F. Zülli,et al.  Potential of plant cells in culture for cosmetic application , 2008, Phytochemistry Reviews.

[82]  J. Mol,et al.  Novel coloured flowers. , 1999, Current opinion in biotechnology.

[83]  S. Delrot,et al.  Differential screening of overexpressed genes involved in flavonoid biosynthesis in North American native grapes: ‘Noble’ muscadinia var. and ‘Cynthiana’ aestivalis var. , 2009 .

[84]  S. Hammond,et al.  An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells , 2000, Nature.

[85]  M. Netzel,et al.  Bioavailability and Biokinetics of Anthocyanins From Red Grape Juice and Red Wine , 2004, Journal of biomedicine & biotechnology.

[86]  J. Ranish,et al.  Transcription: basal factors and activation. , 1996, Current opinion in genetics & development.

[87]  C. Tonelli,et al.  Recent advances on the regulation of anthocyanin synthesis in reproductive organs. , 2011, Plant science : an international journal of experimental plant biology.

[88]  E. Shklarman,et al.  Modification of flower color and fragrance by antisense suppression of the flavanone 3-hydroxylase gene , 2002, Molecular Breeding.

[89]  Kazuki Saito,et al.  Recent advances in the biosynthesis and accumulation of anthocyanins. , 2003, Natural product reports.

[90]  L. Flora INFLUENCE OF HEAT, CULTIVAR AND MATURITY ON THE ANTHOCYANIDIN—3,5—DIGLUCOSIDES OF MUSCADINE GRAPES , 1978 .

[91]  Yoshikazu Tanaka,et al.  A rationale for the shift in colour towards blue in transgenic carnation flowers expressing the flavonoid 3',5'-hydroxylase gene. , 2003, Phytochemistry.

[92]  C. Cruz,et al.  Genetic diversity of table grape based on morphoagronomic traits , 2010 .

[93]  W. E. Ballinger,et al.  ANTHOCYANINS OF BLACK GRAPES OF 10 CLONES OF Vitis rotundifolia, MICHX. , 1973 .

[94]  M. Lila Anthocyanins and Human Health: An In Vitro Investigative Approach , 2004, Journal of Biomedicine and Biotechnology.

[95]  M. Thomas,et al.  White grapes arose through the mutation of two similar and adjacent regulatory genes. , 2007, The Plant journal : for cell and molecular biology.

[96]  P. Goussard,et al.  In Vitro Culture and Propagation of Grapevine , 2001 .

[97]  N. Goto-Yamamoto,et al.  Effects of Temperature on Anthocyanin Biosynthesis in Grape Berry Skins , 2006, American Journal of Enology and Viticulture.

[98]  D. Rivera,et al.  Plant Pigments and their manipulation , 2006 .

[99]  B. Coombe,et al.  Development of the grape berry. II. Changes in diameter and deformability during veraison , 1980 .

[100]  Wei Zhang,et al.  Integration of jasmonic acid and light irradiation for enhancement of anthocyanin biosynthesis in Vitis vinifera suspension cultures , 2002 .

[101]  G. Nedelea,et al.  Experimental results concerning the effect of culture medium pH on the synthesized anthocyanin amount in the callus culture of Vitis vinifera L. , 2012 .

[102]  R. Verpoorte,et al.  Elicitor signal transduction leading to production of plant secondary metabolites. , 2005, Biotechnology advances.

[103]  T. Lacombe,et al.  Wine grape (Vitis vinifera L.) color associates with allelic variation in the domestication gene VvmybA1 , 2007, Theoretical and Applied Genetics.

[104]  Florian C. Stintzing,et al.  Functional properties of anthocyanins and betalains in plants, food, and in human nutrition , 2004 .

[105]  G. Pasqua,et al.  Effects of elicitors on the production of resveratrol and viniferins in cell cultures of Vitis vinifera L. cv Italia. , 2011, Journal of agricultural and food chemistry.

[106]  B. Burr,et al.  Molecular analysis of the maize anthocyanin regulatory locus C1. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[107]  J. Ochieng,et al.  Elevated gene expression in chalcone synthase enzyme suggests an increased production of flavonoids in skin and synchronized red cell cultures of North American native grape berries. , 2012, DNA and cell biology.

[108]  R. Durst,et al.  Characterization of Tomatoes Expressing Anthocyanin in the Fruit , 2008 .

[109]  P. This,et al.  Genetic mechanisms underlying the methylation level of anthocyanins in grape (Vitis vinifera L.) , 2011, BMC Plant Biology.

[110]  Jun Wang,et al.  Anthocyanins Profile of Grape Berries of Vitis amurensis, Its Hybrids and Their Wines , 2010, International journal of molecular sciences.

[111]  I. Smetanska,et al.  Stimulation of anthocyanin synthesis in grape (Vitis vinifera) cell cultures by pulsed electric fields and ethephon , 2011, Plant Cell, Tissue and Organ Culture (PCTOC).

[112]  S. Motoike,et al.  Genetic diversity in table grapes based on RAPD and microsatellite markers , 2011 .

[113]  G. Mazza,et al.  Bioactivity, Absorption, and Metabolism of Anthocyanins , 2007 .

[114]  M. D. Berber-Jimenez,et al.  Anthocyanin Pigments: Comparison of Extract Stability , 1994 .

[115]  R. Dixon,et al.  Proanthocyanidins--a final frontier in flavonoid research? , 2005, The New phytologist.

[116]  J. Mérillon,et al.  Regulation of polyphenol production in Vitis vinifera cell suspension cultures by sugars , 1998, Plant Cell Reports.

[117]  L. Tian,et al.  Expression of the chalcone synthase gene from grape and preparation of an anti-CHS antibody. , 2006, Protein expression and purification.

[118]  C. Socaciu 7.2 Natural Pigments as Food Colorants , 2007 .

[119]  I. Mewis,et al.  Polysaccharide elicitors enhance anthocyanin and phenolic acid accumulation in cell suspension cultures of Vitis vinifera , 2011, Plant Cell, Tissue and Organ Culture (PCTOC).

[120]  Rickey Y. Yada,et al.  ANTHOCYANINS AS FOOD COLORANTS —A REVIEW , 1987 .

[121]  Wei Zhang,et al.  Production of anthocyanins by plant cell cultures , 1999 .

[122]  Bhagyalakshmi Neelwarne Red Beet Biotechnology: Food and Pharmaceutical Applications , 2012 .

[123]  Ronald W. Davis,et al.  Arabidopsis and Nicotiana anthocyanin production activated by maize regulators R and C1. , 1992, Science.

[124]  S. Rao,et al.  Plant cell cultures: Chemical factories of secondary metabolites. , 2002, Biotechnology advances.

[125]  J. Tardaguila,et al.  Assessment of the spatial variability of anthocyanins in grapes using a fluorescence sensor: relationships with vine vigour and yield , 2012, Precision Agriculture.

[126]  A. Azuma,et al.  VvmybA1 genotype determines grape skin color , 2007 .

[127]  H. Honda,et al.  Enhanced anthocyanin production from grape callus in an air-lift type bioreactor using a viscous additive-supplemented medium. , 2002, Journal of bioscience and bioengineering.

[128]  C. Honda,et al.  Myb-related genes of the Kyoho grape (Vitis labruscana) regulate anthocyanin biosynthesis , 2002, Planta.

[129]  Maicun Deng,et al.  Hyper-production of 13C-labeled trans-resveratrol in Vitis vinifera suspension cell culture by elicitation and in situ adsorption , 2011 .

[130]  C. Socaciu Food Colorants Chemical and Functional Properties , 2007 .

[131]  A. Baudry,et al.  MYBL2 is a new regulator of flavonoid biosynthesis in Arabidopsis thaliana. , 2008, The Plant journal : for cell and molecular biology.

[132]  T. Wallace Anthocyanins in cardiovascular disease. , 2011, Advances in nutrition.

[133]  D. Knorr,et al.  Enhanced anthocyanins and resveratrol production in Vitis vinifera cell suspension culture by indanoyl-isoleucine, N-linolenoyl-L-glutamine and insect saliva. , 2012, Enzyme and microbial technology.

[134]  Wei Zhang,et al.  A combination of elicitation and precursor feeding leads to increased anthocyanin synthesis in cell suspension cultures of Vitis vinifera , 2011, Plant Cell, Tissue and Organ Culture (PCTOC).

[135]  G. Gall,et al.  Characterization and content of flavonoid glycosides in genetically modified tomato (Lycopersicon esculentum) fruits. , 2003, Journal of agricultural and food chemistry.

[136]  Da-You Zhao,et al.  Chemistry, Distribution, and Metabolism of Tomato Carotenoids and Their Impact on Human Health , 2002, Experimental biology and medicine.

[137]  B. Winkel-Shirley,et al.  Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology. , 2001, Plant physiology.

[138]  C. Duan,et al.  Biosynthesis and Genetic Regulation of Proanthocyanidins in Plants , 2008, Molecules.

[139]  小林 省藏,et al.  Association of VvmybA1 Gene Expression with Anthocyanin Production in Grape (Vitis vinifera) Skin-color Mutants , 2005 .

[140]  J. Pereira,et al.  Phenolics: From Chemistry to Biology , 2009, Molecules.

[141]  J. Mol,et al.  Regulatory Genes Controlling Anthocyanin Pigmentation Are Functionally Conserved among Plant Species and Have Distinct Sets of Target Genes. , 1993, The Plant cell.

[142]  Pamela S Soltis,et al.  Complex pigment evolution in the Caryophyllales. , 2011, The New phytologist.

[143]  A. Bovy,et al.  Overexpression of petunia chalcone isomerase in tomato results in fruit containing increased levels of flavonols , 2001, Nature Biotechnology.

[144]  P. Bailey,et al.  AtMYB12 regulates caffeoyl quinic acid and flavonol synthesis in tomato: expression in fruit results in very high levels of both types of polyphenol. , 2008, The Plant journal : for cell and molecular biology.

[145]  H. N. Murthy,et al.  In vitro production of gymnemic acid from cell suspension cultures of Gymnema sylvestre R. Br , 2011 .

[146]  V. Georgiev,et al.  Relationship between type and age of the inoculum cultures and betalains biosynthesis by Beta vulgaris hairy root culture , 2003, Biotechnology Letters.

[147]  D. Knorr,et al.  Effects of elicitors and high hydrostatic pressure on secondary metabolism of Vitis vinifera suspension culture , 2011 .

[148]  R. Hall,et al.  Enrichment of tomato fruit with health-promoting anthocyanins by expression of select transcription factors , 2008, Nature Biotechnology.

[149]  T. Mabry Selected topics from forty years of natural products research: betalains to flavonoids, antiviral proteins, and neurotoxic nonprotein amino acids. , 2001, Journal of natural products.

[150]  R. M. Spanswick,et al.  Enhanced anthocyanin production in grape cell cultures , 1991 .

[151]  P. Perata,et al.  Purple as a Tomato: towards High Anthocyanin Tomatoes Update , 2022 .

[152]  E. Schijlen,et al.  High-Flavonol Tomatoes Resulting from the Heterologous Expression of the Maize Transcription Factor Genes LC and C1 Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.004218. , 2002, The Plant Cell Online.

[153]  J. Mol,et al.  An anti-sense chalcone synthase gene in transgenic plants inhibits flower pigmentation , 1988, Nature.

[154]  Yoshikazu Tanaka,et al.  cDNA Cloning, Heterologous Expressions, and Functional Characterization of Malonyl-Coenzyme A:Anthocyanidin 3-O-Glucoside-6"-O-Malonyltransferase from Dahlia Flowers1 , 2002, Plant Physiology.

[155]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[156]  Jean-Hugues B. Hatier,et al.  Anthocyanin Function in Vegetative Organs , 2008 .

[157]  O. Paredes-López,et al.  Natural Pigments: Carotenoids, Anthocyanins, and Betalains — Characteristics, Biosynthesis, Processing, and Stability , 2000, Critical reviews in food science and nutrition.

[158]  C. Petolescu,et al.  Experimental results concerning the synthesized anthocyanin amount in the Vitis vinifera L. suspension cell culture in the laboratory bioreactor. , 2009 .

[159]  D. Knorr,et al.  Effects of Pulsed Electric Field on Secondary Metabolism of Vitis vinifera L. cv. Gamay Fréaux Suspension Culture and Exudates , 2011, Applied biochemistry and biotechnology.

[160]  P. Boss,et al.  Anthocyanin composition and anthocyanin pathway gene expression in grapevine sports differing in berry skin colour , 1996 .

[161]  Wei Zhang,et al.  Instability of anthocyanin accumulation inVitis vinifera L. var. Gamay Fréaux suspension cultures , 2005 .

[162]  Q. Pan,et al.  Three types of ultraviolet irradiation differentially promote expression of shikimate pathway genes and production of anthocyanins in grape berries. , 2012, Plant physiology and biochemistry : PPB.

[163]  E. Schijlen Genetic engineering of flavonoid biosynthesis in tomato , 2007 .

[164]  M. Stephenson,et al.  Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[165]  J. Gray,et al.  Two basic-helix-loop-helix genes (MYC-146 and GL3) from Arabidopsis can activate anthocyanin biosynthesis in a white-flowered Matthiola incana mutant , 2003, Plant Molecular Biology.

[166]  Alison Downham,et al.  Colouring our foods in the last and next millennium , 2000 .

[167]  R. Wrolstad,et al.  Anthocyanin pigments: Bioactivity and coloring properties , 2006 .

[168]  A. Caudy,et al.  Role for a bidentate ribonuclease in the initiation step of RNA interference , 2001 .

[169]  P. Bailey,et al.  A Small Family of MYB-Regulatory Genes Controls Floral Pigmentation Intensity and Patterning in the Genus Antirrhinum[W] , 2006, The Plant Cell Online.

[170]  S. Popescu,et al.  Experimental results concerning the effect of photoperiod and callus culture duration on anthocyanin synthesis. , 2010 .

[171]  Elicitation and precursor feeding influence phenolic acids composition in Vitis vinifera suspension culture , 2012 .

[172]  K. Schwinn,et al.  CH 3 Molecular Biology and Biotechnology of Flavonoid Biosynthesis , 2006 .

[173]  H. Huits,et al.  Flavonoid synthesis in Petunia hybrida: partial characterization of dihydroflavonol-4-reductase genes , 1989, Plant Molecular Biology.

[174]  P. Boss,et al.  Analysis of the Expression of Anthocyanin Pathway Genes in Developing Vitis vinifera L. cv Shiraz Grape Berries and the Implications for Pathway Regulation , 1996, Plant physiology.

[175]  K. R. Markham,et al.  Chalcones, dihydrochalcones, and aurones. , 2006 .

[176]  T. Bley,et al.  Bioreactors for the Cultivation of Red Beet Hairy Roots , 2013 .

[177]  D. Merdinoglu,et al.  Four specific isogenes of the anthocyanin metabolic pathway are systematically co-expressed with the red colour of grape berries , 2006 .

[178]  T. Vogt Phenylpropanoid biosynthesis. , 2010, Molecular plant.

[179]  R. Dixon,et al.  Proanthocyanidin biosynthesis--still more questions than answers? , 2005, Phytochemistry.

[180]  R. Prior,et al.  Systematic identification and characterization of anthocyanins by HPLC-ESI-MS/MS in common foods in the United States: fruits and berries. , 2005, Journal of agricultural and food chemistry.

[181]  A. Aharoni,et al.  The strawberry FaMYB1 transcription factor suppresses anthocyanin and flavonol accumulation in transgenic tobacco. , 2001, The Plant journal : for cell and molecular biology.

[182]  M. Downey,et al.  Proanthocyanidin Synthesis and Expression of Genes Encoding Leucoanthocyanidin Reductase and Anthocyanidin Reductase in Developing Grape Berries and Grapevine Leaves1[w] , 2005, Plant Physiology.

[183]  V. Lauvergeat,et al.  Characterization of a Grapevine R2R3-MYB Transcription Factor That Regulates the Phenylpropanoid Pathway1[W] , 2005, Plant Physiology.

[184]  C. Tonelli,et al.  Cloning and molecular analysis of structural genes involved in flavonoid and stilbene biosynthesis in grape (Vitis vinifera L.) , 1994, Plant Molecular Biology.

[185]  S. Conn,et al.  Anthocyanic vacuolar inclusions (AVIs) selectively bind acylated anthocyanins in Vitis vinifera L. (grapevine) suspension culture , 2003, Biotechnology Letters.

[186]  P. Brat,et al.  Stability and analysis of phenolic pigments , 2007 .

[187]  C. D. Cruz,et al.  Diversidade genética de acessos de uvas de mesa baseada em caracteres morfoagronômicos , 2011 .

[188]  J. Mol,et al.  The flavonoid biosynthetic pathway in plants: Function and evolution , 1994 .