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Collaborative Opportunity for Production of Genistein-rich Plants

Introduction

Plant Research International has been working for the last ten years on the genetic regulation and modification of plant metabolic pathways, such as the amino acid-, alkaloid-, terpenes- and flavonoid biosynthesis pathways. Some of these compounds have received a lot of attention due to their presumed health-benefits. Our research in the past years has been aimed at increasing the levels of such health-promoting flavonoids in crop plants.

We have extensive know-how in the areas of biochemical detection of metabolites (using HPLC-PDA-MS, GC-MS) and engineering of metabolic pathways.

Using genetic engineering approaches we recently have been able to:

  • create metabolic diversity in a plant by introducing all Arabidopsis transcription factors;
  • find a transcription factor which is able to up-regulate the biosynthesis pathway leading to Genistein;
  • use this Arabidopsis transcription factor for the production of Genistein in Medicagotruncatula, the model plant for Legumes;
  • produce high level of Genistein in a continuously growing plant tissue culture (contained growth).

This research led to a genetic tool to induce high-level Genistein production in plants, and to a Genistein-producing tissue culture system. Genistein is an important nutraceutical isoflavonoid present in nature in soybean seeds, and has a wide variety of pharmaceutical effects in animal and human cells. These effects are based on the structural features which it shares with the estrogen, estradiol.

Vision/Strategy

In modern, ageing societies the incidence of diseases such as breast- and prostate cancer and coronary heart diseases increases every year. Also, women may encounter many problems caused by post-menopausal effects. This results in a reduction of life quality and puts an enormous pressure on the health-care system and its associated costs.

Various compounds in foods have a wide range of beneficial biochemical and pharmacological effects, including anticarcinogenic, anti-inflammatory and antioxidant properties. For example, the presence of isoflavonoids and Genistein in the diet (like in a soybean-rich diet) may reduce the risk of breast and prostate cancer, cardiovascular disease and post-menopausal problems.

Due to altered dietary habits and lifestyle, an increasing number of people within the societies of developed countries no longer meet the required intake of beneficial food ingredients. There is an increasing interest both in western and Asian world for either the production of food crops with an increased level of isoflavonoids, or the cheap production of compounds such as Genistein which can be isolated and sold as nutraceutical or pharmaceutical.

Our strategy is to unravel the regulation mechanism of health-promoting flavonoids biosynthesis, in order to be able to develop food crops and production systems in which these compounds are increased. To reach these goals we make use of the latest technologies in metabolite profiling and compound identification (metabolomics), gene expression profiling (DNA microarrays, transcriptomics), gene cloning and genetic engineering.

Specifically our research is directed towards:
  • finding regulatory factors which induce the biosynthesis pathway of pharmaceutical interesting isoflavonoids like Genistein:
  • production of transgenic plants or tissue culture lines with increased Genistein level.

In general our research will focus on:

  • creating metabolic biodiversity in plants, resulting in compound libraries which can be searched for pharmaceutical interesting compounds:
  • analysis of bio-activity of these compounds created by combinatorial biochemistry.

Business opportunities:

  • For Companies with Breeding Interests: access to use a candidate gene for the development of molecular markers for high Genistein content. Or, a candidate gene for the genetic engineering of Legume varieties, such as soybean, to produce plants with an increased level of Genistein.
  • For Food Producers & Retailers: collaborative research opportunities for the development of newplant varieties with increased levels of the health-promoting isoflavonoids such as Genistein.
  • For Companies with Pharma Interests: access to a plant tissue culture system that produces high levels of Genistein, and a gene that can be used to induce Genistein production in other plant systems.

PRI strategy in developing this field:

  • In general, governmental funding is used for fundamental and pre-competitive research to strengthen our scientific knowledge base in the field production and analysis of bio-active plant compounds.
  • PRI is seeking long-term collaborations with commercial partners to jointly co-develop market-ready products for exploitation and commercialisation. Current examples of such partnerships include long-term collaborations with DOW (glycosylation of human antibodies in plants) and DANISCO (production of flavours).
  • IP Strategy: where relevant from commercial point of view, patent protection will be sought. PRI aims at developing joint IP in its collaborative research programmes, with rights of commercial exploitation for its industrial project partners. Where relevant, industrial partners will get access to existing IP of PRI in the field.
Some key references (additional references are available upon request)
  • Van der Meer, I.M., Bovy, A.G. and Bosch D. (2001) Plant-based raw material: improved food quality for better nutrition via plant genomics. Current Opin Biotechnol. 12: 488-492.
  • Sévenier, R., van der Meer, I.M., Bino, R. and Koops, A.J. (2002) Increased production of nutriments by genitically engineered crops. J. Americ. Coll. Nutrition 21: 199S-204S.
  • Bovy A.G., de Vos, C.H.R., Kemper, M., Almenar Pertejo, M., Muir S.R., Collins G.J., Robinson, S., Verhoeyen, M.E., Hughes, S.G. and van Tunen, A.J. (2002) High-flavonol tomatoes through heterologous expression of the maize transcription factor genes LC and C1. Plant Cell 14: 2509-2526.
  • Aharoni A, de Vos C.H., Wein M., Sun Z., Greco R., Kroon A., Mol J.N.M., O'Connell A.P. (2002) The strawberry FaMYB1 transcription factor suppresses anthocyanin and flavonol accumulation in transgenic tobacco. Plant Journal 28: 319-32.
  • Van der Meer, I.M., Stam, M.E., van Tunen, A.J., Mol, J.N.M. and Stuitje, A.R. (1992) Antisense inhibition of flavonoid biosynthesis in Petunia anthers results in male sterility. Plant Cell 4: 253-262.

• Patent applications

  • Bovy, A.G., de Vos, C.H., Hughes, S.G., Muir, S.R., van Tunen, A.J. and Verhoeven, M.E. (1999) Methods and composition for modulating flavonoid content. Over-expression of transcription factors. WO9937794. (This has been developed in collaboration with industrial partners which have ownership and commercial rights).

  • Van der Meer, I.M., de Vos, C.H., Franssen, H., and Bosch, D (2005). In preparation.


All intellectual property rights and copyright on the contents of this document belong solely to Plant Research International B.V. Any disclosure, reproduction, distribution or non-authorised use of the information detailed in this document is not allowed without written permission from Plant Research International B.V.

For further information please contact either:
Euro Japan Marketing Limited
Phone: +81 3 3664 5062 • Email: cjackson@eujapan.co.jp • www.eujapan.co.jp
or
Plant Research International B.V.
Phone: +31 317 47 7377 • E-mail: gionata.leone@wur.nl

For additional details please go to the PRI homepage or contact us.


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