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Plant Research International is currently offering specific opportunities relating to:


Collaborative Opportunities Related to Flavonoid Pathway Engineering

Introduction

Plant Research International has been researching flavonoids for over 10 years.  Areas in which we have particularly extensive experience include biochemical detection of flavonoids(using HPLC-PDA-MS; many standards available), molecular detection (many genes/probes in house) and engineering of the flavonoid pathway.

Some classes of flavonoids, such as isoflavonoids, flavonols and anthocyanins, have received a lot of attention due to their presumed health-benefits. Our research in the past seven years has been aimed at increasing the levels of such health-promoting flavonoids in crop plants (mainly tomato).

Using genetic engineering approaches we have been able to:

  • up-regulate the flavonoid pathway in tomato fruit flesh, a tissue that normally does not produce any flavonoids.This led to a 70-fold induction of the flavonol kaempferol (Ref.1-3);
  • relieve the rate-limiting step in the pathway of the fruit peel, which led to a 60-fold increase in the levels of quercetin (Ref.5);
  • block specific steps in the pathway using RNAi technology, and;
  • produce entirely new classes of flavonoids in tomato fruit, e.g. resveratrol, one of the health-promoting components in red wine.

This research led to an increased insight into this pathway, its regulation and the possibilities for genetic engineering.

Vision/Strategy

We live in a society in which the incidence of diseases, such as coronary heart diseases, cancer and diabetes, increases every year. This 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 flavonoids in the diet may reduce the risk of cardiovascular disease and certain forms of cancer. Several epidemiological studies have shown that coronary heart disease mortality can be decreased by moderate consumption of wine.

Due to altered dietary habits and lifestyle, an increasing number of sub-groups within the socities of developed countries no longer meet the minimum required intake of many beneficial food ingredients. These sub-groups include young urban professionals, teenagers and the elderly. Therefore, there is a growing need for an expanding array of food products with enhanced levels of health-protecting compounds.

Based on the above-mentioned trends ourstrategy is to develop food crops and products with optimal levels and bioavailability of health-related compounds, to meet the needs of both current and future societies in terms of eating trends and the pressure to reduce health-care costs. 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:

  • isolating key genes involved in the production of flavonoids in tomato fruits through differential screening of tomato lines contrasting in flavonoid content:

  • producing tomato fruits with enhanced levels of bioavailable flavonoids.

In general our research will focus on:

  • enhancing levels of compounds with health-promoting effects in food crops
  • increasing flavonoid bioavailability by modification of the sugar conjugation mechanism.

Business opportunities:

  • For Companies with Breeding Interests: a collection of candidate genes for the development of molecular markers for flavonoid content.
  • For Food Producers & Retailers: new varieties with increased levels and bioavailability of health-protecting flavonoids.Also, new ways to increase the wholesomeness of products.
  • For Companies with Pharma Interests: new genes that can be used in combinatorial biochemistry programs to increase diversity in phenolic compounds.

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 of flavonoids.
  • 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.

Track record

• Some key references (additional references are available upon request)
  • 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.

  • Verhoeyen, M.E., Bovy, A., Collins, G., Muir, S. Robinson, S. de Vos, C.H.R. and Colliver, S. (2002) Increasing antioxidant levels in tomatoes through modification of the flavonoid biosynthetic pathway. Journal of Experimental Botany 53: 2099-2116.

  • Colliver, S., Bovy, A., Collins, G., Muir, S. Robinson, S. de Vos, C.H.R. and Verhoeyen, M.E. (2002) Improving the nutritional content of tomatoes through reprogramming their flavonoid biosynthetic pathway. Phytochemistry Reviews 1: 113-123.

  • Aharoni A, De Vos CH, Wein M, Sun Z, Greco R, Kroon A, Mol JN, O'Connell AP (2002) The strawberry FaMYB1 transcription factor suppresses anthocyanin and flavonol accumulation in transgenic tobacco. Plant Journal 28: 319-32.

  • Muir, S.R., Collins, G.J., Robinson, S., Hughes, S. G., Bovy, A.G.,  de Vos, C.H.R, van Tunen, A.J. and Verhoeyen, M.E. (2001) Overexpression of petunia chalcone isomerase in tomato results in fruit containing dramatically increased levels of flavonols. Nature Biotechnology 19: 470-474.

• Patent applications (these have been developed in collaboration with industrial partners which have ownership and commercial rights)

  • 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.
  • Bovy, A.G., de Vos, C.H., Hughes, S.G., Muir, S.R., van Tunen, A.J. and Verhoeyen, M.E. (2000) Methods and composition for modulating flavonoid content. Over-expression of chalcone isomerase. US2004163142.

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.


Plant Research International is currently offering specific opportunities relating to:

 


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