Studies into plant natural products are of major interest to European scientists, but these efforts are often highly diverse. Now, a new pan-European initiative aims to create a shared platform to unite scientists. Professor Dr Heribert Warzecha shares his project’s work and the progress being made

Setting the agendafor PNP research

What knowledge has been gained regarding the biosynthetic capacity of plants and pathways, and how has this led to the formation of plant natural products (PNPs)?

Since the 18th Century, researchers have been interested in isolating PNPs (mainly because of their potential use in medicine), elucidating their chemical structure and revealing how the metabolic network of a given plant forms these sophisticated structures. With biochemistry and molecular biology tools we were able to at least partially understand the plant’s capacity to form such a huge array of metabolites. Over recent decades, advances in modern technologies like genomics and metabolomics have broadened our understanding of plants as versatile chemists. However, you only understand a system if you are able to rebuild it; unfortunately, we are still not there yet.

How will PlantEngine support and enhance the existing pan-European network and help to fully exploit the capacity of engineering plants for the production of high value PNPs?

PNP pathways and their host plants are highly diverse and so are the groups working on their elucidation and engineering. Although the groups have diverse structural targets for their investigation, many common analytical techniques, molecular tools and plant regeneration and propagation technologies are used. The COST Action PlantEngine will

enable us to provide a platform for all PNP researchers beyond the so far very focused existing networks. For example, there are some FP7 projects focusing on compounds like terpenoids, carotenoids, or indole alkaloids. PlantEngine will build a common roof for those small networks and will enable other researchers to join in.

What have been the greatest challenges you have encountered in developing this multidisciplinary approach and in initiating the network?

The greatest challenge so far has been the huge feedback from researchers and their interest in the Action. At the very beginning more than 100 individuals joined the network, which made the fi rst meeting a great success. However, the challenge will be to prioritise without excluding or reducing the innate diversity of the fi eld. Our aim is to strengthen the most developed branches of the fi eld but also let other fi elds of PNP research benefi t from the achieved results.

Another challenge will be to bring together scientists from the fi eld of computational biology with those working in ‘wet-labs’. It is of tremendous importance to fi nd common ways of communication and to use the same ‘language’ to improve PNP research and engineering with computational biology tools.

What efforts have been made to establish dialogue with key industries, stakeholders and policy makers? How will this infl uence the momentum of the European research sector and how will it affect the general public?

Since PlantEngine is a young COST Action, we are still in the process of building up our network. However, we already have a number of industry partners in the consortium and will broaden our activities this year. Plant metabolic engineering will be of great benefi t for society in that

it eventually enables the more effi cient and suffi cient production of much-needed pharmaceuticals. Nevertheless, it needs a lot of communication beforehand since it also might involve genetically engineered plants which are not well perceived in the public opinion today. On the other hand, providing transgenic plants with clear benefi ts for the European citizen might enable GMOs to be seen in the positive light they deserve.

How infl uential has the support of COST been in the realisation of this project?

COST has been of great help during the setup of PlantEngine; it has supported us in administrative issues and helped us to make a smooth start. We fully appreciate that COST also gives unique opportunities in promoting interaction between different Actions and in providing platforms for further activities and the dissemination of results.

How do you see the project evolving in the future and what are your ultimate long-term ambitions for PlantEngine?

I personally believe that this COST Action has already had a great impact in generating new collaborations and setting up new ideas. It’s hard to predict when this will bear fruit, but over the four-year period we will defi nitely see progress in PNP metabolic engineering, for which PlantEngine was the starting point and helped to establish scientifi c cooperations.

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PLANTEN

GIN

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A new dawn for designer plantsPlants are a vital resource in the creation of pharmaceutical drugs – but extracting the precious compounds can be a complex and expensive task. Metabolic engineering offers promising avenues, and a new COST Action, PlantEngine, is tying together the strands of research in this fi eld to aid future discoveries

HUMANS HAVE ALWAYS used plants in numerous ways – not only for food, clothing and construction, but for what we now refer to as ‘plant natural products’ (PNPs), that is, small molecules used as nutrients, colourants, fragrances, fl avours, cosmetics and, most prominently, medicines. These natural products are substances made by the plant in addition to the vital metabolites necessary for its survival, such as sugars and proteins, and thus are often referred to as ‘secondary metabolites’. Many of these substances have specifi c effects on animals – for example, they might stimulate our sense of smell, as is the case with lavender or peppermint essential oils, or be brightly coloured to attract attention to the plant. A number of PNPs have potent pharmacological

effects, such as analgesic morphine from the opium poppy, or toxic alkaloids from nightshade, used for nicotine products.

Such substances have an important role in many aspects of our lives and are in high demand. However, PNPs are complex chemical structures formed via specialist pathways and, even with advancements in chemical synthesis, are frequently diffi cult to synthesise. Plants remain, therefore, the major source for many of these PNPs – but the extraction of suffi cient quantities for vital pharmaceuticals and other uses presents its own challenges. “Some PNPs become very expensive if the plants produce only minute amounts of the desired compound or if extraction is very complex,” says Professor

Dr Heribert Warzecha of Darmstadt Technical University. More research is needed into how such substances could be enhanced in the plant itself, or decoupled from natural sources, to provide greater access to valuable drugs and chemicals. As Project Coordinator of a new COST Action, Warzecha aims to unite such research efforts across Europe. The project, PlantEngine, will support and prioritise European PNP research, building a common platform for scientists and enabling the effective sharing of knowledge and ideas.

UNITING A HIGHLY DIVERSE FIELD

PlantEngine aims, then, to provide an interdisciplinary framework for European

36 INTERNATIONAL INNOVATION

PLANTENGINE

INTELLIGENCE

PLANTENGINEPLANT METABOLIC ENGINEERING FOR HIGH VALUE PRODUCTS

OBJECTIVES

To fully exploit the capacity of engineering plants for the production of high value PNPs, this COST Action will support and enhance a pan-European network which will amalgamate resources, defi ne target pathways and prioritise compounds, disseminate novel technologies and applications, set standards for computational support, and develop synthetic approaches in plant metabolic engineering.

KEY COLLABORATORS

Paul Fraser, Royal Holloway, University of London – RHU, UK • Ludger Wessjohann, Leibniz Institute of Plant Biochemistry – IPB, Germany • Mariana Sottomayor, Institute for Molecular and Cellular Biology – IBMC, Portugal • Antonella Leone, University of Salerno, Italy • Fragiskos Kolisis, National Technical University of Athens – NTU, Greece • Michal Oren-Shamir, Agricultural Research Organization – ARO, Israel • Oliver Kayser, Dortmund University of Technology – TU, Germany

FUNDING

European Science Foundation (ESF)

CONTACT

Professor Dr Heribert WarzechaChair of COST Action FA1006

Technische Universität DarmstadtPlant Biotechnology and Metabolic EngineeringSchnittspahnstrasse 3-564287 Darmstadt, Germany

T +49 615 116 4024E warzecha@bio.tu-darmstadt.de

http://plantengine.eu

www.cost.eu/domains_actions/fa/Actions/FA1006

PROFESSOR DR HERIBERT WARZECHA studied Pharmaceutical Sciences in Mainz and earned his PhD in Pharmaceutical Biology. Having worked at the Boyce Thompson Institute (Ithaca, NY, USA) and the University of Würzburg (Germany), he now heads the group of Plant Biotechnology in Darmstadt. His research interests are in plant metabolic engineering and the production of biopharmaceuticals in plants.

scientists involved in PNP research. In a wider sense, however, the project will defi ne the status quo for what is a highly diverse and specialised fi eld; one which currently comprises many individual research efforts. This objective, to unify the research landscape, is far beyond the scope of the small groups usually participating in research consortia. The Action intends to include end users of such research – for example, those working with the applied science and pharmaceutical engineers – as well as synthetic biologists, computational chemists and biologists who work on new approaches to plant engineering, and phytochemists, plant molecular biologists and physiologists.

To unite these disparate research efforts, one of the major goals of PlantEngine is the development of an inventory of PNP research across Europe and a structure guideline for databases. “To get the most out of the research results achieved so far, it would be highly benefi cial to make data accessible,” says Warzecha. “The generation of a database of any kind has, as prerequisite, the defi nition of what needs to be stored and how it will be accessed. PlantEngine’s aim is to set standards for such a database and defi ne the needs of the community.” The project will set the agenda for plant metabolic engineering across Europe and provide a unique opportunity for a holistic approach to PNP research, from pure scientifi c knowledge to applied techniques and products.

SETTING THE EUROPEANRESEARCH AGENDA

Research indicates that certain compounds hold the most potential for metabolic engineering, as Warzecha explains: “Looking at the research achievements so far, it is clear that terpenoids are the best characterised and most advanced class of compounds regarding metabolic engineering. Regarding their use, terpenoids constitute a very interesting compound class, since among the members of this class are essential oil constituents and carotenoids like provitamin A with health-promoting properties, as well as cancer therapeutics like taxol”.

However, the focus on such promising avenues of research will not come at the expense of other areas. “While trying to prioritise research in one big class of PNPs, we also aim to let all research on other classes of compounds benefi t from the achievements gained in the major group,” Warzecha explains. Indeed, research into PNPs necessitates a collaborative and integrative approach, since compound classes often share features with other classes or are assembled from constituents of different origin. For example, an important class of PNPs – the monoterpenoid indole alkaloids – are a merge of two different classes of compounds. Vincristine, a very important anti-cancer therapeutic, is a prominent example of this.

A NEW GENERATION OF PNP RESEARCHERS

This focus on future areas of potential research clearly necessitates a strong pool of young

scientists, and so another important ambition of PlantEngine is the involvement of early-stage researchers alongside those more experienced. That the project is opening up multidisciplinary training to a core group of motivated young researchers is a key strength, Warzecha asserts. “PlantEngine will be a platform for job opportunities in PNP research, and why should that not happen in industry as well? I personally believe that, for both academia and industry, skilled and devoted young researchers are the best capital investment for the future.”

In addition, the COST Action, through its Short Term Scientifi c Mission, is allowing young scientists to travel to international laboratories to work on specifi c projects to develop skills and techniques not available in their home institution. Crucially, this aspect of the project not only gives the individual researcher a great opportunity to extend his/her skills and knowledge; it also strengthens the ties between various labs all over Europe and further develops the PlantEngine network. This is particularly benefi cial given the project’s explicit ambition to unite research efforts across Europe and create a platform for the sharing of ideas.

The project is also already directing several training schools, where young scientists are trained in new techniques by leading researchers. PlantEngine intends to broaden its scope by organising more training schools jointly with other related COST Actions, to maximise the potential for sharing useful ideas and developing a new generation of scientists with an interdisciplinary approach.

In setting this research agenda for PNP research, and in fostering a new generation of skilled scientists to undertake it, PlantEngine hopes to contribute signifi cantly to an area of critical interest to healthcare and pharmacology as well as many other fi elds. Whilst it is imperative that we have adequate access to vital drugs and chemicals, efforts to engineer plants to enhance the availability of such substances have often been controversial in Europe. Warzecha hopes that their work will encourage a shift in perception in this area, particularly by demonstrating the potential benefi ts to medicine: “We hope that with the example of medicinal plants we can show the public that genetic engineering has huge potential beyond modifi ed food plants, and that ultimately, consumers will benefi t from this technology”.

We hope that with the example of

medicinal plants, we can show the

public that genetic engineering has

huge potential beyond modifi ed

food plants

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