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Eurofung started as a project funded by EC, and has now grown into a foundation with the aim to explore and enlarge the possibilties of filamentous fungi as cellfactories.

Filamentous fungi are known for their ability to produce metabolites important for human health (antibiotics) and enzymes used in the food and feed industry. They are promising hosts for the production of pharmaceutical proteins, antibodies and vaccines and of novel non-ribosomal peptide antibiotics.

Eurofung, a growing European scientific and industrial network on fungal research, designs versatile filamentous fungal cell factories in order to produce such compounds. The Eurofung II research programme therefore focused on three topics:
1. Investigating the fungal secretion process to improve the ability of fungi to produce foreign proteins.
2. Improving the production rate and substrate utilization of the fungal production process of enzymes.
3. Developing new fungal antibiotics to replace the ones for which bacterial resistance appears.

The benefits of the Eurofung research programme for society are directly related to improvements in health and nutrition. Furthermore, fungal gene technology gives impulses to the European biotechnology industry and provides researchers with new options such as alternatives to transgenic animal technology.

Eurofung Position Paper

Filamentous-Fungal Genomics and Biotechnology in the 7th Framework

Introduction
This document is a contribution in the discussion to identify thematic areas of research in FP7 and to assist in establishing research priorities in such thematic areas. It results from discussions within the Eurofung consortium and is prepared by the EUROFUNG management team in response to initiative of the European Commission to stimulate this discussion.
The EUROFUNG network was founded in 1995. Since the leading European groups in the area of filamentous fungal biotechnology have been working together to address important fungal cell factory research issues (see www.eurofung.net). At this moment the consortium counts 35 members whereas a fungal Industrial Platform of 12 small, medium-sized and large European biotechnological and pharmaceutical companies is associated with it1. The mission of the Eurofung consortium is to understand the biological principles specific for filamentous fungi and to effectively explore and enlarge the possibilities of filamentous fungi as cell factories or to cure fungal diseases.

1.Filamentous-Fungal Genomics and Biotechnology; an essential component for European research and industrial exploitation
The European filamentous-fungal biotech industry obtained worldwide a very strong position in the last century. This was due to advanced industrial knowledge in chemical and (bio) process engineering and filamentous-fungal fermentation physiology in combination with a strong European research interest in fungal (molecular) genetics and fungal physiology. The filamentous-fungal biotech industry is very diverse with outlets for application in
• Food, beverages and feed
• Paper and pulping
• Textile and laundry
• (bio) chemical industry
• Health sector
• Environmental protection and bioremediation

Still a major part of the world market for enzymes and secondary metabolites I produced by filamentous-fungal biotech industries located in Europe. The diversity in applications is based on the metabolic versatility and biodiversity of the filamentous-fungal world, producing a wealth of extracellular enzymes with interesting redox and/or stereospecific functions, primary metabolites (e.g. organic acids, polyols, vitamins) and secondary metabolites (antibiotics and other bioactive molecules). It is noteworthy to mention that a) only a fraction of the metabolic potential of filamentous fungi is known and used, b) filamentous fungi of industrial interest usually have high secretory capacity for the relevant products like proteins and metabolites. To keep the European filamentous-fungi biotech industries and research strong and competitive it is of key importance to rapidly implement and exploit technologies and resources in genomics. The filamentous-fungal genome sequencing efforts have largely been undertaken outside of Europe (USA and Japan) and with non-EU finance, although individual European countries have made some contribution2. Fortunately, the Eurofung consortium has nevertheless access to this information.
Since Europe has extensive knowledge in research areas relevant for filamentous-fungal biotechnology the vast opportunities to exploit the genomics resources, which are now available, should have taken.
Biotechnology including filamentous-fungal biotechnology is a key area of growth, expected to be considerably accelerated by 1) a genomics input e.g. by unraveling novel metabolic pathways or relating productivity, protein secretion and filamentous-fungal morphology and 2) the general need for more sustainable developments. We expect a pronounced impact on new developments in
• Enzyme markets with respect to novelty, specificity and volume
• Filamentous-fungal systems as expression host for improved heterologous protein production
• Discovery and production of filamentous-fungal anti-microbial, therapeutic and health-promoting metabolites
• Delivery of key compounds for the (bio) chemical industry derived from renewable carbon sources including wood3
• Environmental issues (bioremediation, reduction in the use of fossil energy)

To stimulate and harvest the results of these new developments, a theme ‘Filamentous Fungal Genomics and Biotechnology’ should be incorporated in the 7th framework covering the above mentioned developments especially since they have both immediate and medium to long-term perspectives.
It is extremely important that the European filamentous-fungal biotech industry and community strengthens its knowledge base by integrating filamentous-fungal genomics and the Cell Factory concept to serve biotechnology. If not there is a potential risk to loose both production facilities (to Asia) and high-tech research (to USA, Asia). Within Consortium and FIP it is our strong opinion that the theme mentioned above meets the EU policy objectives and that the Commission cannot afford to overlook the need for focused support to filamentous-fungal genomics and biotechnology.

2.The European Research Potential
Before 1994 the European Commission funded filamentous-fungal biotechnology research through different consortia of limited size. The political and scientific need to create a more collaborative research climate resulted in two consecutive EUROFUNG programs (1996-2003) carried out by a large community.
Benefits of the investments into these two consecutive programs are the following:
• High quality research groups have been assembled many of which represents worldwide the top of filamentous-fungal research in their specific area of interest
• An open and dynamic research structure has been created with substantial critical mass (documented in the final report of QLRK3 1999-00729, 2003), which changes in composition depending on the skill needed. This structure has been successful in
Promoting European collaboration and sharing resources
• Limiting research overlap
• Stimulating multidisciplinary research on filamentous fungi which is without precedents in other parts of the world
• Providing direct, low-threshold interactions with European biotech industries and efficient dissemination channels
• Generating additional national research resources (see also European added value)

Other benefits of the EUROFUNG activities are the following
• A high level of scientific output (quality and quantity) both in basic and applied aspects has been realized resulting in 190 publications whereas 12 patent applications were filed.
• The easy access of biotech companies to excellent groups for bilateral research.
• The education and delivery of more than 35 well trained researchers of which several are employed now by European Biotech companies
• Biannual meetings did train young scientists, promoted exchange of personnel and transferred experience to a new generation of group leaders
• Very importantly it resulted in an active role of the Fungal Industrial Platform in program evaluation and determining new program contents and priorities.

The relevance of the Eurofung network and our initiatives to rapidly establish integration of Filamentous-Fungal Genomics and Biotechnology is well realized by the European biotech industry (see also appendix 1)
In November 2003 the FIP decided to support the network coordination activities for a period of 2 years in order to develop new research proposals at the European level. Two projects proposals were recently submitted in FP6 viz Eurofungbase and Playful. Initiatives are taken to discuss the potential role of our research area for some of the technology platforms (Sustainable Chemistry; Sustainable Benefits from Renewable Forestry Resources; Innovative Medicines for Europe).

3 European added value
As a result of support in the ‘Biotech’ and ‘Cell Factory’ programs of FP4 and 5, a large, active and closely collaborating European fungal biotechnology community was founded. This community has established excellent relations with European industry through the Fungal Industrial Platform and substantially contributed to the strong position of this industry also through frequent bilateral collaboration. As FP6 offered insufficient opportunities to integrate fungal genomics and biotechnology, at this point in time it is absolutely necessary that basic and applied fungal functional genomics is appropriately stimulated at the European level in FP7. In the mean time a number of activities by public funding or joint public and industrial funding have been initiated within the member nations of the EU like the genome initiative (GEN-AU) in Austria, the Danish National Center for Metabolome Analysis of Microorganisms, Center of Excellence programs including industrial fungi in Finland, fungal genome sequencing and annotation programs in France, The GenoMik network in Germany, BBSRC funded programs (COGEME, GAPSIA) in the UK, the Kluyver Center for Genomics of Industrial fermentation in the Netherlands and the Strategic action for Genomics and Proteomics Research (CSIC, Spain). The Eurofung Network is the instrument ‘by excellence’ to strengthen this area to the extent necessary through intensive collaboration at the European level and mobilization of the critical mass in manpower and expertise required.
The network has track record in stimulating activities that complement each other and avoid unnecessary overlap. The facilities and infrastructure needed for high-level fungal genomics research are expensive. Therefore, Eurofung aims at offering specialized facilities within the Centers of Excellence founded in the various EU member states.
Finally, as filamentous fungi are of great importance in industry, agriculture and medicine, an FP7 research theme ‘Filamentous Fungal Genomics and Biotechnology’ incorporating the ‘Cell Factory’ concept will have a broad impact for the fermentation and pharmaceutical industries as well as for environmental remediation at industrial scale.
1Angel biotechnology; ABenzymes; BASF; Beldem; Biochemie GmbH; Christian Hansen A/S; Danisco; DSM; Genencor International; Novazymes A/S; Royal Oy; Unilever
2Since the appearance of the yeast genome in 1996 approximately 22 fungal genomes are now publicly available in the database. However, for hyphal fungi no gene arrays with complete genome coverage are yet available commercially but will be soon.
3Fungi are particularly well equipped to degrade plant materials including lignocellulose in some cases.
 
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