Business Unit 4

The New Potential of Biotechnology: The Challenge to Learn from Nature for Industrial Exploitation

Overview

An increasing number of vegetable raw materials are becoming interesting as feedstocks for high-quality products. The refinement of these highly diverse raw materials requires completely new synthesis processes. Learning from processes occurring in nature, where complex reactions are single-step, enzymatic, and take place under mild conditions, the Fraunhofer Group for Life Sciences is developing novel biotechnology processes geared to the principles of “sustainable development” and “responsible care”. The Group is laying the foundations to make sure that the required biomass is not only reliably available in the required quantity and quality, but also suits the requirements of the biotechnological manufacturing processes to the highest possible degree. One aim of the Fraunhofer experts is to transfer process steps into the plant production system. This would enhance the competitiveness of the final products. Blue biotechnology likewise occupies a fixed place in the services offered by the Group. Marine microorganisms – algae, bacteria, and zooplankton – are certainly interesting options for mass production of new materials. Enzyme-catalyzed reactions instead of the traditional synthesis paths can often substantially reduce the cost of production and waste disposal. The Group’s potential to optimize existing enzymes and systematically search for novel enzymes is based on methods of, for example, genomics, metagenomics, and proteomics. Enzyme optimization for industrial use is achieved by means of molecular evolution and combinatorial libraries.

This know-how is particularly beneficial for research in the new domain of yellow biotechnology, i.e. insect biotechnology. In this area, a so far unknown number and variety of new enzymes and antibiotic substances are providing the impetus for intensive research activity. Completely in line with the sustainability concept, the Fraunhofer Group for Life Sciences will search for new possible uses for residues from the food industry, agriculture, and forestry for its clients, including development of the required processes up to pilot scale. In the near future, the critical step from the laboratory to industrial application will be supported by the Fraunhofer Center for Chemical Biotechnological Processes, Leuna, Germany. The concept of this biorefinery is highly flexible, allowing a wide range of different raw materials, according to requirements, to be used and tested as feedstocks for chemical products.

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Renewable raw materials and valuable residues

Surging crude oil prices and crises in the petroleum-producing countries have increased people’s awareness of dependence and of the finiteness of our natural resources. The consequent search for novel raw materials for industry has led to surprising results, showing very impressively that nature’s diversity is far from having been completely exploited. Furthermore, in view of ever more stringent regulations and the worldwide quest for sustainable development, the design of sustainable industrial processes in the chemical, pharmaceutical, and food industries is becoming more and more important.

Biomass is the only alternative to fossil raw materials for the manufacture of chemical and pharmaceutical products. Plants with their enormous diversity offer a broad range of potential raw materials. Photosynthesis leads to a huge spectrum of widely differing chemical compounds, which so far have only been partially exploited. A particularly interesting option is the use of these renewable raw materials as chemical intermediates for polymers and special chemicals. A challenge for the future is to expand the industrial use of raw materials from plants, while at the same time safeguarding the production of food and animal feed and protecting areas of unspoiled nature.

In order to improve and increase the industrial use of bio-based raw materials and biotechnological processes, new approaches for research, development, and manufacturing are required: approaches geared to the general principles of “sustainable development” and “responsible care”.

For the use of renewable resources, the product tree is a lot more branched than that for the mineral oil-based line. Synthesis processes taking place in nature can be exploited, for example, by isolating and, if need be, modifying individual fractions of renewable resources; another path using enzymatic biodegradation leads to platform products – the base products for biotechnological or chemical syntheses.

Both these possibilities for exploring new sources of raw materials are being intensively studied by scientists in the Fraunhofer Group for Life Sciences.

White and green biotechnologies going hand in hand

The content of valuable components in a plant for use in industrial biotechnology depends on the type of plant and on its treatment by the grower.

The basis for targeted improvement of a plant’s properties includes systematic analysis of its metabolic pathways and comprehensive knowledge of its ingredients and their respective properties. This has been facilitated by technological progress in functional genomics, proteomics, and metabolomics. The efficiency of biotechnological manufacturing processes in industry can be increased by tailoring the plants which provide the raw material to the particular manufacturing process. Matching the plant properties to the technological and commercial requirements enables specific and broader use of biogenic raw materials for industrial biotechnology. A transfer of process steps into the plant as a production system is another option. Both approaches are being pursued within the Fraunhofer Group for Life Sciences.

Blue and white biotechnologies acting together

The industrial production of novel ingredients by using marine organisms will become more and more important in the future. Marine organisms will be employed not only for the identification of such new ingredients, but will also be put to use for mass production. In this context, marine microorganisms such as single-cell algae or bacteria are of particular interest, as too are zooplankton or cultures of cells isolated from marine organisms. The Fraunhofer Group for Life Sciences is in a position to maintain the corresponding organisms and to develop and offer special customized reactors for this purpose.

Productive use of valuable residues

Besides the targeted search for plants as sources of alternative raw materials, researchers in the Fraunhofer Group for Life Sciences have an interest in plant residues from the food industry, forestry, and agriculture. These often still contain valuable compounds such as proteins, fibers, oil, or phytochemicals, which can be further exploited. For further use in technical applications, they first have to be isolated using appropriate methods with preservation of their valuable properties. We have wide experience in the fractionation of different vegetable raw materials and vegetable residues from the food industry. The development of fractionation processes on a laboratory scale and also the scale-up to pilot scale are among the services offered by the Group.

In many cases, modification of proteins and other vegetable raw materials prior to their technical or energetic use can contribute to achieving the desired physico-chemical properties. The Fraunhofer Group for Life Sciences develops innovative processes for the chemical and, in particular, biotechnological modification of useful plant fractions, to enable high-quality and low-cost substitution of petroleum-based products.

Sustainable ways to products with multiple benefits

Like higher plants, microalgae bind atmospheric carbon dioxide and produce a large variety of valuable chemical compounds such as dyes, unsaturated fatty acids, and active pharmaceutical ingredients via photosynthesis. They grow faster though, and have higher productivity than plants on land. This makes them an interesting alternative source of raw materials for industrial, white biotechnology.

Already today, native and modified biogenic raw materials are used in many different sectors: applications range from energetic uses as solid and liquid fuels to industrial uses as lubricants, adhesives, and coating materials. Due to our many years of experience and comprehensive expertise, the Fraunhofer Group for Life Sciences is a competent and attractive partner for the development, characterization, and industrial implementation of these innovative products.

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Enhanced range of raw materials for biotechnological processes

The main tasks in the biotechnological area are to make available low-cost substrates and to develop new or improved enzymes. Further challenges are to develop new biotechnological processes and optimize existing ones, to couple these with chemical processes in order to achieve process integration, and to develop new processing methods and optimize existing ones.

Biotechnological processes use sugars as a carbon source, obtained either directly from plants or created from starch-containing plants by hydrolysis of polysaccharides. In view of the worldwide debate about the competing use of sugar- and starch-containing plants for industrial purposes, it is becoming increasingly important to make available alternative raw materials for fermentation based on lignocellulosis. The institutes of the Fraunhofer Group for Life Sciences are investigating and developing novel enzymes and methods for substrate digestion based on lignocellulosis.

New biocatalysts

Microorganisms and their enzymes are of major importance for the manufacture of chemical and pharmaceutical products using biotechnological methods. New applications, for example the recovery or modification of special chemicals, require new or improved enzymes. Enzymes as bio-catalysts offer the benefit of high substrate specificity and stereo-selective reaction. This makes them attractive for technical industrial solutions such as the synthesis of enantiopure products or intermediates. The use of enzymes frequently allows substantial cost reductions both in production and waste disposal processes. Furthermore, this process technology opens up completely new market opportunities. In fact, it is often enzymes that make it possible for certain products to be manufactured at all.

The search for microorganisms and their enzymes involves traditional methods, but also innovative methods such as the complete screening of genes or proteins, which is referred to as genomics, metagenomics, and proteomics.

In order to develop efficient and low-cost processes, the Fraunhofer researchers are concentrating on the following:

  • Identification and characterization of new or improved industrial enzymes, in particular by establishing culturing methods for microorganisms which to date have not been able to be cultured
  • Optimization of enzymes suitable for industrial use by molecular evolution and combinatorial libraries
  • Development of manufacturing and purification processes for recombinant technical enzymes
  • Immobilization of enzymes and coupling of biocatalysis and chemocatalysis



Experts reckon that the percentage of microorganisms which have not yet been able to be cultured is about 99% of the whole population. To enable this promising genetic resource to be used, Fraunhofer researchers in cooperation with partners from industry have set up metagenomic gene libraries based on environmental samples. For this purpose, they isolated the microbial DNA directly from the environmental sample and introduced it into a cultivable host species.

Metagenomics as an advanced level of genome research in prokaryotes systematically provides access to the whole complexity of genetic information obtained from microbial communities. By means of high-throughput assays, the gene libraries can be screened for desired enzyme activities. Using this method, a large number of enzymes have already been identified which were not in the known databases and thus can now be used without limitations.

Furthermore, the genomic information obtained in sequencing projects is used systematically in the Fraunhofer Group for Life Sciences in order to isolate novel enzymes for technical applications.

Enzyme diversity of yellow biotechnology

Insect biotechnology, also referred to as yellow biotechnology, is a promising research area of the Fraunhofer Group for Life Sciences. Insects are the organisms having the highest biodiversity. Four to six million species of insect exist, compared to only about 250,000 plant species. The evolutionary success of insects is due on the one hand to the large variety of antibiotic substances which provide effective protection against infection, and on the other hand to a large variety of enzymes which help them exploit almost any organic material as a food source. The exploration of this diversity of molecules occurring in insects and the systematic exploitation for red, green, and white biotechnology is a challenge for researchers.

The enormous diversity of enzymes which enables insects to use almost any organic material as a food source represents another very interesting resource for white biotechnology. Due to their novel properties, these may help open up new or expanded application areas, make methods of synthesis more economic, and enable material or energy recovery from waste material which hitherto has been used insufficiently or not at all.

Process development for fermentation and downstream processing

High demands on product quality and a renaissance of natural materials for industrial applications require new and efficient production and processing methods. The Fraunhofer Group for Life Sciences is an attractive partner in this regard, thanks to its expertise in process development for biocatalysis, fermentation, and downstream processing as well as in upscaling up to pilot scale. It develops solutions for optimized fermentation and for the isolation, separation, and purification of biotechnical products using mechanic and thermal separation techniques. Membranes and membrane processes in particular are applied, because these processes can be used specifically to suit the particular chemical and physical properties of the product (size, charge etc.). Examples are membrane filtration, electrodialysis, and combinations of membrane with conventional separation techniques or with powerful chromatographic methods.

Scheme 1: Renewable raw materials for chemical products. Source: Fraunhofer IGB



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Fraunhofer Center for Chemical Biotechnological Processes, Leuna

Petroleum is a highly coveted feedstock for numerous products such as plastics, lacquers, detergents, adhesives, and cosmetics. Its availability, however, is limited. Renewable raw materials such as straw, wood, microalgae, and many others have the potential to replace petroleum. Chemical companies all over the world are working to develop novel processes. Today, however, the use of renewable raw materials on an industrial scale is still a financial and technological challenge for companies.

Aiming to support the critical step from the laboratory to industrial application, the German Land Saxony-Anhalt, the German federal government, and the Fraunhofer-Gesellschaft have been planning to set up a chemical biotechnological process center which is now being established as Fraunhofer Center for Chemical Biotechnological Processes CBP at the German chemical industry center Leuna. The biorefinery concept, which can be used very flexibly, will offer innovative possibilities for the future use of biological raw materials based on oils and fats, cellulose, and of starch- or sugar-containing raw materials as precursors for chemical products. This will allow the development of new products and processes involving industrial biotechnology up to the point that they are ready for industrial use. The CBP will thus contribute to reducing our dependence on fossil fuels and to reducing carbon dioxide emissions.

By providing the required infrastructure and pilot plant/mini-plant facilities, the Fraunhofer CBP will enable cooperation partners from research and industry to develop and scale up biotechnological processes for the use of renewable raw materials up to industrial scale. Seven process plants for process development and scale-up will be set up consecutively.

A critical factor for the success of the biorefinery concept is collaboration with partners from industry from the very beginning. For every project, the industrial partners perform economic and ecological sustainability analyses. The design and conception of the different plants in each case allows a comprehensive efficiency analysis that can be extrapolated to large-scale production situations. In fact, this provides ideal preconditions for technology transfer.

www.cbp.fraunhofer.de

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