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Biotechnology and Life Sciences in Baden-Württemberg

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Custom-designed enzymes to conquer markets

A few years ago, only insiders knew what white biotechnology was all about. This situation has now changed: white biotechnology is now the focus of many conferences and it is even backed by a European association. And this does not look as if it will change in the foreseeable future, as the economic prospects are tempting. At least, this is the impression given by a VDI study entitled “Biocatalysis in industrial production”.

Enzymes have the ability to catalyse reactions in living organisms without themselves being consumed in the process. They also speed up a process that would otherwise happen very slowly or not at all. Biotechnological processes in industrial production have several advantages, including the possibility of creating new reactions and products, less costly production processes, lower energy consumption and less pollutants, as well as new energy sources. Enzymes can lead to new substances and be part of production processes as well as be the products themselves.

120 natural enzymes are used in industrial applications

Extremophile microorganisms know how to survive; the photo shows a deep sea bacterium, highly sought after by scientists (Photo: Foto: Karl Johaentges)
Extremophile microorganisms know how to survive; the photo shows a deep sea bacterium, highly sought after by scientists (Photo: Foto: Karl Johaentges) 
It is estimated that there are approximately 10,000 natural enzymes; 25% of these are known and 120 of them used in industrial applications. Industry is particularly interested in extremophile microorganisms that can be used under production conditions requiring high temperatures or high salt concentrations.
Biocatalysts can be used inside the cell (cell systems) or as isolated enzymes that can be added to a reaction mixture. Industrial enzymes are produced by microorganisms (bacteria, fungi) in closed systems or using animals or plants.

To date, up to 60 percent of all technical enzymes are produced with genetically modified organisms (GMO). In future, this number will continue to increase because GMO-based enzyme production requires about 40 to 50 percent less energy and raw material than traditional enzyme production. Equally high is the percentage in reduced amounts of waste, wastewater and contaminants. There are two major strategies for the production of custom-designed enzymes: these are “rational design” (site-specific mutagenesis) and “directed evolution” (mimicking natural evolution). High throughput screening, specific protein design and process-optimised metabolic engineering on the basis of comprehensive genome databases will in future allow made-to-measure biocatalysts to be produced.

A market with an enormous growth potential that is already worth billions

Textile industry often uses enzymes (Photo: Novozymes)
Textile industry often uses enzymes (Photo: Novozymes)  
To date, the world market for enzymes already amounts to several billion euros and is continuing to grow rapidly. The study has found that revenue from industrial biotechnological production in German companies alone amounts to several 100 million euros. The study also suggests that the proportion of biotechnological processes in the chemical industry will increase from 5 to 20 percent within the next five years. Experts estimate that the market share of biotechnological processes in the fine chemical industry will increase five-fold (enantiomer-pure pharmaceutical compounds) within the next 20 years to approximately 250 billion US$. In 2010, 60 percent of the total sales volume will be accounted for by pharmaceutical products that are produced with biotechnological methods and the proportion of biotechnologically-produced basic chemicals and polymers will climb to 15 percent.

Focus on chemicals

Bioplastics - a market with an enormous future potential. (Photo: IBAW)
Bioplastics - a market with an enormous future potential. (Photo: IBAW) 
If the price of petrochemical raw materials continues to rise, the large-scale production of bioethanol and ethyllactate from glucose will become more attractive, as will the production of acetone and butanol. The authors of the study regard the production of acrylamide as a paradigm for the potential of enzymatic processes in the production of basic chemicals. Every year, 100,000 tons of acrylamide are synthesised using biotechnological techniques rather than the traditional copper-catalysed chemical techniques.

According to the study, the market segment of monomeric components and polymers seems to be most promising for the plastics and polymer industry. Bioplastics currently account for 20 percent of the world market. For example, Toyota’s PLA (polylactide) plant hopes to account for 66 percent of the bioplastics world market in 2020. The Japanese estimate that this will represent annual sales of 38 billion US$.

Biorefinery is a key technology that needs to be developed further. It maximises the yield and utilisation of raw products, prevents the generation of non-usable side products and will close the process chain. To achieve this, it is necessary to separate the three main plant components cellulose, lignin and hemi-cellulose from each other.

The USA and EU have set themselves similar goals with regard to biofuels, which are hoped to account for 20 percent of the world market in 2020. The authors of the study cite bioethanol, biogas (both processes are technically fully developed) and in the long term also hydrogen as the major biofuels. Unfortunately, data on the potential of raw materials and actual costs involved are lacking as it would have been useful to have concrete data to support the authors’ vision of a biomass-based economy.

Enormous market – washing agents and detergents

The biggest markets for industrial enzymes are washing agents and detergents, which account for 40 percent of all industrial enzymes in the EU. According to the study, the demand for proteases produced using genetic engineering methods amounts to more than 1,000 tons per year. A smaller amount of enzymes are used in the cellulose and paper industries (10 million euros/year), which rely to a growing extent on environmentally friendly products that are chlorine-free.

A great demand for functional food

The study estimates that functional food will gain in importance (a growth of up to 20%). The current global market volume of functional food is estimated at 60 billion US$, with the major share being amino acids, vitamins, enzymes and fatty acids for neutraceuticals. The worldwide demand for enzymes used in the textile industry (pre- and after treatment of textile tissue and functional textiles) amounts to 125 million euros; that used in the leather industry totals 10 million US$.

The use of enzymes in animal feed is also gaining in importance and is indeed one of the fastest growing markets for enzymes. The authors of the study estimate that the sales volume amounts to more than 120 million US$. Enzymes favour digestion and the utilisation of food in farm animals and reduce the amount of phosphate included in pig manure by 30 percent. Enzymes are also used in plant protection, either in pure form or in transgenic plants.

Still no breakthrough in environmental analytics

Enzymes as successful therapeutics

Enzyme therapeutics are used successfully in extracellular applications. Despite high production costs, therapeutic enzymes can compete with traditional preparations because they are highly effective and quick acting. The authors cite urokinase as an example that is either prepared from human urine or genetically engineered. This enzyme is used as a trombolytic drug to dissolve blood clots in patients suffering from acute heart and brain infarctions. The market is estimated at 1.7 billion US$. The development of non-cytotoxic treatment methods is another promising field of application for therapeutic enzymes.

wp – 2 Feb. 06
© BIOPRO- Baden-Württemberg GmbH

The study can be downloaded as PDF file from www.zt-consulting.de (2,6 MB). A print version can also be obtained free of charge from the VDI Biotechnology Competence Area.
E-mail: biotechnologie@vdi.de.
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