According to expert predictions, the contribution of biotechnologies to the total output of world chemical production will increase 10f old by the year 2010. Each country, willing to retain or occupy an appropriate niche in this industry, relies on its competitive advantages. What priorities in the development of industrial biotechnologies will be Russia's choice? Alexander Yanenko, Doctor of Biological Sciences, Vice-Director of the Institute of Genetics and Selection of Industrial Microorganisms, was interviewed by our correspondent Yevgeniya Sidorova.

RF Institute of Genetics and Selection of Industrial Microorganisms.

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Contribution of industrial biotechnology to production of chemicals.

Monomers produced in bioprocesses.

- Now you took part in the conference "High Technologies-the Strategy of the 21st Century". Reports about priority projects in biotechnology were acknowledged to be most interesting and truly substantive. Your report, too.

- Research carried out at our Institute has been for many years connected with the microbiological industry. Ideologically and methodologically we were ready for the emergence of the so-called "white" biotechnology- this term implies effective or ecologically safe production of chemical compounds, energy, and materials by using microorganisms and their enzymes. Twenty years ago we got down to the creation of microorganisms producing cell metabolites (amino acids, antibiotics, carotenoids, etc.); in time this work became the main trend in our research. We are developing biotechnologies for the production of these substances by fermentation of sugars obtained from renewable raw materials. Today the idea of getting various chemical compounds from renewable source materials is gaining priority significance in the world.

The basic tradition of our institute ever since its foundation has been combination of basic research with practical innovations. This approach goes back to our first director Sos Alikhanyan; this year we mark his birth centennial. Research groups engaged in the selection and creation of new strains of microorganisms obtained unique results. For example, microorganisms producing threonine (amino acid) or riboflavin (vitamin) were for the first time in world practice created by gene engineering methods. We have always thought that the basic condition for effective work is utilization of the hereditary potential of bacteria and application of novel genetic methods. It is obvious that by neglecting the basic approaches to strain selection, we shall get nowhere. On the other hand, we cannot maintain a high level of our studies without using modern designing methods.

- Advocating the catchall mottoes of "white" biotechnology and "green" chemistry, countries with a high scientific potential choose different strategies of development none the less. What determines their choice?

- Countries developing their biotechnology programs are proceeding from national competitive advantages and striving to solve their strategic problems. Let us compare the European and American priorities in industrial biotechnology.

For the USA it is important to provide energy safety: having a huge agricultural sector, it is trying to develop new technologies for the production of energy

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MSP Russian-German Venture (city of Perm).

resources, bioethanol production in particular. This makes USA less dependent on oil import. The American program of biotechnology development also includes output of large-capacity organic chemistry products (polylactides, 1,3-propanediol) from renewed raw materials. With its considerable financial resources the USA is planning to expand such industries.

In Europe the "white" biotechnology program is aimed at improving the ecology and retaining the traditional leadership in the chemical industry. China, Malaysia and Korea are strong competitors for the Old World today. That is why the European countries have to master progressive technologies and put out absolutely new products.

- Does Russia have competitive advantages and which, you think, are its priorities in the development of industrial biotechnologies?

- Today it is very important to identify our national competitive advantages and, proceeding from this, choose the priorities.

Russia has an extensive agricultural sector, capable of producing an appreciable amount of cheap grain. Its comprehensive processing can be regarded as a basis for the development of industrial biotechnology. Realization of such a project might give new products from renewable raw materials, stabilize the country's grain market, and create a raw material base for industrial biotechnology.

We should not forget that Russia possesses a quarter of the world's wood resources. New technologies based on the use of enzymes can appreciably improve the ecology and quality of wood products.

However, the most important competitive advantage of our country is in the tremendous reserves of hydrocarbon (oil and gas), which will continue to be the main energy source and the main raw material for the chemical industry as well as the base for our country's development in the next two decades. Upgraded hydrocarbon processing as well as effective and ecologically safe output of related chemicals is an important objective of Russian industrial biotechnology.

True, we cannot yet export competitive products of fine chemical synthesis. But this does not mean that we should confine ourselves to the production and export of just primary hydrocarbon processing products on the international market. Unfortunately, today many compounds of this kind, often highly toxic, are exported from Russia to Europe. Large-scale transportation of such materials is hazardous for man and the environment. It is much more expedient to process oil at home and then transport nontoxic compounds.

Today industrial biotechnology can offer effective and ecologically safe approaches to the development of the chemical industry, and this trend will keep on in the future. We are exporting to Western countries tens of thousands tons of acrylonitrile (highly toxic compound used for the manufacture of numerous valuable derivatives). But if this raw material is more finely processed at Russian plants, and if we offer end products of such processing, less toxic and in demand in the fine organic synthesis industry, it will elicit great interest from our foreign partners. The price of such products will be much higher, too.

This approach is quite in line with the European program for the steady development of the chemical indus-

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Active slime-processing plant. Ekotekhnopark (Moscow region).

try and efforts to retain its status of the world's largest in the output of chemical products. Huge raw material resources are needed for that, and Russia can offer them. One of the topics up for discussion at the EC-Russia workshop in St. Petersburg in June, 2006, were problems of cooperation in biotechnology, specifically, in "white" biotechnology. I think that such cooperation will be useful for both sides.

- Could you give examples of biotechnologies used for raw oil processing?

- I have studied nitrile metabolism enzymes for many years and thus can give an example from this sphere. We have developed a biocatalyzer on the basis of bacterial cells for acrylonitrile conversion into acrylamide. Industrial technology has been developed in cooperation with Biomid Firm and Saratov Institute of Polymers. Stockhausen of Germany has purchased this technology now being used in Russia at the MSP plant in the city of Perm for the manufacture of bioacrylamide-based polymers. The main product is flocculants (water-soluble polymers); they are adsorbed on hard particles suspended in the liquid phase, modify their charge, and catalyze precipitation. Today the drinking water in Moscow is purified by this method. Moreover, Mosvodokanal (Moscow Water Management Authority) utilizes these polymers at its cleansing plants for dehydration of active slime and thus improves the ecological situation at storage sites.

- How was acrylonitrile processed before the introduction of biocatalysis technology?

- It was mixed with hydrochloric acid at 100°C. The process is poorly regulated under these conditions. Rubber boots, which the workers had to wear, did not last longer than three months. Biotechnology changed the "countenance" of chemistry: room temperature, clean floor and cultures grown in water media. It is noteworthy that the production of acryl monomers is our first positive experience of hands-on application of biotechnology in the chemical industry.

Our next step is to work out a comprehensive program for the output of acryl monomers by means of biocatalysis and biosynthesis. We shall thus increase the degree of raw material processing, obtain monomers for the production of a wide spectrum of polymers, and create a technological base for further development. It is in the hybrid chemical biological technologies that the future of the chemical industry lies.

- Speaking about the advantages of Russia that enable her to develop industrial biotechnologies, you said we had a surplus of grain. The USA also has a potent agrarian sector. In what the two countries are similar and different in their approaches ?

- In the USA they mean Indian corn by and large. Among the products made from it are glucose syrups; they are transformed by microorganisms into such cell metabolites as bioethanol, organic acids, amino acids, and so on. Today the Americans produce about 14 billion tons of ethanol fuel annually; and its output is increasing. However, it is clear that in future corn will not completely meet the requirements of this industry, and specialists are looking into the possibility of using straw and other wastes as raw material.

Russia also has a raw material base for industrial fermentation: low-cost wheat and rye grain. But we do not process it and have no glucose syrups, we do not develop large-capacity fermentation industry. True, some changes now seem to be taking place in this sphere: the production of lactic acid, from which biodegraded plastics can be obtained, and Russian grain producers showing an interest. We hope that we shall have plants for comprehensive processing of grain and thus, we shall get both glucose syrups and a raw material base for industrial biotechnology.

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An Institute of Genetics laboratory.

- One more, third competitive "plus" for Russia in the development of biotechnology are our immense wood resources. What does the Institute of Genetics offer for the realization of this advantage?

- The program of the Institute is aimed at the introduction of enzymatic technologies in the paper-and-pulp industry. Chlorine-containing reagents are traditionally used for cellulose bleaching. The use of the xylanase enzyme for pulp processing allows to upgrade the production process, it brings down the release of toxic chlorine-containing organic compounds into the environment, and improves the quality of the product by reducing the chlorine content in it. We know that Russian paper manufactured by the traditional technology cannot compete with Finnish paper because of this parameter.

For years our scientists have been engaged in the development of new reagents for pulp bleaching. The point is that natural wood-destroying fungal strains contain a complex of enzymes, xylanase for one. We were out to obtain a strain producing xylanase and cellulose. This problem was solved through gene engineering. The enzymatic complex of the native strain was characterized, genes coding for it were identified, and cellulose genes were inactivated or, as the geneticists call it, were "knocked out". It was a very difficult job. Although gene engineering has been developing for almost three decades, the technologies have been mastered for just the model object, the colibacillus E. coli. Creation of microorganism strains-here we mean the Penicillium canescens fungus-requires a good deal of preliminary work for development of a genetic system, including methods for selection of mutations, vector for cloning, insertion of recombinant DNA in the cells, etc., all this taking years of work. Our institute finances studies of this kind from our innovation projects. But as the genetics of industrial microorganisms makes up a base for the further development of industrial biotechnology in this country, it is desirable that finances be allotted within the framework of Federal Target Research and Technological Program.

- You said that scientists in the USA are developing straw-processing technologies. How probable is it to solve this problem in the nearest future, and is such a breakthrough possible for wood?

- Such technology for the production of bioethanol is being tested in the USA at pilot unit. As for the economically efficient processing of wood into ethanol, it is a more difficult problem. The USSR ran a network of hydrolysis plants making ethanol from wood wastes by using sulfuric acid. However, these plants became unprofitable under new conditions. No doubt, modernization of these plants via introduction of enzymatic technologies is an important objective for our specialists.