Using Biotechnology in the Fine Chemicals Industry: Opportunities

Introduction

Biotechnology in its broadest sense has been around for a long time, but the term has only been coined relatively recently. Although revolutionised by genetic engineering-techniques, biotechnology encompasses the pre-existing use of fermentation and enzyme extracts. A generally accepted working definition is: the use of microorganisms and enzymes to produce commercially useful biochemicals and other fine chemicals.

Leading edge technologies generally first appear in the research laboratories of universities, other pure science institutes or applications companies (pharmaceuticals, agrochemicals etc). As they mature, they tend to be transferred first into fine chemical development, then into production. Along the way, the techniques employed can change quite dramatically. Acceptance from these increasingly conservative groups is slow. The evolution of the technology takes time, typically a generation (significant?), with much of the pioneer work being undertaken by individuals or small companies. Very often the fruits of the discoveries are enjoyed mainly by large corporations which have the financial and marketing muscle to develop and launch the product.

So it has been with biotechnology.

The technology has been applied in a number of different bioscience industries. Its use has resulted in the development of novel drugs (EPO, human insulin, GCSF, MCSF), novel food crops (pest-resistant strains, fruits with improved storage characteristics) and also novel fine chemical technologies. The current and future impact of the application of biotechnology to manufacturing fine chemicals is the subject of this review.


Opportunities and Threats

When considering the development of a new fine chemical process, the key route selection criteria to be considered should be:

• Target cost of production
  
• Scale of manufacture, now and in the future
  
• Project lead-time and development budget
  
• Technology operated by competitors, actual or potential
  
• Existing technologies and raw materials

This analysis may be usefully carried out in research labs, in development and in production. The final decision on the most suitable route therefore depends critically upon the scale of production, be it milligrams, kilograms or metric tons.

Over the past 25 years, biotechnological techniques have moved from the research labs intodevelopment and in a number of cases they have been scaled up to full production. In Table 1 some representative examples of mature biotechnical fine chemical processes are given (this list excludes commodities such as citric acid, ethanol, L-glutamic acid, HFCS, L-lactic acid, penicillin G and V, L-lysine, tetracyclin, vitamin C and xanthan gum).

In the manufacture of fine chemicals, biotechnology has made itself felt in three basic ways:

• It has created new molecular targets for the industry to manufacture, often with the aid of biotechnology, but not in all cases
  
• It has offered the chemist new catalysts for carrying out chemical unit processes
  
• It has made available new raw materials, sometimes very complex ones, but also relatively cheap feedstocks which have opened up new areas of chemistry

Illustrative examples of these three influences of biotechnology on the manufacture of fine chemicals will be discussed in some detail in the presentation.

There are, however, threats as well. Replacement of existing products with newer, more effective biotechnical ones will reduce or destroy demand for their fine chemical ingredients. Thus existing pharmaceutical therapies (and their consequent demand for fine chemicals) are threatened by newer biotechnological products which are manufactured without recourse to chemical processing. To some extent this threat is reduced by the continuing requirement for chemical modification of the naturally occuring materials, the semi-synthetic antiobiotics present a comforting example of the hidden opportunities in what might have been a major threat to the industry.

A more serious threat is represented by the possible mdodification of genes so a to endow resistance to pests or, in humans, susceptibility to diseases. These really could sweep away sectors of the industry! However, as with all novel technologies there are severe entry barriers to genetic manipulation, particularly that of humans, so that this threat remains a relatively distant one.

The likely medium term impact of biotechnology on fine chemical manufacture will be a continuing development of better processes for many biological molecules and a growing acceptance of the benefits of biotechnology. In particular as the isolation, immobilisation and application of enzymes becomes more common-place, so will their use develop, especially in the production of chirally pure chemicals. Catalysis is the norm in the chemical industry and the use of enzymes in fine chemical processing will become routine, particularly where they-can be used in high concentrations.


Fine Chemical Biotechnology: the Players

The emergence of biotechnology companies specialising in biotransformations as new fine-chemical start-ups has been a feature of the maturing of the biotechnology industry. In general, these companies have built upon a core business in which they supply high value chirally pure intermediates to research-based pharmaceutical companies. In some cases, the companies have tried to hedge their bets by developing pharmaceutical products as well.

Many in the fine chemical industry have viewed the emergence of these generously funded, high profile companies with a mixture of distaste and envy, swiftly followed by outright scepticism. This is a shame. These companies have identified ways of raising finance for invigorating an industry which should always be open to new ideas. The industry is driven by research-based businesses and companies must continually develop their capabilities, or face inevitable decline.

This mutual mistrust is based upon several factors, some of which will be explored, since they have created barriers to a more rapid development of biotechnology as a fine chemical tool, than would otherwise have been the case. A better understanding of these factors will help companies in the fine chemical industry grasp the opportunities that do exist for developing their businesses and increasing their profits.

Comparing and contrasting a typical fine chemical company with a biotechnology company, one is struck by numerous potential areas of conflict, as shown in the table below.

The possibilities for misunderstandings and conflict stem from the companies' very different backgrounds and approaches to the conduct of their businesses. The successful companies on "both sides" will be those that can mangage the differences and develop working relationships with their opposite numbers. This process is beginning but time is limited for individual companies, particularly the biotechnology companies which must move into profit (since there are none which are yet profitable) within the next few years.

Individual fine chemical companies are threatened in a longer term way, since the industry is essentially innovative and its clients clearly do require the products of these new technologies. There has never been a long term future for independent fine chemical companies which do not innovate.


The Outlook

Biotechnology will continue to mature and new processes will be developed which take advantage of its benefits. The current specialist companies will evolve into fine chemical companies by partnerships, acquistions and evolution or they will go under. Some older chemical processes (and specialist companies which depend upon them) will become obsolete and be replaced by newer technologies, some biotechnical others inspired by biotechnology.

Fermentation is an established technology for producing a wide range of chemicals and the yield and costs of fermentation products will continue to be improved by the application of biotechnology.

The use of industrial enzymes will increase as the isolates become more effective and the range of practical transformations they catalyse increases. Again biotechnology will greatly accelerate this development.

By the turn of the century, the fine chemical industry will have come to terms with biotechnology and consultants will be addressing learned meetings on the opportunities presented by micromachines or some other new area of development. Biotechnology will have been absorbed and accepted as an important part of the technical resources of the industry. The industry will also have benefited from the absorption of the skills and outlook of the biochemists and molecular biologists who will become an integral part of its manpower. 

© Brychem, 1994