Introduction to Biocatalysis (2)

Applications of Biocatalysis in Industry

Chemical Industry of the Future: Environmentally Benign Manufacturing, Green Chemistry, Sustainable Development in the Future

Owing to two very strong and important driving forces the chemical industry of the future will look considerably different from today’s version:

• cost and margin pressure resulting from competition in an increasingly open market-oriented economy, and
• operation of the industry in a societal framework which puts emphasis on a clean (or at least less polluted) environment

Processing with a view towards this new set of conditions focuses on the development of production routes with fewer processing steps, with higher yields on each step, to save material and energy costs. Less waste is generated, and treatment and disposal costs go down. Both pressures come together in the cases of environmental compliance costs.

In many cases, such as high-fructose corn syrup, or biotechnology and biocatalysis offer technology options and solutions that are not available through any other technology; in such situations such as acrylamide, nicotinamide or intermediates for antibiotics, biotechnology and biocatalysis act as “enabling technologies”. In the remaining situations, biotechnology and biocatalysis offer one solution among several others, which all have to be evaluated according to criteria developed in Chapter 2: yield to product, selectivity, productivity, (bio)catalyst stability, and space–time-yield.

In this context, the three terms in the title are to a good extent synonymous; nevertheless, they have been developed in a slightly different context:

• environmentally benign manufacturing is a movement towards manufacturing systems that are both economically and environmentally sound;
• sustainable development is a worldwide Chemical Industry movement and represents a set of guidelines on how to manage resources such that non-renewables are minimized as much as possible;
• green chemistry is the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances.

“Green chemistry is an overarching approach that is applicable to all aspects of chemistry” (Anastas, 2002). Green chemistry methodologies can be viewed through the framework of the “Twelve Principles of Green Chemistry” (Anastas, 1998):

1. It is better to prevent waste than to treat or clean up waste after it is formed.
2. Synthetic methods should be designed to maximize the incorporation of all
3. materials used in the process into the final product. Wherever practicable, synthetic methodologies should be designed to use and generate substances that possess little or no toxicity towards human health and the environment.
   
4. Chemical products should be designed to preserve efficacy of function while reducing toxicity.
5. The use of auxiliary substances (e.g., solvents, separation agents, etc.) should be made unnecessary wherever possible, and should be innocuous when used.
6. Energy requirements should be recognized for their environmental and economic impacts and should be minimized. Synthetic methods should be conducted at ambient temperatures and pressures.
7. A raw material or feedstock should be renewable rather than depleting wherever technically and economically practicable.
8. Unnecessary derivatization (blocking group, protection/deprotection, temporary modification of physical/chemical processes) should be avoided wherever possible.
9. Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.
10. Chemical products should be designed so that at the end of their function they do not persist in the environment and they do break down into innocuous degradation products.
11. Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances.
12. Substances and the form of a substance used in a chemical process should be selected so as to minimize the potential for chemical accidents, including releases, explosions, and fires.

Catalysis offers numerous advantages for achieving green chemistry goals: novel, high-yield, shorter process routes; increased selectivity; and lower temperatures and pressures. Biocatalysis combines the goals of all three topics above. Biocatalysts, as well as many of the raw materials, especially those for fermentations, are themselves completely renewable and for the most part do not pose any harm to humans or animals. Through the avoidance of high temperatures and pressures and of large consumptions of metals and organic solvents, the generation of waste per unit of product is drastically reduced.

Introduction to Biocatalysis (1)

Summary

Over the last 20 years, many reservations with respect to biocatalysis have been voiced, contending that: (i) enzymes only feature limited substrate specificity; (ii) there is only limited availability of enzymes; (iii) only a limited number of enzymes exist; (iv) protein catalyst stability is limited; (v) enzyme reactions are saddled with limited space–time yield; and (vi) enzymes require complicated cosubstrates such as cofactors.

Driven by the discovery of many novel enzymes, by recombinant DNA technology which allows both more efficient production and targeted or combinatorial alterations of individual enzymes, and by process development towards higher stability and volumetric productivity, synthesis routes in which one or all of the steps are biocatalytic have advanced dramatically in recent years. Design rules for improved biocatalysts are increasingly precise and easy to use.

Biocatalysts do not operate by different scientific principles from organic catalysts. The existence of a multitude of enzyme models including oligopeptidic or polypeptidic catalysts proves that all enzyme action can be explained by rational chemical and physical principles. However, enzymes can create unusual and superior reaction conditions such as extremely low pKa values or a high positive potential for a redox metal ion. Enzymes increasingly have been found to catalyze almost any reaction of organic chemistry.

Biotechnology and biocatalysis differ from conventional processes not only by featuring a different type of catalyst; they also constitute a new technology base. The raw materials base of a biologically-based process is built on sugar, lignin, or animal or plant wastes; in biotechnology, unit operations such as membrane processes, chromatography, or biocatalysis are prevalent, and the product range of biotechnological processes often encompasses chiral molecules or biopolymers such as proteins, nucleic acids or carbohydrates.

Cost and margin pressure from less expensive competitors and operation with emphasis on a clean (or less polluted) environment are two major developments. Fewer processing steps, with higher yields at each step, lower material and energy costs, and less waste are the goals. Biotechnology and biocatalysis often offer unique technology options and solutions, they act as enabling technologies; in other cases, biocatalysis has to outperform competing technologies to gain access. In the phar-maceutical industry, the reason for the drive for enantiomeric purity is that the vast majority of novel drugs are chiral targets, favoring biocatalysis as the technology with the best selectivity performance.

Biocatalytic processes increasingly penetrate the chemical industry. In a recent study, 134 industrial-scale biotransformations, on a scale of > 100 kg with whole cells or enzymes starting from a precursor other than a C-source, were analyzed. Hydrolases (44%), followed by oxido-reductases (30%), dominate industrial biocatalytic applications. Average performance data for fine chemicals (not pharmaceuticals) applications are 78% yield, a final product concentration of 108 g L, and a volumetric productivity of 372 g (L · d)

Biocatalysis. Andreas S. Bommarius and Bettina R. Riebel
Copyright © 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30344-8

Advanced Control Engineering

BURNS, Roland S. (2001):
Advanced Control Engineering.
Oxford, UK: Butterworth-Heinemann. A division of Reed Educational and Professional Publishing Ltd.
ISBN: 0-7506-5100-8. 464p

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