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
