Enzymes enter the field of functional genomics

Abstract

Enzyme technologies for pharmaceutical and biotechnological applicationsEdited by Herbert A. Kirst, Wu-Kuang Yeh and Milton J. Zmijewski Jr.Marcel Dekker Inc. New York, 2001. US$ 195 hdbk (xv + 611 pages) ISBN 0 8247 0549 1As gene products, enzymes are being explored for their functions and applications in the rapidly emerging field of functional genomics. Two major themes that will dominate enzyme technologies in the coming years are discovering new enzymes using the genomic approach and optimizing enzymes by protein engineering. Instead of random mutagenesis, knowledge-based rational design by side-directed mutagenesis, which requires an understanding of structure–function relationships, will become more and more important.This book focuses on the application of these novel enzyme technologies in pharmaceutical and biotechnological industries. Other areas of enzyme technology are not included because, according to the editors, they are well reviewed elsewhere. The editors aim to highlight how, what and where enzymes have become important or are rapidly emerging in these two overlapping and interdependent industries. The use of functional genomics, functional proteomics, combinatorial biosynthesis and combinatorial enzymology in drug discovery is illustrated using real examples.The book covers basic principles and applications in antibiotic biosynthesis, biocatalysis, screening and optimization, as well as new emerging technologies. The first part is about antibiotic synthesis and focuses on the interpretation on structure–function relations and metabolic engineering. Recombinant techniques (combined with traditional techniques) are used to increase the yield of the antibiotic and to produce novel antibiotic structures.The second part of the book is about biocatalysis of chiral drug intermediates and focuses on the manipulation of the enzyme tools by genetic engineering. Although the production of chiral intermediates is of extreme importance in the pharmaceutical industry, this part of the book contains only four chapters. Probably because organic chemistry has been one of the most successful scientific disciplines in industry and the editors want to provide real-world and practical industrial examples. The chapter about the development and use of cross-linked enzyme crystals is very interesting for organic chemists and biochemists. These cross-linked enzyme crystals can be seen as bioorganic zeolites, which are similar in structure to chemical catalysts. Therefore, the organic chemist might become more familiar with the use of these enzyme structures than ‘normal’ (immobilized) enzymes. Application of these enzyme-crystals provides the industry with opportunities to overcome the problems associated with the use of (immobilized) enzymes, such as those associated with stability. Further development of this technique combined with the other enzyme technologies described in this book will support the benefits and use of biocatalysis in industry by reducing the gap between biochemists and organic chemists.The screening section of the book describes the screening for and optimization of enzyme inhibitors using enzymes as targets for (new) drugs. The development in high-throughput screening in combination with structure–function studies has undergone rapid progress and has opened up new possibilities in identifying enzymes and inhibitors. The seven chapters show how high-throughput screening has enriched the field of drug discovery.The last part of the book deals with emerging enzyme technologies. There are three chapters about multistep biosynthesis of complex products; instead of focussing on one enzyme or step in the synthesis of drug the complete ‘pathway’ is taken into account. The location and sequencing of complete gene clusters responsible for multistep biosynthesis is described. Engineering of the corresponding multi-enzyme modules is the new challenge. Modifying parts of gene clusters within or, even more challenging, between organisms can lead to new products. The last four chapters include a description of future functional genomics and proteomics-based approaches.In summary, this book is informative about modern enzyme technology in pharmaceutical drug discovery. Assigning the precise function to genes and the rational redesign of enzymes is becoming more and more important in enzyme technology, which is well illustrated by the examples and the numerous references given. Although it is said that graduate and post-graduate students can use the book, the content seems to be intended for industrial and scientific researchers, who will find useful information on enzyme technology for pharmaceutical discovery and development.