Biocatalise
Industrial biocatalysis Aleksey Zaks
The number of industrial processes for the synthesis of fine and commodity chemicals, pharmaceutical and agrochemical intermediates and drug substances utilizing biological catalysts continues to grow. The combination of new molecular biology techniques, such as directed evolution and pathway engineering, with new and efficient high-throughput screening methods is poised to bolster this field and further advance the contribution of biocatalysis to the chemical and the pharmaceutical industries.
Addresses Schering-Plough Research Institute, 1011 Morris Avenue, Union, New Jersey 07083, USA; e-mail: alex.zaks@spcorp.com Current Opinion in Chemical Biology 2001, 5:130–136 1367-5931/01/$ — see front matter © 2001 Elsevier Science Ltd. All rights reserved. Abbreviations DEAE diethylaminoethyl ee enantiomeric excess
Pharmaceutical industry
The use of biological catalysts in the synthesis of pharmaceutical intermediates, drug metabolites and drug products is now common. The growing list of compounds synthesized with the assistance of enzymes now includes anti-cancer, anti-viral, anti-infective, antipsychotic, anti-arrhythmic, and cholesterol-lowering agents, calcium channel blockers, ACE inhibitors and many others [3••,6•]. Although it is well accepted that enzymes are extremely versatile and capable of catalyzing a wide variety of chemical reactions, their practical use is often curtailed by their limited commercial availability. Among the approaches utilized in the search for new catalytic activities, high-throughput microbial screening and the selective enrichment technique are considered to be the most reliable. The latter approach was efficiently utilized by a Bristol–Myers Squibb team for the synthesis of Omapatrilat, a vasopeptidase inhibitor targeted for the treatment of hypertension (Figure 1) [23••]. By using the selective enrichment technique, the authors have isolated a novel L -lysine ε-aminotransferase capable