CHRIS SAVILE
Codexis, 200 Penobscot Drive, Redwood City, CA 94063, USA.

Abstract

In recent years, biocatalysis has developed from small scale, laboratory-based experimental research into industrial scale methods for alternative chemical synthesis. Incorporating enzymatic approaches into pharmaceutical manufacturing can offer a number of advantages, such as reducing costs, increasing quality, improving safety, and reducing harmful impacts on the environment. However, the adoption of biocatalytic approaches into existing manufacturing processes is not necessarily straightforward. Natural enzymes may lack the stability, selectivity and activity required for industrial reactions, so considerable effort can be required in order to find and optimise suitable enzymes. Over the past three decades, rapid technological developments in the fields of genomics and bioinformatics have contributed to significant advances in protein engineering and directed evolution. As a result, enzyme optimisation and the identification of new candidate enzymes has improved, and the scope of biocatalytic applications is expanding. This article reviews some recent developments in the field and the promise of biocatalysis for providing economically competitive processes to help deliver profitable and innovative new therapies.

INTRODUCTION 

Enzyme-catalysed reactions can offer a number of economic advantages over chemical synthesis, and over the past few years there has been increasing use of biocatalysts in pharmaceutical manufacturing. The use of enzymes in place of certain chemical processes can provide higher activity and selectivity, faster and less onerous processes, as well as easier and safer operating conditions that are less environmentally harmful. Enzymes are particularly suitable for enantio- and regioselective chiral chemistry, because their chiral active sites can discriminate between different stereoisomers and regioisomers in order to generate isomerically pure pharmaceuticals and fine chemicals (1, 2). All of these advantages can also help to reduce costs and offer considerable benefits for drug development and manufacturing. Here we review some recent developments in protein engineering, directed evolution and computer algorithms that have helped scientists to develop enhanced and economically competitive biocatalysts, which promise to deliver more efficient, cost-effective pharmaceutical manufacturing processes.

The use of enzymes in chemical proce ...