Enzymes are remarkable catalysts that perform their tasks with alacrity in water at room temperature, and with a high degree of regioselectivity (for example, substitution at a particular position in an aromatic ring) and enantioselectivity (for a particular optical isomer). Because of the trend towards more environmentally friendly processes, and drugs that are more effective and cause fewer side effects (such as optically pure isomers), biocatalysis is rapidly becoming an attractive option for the manufacture of fine chemicals. The industrial application of certain enzymes, for example most hydrolytic enzymes, is relatively straightforward, whereas for others, such as the reduction-oxidation, or redox, enzymes, the need for enzyme cofactors makes their use more problematic. Nonetheless, it is precisely these enzymes that mediate the most interesting synthetic conversions.
A major challenge in biocatalysis is to harness the enormous potential of the ubiquitous cytochrome P450 monooxygenases1. These enzymes play key roles in the biosynthesis of prostaglandins and steroids, among others, and in the detoxification of foreign substances in the body, including drugs, pesticides and petroleum hydrocarbons. They are promiscuous catalysts, using molecular oxygen to insert an oxygen atom into a number of substrates. Many of these conversions are of potential industrial interest, for example in the production of pure enantiomers of epoxides. Unfortunately, they suffer from several drawbacks — low stability and turnover rates and the need for a complex cofactor regeneration system — that prohibit their industrial application. The paper by Arnold and co-workers on page 670 of this issue2 constitutes an important step towards the ultimate goal of commercial viability. They successfully apply the technique of ‘directed evolution’, using random mutagenesis and DNA shuffling, to develop mutants of a bacterial cytochrome P450 enzyme that efficiently use hydrogen peroxide (H202) as the source of oxygen, thereby bypassing the need for cofactor regeneration.
This is a preview of subscription content, access via your institution
