Virtual enzymes

Excerpt

In biochemical systems, a host of “nature’s catalysts” conduct chemical transformations at physiological temperatures, high substrate conversion, and high optical activity integrity, and by means of single reactive center substrate changes. All of these traits are highly esteemed in the pursuit of “green” chemical synthetic technology for fine chemicals and pharmaceuticals. Researchers have recently reported the ability to use computer design approaches to elicit the active site architecture and the synthesis of 72 candidate retro-aldol enzymes from a field of more than 180,000. The Rosetta protein structure program was employed to generate the field of potential enzyme structures, which were confirmed by X-ray crystallography. Of the synthesized enzymes, 32 showed desired enzymatic activity with a range of catalytic activities. Despite this success, these catalytic activities were less than 100,000 times as active as comparable naturally occurring enzymes. However, the synthetic enzymes were shown to have activity to non-naturally occurring substrates such as 4-hydroxy-4-(6-methoxy-2-naphthyl)-1-butanone. This activity is promising for the enzymatic conversion of synthetic intermediates used to construct fine chemicals and pharmaceuticals.

(Science 2008, 319, 1387). …