Developing new enzymatic catalysts by resurrecting ancestral alpha/beta hydrolases

Abstract

In our daily lives, we use items created by synthetic chemistry. In some cases, traditional chemical synthesis of these items requires harsh solvents, extreme temperatures, and results in large amounts of waste generated by side reactions. Developing enzymatic catalysts is a possible solution to this problem because enzymes are more selective, easy to dispose of, and react at ambient conditions. Modern day specialist enzymes are thought to have evolved from ancient generalists that catalyzed several reactions promiscuously. Our lab has reconstructed a number of ancestral enzymes from extant members of the alpha/beta hydrolase family. We have screened these enzymes for promiscuous reaction and substrate activities. The aldol and nitroaldol reactions are very important for the catalysis of many pharmaceuticals and commodity chemicals. One of our reconstructed ancestral enzymes catalyzes a nitroaldol reaction at a higher rate than modern day enzymes. We have also identified what is potentially a partial aldol reaction.