The intelligent design of evolution

Mol Syst Biol. 2: 2006.0020The debate between intelligent design and evolution in education may still rage in school boards and classrooms, but intelligent design is making headway in the laboratory. In this case, though, the designer turned out to be just some clever scientist. A recent paper in Nature (Yoshikuni et al , 2006) presented the iterative evolution of highly specific catalysts from a promiscuous wild‐type enzyme via what the authors refer to as designed divergent evolution.The paper investigated whether catalytic functionality could be rationally engineered into a protein, without recourse to the high‐throughput screening techniques necessary for directed evolution. Yoshikuni et al (2006) started with a terpene synthase enzyme, γ‐humulene synthase, that is promiscuous not in its substrate specificity but in its product selectivity—it catalyzes the formation of 52 different sesquiterpene products from one single substrate, farnesyl diphosphate. (Sesquiterpenes naturally occur in a variety of plants, and their derivatives are used in applications ranging from chemical feedstocks to antifungal compounds.) The predominant product for the wild‐type enzyme is γ‐humulene, but Yoshikuni et al designed seven mutant variants with improved selectivities for eight of the products.How did they do it? Using prior knowledge of the active sites in the terpene synthase family and the crystal structure of another terpene synthase, the authors identified a set of 19 candidate ‘plasticity’ residues in γ‐humulene synthase that lie along the contour of the active site. …