Molecular breeding directed evolution

Applied molecular evolution, directed evolution, molecular breeding—the process is known by different names—all use some variation... 

In the following case, we shall look at the molecular breeding of the lipase from the bacterium Pseudomonas aeruginosa. This particular molecular breeding experiment was the first example of the directed evolution of an enantioselective enzyme. The wild-type enzyme catalyses the hydrolysis of esters to carboxylic acid (Figure 10.10),and shows very little enantioselectivity-only two per cent enantiomeric excess biased towards the (S) configuration. 

Mike Lassner (Verdia Inc.) presented examples of the usefulness of directed molecular evolution as an in vitro process that more easily achieves what was traditionally attempted via reproductive crossing and recurrent selection (plant breeding). Proteins may be engineered that have specific desirable characteristics via methods that "evolve" the basic underlying DNA. For example, the outcome can be enzymes with improved kinetic properties that result in enhanced primary production, or proteins that remain operational under extreme conditions. In addition, compositional proteins may be enhanced to provide functional performance that was not achievable via conventional methods. 

Figure 1 The comparison between dog breeding and directed molecular evolution. Over many generations, humans have directed the evolution of dogs to suit certain needs. Likewise, over several generations of directed molecular evolution, humans can direct the evolution of a hydrolase in different directions.

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