Protein function evolution engineering

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. 

Nature has solved the problem of protein design through the mechanism of Darwinian evolution. Every one of the proteins in our cells, from enzymes and receptors to structural proteins, has arisen by this process. As the examples presented here with chor-ismate mutase amply demonstrate, evolutionary strategies can also be successfully exploited in the laboratory to study the structure and function of existing proteins and to engineer new ones. 

A readily available and abundant resource for examples on how to engineer proteins is Nature itself. The mechanisms of natural protein evolution have repeatedly succeeded in adapting protein function to ever changing environments. Understanding the principles and motives whereby new protein structures and functions emerge can provide useful guidelines for protein engineering. This chapter is directed towards the mechanisms of natural protein evolution, their implications on structure and function, and their experimental implementation in vitro. 

With the considerable evolution achieved in recent years in the elucidation of structure-function relationship of proteins, as well as in the areas of protein engineering and bioinformatics, many new developments are expected in the field of new-generation biopharmaceuticals. These will have significant advantages for patients, including lower immunogenicity, lower frequency of injections, and enhanced stability in serum. 

---