Rational enzyme redesign

Cedrone F, Menez A, Quemeneur E (2000) Tailoring new enzyme functions by rational redesign. Curr Opin Struct Biol 10 405 -10... 

Finally, the similar computational strategy discussed in this chapter in combination with appropriate wet experiments may also be useful in rational redesign of many other metabolic enzymes for the therapeutic treatments of metabolic diseases. 

Protein engineering is of very wide interest, offering the potential to provide new or better enzymes. As we begin to understand the process of molecular recognition and catalysis in flavocytochrome 2 in more detail, we should increase the scope for rational redesign of this enzyme. 

Chen, R. (2001) Enzyme engineering rational redesign versus directed evolution. Trends Bio-technol. 19, 13-14. 

The quest for purpose-designed biocatalysts relies on the rational redesign of natural biocatalysts and on evolutionary procedures to obtain novel catalysts. To rationally design biocatalysts requires knowledge of the connection between structure and function, for proteins as well as for ribozymes. The capabilities for manipulations of novel structures, organisms, bio-electronic hybrid devices will be targeted at process biocatalysts, novel therapeutic enzymes, specifically designed cellular machinery and metabolic networks. 

It is wrong to dismiss these efforts as impractical. They provide much valuable information about the chemical mechanism of enzyme catalysis. Once the basic rules are understood, they hold a promise for the rational redesign of enzymes. 

Ornstein, R. L. (1991)- Why timely bioremediation of synthetics may require rational enzyme redesign preliminary report on redesigning cytochrome P450cam for trichloroethylene dehalogenation. In On-Site Bioreclamation. Processes for Kenobiotic and Hydrocarbon Treatment, ed. R. E. Hinchee and R. F. Olfenbuttel, pp. 509-14. Boston Butterworth-Heinemann. 

The different but complementary strategies for redesigning natural enzyme can be approached from the perspective of how rational the strategy could be. Thus, the existing biocatalyst can be fine-tuned by rational design, being information intensive and computer assisted. In other words, the more rational the desired approach, the more knowledge is necessary to exactly interplay protein sequence and function. 

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