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Intelligently designed molecular evolution

Evolutionary paths to new therapeutic drugs, as well as a wide assortment of other enzyme products, have been created through, of all things, intelligent design. A team of researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California at Berkeley have developed a technique in which the evolution of an important class of proteins is steered towards a desired outcome.

"We've taken enzymes that are promiscuous, meaning they have the capacity to evolve along many different functional lines, and trained them to become specialists," said chemical engineer Jay Keasling, who led this study.

"This technology could be used by pharmaceutical manufacturers in the future to create specific enzyme products."

Keasling is director of Berkeley Lab's Physical Biosciences Division, and a professor of chemical engineering with UC Berkeley's Chemical Engineering Department. Collaborating with him on this project were his graduate student, Yasuo Yoshikuni, and Thomas Ferrin, a professor of pharmaceutical chemistry and biopharmaceutical sciences at UC San Francisco.

The results of this study were reported in the February 22, 2006, on-line edition of the journal Nature.

According to the theory of divergent molecular evolution, primordial enzymes and other proteins started out as "promiscuous" so that primitive organisms would be better able to adapt to their environment. Driven by selective pressures, these promiscuous enzymes and other proteins evolved along divergent lines to acquire the specialized functions needed by a host organism to survive.

"This process is highly dependent on the fact that the functions of promiscuous proteins can be altered with just a small number of amino acid substitutions, a property known as plasticity," said Keasling. "It was our contention that the application of the theory of divergent molecular evolution to promiscuous enzymes would enable us to desi
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Source:DOE/Lawrence Berkeley National Laboratory


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