The modification of cellular metabolism is of biotechnological and commercial significance because naturally occurring metabolic pathways are the source of diverse compounds used in fields ranging from medicine to bioremediation. Directed evolution is the experimental improvement of biocatalysts or cellular properties through iterative genetic diversification and selection procedures. The creation of novel metabolic functions without disrupting the balanced intracellular pool of metabolites is the primary challenge of pathway manipulation. The introduction of coordinated changes across multiple genetic elements, in conjunction with functional selection, presents an integrated approach for the modification of metabolism with benign physiological consequences. Directed evolution formats take advantage of the dynamic structures of genomes and genomic sub-structures and their ability to evolve in multiple directions in response to external stimuli. The elucidation, design and application of genome-restructuring mechanisms are key elements in the directed evolution of cellular metabolic pathways.
|Number of pages||11|
|Journal||Trends in Biotechnology|
|State||Published - Jan 2006|
Bibliographical noteFunding Information:
We would like to thank K. Shen for critical reading of the manuscript and S. Copley for insightful suggestions on evolution of the PCP degradation pathway. This work is supported in part by a grant (to L.Y.) from the Kentucky Tobacco Research and Development Center, University of Kentucky.
ASJC Scopus subject areas