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Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16587-91. Epub 2002 Nov 25.

Directed evolution of a genetic circuit.

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  • 1Division of Chemistry and Chemical Engineering, California Institute of Technology, 210-41, 1200 East California Boulevard, Pasadena, CA 91125, USA.

Abstract

The construction of artificial networks of transcriptional control elements in living cells represents a new frontier for biological engineering. However, biological circuit engineers will have to confront their inability to predict the precise behavior of even the most simple synthetic networks, a serious shortcoming and challenge for the design and construction of more sophisticated genetic circuitry in the future. We propose a combined rational and evolutionary design strategy for constructing genetic regulatory circuits, an approach that allows the engineer to fine-tune the biochemical parameters of the networks experimentally in vivo. By applying directed evolution to genes comprising a simple genetic circuit, we demonstrate that a nonfunctional circuit containing improperly matched components can evolve rapidly into a functional one. In the process, we generated a library of genetic devices with a range of behaviors that can be used to construct more complex circuits.

Comment in

  • Design then mutate. [Proc Natl Acad Sci U S A. 2002]
PMID:
12451174
[PubMed - indexed for MEDLINE]
PMCID:
PMC139187
Free PMC Article

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