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Directed evolution of a genetic circuit.

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.

SUBMITTER: Yokobayashi Y

PROVIDER: S-EPMC139187 | biostudies-literature | 2002 Dec

REPOSITORIES: biostudies-literature

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Directed evolution of a genetic circuit.

Yokobayashi Yohei Y Weiss Ron R Arnold Frances H FH

Proceedings of the National Academy of Sciences of the United States of America 20021125 26

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 constructin ...[more]

PMID: 12451174

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