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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 16587-16591 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 99 |
| Issue number | 26 |
| DOIs | |
| State | Published - Dec 24 2002 |
| Externally published | Yes |
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Keywords
- Biocomputation
- Molecular evolution
- Random mutagenesis
- Repressor gene regulation
ASJC Scopus subject areas
- Genetics
- General
Cite this
Directed evolution of a genetic circuit. / Yokobayashi, Yohei; Weiss, Ron; Arnold, Frances H.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 26, 24.12.2002, p. 16587-16591.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Directed evolution of a genetic circuit
AU - Yokobayashi, Yohei
AU - Weiss, Ron
AU - Arnold, Frances H.
PY - 2002/12/24
Y1 - 2002/12/24
N2 - 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.
AB - 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.
KW - Biocomputation
KW - Molecular evolution
KW - Random mutagenesis
KW - Repressor gene regulation
UR - http://www.scopus.com/inward/record.url?scp=0037168510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037168510&partnerID=8YFLogxK
U2 - 10.1073/pnas.252535999
DO - 10.1073/pnas.252535999
M3 - Article
C2 - 12451174
AN - SCOPUS:0037168510
VL - 99
SP - 16587
EP - 16591
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 26
ER -