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) |
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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 |
Keywords
- Biocomputation
- Molecular evolution
- Random mutagenesis
- Repressor gene regulation
ASJC Scopus subject areas
- Genetics
- General