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Directed evolution of a genetic circuit

Yokobayashi, Yohei and Weiss, Ron and Arnold, Frances H. (2002) Directed evolution of a genetic circuit. Proceedings of the National Academy of Sciences of the United States of America, 99 (26). pp. 16587-16591. ISSN 0027-8424. PMCID PMC139187. https://resolver.caltech.edu/CaltechAUTHORS:YOKpnas02

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.252535999DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139187/PubMed CentralArticle
ORCID:
AuthorORCID
Yokobayashi, Yohei0000-0002-2417-1934
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2002 by The National Academy of Sciences. From the Cover. Edited by Charles R. Cantor, Sequenom, Inc., San Diego, CA, and approved October 21, 2002 (received for review September 3, 2002) This paper was submitted directly (Track II) to the PNAS office. This research was supported by National Science Foundation, Biological Information Technology and Storage (BITS) Grant EIA-0130613 and Maxygen Corporation. Y.Y. is supported by a Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad.
Funders:
Funding AgencyGrant Number
NSFEIA-0130613
Maxygen, Inc.UNSPECIFIED
Japan Society for the Promotion of Science (JSPS)UNSPECIFIED
Subject Keywords:biocomputation, molecular evolution, repressor, gene regulation, random mutagenesis
Issue or Number:26
PubMed Central ID:PMC139187
Record Number:CaltechAUTHORS:YOKpnas02
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:YOKpnas02
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:642
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:09 Sep 2005
Last Modified:11 Nov 2020 00:46

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