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Engineering orthogonal dual transcription factors for multi-input synthetic promoters
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Brodel, Andreas K., Jaramillo, Alfonso and Isalan, Mark (2016) Engineering orthogonal dual transcription factors for multi-input synthetic promoters. Nature Communications, 7 . 13858 . doi:10.1038/ncomms13858 ISSN 2041-1723.
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Official URL: http://doi.org/10.1038/ncomms13858
Abstract
Synthetic biology has seen an explosive growth in the capability of engineering artificial gene circuits from transcription factors (TFs), particularly in bacteria. However, most artificial networks still employ the same core set of TFs (for example LacI, TetR and cI). The TFs mostly function via repression and it is difficult to integrate multiple inputs in promoter logic. Here we present to our knowledge the first set of dual activator-repressor switches for orthogonal logic gates, based on bacteriophage l cI variants and multi-input promoter architectures. Our toolkit contains 12 TFs, flexibly operating as activators, repressors, dual activator–repressors or dual repressor–repressors, on up to 270 synthetic promoters. To engineer non crossreacting cI variants, we design a new M13 phagemid-based system for the directed evolution of biomolecules. Because cI is used in so many synthetic biology projects, the new set of variants will easily slot into the existing projects of other groups, greatly expanding current engineering capacities.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QH Natural history > QH426 Genetics Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Library of Congress Subject Headings (LCSH): | Transcription factors, Insertional mutagenesis, Synthetic biology, Promoters (Genetics) | ||||||||
Journal or Publication Title: | Nature Communications | ||||||||
Publisher: | Nature Publishing Group | ||||||||
ISSN: | 2041-1723 | ||||||||
Official Date: | December 2016 | ||||||||
Dates: |
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Volume: | 7 | ||||||||
Article Number: | 13858 | ||||||||
DOI: | 10.1038/ncomms13858 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 8 February 2017 | ||||||||
Date of first compliant Open Access: | 8 February 2017 | ||||||||
Funder: | Seventh Framework Programme (European Commission) (FP7), Wellcome Trust (London, England) | ||||||||
Grant number: | Grant no 610730, EVOPROG, Grant no 613745, PROMYS (FP7), Award no WT102944 (Wellcome Trust) | ||||||||
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