Abstract
Sustainable production of chemicals, materials, and pharmaceuticals is increasingly performed by genetically engineered cell factories. Engineering of complex metabolic routes or cell behavior control systems requires robust and predictable gene expression tools. In this challenging task, orthogonality is a fundamental prerequisite for such tools. In this study, we developed and characterized in depth a comprehensive gene expression toolkit that allows accurate control of gene expression in Saccharomyces cerevisiae without marked interference with native cellular regulation. The toolkit comprises a set of transcription factors, designed to function as synthetic activators or repressors, and transcription-factor-dependent promoters, which together provide a broad expression range surpassing, at high end, the strongest native promoters. Modularity of the developed tools is demonstrated by establishing a novel bistable genetic circuit with robust performance to control a heterologous metabolic pathway and enabling on-demand switching between two alternative metabolic branches.
| Original language | English |
|---|---|
| Pages (from-to) | 1573-1587 |
| Number of pages | 15 |
| Journal | ACS Synthetic Biology |
| Volume | 7 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 15 Jun 2018 |
| MoE publication type | A1 Journal article-refereed |
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Keywords
- bistable switch
- core promoter
- gene regulation
- synthetic transcription factor
- yeast
Cite this
}
Synthetic Toolkit for Complex Genetic Circuit Engineering in Saccharomyces cerevisiae. / Rantasalo, Anssi; Kuivanen, Joosu; Penttilä, Merja; Jäntti, Jussi; Mojzita, Dominik (Corresponding Author).
In: ACS Synthetic Biology, Vol. 7, No. 6, 15.06.2018, p. 1573-1587.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - Synthetic Toolkit for Complex Genetic Circuit Engineering in Saccharomyces cerevisiae
AU - Rantasalo, Anssi
AU - Kuivanen, Joosu
AU - Penttilä, Merja
AU - Jäntti, Jussi
AU - Mojzita, Dominik
N1 - ISSN tarkistettu 26.9.18
PY - 2018/6/15
Y1 - 2018/6/15
N2 - Sustainable production of chemicals, materials, and pharmaceuticals is increasingly performed by genetically engineered cell factories. Engineering of complex metabolic routes or cell behavior control systems requires robust and predictable gene expression tools. In this challenging task, orthogonality is a fundamental prerequisite for such tools. In this study, we developed and characterized in depth a comprehensive gene expression toolkit that allows accurate control of gene expression in Saccharomyces cerevisiae without marked interference with native cellular regulation. The toolkit comprises a set of transcription factors, designed to function as synthetic activators or repressors, and transcription-factor-dependent promoters, which together provide a broad expression range surpassing, at high end, the strongest native promoters. Modularity of the developed tools is demonstrated by establishing a novel bistable genetic circuit with robust performance to control a heterologous metabolic pathway and enabling on-demand switching between two alternative metabolic branches.
AB - Sustainable production of chemicals, materials, and pharmaceuticals is increasingly performed by genetically engineered cell factories. Engineering of complex metabolic routes or cell behavior control systems requires robust and predictable gene expression tools. In this challenging task, orthogonality is a fundamental prerequisite for such tools. In this study, we developed and characterized in depth a comprehensive gene expression toolkit that allows accurate control of gene expression in Saccharomyces cerevisiae without marked interference with native cellular regulation. The toolkit comprises a set of transcription factors, designed to function as synthetic activators or repressors, and transcription-factor-dependent promoters, which together provide a broad expression range surpassing, at high end, the strongest native promoters. Modularity of the developed tools is demonstrated by establishing a novel bistable genetic circuit with robust performance to control a heterologous metabolic pathway and enabling on-demand switching between two alternative metabolic branches.
KW - bistable switch
KW - core promoter
KW - gene regulation
KW - synthetic transcription factor
KW - yeast
UR - http://www.scopus.com/inward/record.url?scp=85047093361&partnerID=8YFLogxK
U2 - 10.1021/acssynbio.8b00076
DO - 10.1021/acssynbio.8b00076
M3 - Article
VL - 7
SP - 1573
EP - 1587
JO - ACS Synthetic Biology
JF - ACS Synthetic Biology
SN - 2161-5063
IS - 6
ER -