Synthetic Toolkit for Complex Genetic Circuit Engineering in Saccharomyces cerevisiae

Anssi Rantasalo, Joosu Kuivanen, Merja Penttilä, Jussi Jäntti, Dominik Mojzita (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

6 Citations (Scopus)

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 languageEnglish
Pages (from-to)1573-1587
Number of pages15
JournalACS Synthetic Biology
Volume7
Issue number6
DOIs
Publication statusPublished - 15 Jun 2018
MoE publication typeA1 Journal article-refereed

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Genetic Engineering
Gene expression
Yeast
Saccharomyces cerevisiae
Transcription factors
Gene Expression
Networks (circuits)
Transcription Factors
Metabolic Engineering
Behavior Control
Metabolic Networks and Pathways
Drug products
Industrial plants
Control systems
Pharmaceutical Preparations

Keywords

  • bistable switch
  • core promoter
  • gene regulation
  • synthetic transcription factor
  • yeast

Cite this

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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.",
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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 journalArticleScientificpeer-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

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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.

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