Journal Article

FZJ-2020-03237

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Inducible Expression Systems Based on Xenogeneic Silencing and Counter-Silencing and Design of a Metabolic Toggle Switch

Wiechert, J.FZJ* ; Gätgens, C. ; Wirtz, A.FZJ* ; Frunzke, J. (Corresponding author)FZJ*

2020
ACS Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/25736  doi:10.1021/acssynbio.0c00111

Abstract: Inducible expression systems represent key modules in regulatory circuit design and metabolic engineering approaches. However, established systems are often limited in terms of applications due to high background expression levels and inducer toxicity. In bacteria, xenogeneic silencing (XS) proteins are involved in the tight control of horizontally acquired, AT-rich DNA. The action of XS proteins may be opposed by interference with a specific transcription factor, resulting in the phenomenon of counter-silencing, thereby activating gene expression. In this study, we harnessed this principle for the construction of a synthetic promoter library consisting of phage promoters targeted by the Lsr2-like XS protein CgpS of Corynebacterium glutamicum. Counter-silencing was achieved by inserting the operator sequence of the gluconate-responsive transcription factor GntR. The GntR-dependent promoter library is comprised of 28 activated and 16 repressed regulatory elements featuring effector-dependent tunability. For selected candidates, background expression levels were confirmed to be significantly reduced in comparison to established heterologous expression systems. Finally, a GntR-dependent metabolic toggle switch was implemented in a C. glutamicuml-valine production strain allowing the dynamic redirection of carbon flux between biomass and product formation.

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Contributing Institute(s):

1. Biotechnologie (IBG-1)

Research Program(s):

1. 581 - Biotechnology (POF3-581) (POF3-581)

Appears in the scientific report 2020

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Database coverage:
; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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