Engineered bidirectional promoters enable rapid multi-gene co-expression optimization

Open access
Author
Vogl, Thomas
Kickenweiz, Thomas
Pitzer, Julia
Sturmberger, Lukas
Weninger, Astrid
Biggs, Bradley W.
Köhler, Eva-Maria
Baumschlager, Armin
Fischer, Jasmin E.
Hyden, Patrick
Wagner, Marlies
Baumann, Martina
Borth, Nicole
Geier, Martina
Ajikumar, Parayil K.
Glieder, Anton
Date
2018Type
- Journal Article
Abstract
Numerous synthetic biology endeavors require well-tuned co-expression of functional components for success. Classically, monodirectional promoters (MDPs) have been used for such applications, but MDPs are limited in terms of multi-gene co-expression capabilities. Consequently, there is a pressing need for new tools with improved flexibility in terms of genetic circuit design, metabolic pathway assembly, and optimization. Here, motivated by nature’s use of bidirectional promoters (BDPs) as a solution for efficient gene co-expression, we generate a library of 168 synthetic BDPs in the yeast Komagataella phaffii (syn. Pichia pastoris), leveraging naturally occurring BDPs as a parts repository. This library of synthetic BDPs allows for rapid screening of diverse expression profiles and ratios to optimize gene co-expression, including for metabolic pathways (taxadiene, β-carotene). The modular design strategies applied for creating the BDP library could be relevant in other eukaryotic hosts, enabling a myriad of metabolic engineering and synthetic biology applications Show more
Permanent link
https://doi.org/10.3929/ethz-b-000287964Publication status
publishedJournal / series
Nature CommunicationsVolume
Pages / Article No.
Publisher
Nature Publishing GroupRelated publications and datasets
Is referenced by: https://doi.org/10.1038/s41467-018-07112-1
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