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A programmable high-expression yeast platform responsive to user-defined signals.
Qi Liu1, Lili Song1, Qiangqiang Peng1
1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Science Advances
|February 11, 2022
Summary
We developed SynPic-X, a programmable yeast platform that enhances protein production capacity and regulatory flexibility. This system uses a synthetic transcriptional signal amplification device (iTSAD) and CRISPR technology for precise control, enabling efficient recombinant protein expression.
Area of Science:
- Biotechnology
- Synthetic Biology
- Microbial Engineering
Background:
- Yeasts are favored hosts for biopharmaceutical protein production due to posttranslational modifications.
- Current yeast systems face limitations in production capacity and transcriptional regulation, hindering adaptability.
Purpose of the Study:
- To develop a programmable, high-expression yeast platform (SynPic-X) with enhanced regulatory control.
- To overcome limitations in yeast-based recombinant protein production.
Main Methods:
- Engineered a synthetic improved transcriptional signal amplification device (iTSAD) using bacterial-yeast components.
- Integrated CRISPR activation and interference for precise, signal-responsive regulation of iTSAD.
- Constructed engineered switches to demonstrate SynPic-X response to exogenous signals.
Main Results:
- The iTSAD significantly increased protein expression capacity in *Pichia pastoris*.
- CRISPR-based devices enabled strict, signal-dependent regulation of the iTSAD.
- Demonstrated a methanol-free, high-yield recombinant protein production process using SynPic-X.
Conclusions:
- The SynPic-X platform offers a customizable yeast host for high-level protein production.
- Provides enhanced regulatory flexibility for controlling gene expression in yeast.
- Presents a novel solution for efficient and adaptable biopharmaceutical manufacturing.

