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Harnessing Interactional Sensory Genes for Rationally Reprogramming Chaotic Metabolism
Chunlin Tan1, Ping Xu1, Fei Tao1
1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Research (Washington, D.C.)
|September 18, 2024
Summary
A new platform enables precise control over cellular metabolism by decoding gene interactions. This strategy significantly reduces antibiotic resistance in Vibrio and enhances glycine production, offering a rational approach for metabolic reprogramming.
Area of Science:
- Synthetic Biology
- Metabolic Engineering
- Genomics
Background:
- Cellular metabolism is complex and difficult to control.
- Histidine kinases (HKs) act as sensitive nodes in biological networks, influencing metabolic reprogramming (MRP).
Purpose of the Study:
- To develop a global MRP platform for decoding high-order gene interactions.
- To investigate the impact of HKs on antibiotic resistance and glycine production in *Vibrio* sp. FA2.
Main Methods:
- CRISPR interference-mediated dual-gene combinational knockdown toolbox.
- Survivorship-based metabolic interaction decoding algorithm.
- Analysis of 35 HK genes and 24 glycine metabolic genes in *Vibrio* sp. FA2.
Main Results:
- Combined knockdown of HK genes (*sasA_8*, *04288*) reduced *Vibrio* antibiotic resistance by 108-fold.
- Combined knockdown of glycine pathway genes (*gcvT*, *ltaE*) and HK genes (*cpxA*, *btsS*) increased glycine production.
- The platform efficiently decodes n x n gene pair interactions with minimal primer synthesis.
Conclusions:
- The developed platform enables efficient and rational global MRP.
- Elucidation of high-order gene interactions is key for targeted metabolic control.
- A web-based service simplifies the implementation of this strategy across various cell types.
