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Updated: Feb 3, 2026

An Integrated Workflow of Identification and Quantification on FDR Control-Based Untargeted Metabolome
Published on: September 20, 2022
Integrated dynamic control and enzyme co-localization strategies enable high-efficiency stilbenoid biosynthesis
Guofu Zhao1, Pengpai Li1, Xinyao Ding1
1MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, Dalian 116024, China.
Engineered E. coli efficiently produce stilbenoids like piceatannol and pterostilbene using CRISPRi and enzyme fusion. This microbial biosynthesis offers a sustainable alternative to plant extraction and chemical synthesis for valuable natural products.
Area of Science:
- Metabolic Engineering
- Synthetic Biology
- Natural Product Biosynthesis
Background:
- Stilbenoids are valuable plant-derived polyphenols with significant bioactivities.
- Challenges in stilbenoid production include low natural abundance and toxic chemical synthesis routes.
Purpose of the Study:
- To engineer Escherichia coli for efficient biosynthesis of multiple stilbenoids.
- To overcome limitations in natural product manufacturing through metabolic engineering.
Main Methods:
- Developed a p-coumaric acid-responsive CRISPRi system for dynamic metabolic regulation.
- Employed enzyme co-localization strategies, including dual-enzyme fusion design.
- Utilized orthogonal protein ligation systems (SpyTag/SpyCatcher, SnoopTag/SnoopCatcher) for pathway optimization.
Main Results:
- Achieved highest reported titers for piceatannol (583.10 mg/L) and pterostilbene (1110.92 mg/L) from glycerol with L-tyrosine supplementation.
- Demonstrated significant enhancement of pathway flux through optimized intermediate channeling.
- Techno-economic analysis confirmed the feasibility of microbial stilbenoid manufacturing.
Conclusions:
- The integrated strategy provides a robust platform for microbial stilbenoid biosynthesis.
- This approach offers a sustainable and efficient alternative for producing high-value natural products.
- Presents a valuable paradigm for the biosynthesis of other complex natural products.
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