Liquid-liquid phase separation in metabolic engineering: Mechanistic insights, emerging applications, and future
Weiwei Liu1, Linyue Tian2, Jiupan Xie1
1Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Key Laboratory for Synthetic Biotechnology of Xiamen City, Xiamen University, Xiamen 361005, China.
Biotechnology Advances
|June 1, 2026
Summary
Liquid-liquid phase separation (LLPS) enables precise cellular regulation via membraneless organelles (MLOs). This review explores LLPS applications in metabolic engineering and synthetic biology, highlighting AI
Area of Science:
- Synthetic Biology and Metabolic Engineering
- Biochemistry and Biophysics
- Cellular Organization and Regulation
Background:
- Cells utilize membraneless organelles (MLOs) formed by liquid-liquid phase separation (LLPS) for precise regulation of metabolic activities.
- LLPS offers advanced strategies for metabolic engineering, enhancing efficiency, robustness, and dynamic control beyond conventional methods.
Purpose of the Study:
- To systematically review design principles, molecular determinants, and regulatory strategies of LLPS-based artificial condensates.
- To highlight applications in metabolic channeling, gene expression control, and constructing programmable cellular modules.
- To explore the role of AI and deep learning in advancing LLPS-based synthetic biology.
Main Methods:
- Systematic review of literature on LLPS, MLOs, and their applications in metabolic engineering.
- Analysis of AI and deep learning contributions to understanding and designing intrinsically disordered regions (IDRs).
- Evaluation of challenges and opportunities in developing tunable LLPS-based systems.
Main Results:
- LLPS-based artificial condensates provide tunable platforms for metabolic channeling and gene expression control.
- AI and deep learning facilitate the design of synthetic IDRs, establishing quantitative sequence-phase behavior relationships.
- Progress is being made towards predictive, engineering-oriented frameworks for LLPS applications.
Conclusions:
- LLPS-based platforms offer a promising avenue for developing next-generation microbial cell factories with enhanced capabilities.
- Addressing challenges like condensate aging and host cell compatibility is crucial for future development.
- This review provides a framework for advancing LLPS-based synthetic biology and metabolic engineering.
Keywords:
Intrinsically disordered regionsLiquid-liquid phase separationMembraneless organelleMetabolic engineeringMore Related Videos
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