Liquid-liquid phase separation in metabolic engineering: Mechanistic insights, emerging applications, and future challenges.

Liquid-liquid phase separation (LLPS) enables precise regulation of metabolic activities and biochemical networks through membraneless organelles, advancing metabolic engineering.

• Why it matters: Understanding LLPS mechanisms addresses the need for dynamic, efficient, and robust control of metabolic processes that are difficult to achieve with traditional strategies, supporting the development of advanced microbial cell factories.
• What they did: The review summarizes design principles, molecular determinants, and regulatory strategies of artificial condensates, emphasizing applications in metabolic channeling, gene expression, and programmable cellular modules, alongside AI and deep learning tools.
• The result: This work highlights how LLPS-based platforms can enhance biosynthetic efficiency and robustness, while identifying challenges like condensate aging and host compatibility, guiding future development of stable, tunable cellular systems.