A research team led by Prof. WANG Peng from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences, in collaboration with international partners, has published a comprehensive review on liquid–liquid phase separation (LLPS)-driven membraneless organelles (MLOs) and their emerging applications in biotechnology.

The review was published in Synthetic and Systems Biotechnology.

In this article, the researchers systematically summarized the design principles and construction strategies of synthetic MLOs from three key perspectives: scaffold molecule types, client recruitment strategies, and characterization approaches. They integrated recent advances in the field and provided a clear framework for engineering programmable phase-separated systems in living cells.

The researchers also highlighted a wide range of practical applications. Synthetic MLOs have shown great potential in metabolic pathway reprogramming, enhancing enzyme activity, regulating gene expression, producing and purifying high-yield recombinant proteins, developing biomaterials, and delivering molecules. These condensates improve reaction efficiency and enable more precise cellular control by spatially organizing biomolecules into membrane-free microreactors.

"In recent years, LLPS-driven membraneless organelles have evolved from a biological curiosity into a practical engineering toolkit," said Dr. SUN Manman, a member of the team. "These programmable, membrane-free compartments enhance bioproduction efficiency, enable the safer expression of toxic products, and create new opportunities for green manufacturing and precision medicine."

Researchers further emphasized the promise of artificial MLOs in reducing product cytotoxicity and facilitating the biosynthesis of high-value or otherwise toxic compounds. They pointed out that advances in AI-assisted protein design, high-resolution imaging, and high-throughput screening technologies will accelerate the development of more stable, controllable, and orthogonal phase-separation systems. Such progress is expected to provide a solid foundation for next-generation programmable cell factories, functional biomaterials, and precision drug delivery platforms.

Construction and applications of membraneless organelles (Image by SUN Manman)