Synthetic organelles enable protein purification in a single operation

Protein purification is crucial for various applications in life sciences research and biotechnological industry, yet traditional chromatography methods are often complex and suffer from limited scalability and sustainability. Here we report a biological approach utilizing synthetic organelles for protein purification, termed Program Architecture of Nano-Device Actions for Purification (PandaPure). PandaPure includes a biomimetic mechanism of sorting proteins of interest into organelles through signal sequence domains during expression, and subsequently releasing said proteins via cleavage of organelle-locating signals in a single operation. In the commonly-used expression host Escherichia coli, PandaPure enables high-yield, high-purity production of target proteins, and significantly reducing environmental impact. We demonstrate its scalability and versatility with different designs, scales, and across diverse proteins, promising wide-ranging benefits in research and industrial settings.