N Nature Chemical Engineering · Nov 19, 2025 An industrial automated laboratory for programmable protein evolution Current methods for protein engineering are constrained by limited understanding of sequence–function relationships, the difficulty of designing complex properties by artificial intelligence methods and labor-intensive directed evolution. Here, to enable continuous and scalable protein evolution and systematic exploration of protein adaptive landscapes, we established an industrial-grade automation platform featuring high throughput, high efficiency, enhanced reliability and minimal human intervention (operational for ~1 month). We then developed new genetic circuits for the OrthoRep continuous evolution system to achieve growth-coupled evolution for proteins with diverse and complex functionalities. This included improving lactate sensitivity of LldR via dual selection and increasing operator selectivity for LmrA using the NIMPLY circuit. We integrated these components into an all-in-one laboratory, iAutoEvoLab, and evolved proteins from inactive precursors to fully functional entities, such as a T7 RNA polymerase fusion protein CapT7 with mRNA capping properties, which can be directly applied to in vitro mRNA transcription and mammalian systems. Our system represents a versatile tool for protein engineering and expands the scope for investigating the origins and evolutionary trajectories of protein functions. Biomedical engineering Biotechnology Proteins Protein Engineering Automation Directed Evolution Genetic Circuits
N Nature Chemical Engineering · Aug 15, 2025 Hydrogen evolution and dynamics in hydrogel electrochemical cells for ischemia–reperfusion therapy Molecular hydrogen (H2) protects organs from reactive oxygen species damage associated with ischemia–reperfusion (I/R) injury. Existing H2delivery methods, such as gas inhalation and H2-rich water consumption, target the entire body and experience leakage during administration. Here we engineer a portable hydrogel electrochemical cell that enables on-demand H2production via the hydrogen evolution reaction. The system enables H2controlled generation, localized storage and sustained diffusion to the tissue–device interface, with better controllability and sustainability. We conduct a thorough study of H2evolution and dynamics in the hydrogel system, evaluating the influence of hydrogel polymer composition on the hydrogen evolution reaction kinetics, bubble morphologies and storage. We validate its protective effects (1) in vitro with cardiomyocytes and keratinocytes, (2) ex vivo in I/R hearts and (3) in vivo in skin I/R pressure ulcers. These findings demonstrate the potential of the hydrogel electrochemical cell design for efficient and sustainable H2delivery in I/R therapy, which could be broadly applied in other gas-based therapies and drug delivery research. Biomedical engineering Chemical engineering Energy science and technology Mechanical engineering Drug Development Clinical Human Cell Biology Metabolism
