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Visible Light-Driven Membrane-Bound Compartment for Precise Regulation of Enzyme Activity
Zilu Li1,2, Jialiang Wang1,3, Hao Zhuo4
1State Key Laboratory of Advanced Drug Delivery and Release Systems, Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
None:
Photo-responsive systems provide a powerful tool to reversibly regulate enzyme activity. However, inhibitor-based strategies, though widely used, are often restricted to specific enzymes. Noninhibitor strategies, such as enzyme surface modification or genetic mutation, often compromise structural integrity or residual activity. Inspired by the gating mechanisms of biological membranes, we reported a visible light-driven membrane-bound compartment system constructed from phenylazothiazole gated lipids and phospholipids. In this design, phenylazothiazole lipids undergo reversible isomerization between trans and cis configurations under alternating purple and green light, generating continuous nanomechanical motions that transiently enhance membrane permeability. This dynamic gating behavior enables substrate diffusion across the membrane under light exposure and allows the activity of encapsulated enzymes to be switched on and off in a noninvasive, temporally defined manner. This system requires no chemical modification or mutagenesis, thus preserving the native structure and activity of encapsulated enzymes. Beyond binary regulation, precise modulation of the irradiation pattern permits graded control over enzyme activity, offering an advanced level of functional tunability. Using carbonic anhydrase, catalase, and glucose oxidase as models, we demonstrate that enzyme activity can be reversibly and quantitatively regulated via programmable light inputs. This strategy offers a broadly applicable and biocompatible platform for spatiotemporal enzyme regulation.
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