Reversible Photoswitchable Inhibitors Enable Wavelength‐Selective Regulation of Out‐of‐Equilibrium Bi‐enzymatic Systems

Abstract

AbstractThe construction of synthetic enzymatic reaction networks can provide new insights into the design principles of living systems. However, the programmable connection of enzymes into a wide range of network topologies has been challenging due to the lack of a general strategy enabling a reversible activity regulation of individual network enzymes. Here, we exploit a general and modular strategy based on the external regulation of enzymes using light and photoswitchable inhibitors (PIs) that enables the bottom‐up construction and control of enzymatic systems studied under out‐of‐equilibrium conditions. Upon synthesis and incorporation of potent photoswitchable trypsin inhibitors (Tr‐PIs), the output of several functional enzymatic systems could be photoregulated using 390/460 nm light as a trigger signal. In addition, the wavelength‐selective control over the activity of two enzymes within a functional bi‐enzymatic system was achieved using a suitable combination of two PIs.