Bottom‐Up Construction of an Adaptive Enzymatic Reaction Network

Abstract

The reproduction of emergent behaviors in nature using reaction networks is an important objective in synthetic biology and systems chemistry. Herein, the first experimental realization of an enzymatic reaction network capable of an adaptive response is reported. The design is based on the dual activity of trypsin, which activates chymotrypsin while at the same time generating a fluorescent output from a fluorogenic substrate. Once activated, chymotrypsin counteracts the trypsin output by competing for the fluorogenic substrate and producing a non‐fluorescent output. It is demonstrated that this network produces a transient fluorescent output under out‐of‐equilibrium conditions while the input signal persists. Importantly, in agreement with mathematical simulations, we show that optimization of the pulse‐like response is an inherent trade‐off between maximum amplitude and lowest residual fluorescence.

Dynamic Environments as a Tool to Preserve Desired Output in a Chemical Reaction Network

“…Inspired by life, systems chemists have made significant progress in the bottom‐up design of synthetic life‐like systems and materials . Examples of networks giving temporal, or spatiotemporal, control over the concentrations of the molecules in the system include the generation of wave fronts, pattern formation with a so‐called go‐fetch model, oscillations, supramolecular oscillators synchronisation and pattern formation with multiple oscillators through diffusional spatiotemporal coupling, adaptive response networks, systems showing homeostasis, self‐replicating systems that can diversify into different species, self‐replicators that can transiently form micelles, temporally controlled material properties and transient vesicle, droplet, fibril and gel formation …”

Engineering bioinks for 3D bioprinting

“…Recently, numerous studies have also focused on temporally incorporating materials with highly complex self-assembly/disassembly mechanisms based on outof-equilibrium dynamics. These mechanisms include enzymatic reactions [229][230][231][232][233][234],…”

“…Recently, numerous studies have also focused on temporally incorporating materials with highly complex self-assembly/disassembly mechanisms based on out-of-equilibrium dynamics. These mechanisms include enzymatic reactions [229][230][231][232][233][234], chemically driven [235][236][237][238][239], redox reactive species [240,241], light-induced [242], and magnetic field-induced [243], and could potentially allow to closely mimic natural tissue generation. However, such strategies still have a long road ahead before making their way into biofabrication and bioprinting.…”