Premium
Bottom‐Up Construction of an Adaptive Enzymatic Reaction Network
Author(s) -
Helwig Britta,
van Sluijs Bob,
Pogodaev Aleksandr A.,
Postma Sjoerd G. J.,
Huck Wilhelm T. S.
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201806944
Subject(s) - fluorescence , trypsin , substrate (aquarium) , realization (probability) , chemistry , biological system , chymotrypsin , residual , enzyme , combinatorial chemistry , biophysics , computer science , biochemistry , physics , mathematics , biology , algorithm , ecology , statistics , quantum mechanics
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.