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Modular Design of Small Enzymatic Reaction Networks Based on Reversible and Cleavable Inhibitors
Author(s) -
Pogodaev Aleksandr A.,
Fernández Regueiro Cristina Lía,
Jakštaitė Miglė,
Hollander Marijn J.,
Huck Wilhelm T. S.
Publication year - 2019
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.201907995
Subject(s) - modular design , enzyme , scalability , computer science , combinatorial chemistry , chemistry , synthetic biology , simple (philosophy) , cascade reaction , distributed computing , biochemistry , computational biology , biology , catalysis , database , operating system , philosophy , epistemology
Systems chemistry aims to mimic the functional behavior of living systems by constructing chemical reaction networks with well‐defined dynamic properties. Enzymes can play a key role in such networks, but there is currently no general and scalable route to the design and construction of enzymatic reaction networks. Here, we introduce reversible, cleavable peptide inhibitors that can link proteolytic enzymatic activity into simple network motifs. As a proof‐of‐principle, we show auto‐activation topologies producing sigmoidal responses in enzymatic activity, explore cross‐talk in minimal systems, design a simple enzymatic cascade, and introduce non‐inhibiting phosphorylated peptides that can be activated using a phosphatase.