Multisite Enzymes as a Mechanism for Bistability in Reaction Networks
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Multisite Enzymes as a Mechanism for Bistability in Reaction Networks. / Hayes, Clarmyra; Feliu, Elisenda; Soyer, Orkun S.
I: ACS Synthetic Biology, Bind 11, Nr. 2, 2022, s. 596-607.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Multisite Enzymes as a Mechanism for Bistability in Reaction Networks
AU - Hayes, Clarmyra
AU - Feliu, Elisenda
AU - Soyer, Orkun S.
N1 - Publisher Copyright: © 2022 The Authors. Published by American Chemical Society
PY - 2022
Y1 - 2022
N2 - Here, we focus on a common class of enzymes that have multiple substrate binding sites (multisite enzymes) and analyze their capacity to generate bistable dynamics in the reaction networks that they are embedded in. These networks include both substrate-product-substrate cycles and substrate-to-product conversion with subsequent product consumption. Using mathematical techniques, we show that the inherent binding and catalysis reactions arising from multiple substrate-enzyme complexes create a potential for bistable dynamics in such reaction networks. We construct a generic model of an enzyme with n-substrate binding sites and derive an analytical solution for the steady-state concentration of all enzyme-substrate complexes. By studying these expressions, we obtain a mechanistic understanding of bistability, derive parameter combinations that guarantee bistability, and show how changing specific enzyme kinetic parameters and enzyme levels can lead to bistability in reaction networks involving multisite enzymes. Thus, the presented findings provide a biochemical and mathematical basis for predicting and engineering bistability in multisite enzymes.
AB - Here, we focus on a common class of enzymes that have multiple substrate binding sites (multisite enzymes) and analyze their capacity to generate bistable dynamics in the reaction networks that they are embedded in. These networks include both substrate-product-substrate cycles and substrate-to-product conversion with subsequent product consumption. Using mathematical techniques, we show that the inherent binding and catalysis reactions arising from multiple substrate-enzyme complexes create a potential for bistable dynamics in such reaction networks. We construct a generic model of an enzyme with n-substrate binding sites and derive an analytical solution for the steady-state concentration of all enzyme-substrate complexes. By studying these expressions, we obtain a mechanistic understanding of bistability, derive parameter combinations that guarantee bistability, and show how changing specific enzyme kinetic parameters and enzyme levels can lead to bistability in reaction networks involving multisite enzymes. Thus, the presented findings provide a biochemical and mathematical basis for predicting and engineering bistability in multisite enzymes.
KW - enzyme kinetics
KW - multistability
KW - phenotypic heterogeneity
KW - protein engineering
KW - reaction system dynamics
KW - substrate inhibition
KW - synthetic biology
UR - http://www.scopus.com/inward/record.url?scp=85124136567&partnerID=8YFLogxK
U2 - 10.1021/acssynbio.1c00272
DO - 10.1021/acssynbio.1c00272
M3 - Journal article
C2 - 35073044
AN - SCOPUS:85124136567
VL - 11
SP - 596
EP - 607
JO - ACS Synthetic Biology
JF - ACS Synthetic Biology
SN - 2161-5063
IS - 2
ER -
ID: 301140479