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Multistability in enzymatic networks
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Hayes, Clarmyra (2023) Multistability in enzymatic networks. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3981545
Abstract
In this work, we attempt to better understand how simple networks of enzymes that bind more than one substrate molecule can result in multistability. We are motivated by a background in synthetic biology, and the desire to potentially engineer multistability into enzymatic networks through a combination of reaction network structure and enzyme properties. We start our investigation by looking at simple cycles of substrate to product interconversion, mediated by an enzyme that binds two substrate molecules. Using numerical then analytical methods we explore how enzyme-substrate catalytic rates relate to bistability, and derive a condition on the rate parameters of the system for which bistability is guaranteed. We then use graphical methods to show that this condition is an expression of competition between enzyme-substrate complexes, is inherent in network architecture, and extends to an enzyme with any number (n) of substrate binding sites. Using graphical methods, we derive parametric conditions that guarantee bistability for some concentration of conserved species values for an n-binding site enzyme network, and show that our conclusions also apply to systems in which the product to substrate conversion reaction takes various forms, such as being mediated by a different enzyme, or consists of input and output fluxes. Next, we use the same graphical methods to examine the steady state behaviour of enzyme-substrate complexes that have multiple open binding sites, and show that these complexes enable the system to go to more than three steady states. We derive parametric conditions necessary for multistability and which help us to intuitively understand how to tune enzyme properties so networks are capable of more than three steady states. Finally, we extend our graphical method of analysis to networks that only bind one substrate molecule, and show that though the mechanism of bistability is different, some of the same fundamental principles apply.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QD Chemistry Q Science > QR Microbiology T Technology > TP Chemical technology |
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Library of Congress Subject Headings (LCSH): | Enzymes -- Research, Enzymes -- Stability, Bistability, Metabolism -- Regulation, Synthetic biology | ||||
Official Date: | March 2023 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | School of Life Sciences | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Soyer, Orkun S. | ||||
Format of File: | |||||
Extent: | 133 pages : illustrations | ||||
Language: | eng |
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