Total enzyme activity constraint and homeostatic constraint impact on the optimization potential of a kinetic model

Vitalijs Komasilovs; Agris Pentjuss; Atis Elsts; Egils Stalidzans

doi:10.1016/j.biosystems.2017.09.016

Total enzyme activity constraint and homeostatic constraint impact on the optimization potential of a kinetic model

Vitalijs Komasilovs^*, Agris Pentjuss, Atis Elsts, Egils Stalidzans

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

The application of biologically and biochemically relevant constraints during the optimization of kinetic models reduces the impact of suggested changes in processes not included in the scope of the model. This increases the probability that the design suggested by model optimization can be carried out by an organism after implementation of design in vivo.

A case study was carried out to determine the impact of total enzyme activity and homeostatic constraints on the objective function values and the following ranking of adjustable parameter combinations. The application of constraints on the model of sugar cane metabolism revealed that a homeostatic constraint caused heavier limitations of the objective function than a total enzyme activity constraint. Both constraints changed the ranking of adjustable parameter combinations: no “universal” constraint-independent top-ranked combinations were found. Therefore, when searching for the best subset of adjustable parameters, a full scan of their combinations is suggested for a small number of adjustable parameters, and evolutionary search strategies are suggested for a large number. Simultaneous application of both constraints is suggested.

Original language	English
Pages (from-to)	128-134
Number of pages	7
Journal	BioSystems
Volume	162
Early online date	28 Sept 2017
DOIs	https://doi.org/10.1016/j.biosystems.2017.09.016
Publication status	Published - Dec 2017

Research Groups and Themes

Bristol BioDesign Institute

Keywords

synthetic biology
Adjustable parameters
Optimization
Optimization potential
Kinetic model

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10.1016/j.biosystems.2017.09.016

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Accepted author manuscript, 988 KBLicence: CC BY-NC-ND

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title = "Total enzyme activity constraint and homeostatic constraint impact on the optimization potential of a kinetic model",

abstract = "The application of biologically and biochemically relevant constraints during the optimization of kinetic models reduces the impact of suggested changes in processes not included in the scope of the model. This increases the probability that the design suggested by model optimization can be carried out by an organism after implementation of design in vivo. A case study was carried out to determine the impact of total enzyme activity and homeostatic constraints on the objective function values and the following ranking of adjustable parameter combinations. The application of constraints on the model of sugar cane metabolism revealed that a homeostatic constraint caused heavier limitations of the objective function than a total enzyme activity constraint. Both constraints changed the ranking of adjustable parameter combinations: no “universal” constraint-independent top-ranked combinations were found. Therefore, when searching for the best subset of adjustable parameters, a full scan of their combinations is suggested for a small number of adjustable parameters, and evolutionary search strategies are suggested for a large number. Simultaneous application of both constraints is suggested.",

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AU - Komasilovs, Vitalijs

AU - Pentjuss, Agris

AU - Elsts, Atis

AU - Stalidzans, Egils

PY - 2017/12

Y1 - 2017/12

N2 - The application of biologically and biochemically relevant constraints during the optimization of kinetic models reduces the impact of suggested changes in processes not included in the scope of the model. This increases the probability that the design suggested by model optimization can be carried out by an organism after implementation of design in vivo. A case study was carried out to determine the impact of total enzyme activity and homeostatic constraints on the objective function values and the following ranking of adjustable parameter combinations. The application of constraints on the model of sugar cane metabolism revealed that a homeostatic constraint caused heavier limitations of the objective function than a total enzyme activity constraint. Both constraints changed the ranking of adjustable parameter combinations: no “universal” constraint-independent top-ranked combinations were found. Therefore, when searching for the best subset of adjustable parameters, a full scan of their combinations is suggested for a small number of adjustable parameters, and evolutionary search strategies are suggested for a large number. Simultaneous application of both constraints is suggested.

AB - The application of biologically and biochemically relevant constraints during the optimization of kinetic models reduces the impact of suggested changes in processes not included in the scope of the model. This increases the probability that the design suggested by model optimization can be carried out by an organism after implementation of design in vivo. A case study was carried out to determine the impact of total enzyme activity and homeostatic constraints on the objective function values and the following ranking of adjustable parameter combinations. The application of constraints on the model of sugar cane metabolism revealed that a homeostatic constraint caused heavier limitations of the objective function than a total enzyme activity constraint. Both constraints changed the ranking of adjustable parameter combinations: no “universal” constraint-independent top-ranked combinations were found. Therefore, when searching for the best subset of adjustable parameters, a full scan of their combinations is suggested for a small number of adjustable parameters, and evolutionary search strategies are suggested for a large number. Simultaneous application of both constraints is suggested.

KW - synthetic biology

KW - Adjustable parameters

KW - Optimization

KW - Optimization potential

KW - Kinetic model

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U2 - 10.1016/j.biosystems.2017.09.016

DO - 10.1016/j.biosystems.2017.09.016

M3 - Article (Academic Journal)

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AN - SCOPUS:85031757134

SN - 0303-2647

VL - 162

SP - 128

EP - 134

JO - BioSystems

JF - BioSystems

ER -

Total enzyme activity constraint and homeostatic constraint impact on the optimization potential of a kinetic model

Abstract

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Keywords

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