Author, as appears in the article.: Guillén-Gosálbez G, Sorribas A

Department: Enginyeria Química

e-ISSN: 1471-2105

URV's Author/s: Guillen Gosalbez, Gonzalo

Keywords: Yeast Predictive reconstruction Outer-approximation Optimization Law Gene-expression Evolution Design principles Cluster assembly metabolism Biochemical systems

Abstract: Background: Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements. Results: We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA) representation. The optimization task is posed as a nonconvex nonlinear programming (NLP) problem that is solved by an outer-approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP) master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in Saccharomyces cerevisiae. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast Saccharomyces cerevisiae to heat shock Conclusion: Our results show the utility of the suggested approach for investigating the evolution of adaptive responses to environmental changes. The proposed method can be used in other important applications such as the evaluation of parameter changes that are compatible with health and disease states.

Thematic Areas: Structural biology Saúde coletiva Química Molecular biology Medicina veterinaria Medicina ii Medicina i Mathematical & computational biology Matemática / probabilidade e estatística Interdisciplinar Farmacia Engenharias iv Engenharias iii Computer science applications Ciências sociais aplicadas i Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências agrárias i Ciência da computação Biotecnología Biotechnology & applied microbiology Biodiversidade Biochemistry Biochemical research methods Applied mathematics

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: gonzalo.guillen@urv.cat

Author identifier: 0000-0003-2923-1518

Record's date: 2023-02-22

Journal volume: 10

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-10-386

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Bmc Bioinformatics. 10

APA: Guillén-Gosálbez G, Sorribas A (2009). Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses. Bmc Bioinformatics, 10(), -. DOI: 10.1186/1471-2105-10-386

Article's DOI: 10.1186/1471-2105-10-386

Entity: Universitat Rovira i Virgili

Journal publication year: 2009

Publication Type: Journal Publications