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Towards Constraint-Based Burden-Aware Models for Metabolic Engineering

Publicated to:Ifac-Papersonline. 58 (14): 247-252 - 2024-01-01 58(14), DOI: 10.1016/j.ifacol.2024.08.344

Authors: Maton, M; Santos-Navarro, F N; Pico, J; Bogaerts, Ph; Vande Wouwer, A

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Abstract

Over the years, hundreds of applications have proved the effectiveness of constraint-based methods to validate the definition of metabolic networks, determine the robustness of metabolic models, and analyze the flow of metabolites through a network. However, stoichiometric models do not include information on flux capacity via enzymatic activity. Methods combining biological data from genome to metabolome have been developed to obtain improved flux predictions and constrain the range of possible flux distributions. Yet, these models still lack relevant information to design de novo metabolic pathways. Expressing the exogenous enzymes induces a cell burden due to competition for cell resources between the exogenous genes and the endogenous host ones, compromising the performance of the designed pathway. Thus, optimal selection of the expression strength of the pathway enzymes is still a challenge. Host-aware models have been developed to tackle cell burden in the context of designing increasingly complex synthetic genetic circuits in synthetic biology. This paper suggests a method to integrate host-aware gene expression models with constraint-based modeling to maximize the flux through an exogenous pathway by optimizing promoter and ribosome binding site strengths, crucial parameters that define the required transcription and translation strengths of the pathway enzymes' genes. This study considers the formation of p-coumaric acid, shows promising results, and paves the way for further investigations. Copyright (C) 2024 The Authors.

Keywords

BioinformaticsBurden-aware modelingConstraint based methodConstraint theoryConstraint-basedEnzymatic activitiesEnzymatic activityGene-expressionMetabolic analysisMetabolic engineeringMetabolic flux analysisMetabolic networkMetabolitesMulti-scale modelingMultiscale modelingNetworksPredictioSynthetic biologSynthetic biologySynthetic gene circuitsSynthetic-gene circuitTranscription

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Ifac-Papersonline, Q3 Agency Scopus (SJR), its regional focus and specialization in Control and Systems Engineering, give it significant recognition in a specific niche of scientific knowledge at an international level.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-08:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 1 (PlumX).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Belgium.