The best models of metabolism

Voit, Eberhard O.

doi:10.1002/wsbm.1391

Cited by 45 publications

(38 citation statements)

References 290 publications

(453 reference statements)

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“…In stark contrast to the ease of capturing the system structure with a BST model, the determination of parameter values is a true challenge. If kinetic data on enzymes and regulators or metabolic time series data were available, one could use one of the uncounted methods that have been developed for this purpose of parameter estimation (e.g., [ 20 – 26 ]). Unfortunately, the information needed for these methods is not available in our case.…”

Section: Resultsmentioning

confidence: 99%

A dynamic model of lignin biosynthesis in Brachypodium distachyon

Faraji

Fonseca

Escamilla‐Treviño

et al. 2018

Biotechnol Biofuels

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BackgroundLignin is a crucial molecule for terrestrial plants, as it offers structural support and permits the transport of water over long distances. The hardness of lignin reduces plant digestibility by cattle and sheep; it also makes inedible plant materials recalcitrant toward the enzymatic fermentation of cellulose, which is a potentially valuable substrate for sustainable biofuels. Targeted attempts to change the amount or composition of lignin in relevant plant species have been hampered by the fact that the lignin biosynthetic pathway is difficult to understand, because it uses several enzymes for the same substrates, is regulated in an ill-characterized manner, may operate in different locations within cells, and contains metabolic channels, which the plant may use to funnel initial substrates into specific monolignols.ResultsWe propose a dynamic mathematical model that integrates various datasets and other information regarding the lignin pathway in Brachypodium distachyon and permits explanations for some counterintuitive observations. The model predicts the lignin composition and label distribution in a BdPTAL knockdown strain, with results that are quite similar to experimental data.ConclusionGiven the present scarcity of available data, the model resulting from our analysis is presumably not final. However, it offers proof of concept for how one may design integrative pathway models of this type, which are necessary tools for predicting the consequences of genomic or other alterations toward plants with lignin features that are more desirable than in their wild-type counterparts.Electronic supplementary materialThe online version of this article (10.1186/s13068-018-1241-6) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

A dynamic model of lignin biosynthesis in Brachypodium distachyon

Faraji

Fonseca

Escamilla‐Treviño

et al. 2018

Biotechnol Biofuels

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“…See the review for a concise overview of metabolic models. 82 Several attempts have been made to address dynamic behavior of mammalian cell cultures. Nolan et al used the metabolic network with 34 reactions to describe CHO cell metabolism.…”

Section: Figurementioning

confidence: 99%

Metabolic Network Modelling of Chinese Hamster Ovary (CHO) Culture Bioreactors Operated as Microbial Cell Factories

Gašperšič

Kastelic

Novak

et al. 2018

ACSi

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Chinese hamster ovary (CHO) epithelial cells are one of the most used therapeutic medical lines for the production of different biopharmaceutical drugs. They have a high consumption rate with a fast duplication cycle that makes them an ideal biological clone. The higher accumulated amounts of toxic intracellular intermediates may lead to lower organism viability, protein productivity and manufactured biosimilar, so a careful optimal balance of medium, bioreactor operational parameters and bioprocess is needed. A precise phenomenological knowledge of metabolism's chemical transformations can predict problems that may arise during batch, semi-continuous fed batch and continuous reactor operation. For a better detailed understanding (and relations), future performance optimization and scaling, mechanistic model systems have been built. In this specific work, the main metabolic pathways in mammalian structured CHO cultures are reviewed. It starts with organic biochemical background, controlling associated phenomena and kinetics, which govern the sustaining conversion routes of biology. Then, individual turnover paths are described, overviewing standard mathematical formulations that are commonly applied in engineering. These are the core of black box modeling, which relates the substrates/products in a simplified relationship manner. Moreover, metabolic flux analysis (MFA)/flux balance analysis (FBA), that are traditionally characterizing mechanisms, are presented to a larger portion extent. Finally, similarities are discussed, illustrating the approaches for their structural design. Stated variables' equations, employed for the description of the growth in the controllable environmental conditions of a vessel, the researched reaction series of proliferating dividing CHO population, joint with the values of maximal enzymatic activity, and solutions are outlined. Processes are listed in a way so that a reader can integrate the state-of-the-art. Our particular contribution is also denoted.

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“…These variants have been reviewed numerous times [104,107,108], and are not described here much. Instead, we focus on more global approaches that permit streamlined representations of entire pathway systems.…”

Section: Explicit Kinetic Modelsmentioning

confidence: 99%

Improving Bioenergy Crops through Dynamic Metabolic Modeling

Faraji

Voit

2017

Processes

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Enormous advances in genetics and metabolic engineering have made it possible, in principle, to create new plants and crops with improved yield through targeted molecular alterations. However, while the potential is beyond doubt, the actual implementation of envisioned new strains is often difficult, due to the diverse and complex nature of plants. Indeed, the intrinsic complexity of plants makes intuitive predictions difficult and often unreliable. The hope for overcoming this challenge is that methods of data mining and computational systems biology may become powerful enough that they could serve as beneficial tools for guiding future experimentation. In the first part of this article, we review the complexities of plants, as well as some of the mathematical and computational methods that have been used in the recent past to deepen our understanding of crops and their potential yield improvements. In the second part, we present a specific case study that indicates how robust models may be employed for crop improvements. This case study focuses on the biosynthesis of lignin in switchgrass (Panicum virgatum). Switchgrass is considered one of the most promising candidates for the second generation of bioenergy production, which does not use edible plant parts. Lignin is important in this context, because it impedes the use of cellulose in such inedible plant materials. The dynamic model offers a platform for investigating the pathway behavior in transgenic lines. In particular, it allows predictions of lignin content and composition in numerous genetic perturbation scenarios.

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The best models of metabolism

Cited by 45 publications

References 290 publications

A dynamic model of lignin biosynthesis in Brachypodium distachyon

A dynamic model of lignin biosynthesis in Brachypodium distachyon

Metabolic Network Modelling of Chinese Hamster Ovary (CHO) Culture Bioreactors Operated as Microbial Cell Factories

Improving Bioenergy Crops through Dynamic Metabolic Modeling

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