Recent advances in elementary flux modes and yield space analysis as useful tools in metabolic network studies

Abstract

A review of the use of elementary flux modes (EFMs) and their applications in metabolic engineering covered with yield space analysis (YSA) is presented. EFMs are an invaluable tool in mathematical modeling of biochemical processes. They are described from their inception in 1994, followed by various improvements of their computation in later years. YSA constitutes another precious tool for metabolic network modeling, and is presented in details along with EFMs in this article. The application of these techniques is discussed for several case studies of metabolic network modeling provided in respective original articles. The article is concluded by some case studies in which the application of EFMs and YSA turned out to be most useful, such as the analysis of intracellular polyhydroxyalkanoate (PHA) formation and consumption in Cupriavidus necator, including the constraint-based description of the steady-state flux cone of the strain's metabolic network, the profound analysis of a continuous five-stage bioreactor cascade for PHA production by C. necator using EFMs and, finally, the study of metabolic fluxes in the metabolic network of C. necator cultivated on glycerol.

SAFEPPP: a Simple And Fast method to Find and analyze Extreme Points of a metabolic Phenotypic Phase Plane

“…Fast determination of phase plane of any two reactions, is one the most important applications of the software which is necessary for phase plane analysis [11,10,5]. The phase plane of biomass and ethanol in E. coli under anaerobic condition (in which O2 uptake is blocked) is shown in Figure4.…”

Design of a proteolytic module for improved metabolic modeling of Bacteroides caccae

“…In the last decade, several mathematical methods were developed to study the bacterial metabolism in various environments ( 19 ). Among them, genome-scale metabolic reconstructions (GENREs) were based on the core metabolism of whole genomes and generated using the annotated genome of given microorganisms ( 20 – 22 ). Semi-automatic reconstruction allowed the generation of hundreds of GENREs ( 23 ), especially among the gut microbiota species ( 24 ).…”

Structural variability, implementational irregularities in mathematical modelling of polyhydroxyalkanoates (PHAs) production—A state‐of‐the‐art review

“…Modelling aspects have been included as one of the subtopics in a handful of reviews (Afreen et al, 2021; Koller, 2019; J. Wang et al, 2021). Except for a few specialized reviews on selected model variants (i.e., activated sludge models, metabolic models, ANN) and model‐based optimization of PHA production (Novak, 2015), balanced reviews focusing on the structural aspect of the model, parameter estimation approaches, and implementation of models in optimized PHA production are limited (Hauduc et al, 2013; Horvat et al, 2015; Patnaik, 2005).…”

“…Wang et al, 2021). Except for a few specialized reviews on selected model variants (i.e., activated sludge models, metabolic models, ANN) and model-based optimization of PHA production (Novak, 2015), balanced reviews focusing on the structural aspect of the model, parameter estimation approaches, and implementation of models in optimized PHA production are limited (Hauduc et al, 2013;Horvat et al, 2015;Patnaik, 2005). This review is intended to provide an assessment of model complexity, highlighting their key attributes, and limitations in describing the underlying process.…”