SummaryIron is essential for most living organisms. In addition, its biogeochemical cycling influences important processes in the geosphere (e.g., the mobilization or immobilization of trace elements and contaminants). The reduction of Fe(III) to Fe(II) can be catalysed microbially, particularly by metal‐respiring bacteria utilizing Fe(III) as a terminal electron acceptor. Furthermore, Gram‐positive fermentative iron reducers are known to reduce Fe(III) by using it as a sink for excess reducing equivalents, as a form of enhanced fermentation. Here, we use the Gram‐positive fermentative bacterium Clostridium acetobutylicum as a model system due to its ability to reduce heavy metals. We investigated the reduction of soluble and solid iron during fermentation. We found that exogenous (resazurin, resorufin, anthraquinone‐2,6‐disulfonate) as well as endogenous (riboflavin) electron mediators enhance solid iron reduction. In addition, iron reduction buffers the pH, and elicits a shift in the carbon and electron flow to less reduced products relative to fermentation. This study underscores the role fermentative bacteria can play in iron cycling and provides insights into the metabolic profile of coupled fermentation and iron reduction with laboratory experiments and metabolic network modelling.
Motivation Large-scale kinetic models are an invaluable tool to understand the dynamic and adaptive responses of biological systems. The development and application of these models have been limited by the availability of computational tools to build and analyze large-scale models efficiently. The toolbox presented here provides the means to implement, parametrize and analyze large-scale kinetic models intuitively and efficiently. Results We present a Python package (SKiMpy) bridging this gap by implementing an efficient kinetic modeling toolbox for the semiautomatic generation and analysis of large-scale kinetic models for various biological domains such as signaling, gene expression, and metabolism. Furthermore, we demonstrate how this toolbox is used to parameterize kinetic models around a steady-state reference efficiently. Finally, we show how SKiMpy can implement multispecies bioreactor simulations to assess biotechnological processes. Availability The software is available as a Python 3 package on GitHub: https://github.com/EPFL-LCSB/SKiMpy, along with adequate documentation. Supplementary information Supplementary data are available at Bioinformatics online.
Flux coupling analysis is a computational method which is able to explain co-expression of metabolic genes by analyzing the topological structure of a metabolic network. It has been suggested that if genes in two seemingly fully-coupled reactions are not highly co-expressed, then these two reactions are not fully coupled in reality, and hence, there is a gap or missing reaction in the network. Here, we present GAUGE as a novel approach for gap filling of metabolic networks, which is a two-step algorithm based on a mixed integer linear programming formulation. In GAUGE, the discrepancies between experimental co-expression data and predicted flux coupling relations is minimized by adding a minimum number of reactions to the network. We show that GAUGE is able to predict missing reactions of E. coli metabolism that are not detectable by other popular gap filling approaches. We propose that our algorithm may be used as a complementary strategy for the gap filling problem of metabolic networks. Since GAUGE relies only on gene expression data, it can be potentially useful for exploring missing reactions in the metabolism of non-model organisms, which are often poorly characterized, cannot grow in the laboratory, and lack genetic tools for generating knockouts.
Motivation: Large-scale kinetic models are an invaluable tool to understand the dynamic and adaptive responses of biological systems. The development and application of these models have been limited by the availability of computational tools to build and analyze large-scale models efficiently. The toolbox presented here provides the means to implement, parametrize and analyze large-scale kinetic models intuitively and efficiently. Results: We present a Python package (SKiMpy) bridging this gap by implementing an efficient kinetic modeling toolbox for the semiautomatic generation and analysis of large-scale kinetic models for various biological domains such as signaling, gene expression, and metabolism. Furthermore, we demonstrate how this toolbox is used to parameterize kinetic models around a steady-state reference efficiently. Finally, we show how SKiMpy can implement multispecies bioreactor simulations to assess biotechnological processes. Availability: The software is available as a Python 3 package on GitHub: https://github.com/EPFL-LCSB/SKiMpy, along with adequate documentation.
Two reactions are in the same "correlated reaction set" (or "Co-Set") if their fluxes are linearly correlated. On the other hand, two reactions are "coupled" if nonzero flux through one reaction implies nonzero flux through the other reaction. Flux correlation analysis has been previously used in the analysis of enzyme dysregulation and enzymopathy, while flux coupling analysis has been used to predict co-expression of genes and to model network evolution. The goal of this paper is to emphasize, through a few examples, that these two concepts are inherently different. In other words, except for the case of full coupling, which implies perfect correlation between two fluxes (R(2) = 1), there are no constraints on Pearson correlation coefficients (CC) in case of any other type of (un)coupling relations. In other words, Pearson CC can take any value between 0 and 1 in other cases. Furthermore, by analyzing genome-scale metabolic networks, we confirm that there are some examples in real networks of bacteria, yeast and human, which approve that flux coupling and flux correlation cannot be used interchangeably.
Background:A genome-scale metabolic network model (GEM) is a mathematical representation of an organism's metabolism. Today, GEMs are popular tools for computationally simulating the biotechnological processes and for predicting biochemical properties of (engineered) strains. Objectives: In the present study, we have evaluated the predictive power of two GEMs, namely iBsu1103 (for Bacillus subtilis 168) and iMZ1055 (for Bacillus megaterium WSH002). Materials and Methods: For comparing the predictive power of Bacillus subtilis and Bacillus megaterium GEMs, experimental data were obtained from previous wet-lab studies included in PubMed. By using these data, we set the environmental, stoichiometric and thermodynamic constraints on the models, and FBA is performed to predict the biomass production rate, and the values of other fluxes. For simulating experimental conditions in this study, COBRA toolbox was used. Results: By using the wealth of data in the literature, we evaluated the accuracy of in silico simulations of these GEMs. Our results suggest that there are some errors in these two models which make them unreliable for predicting the biochemical capabilities of these species. The inconsistencies between experimental and computational data are even greater where B. subtilis and B. megaterium do not have similar phenotypes. Conclusions: Our analysis suggests that literature-based improvement of genome-scale metabolic network models of the two Bacillus species is essential if these models are to be successfully applied in biotechnology and metabolic engineering.
J. Garcia-Falset, E. Llorens-Fuster and S. Prus in [2] studied the existence of fixed point of J-type mappings in Banach spaces. In this paper, we extend these mappings in Menger spaces and prove the fixed point theorems of these mappings in complete Menger spaces. In this paper, we also prove theorems for the new class of mappings which is called altering J-type.
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