Flux balance analysis

Cystic fibrosis (CF), an inherited genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, results in sticky and thick mucosal fluids. This environment facilitates the colonization of various microorganisms, some of which can cause acute and chronic lung infections, while others may positively impact the disease. Rothia mucilaginosa , an oral commensal, is relatively abundant in the lungs of CF patients. Recent studies have unveiled its anti-inflammatory properties using in vitro three-dimensional lung epithelial cell cultures and in vivo mouse models relevant to chronic lung diseases...

The microbial agent technology has made significant progress in remediating nitro-aromatic compounds (NACs), such as p -nitrophenol, 2,4-dinitrophenol, and 2,4,6-Trinitrotoluene, in farmland soil over the past decade. However, there are still gaps in our understanding of the bioavailability and degradation mechanisms of these compounds in low-temperature environments. In this review, we provide a comprehensive summary of the strategies employed by cold-adapted microorganisms and elucidate the degradation pathways of NACs pollutants...

Landfills play a key role as greenhouse gas (GHGs) emitters, and urgently need assessment and management plans development to swiftly reduce their climate impact. In this context, accurate emission measurements from landfills under different climate and management would reduce the uncertainty in emission accounting. In this study, more than one year of long-term high-frequency data of CO2 and CH4 fluxes were collected in two Italian landfills (Giugliano and Case Passerini) with contrasting management (gas recovery VS no management) using eddy covariance (EC), with the aim to i) investigate the relation between climate drivers and CO2 and CH4 fluxes at different time intervals and ii) to assess the overall GHG balances including the biogas extraction and energy recovery components...

Microbial fermentation employs two strategies: growth- and nongrowth-coupled productions. Stoichiometric metabolic models with flux balance analysis enable pathway engineering to couple target synthesis with growth, yielding numerous successful results. Growth-coupled engineering also contributes to improving bottleneck flux through subsequent adaptive evolution. However, because growth-coupled production inevitably shares resources between biomass and target syntheses, the cost-effective production of bulk chemicals mandates a nongrowth-coupled approach...

The Lipomyces clade contains oleaginous yeast species with advantageous metabolic features for biochemical and biofuel production. Limited knowledge about the metabolic networks of the species and limited tools for genetic engineering have led to a relatively small amount of research on the microbes. Here, a genome-scale metabolic model (GSM) of Lipomyces starkeyi NRRL Y-11557 was built using orthologous protein mappings to model yeast species. Phenotypic growth assays were used to validate the GSM (66% accuracy) and indicated that NRRL Y-11557 utilized diverse carbohydrates but had more limited catabolism of organic acids...

BACKGROUND: Helicobacter pylori is considered a true human pathogen for which rising drug resistance constitutes a drastic concern globally. The present study aimed to reconstruct a genome-scale metabolic model (GSMM) to decipher the metabolic capability of H. pylori strains in response to clarithromycin and rifampicin along with identification of novel drug targets. MATERIALS AND METHODS: The iIT341 model of H. pylori was updated based on genome annotation data, and biochemical knowledge from literature and databases...

Engineering Yarrowia lipolytica to produce astaxanthin provides a promising route. Here, Y. lipolytica M2 producing a titer of 181 mg/L astaxanthin was isolated by iterative atmospheric and room-temperature plasma mutagenesis and diphenylamine-mediated screening. Interestingly, a negative correlation was observed between cell biomass and astaxanthin production. To reveal the underlying mechanism, RNA-seq analysis of transcriptional changes was performed in high producer M2 and reference strain M1, and a total of 1379 differentially expressed genes were obtained...

UNLABELLED: We present dingo, a Python package that supports a variety of methods to sample from the flux space of metabolic models, based on state-of-the-art random walks and rounding methods. For uniform sampling, dingo's sampling methods provide significant speed-ups and outperform existing software. Indicatively, dingo can sample from the flux space of the largest metabolic model up to now (Recon3D) in less than a day using a personal computer, under several statistical guarantees; this computation is out of reach for other similar software...

Genome-scale metabolic models (GEMs) are promising computational tools that contribute to elucidating host-virus interactions at the system level and developing therapeutic strategies against viral infection. In this study, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on liver metabolism was investigated using integrated GEMs of human hepatocytes and SARS-CoV-2. They were generated for uninfected and infected hepatocytes using transcriptome data. Reporter metabolite analysis resulted in significant transcriptional changes around several metabolites involved in xenobiotics, drugs, arachidonic acid, and leukotriene metabolisms due to SARS-CoV-2 infection...

BACKGROUND: Elderly hemodialysis (HD) patients have a high risk of death. The effect of different types of HD membranes on survival is still controversial. The purpose of this study was to determine the relationship between the use of low-flux or high-flux membranes and all-cause and cardiovascular mortality in elderly hemodialysis patients. METHODS: This was a retrospective clinical study involving maintenance hemodialysis patients which were categorized into low-flux and high-flux groups according to the dialyzer they were using...

In multiple sclerosis (MS), alterations of the gut microbiota lead to inflammation. However, the role of other microbiomes in the body in MS has not been fully elucidated. In a pilot case-controlled study, we carried out simultaneous characterization of faecal and oral microbiota and conducted an in-depth analysis of bacterial alterations associated with MS. Using 16S rRNA sequencing and metabolic inference tools, we compared the oral/faecal microbiota and bacterial metabolism pathways in French MS patients (n = 14) and healthy volunteers (HV, n = 21)...

Predicting the plant cell response in complex environmental conditions is a challenge in plant biology. Here we developed a resource allocation model of cellular and molecular scale for the leaf photosynthetic cell of Arabidopsis thaliana, based on the Resource Balance Analysis (RBA) constraint-based modeling framework. The RBA model contains the metabolic network and the major macromolecular processes involved in the plant cell growth and survival and localized in cellular compartments. We simulated the model for varying environmental conditions of temperature, irradiance, partial pressure of CO2 and O2 , and compared RBA predictions to known resource distributions and quantitative phenotypic traits such as the relative growth rate, the C:N ratio, and finally to the empirical characteristics of CO2 fixation given by the well-established Farquhar model...

Genome-scale metabolic models (GEMs) of Chinese hamster ovary (CHO) cells are valuable for gaining mechanistic understanding of mammalian cell metabolism and cultures. We provide a comprehensive overview of past and present developments of CHO-GEMs and in silico methods within the flux balance analysis (FBA) framework, focusing on their practical utility in rational cell line development and bioprocess improvements. There are many opportunities for further augmenting the model coverage and establishing integrative models that account for different cellular processes and data for future applications...

Key operating variables to predict the necessary scour air flowrate in full-scale Membrane Bioreactor (MBR) systems are identified, aiming to optimize energy consumption while avoiding the limiting condition (i.e., rapid increasing total resistance). The resulting metric, referred to here as the K value, was derived by balancing hydrodynamic conditions between the particle deposit rate imposed by permeate flux normalized by fouling condition and its removal by shear stress induced from air scouring. The metric includes air scouring flow, permeate flow, Mixed Liquor Suspended Solids (MLSS) concentration, Mixed Liquor (ML) viscosity, membrane packing density, and total resistance...

The genome-scale metabolic model (GSMM) of Cordyceps militaris provides a comprehensive basis of carbon assimilation for cell growth and metabolite production. However, the model with a simple mass balance concept shows limited capability to probe the metabolic responses of C. militaris under light exposure. This study, therefore, employed the transcriptome-integrated GSMM approach to extend the investigation of C. militaris 's metabolism under light conditions. Through the gene inactivity moderated by metabolism and expression (GIMME) framework, the i PS1474- ti GSMM model was furnished with the transcriptome data, thus providing a simulation that described reasonably well the metabolic responses underlying the phenotypic observation of C...

l-Methionine (l-Met) has gained remarkable interest due to its multifaceted and versatile applications in the fields of nutrition, pharmaceuticals and clinical practice. In this study, the fluxes of the challenging l-Met biosynthesis in the producer strain Escherichia coli (E. coli) DM2853 were fine-tuned to enable improved l-Met production. The potential bottlenecks identified in sulfur assimilation and l-Met synthesis downstream of O-succinyl-l-homoserine (OSHS) were addressed by overexpressing glutaredoxin 1 (grxA), thiosulfate sulfurtransferase (pspE) and O-succinylhomoserine lyase (metB)...

The effective design of perfusion cell culture is currently challenging regarding balancing the operating parameters associated with the hydrodynamic conditions due to increased system complexity. To address this issue, cellular responses of an industrial CHO cell line to different types of hydrodynamic stress in benchtop perfusion bioreactors originating from agitation, sparging, and hollow fibers (HF) in the cell retention devices were systematically investigated here with the analysis of cell lysis. It was found that cell lysis was very common and most associated with the sparging stress, followed by the HF and lastly the agitation, consequently heavily impacting the estimation of process descriptors related to biomass...

The gut microbiota plays a crucial role in health and is significantly modulated by human diets. In addition to Western diets which are rich in proteins, high-protein diets are used for specific populations or indications, mainly weight loss. In this study, we investigated the effect of protein supplementation on Bacteroides caccae , a Gram-negative gut symbiont. The supplementation with whey proteins led to a significant increase in growth rate, final biomass, and short-chain fatty acids production. A comprehensive genomic analysis revealed that B...

Maintaining an optimal leaf and stem orientation to yield a maximum photosynthetic output is accomplished by terrestrial plants using sophisticated mechanisms to balance their orientation relative to the Earth's gravity vector and the direction of sunlight. Knowledge of the signal transduction chains of both gravity and light perception and how they influence each other is essential for understanding plant development on Earth and plant cultivation in space environments. However, in situ analyses of cellular signal transduction processes in weightlessness, such as live cell imaging of signaling molecules using confocal fluorescence microscopy, require an adapted experimental setup that meets the special requirements of a microgravity environment...

Marine thraustochytrids produce metabolically important lipids such as the long-chain omega-3 polyunsaturated fatty acids, carotenoids, and sterols. The growth and lipid production in thraustochytrids depends on the composition of the culture medium that often contains yeast extract as a source of amino acids. This work discusses the effects of individual amino acids provided in the culture medium as the only source of nitrogen, on the production of biomass and lipids by the thraustochytrid Thraustochytrium sp...