Contextualized Metabolic Modelling Revealed Factors Affecting Isoflavone Accumulation in Soybean Seeds.

Isoflavones, secondary metabolites with numerous health benefits, are predominantly found in legume seeds, especially soybean; however, their contents in domesticated soybean seeds are highly variable. Wild soybeans are known for higher seed isoflavone contents than cultivars. Here we used experimental and modelling approaches on wild soybean (W05) and cultivated soybean (C08) to delineate factors influencing isoflavone accumulation.

Microbial interactions from a new perspective: reinforcement learning reveals new insights into microbiome evolution.

Motivation: Microbes are essential part of all ecosystems, influencing material flow and shaping their surroundings. Metabolic modeling has been a useful tool and provided tremendous insights into microbial community metabolism. However, current methods based on flux balance analysis (FBA) usually fail to predict metabolic and regulatory strategies that lead to long-term survival and stability especially in heterogenous communities.

kb_DRAM: annotation and metabolic profiling of genomes with DRAM in KBase.

Unlabelled: Microbial genome annotation is the process of identifying structural and functional elements in DNA sequences and subsequently attaching biological information to those elements. DRAM is a tool developed to annotate bacterial, archaeal, and viral genomes derived from pure cultures or metagenomes. DRAM goes beyond traditional annotation tools by distilling multiple gene annotations to genome level summaries of functional potential.

Integrated Profiling of Gram-Positive and Gram-Negative Probiotic Genomes, Proteomes and Metabolomes Revealed Small Molecules with Differential Growth Inhibition of Antimicrobial-Resistant Pathogens.

Probiotics produce small molecules that may serve as alternatives to conventional antibiotics by suppressing growth of antimicrobial resistant (AMR) pathogens. The objective of this study was to identify and examine antimicrobials produced and secreted by probiotics using 'omics' profiling with computer-based metabolic flux analyses. The cell-free supernatant of Gram-positive GG (LGG) and Gram-negative Nissle (ECN) probiotics inhibited growth of AMR Typhimurium, , and ranging between 28.

Metabolic Engineering Interventions for Sustainable 2,3-Butanediol Production in Gas-Fermenting .

Gas fermentation provides a promising platform to turn low-cost and readily available single-carbon waste gases into commodity chemicals, such as 2,3-butanediol. Clostridium autoethanogenum is usually used as a robust and flexible chassis for gas fermentation. Here, we leveraged constraint-based stoichiometric modeling and kinetic ensemble modeling of the metabolic network to provide a systematic analysis of metabolic engineering interventions for 2,3-butanediol overproduction and low carbon substrate loss in dissipated CO.

Predicting Microbiome Metabolism and Interactions through Integrating Multidisciplinary Principles.

In this Commentary, we will discuss some of the current trends and challenges in modeling microbiome metabolism. A focus will be the state of the art in the integration of metabolic networks, ecological and evolutionary principles, and spatiotemporal considerations, followed by envisioning integrated frameworks incorporating different principles and data to generate predictive models in the future.

Predicting Nash equilibria for microbial metabolic interactions.

Motivation: Microbial metabolic interactions impact ecosystems, human health and biotechnology profoundly. However, their determination remains elusive, invoking an urgent need for predictive models seamlessly integrating metabolism with evolutionary principles that shape community interactions.

Results: Inspired by the evolutionary game theory, we formulated a bi-level optimization framework termed NECom for which any feasible solutions are Nash equilibria of microbial community metabolic models with/without an outer-level (community) objective function.

Genome-scale metabolic reconstruction of the non-model yeast SD108 and its application to organic acids production.

Many platform chemicals can be produced from renewable biomass by microorganisms, with organic acids making up a large fraction. Intolerance to the resulting low pH growth conditions, however, remains a challenge for the industrial production of organic acids by microorganisms. SD108 is a promising host for industrial production because it is tolerant to acidic conditions as low as pH 2.

Bacterial colonization reprograms the neonatal gut metabolome.

Initial microbial colonization and later succession in the gut of human infants are linked to health and disease later in life. The timing of the appearance of the first gut microbiome, and the consequences for the early life metabolome, are just starting to be defined. Here, we evaluated the gut microbiome, proteome and metabolome in 88 African-American newborns using faecal samples collected in the first few days of life.

Metabolic Analyses of Nitrogen Fixation in the Soybean Microsymbiont Sinorhizobium fredii Using Constraint-Based Modeling.

Rhizobia are soil bacteria able to establish symbiosis with diverse host plants. Specifically, is a soil bacterium that forms nitrogen-fixing root nodules in diverse legumes, including soybean. The strain CCBAU45436 is a dominant sublineage of that nodulates soybeans in alkaline-saline soils in the Huang-Huai-Hai Plain region of China.

A comprehensive genome-scale model for IFO0880 accounting for functional genomics and phenotypic data.

is a red, basidiomycetes yeast that can accumulate a large amount of lipids and produce carotenoids. To better assess this non-model yeast's metabolic capabilities, we reconstructed a genome-scale model of IFO0880's metabolic network (1108) accounting for 2204 reactions, 1985 metabolites and 1108 genes. In this work, we integrated and supplemented the current knowledge with in-house generated biomass composition and experimental measurements pertaining to the organism's metabolic capabilities.

Systems Biology - A Guide for Understanding and Developing Improved Strains of Lactic Acid Bacteria.

Lactic Acid Bacteria (LAB) are extensively employed in the production of various fermented foods, due to their safe status, ability to affect texture and flavor and finally due to the beneficial effect they have on shelf-life. More recently, LAB have also gained interest as production hosts for various useful compounds, particularly compounds with sensitive applications, such as food ingredients and therapeutics. As for all industrial microorganisms, it is important to have a good understanding of the physiology and metabolism of LAB in order to fully exploit their potential, and for this purpose, many systems biology approaches are available.

Accelerating flux balance calculations in genome-scale metabolic models by localizing the application of loopless constraints.

Background: Genome-scale metabolic network models and constraint-based modeling techniques have become important tools for analyzing cellular metabolism. Thermodynamically infeasible cycles (TICs) causing unbounded metabolic flux ranges are often encountered. TICs satisfy the mass balance and directionality constraints but violate the second law of thermodynamics.

Standardizing biomass reactions and ensuring complete mass balance in genome-scale metabolic models.

Motivation: In a genome-scale metabolic model, the biomass produced is defined to have a molecular weight (MW) of 1 g mmol-1. This is critical for correctly predicting growth yields, contrasting multiple models and more importantly modeling microbial communities. However, the standard is rarely verified in the current practice and the chemical formulae of biomass components such as proteins, nucleic acids and lipids are often represented by undefined side groups (e.

SteadyCom: Predicting microbial abundances while ensuring community stability.

Genome-scale metabolic modeling has become widespread for analyzing microbial metabolism. Extending this established paradigm to more complex microbial communities is emerging as a promising way to unravel the interactions and biochemical repertoire of these omnipresent systems. While several modeling techniques have been developed for microbial communities, little emphasis has been placed on the need to impose a time-averaged constant growth rate across all members for a community to ensure co-existence and stability.

Re-wiring of energy metabolism promotes viability during hyperreplication stress in E. coli.

Chromosome replication in Escherichia coli is initiated by DnaA. DnaA binds ATP which is essential for formation of a DnaA-oriC nucleoprotein complex that promotes strand opening, helicase loading and replisome assembly. Following initiation, DnaAATP is converted to DnaAADP primarily by the Regulatory Inactivation of DnaA process (RIDA).

Can microbes compete with cows for sustainable protein production - A feasibility study on high quality protein.

An increasing population and their increased demand for high-protein diets will require dramatic changes in the food industry, as limited resources and environmental issues will make animal derived foods and proteins, gradually more unsustainable to produce. To explore alternatives to animal derived proteins, an economic model was built around the genome-scale metabolic network of E. coli to study the feasibility of recombinant protein production as a food source.

Farnesoid X Receptor Signaling Shapes the Gut Microbiota and Controls Hepatic Lipid Metabolism.

The gut microbiota modulates obesity and associated metabolic phenotypes in part through intestinal farnesoid X receptor (FXR) signaling. Glycine-β-muricholic acid (Gly-MCA), an intestinal FXR antagonist, has been reported to prevent or reverse high-fat diet (HFD)-induced and genetic obesity, insulin resistance, and fatty liver; however, the mechanism by which these phenotypes are improved is not fully understood. The current study investigated the influence of FXR activity on the gut microbiota community structure and function and its impact on hepatic lipid metabolism.

Elucidation of the regulatory role of the fructose operon reveals a novel target for enhancing the NADPH supply in Corynebacterium glutamicum.

The performance of Corynebacterium glutamicum cell factories producing compounds which rely heavily on NADPH has been reported to depend on the sugar being metabolized. While some aspects of this phenomenon have been elucidated, there are still many unresolved questions as to how sugar metabolism is linked to redox and to the general metabolism. We here provide new insights into the regulation of the metabolism of this important platform organism by systematically characterizing mutants carrying various lesions in the fructose operon.

Combining metabolic engineering and biocompatible chemistry for high-yield production of homo-diacetyl and homo-(S,S)-2,3-butanediol.

Biocompatible chemistry is gaining increasing attention because of its potential within biotechnology for expanding the repertoire of biological transformations carried out by enzymes. Here we demonstrate how biocompatible chemistry can be used for synthesizing valuable compounds as well as for linking metabolic pathways to achieve redox balance and rescued growth. By comprehensive rerouting of metabolism, activation of respiration, and finally metal ion catalysis, we successfully managed to convert the homolactic bacterium Lactococcus lactis into a homo-diacetyl producer with high titer (95mM or 8.

Estimating biological elementary flux modes that decompose a flux distribution by the minimal branching property.

Motivation: Elementary flux mode (EFM) is a useful tool in constraint-based modeling of metabolic networks. The property that every flux distribution can be decomposed as a weighted sum of EFMs allows certain applications of EFMs to studying flux distributions. The existence of biologically infeasible EFMs and the non-uniqueness of the decomposition, however, undermine the applicability of such methods.

Acetate kinase isozymes confer robustness in acetate metabolism.

Acetate kinase (ACK) (EC no: 2.7.2.

Decomposing flux distributions into elementary flux modes in genome-scale metabolic networks.

Motivation: Elementary flux mode (EFM) is a fundamental concept as well as a useful tool in metabolic pathway analysis. One important role of EFMs is that every flux distribution can be decomposed into a set of EFMs and a number of methods to study flux distributions originated from it. Yet finding such decompositions requires the complete set of EFMs, which is intractable in genome-scale metabolic networks due to combinatorial explosion.