mGem: Revisiting bacterial overflow metabolism.

Bacterial overflow metabolism, where cells perform oxidative fermentation despite the availability of ample oxygen and carbon sources, remains a long-standing paradox in microbial metabolism. Traditional explanations attribute this phenomenon to bacterial physiology, including rapid growth, redox imbalances, competitive advantages in microbiomes, and catabolite repression. However, recent advances in systems biology have revealed additional contributing factors, such as thermodynamic constraints, proteome allocation efficiency, bioenergetics, and the membrane real estate hypothesis.

High enzyme promiscuity in lignin degradation mechanisms in CGA009.

Lignin is a universal waste product of the agricultural industry and is currently seen as a potential feedstock for more sustainable manufacturing. While it is the second most abundant biopolymer in the world, most of it is currently burned as it is a very recalcitrant material. Many recent studies, however, have demonstrated the viability of biocatalysis to improve the value of this feedstock and convert it into more useful chemicals, such as polyhydroxybutyrate, and clean fuels like hydrogen and n-butanol.

Transcriptome enhanced rice grain metabolic model identifies histidine level as a marker for grain chalkiness.

Rising temperatures due to global warming can negatively impact rice grain quality and yield. This study investigates the effects of increased warmer night temperatures (WNT), a consequence of global warming, on the quality of rice kernel, particularly grain chalkiness. By integrating computational and experimental approaches, we used a rice grain metabolic network to discover the metabolic factors of chalkiness.

Enzyme-constrained metabolic model of identified glycerol-3-phosphate dehydrogenase as an alternate electron sink.

Unlabelled: , the causative agent of syphilis, poses a significant global health threat. Its strict reliance on host-derived nutrients and difficulties in cultivation have impeded detailed metabolic characterization. In this study, we present iTP251, the first genome-scale metabolic model of , reconstructed and extensively curated to capture its unique metabolic features.

Fermi calculations enable quick downselection of target genes and process optimization in photosynthetic systems.

Understanding how photosynthetic organisms including plants and microbes respond to their environment is crucial for optimizing agricultural practices and ensuring food and energy security, particularly in the context of climactic change and sustainability. This perspective embeds back-of-the-envelope calculations across a photosynthetic organism design and scale up workflow. Starting from the whole system level, we provide a recipe to pinpoint key genetic targets, examine the logistics of detailed computational modeling, and explore environmentally driven phenotypes and feasibility as an industrial biofuel production chassis.

Robust Prediction of Enzyme Variant Kinetics with RealKcat.

Accurate prediction of kinetic parameters is crucial for understanding known and tailoring novel enzymes for biocatalysis. Current models fail to capture mutation effects on catalytically essential residues, limiting their utility in enzyme design. We grid-searched through ten model architectures (25,671 hyperparameter combinations) to identify a gradient-based additive framework called RealKcat, trained on 27,176 experimental entries curated manually (KinHub-27k) by screening 2,158 articles.

A thermodynamic bottleneck in the TCA cycle contributes to acetate overflow in .

During aerobic growth, relies on acetate overflow metabolism, a process where glucose is incompletely oxidized to acetate, for its bioenergetic needs. Acetate is not immediately captured as a carbon source and is excreted as waste by cells. The underlying factors governing acetate overflow in have not been identified.

Enzyme-constrained Metabolic Model of Identified Glycerol-3-phosphate Dehydrogenase as an Alternate Electron Sink.

, the causative agent of syphilis, poses a significant global health threat. Its strict intracellular lifestyle and challenges in cultivation have impeded detailed metabolic characterization. In this study, we present iTP251, the first genome-scale metabolic model of , reconstructed and extensively curated to capture its unique metabolic features.

A thermodynamic bottleneck in the TCA cycle contributes to acetate overflow in .

During aerobic growth, relies on acetate overflow metabolism, a process where glucose is incompletely oxidized to acetate, for its bioenergetic needs. Acetate is not immediately captured as a carbon source and is excreted as waste by cells. The underlying factors governing acetate overflow in have not been identified.

Metabolic model guided CRISPRi identifies a central role for phosphoglycerate mutase in persistence.

Unlabelled: Upon nutrient starvation, serovar L2 (CTL) shifts from its normal growth to a non-replicating form, termed persistence. It is unclear if persistence reflects an adaptive response or a lack thereof. To understand this, transcriptomics data were collected for CTL grown under nutrient-replete and nutrient-starved conditions.

Optimal Protein Allocation Controls the Inhibition of GltA and AcnB in .

(Ngo) is a major concern for global public health due to its severe implications for reproductive health. Understanding its metabolic phenotype is crucial for comprehending its pathogenicity. Despite Ngo's ability to encode TCA cycle proteins, GltA and AcnB, their activities are notably restricted.

A multi-organ maize metabolic model connects temperature stress with energy production and reducing power generation.

Climate change has adversely affected maize productivity. Thereby, a holistic understanding of metabolic crosstalk among its organs is important to address this issue. Thus, we reconstructed the first multi-organ maize metabolic model, ZMA6517, and contextualized it with heat and cold stress transcriptomics data using expression distributed reaction flux measurement (EXTREAM) algorithm.

The Inherited Intestinal Microbiota from Myeloid-Specific ZIP8KO Mice Impairs Pulmonary Host Defense against Pneumococcal Pneumonia.

Intestinal dysbiosis increases susceptibility to infection through the alteration of metabolic profiles, which increases morbidity. Zinc (Zn) homeostasis in mammals is tightly regulated by 24 Zn transporters. ZIP8 is unique in that it is required by myeloid cells to maintain proper host defense against bacterial pneumonia.

Supplementation of Sulfide or Acetate and 2-Mercaptoethane Sulfonate Restores Growth of the Δ Deletion Mutant during Methylotrophic Methanogenesis.

Methanogenic archaea are important organisms in the global carbon cycle that grow by producing methane gas. is a methanogenic archaeum that can grow using methylated compounds, carbon monoxide, or acetate and produces renewable methane as a byproduct. However, there is limited knowledge of how combinations of substrates may affect metabolic fluxes in methanogens.

Opening the door to nitrogen fixation in oxygenic phototrophs.

Conveying biological nitrogen fixation (BNF) to photosynthetic species may be the next agricultural revolution, yet poses major engineering challenges. Liu et al. created a diazotrophic strain of a previously non-nitrogen-fixing species, the cyanobacterium Synechocystis sp.

Characterizing the Interplay of Rubisco and Nitrogenase Enzymes in Anaerobic-Photoheterotrophically Grown Rhodopseudomonas palustris CGA009 through a Genome-Scale Metabolic and Expression Model.

Rhodopseudomonas palustris CGA009 is a Gram-negative purple nonsulfur bacterium that grows phototrophically by fixing carbon dioxide and nitrogen or chemotrophically by fixing or catabolizing a wide array of substrates, including lignin breakdown products for its carbon and fixing nitrogen for its nitrogen requirements. It can grow aerobically or anaerobically and can use light, inorganic, and organic compounds for energy production. Due to its ability to convert different carbon sources into useful products during anaerobic growth, this study reconstructed a metabolic and expression (ME) model of R.

Dissecting the metabolic reprogramming of maize root under nitrogen-deficient stress conditions.

The growth and development of maize (Zea mays L.) largely depends on its nutrient uptake through the root. Hence, studying its growth, response, and associated metabolic reprogramming to stress conditions is becoming an important research direction.

Enhancing in silico strain design predictions through next generation metabolic modeling approaches.

The reconstruction and analysis of metabolic models has garnered increasing attention due to the multitude of applications in which these have proven to be practical. The growing number of generated metabolic models has been accompanied by an exponentially expanding arsenal of tools used to analyze them. In this work, we discussed the biological relevance of a number of promising modeling frameworks, focusing on the questions and hypotheses each method is equipped to address.